Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells.

BACKGROUND: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. METHODS: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. RESULTS: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. CONCLUSION: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.Cur-NPs induce apoptotic cell death of Liver cancer cells.Cur-NPs have ant-angiogenesis and metastasis effect.

An Integrative Multi-Omics Analysis of The Molecular Links between Aging and Aggressiveness in Thyroid Cancers.

Aging modifies risk in all cancers, but age is used as a clinical staging criterion uniquely in thyroid cancer (TC). The molecular drivers of age-dependent TC onset and aggressiveness remain poorly understood. We applied an integrative, multi-omics data analysis approach to characterize these signatures. Our analysis reveals that aging, independent of BRAFV600E mutational status, drives a significant accumulation of aggressiveness-related markers and poorer survival outcomes, most noticeably at age 55 and over. We identified that chromosomal alterations in loci 1p/1q as aging-associated drivers of aggressiveness, and that depleted infiltration with tumor surveillant CD8+T and follicular helper T cells, dysregulation of proteostasis- and senescence-related processes, and ERK1/2 signaling cascade are key features of the aging thyroid and TC onset/progression and aggressiveness in aging patients but not in young individuals. A panel of 23 genes, including those related to cell division such as CENPF, ERCC6L, and the kinases MELK and NEK2, were identified and rigorously characterized as aging-dependent and aggressiveness-specific markers. These genes effectively stratified patients into aggressive clusters with distinct phenotypic enrichment and genomic/transcriptomic profiles. This panel also showed excellent performance in predicting metastasis stage, BRAFV600E, TERT promoter mutation, and survival outcomes and was superior to the American Thyroid Association (ATA) methodology in predicting aggressiveness risk. Our analysis established clinically relevant biomarkers for TC aggressiveness factoring in aging as an important component.

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na2SeO3) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na2SeO3 (2 mg/kg), and AMPH + PDG + Na2SeO3. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na2SeO3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na2SeO3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na2SeO3 displayed markedly lower IL-1ß and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na2SeO3. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na2SeO3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity.

BACKGROUND: The present study was conducted to investigate the chemopreventive effects of garlic extract and silymarin on N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl(4))-induced hepatotoxicity in male albino rats. METHODS AND RESULTS: Animals were pretreated with garlic, silymarin or both for one week prior to the injection of NDEA. Then animals received a single injection of NDEA followed by weekly subcutaneous injections of CCl(4) for 6 weeks. Oral administration was then continued along with the injection of CCl(4) for the duration of the experiment. Serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST) and glutathione reductase (GSR) were measured. Injection of NDEA induced a significant elevation in serum AST, ALT and ALP. In the liver, NDEA increased oxidative stress through the increase in LPO and decrease in SOD, and GSH-dependent enzymes. Although administration of garlic or silymarin significantly reduced the liver toxicity, combined administration was more effective in preventing the development of hepatotoxicity. CONCLUSION: These novel findings suggest that silymarin and garlic have a synergistic effect, and could be used as hepatoprotective agents against hepatotoxicity.