Search Results (35)

To further explore the anti-inflammatory components of the seeds of Dolichos lablab L., a comprehensive phytochemical investigation was conducted using diverse chromatographic and spectrometric technologies, as well as chemical reactions. As a result, ten previously unreported terpenoid glycosides, namely dolilabterpenosides A, B, C₁–C₃, D, E, and F₁–F₃ (1–10), along with four known analogues (11–14), initially identified from Dolichos genus, were obtained. In addition, the lipopolysaccharide (LPS)-induced RAW264.7 cell model was employed to detect the expression levels of nitric oxide (NO), inflammatory cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-1β to assess the anti-inflammatory activities of the obtained compounds. The results of bioactive assay showed that compounds 1, 4–7, and 10–12 showed significant inhibitory activity on NO release in RAW264.7 cells in a dose-dependent manner, and all of them were demonstrated to inhibit the increase in TNF-α and IL-Iβ levels in the supernatant of RAW264.7 cells stimulated by LPS. Full article

Pomegranate (Punica granatum L.) has long been recognised for its rich antioxidant profile and potential health benefits. Recent research has expanded its therapeutic potential to include antiangiogenic properties, which are crucial for inhibiting the growth of tumours and other pathological conditions involving aberrant blood vessel formation. This review consolidates current findings on the antiangiogenic effects of pomegranate extracts. We explore the impact of pomegranate polyphenols, including ellagic acid, punicalagin, anthocyanins, punicic acid and bioactive polysaccharides on key angiogenesis-related pathways and endothelial cell function. Emphasis is placed on the effects of these extracts as phytocomplexes rather than isolated compounds. Additionally, we discuss the use of pomegranate by-products, such as peels and seeds, in the preparation of extracts within a green chemistry and circular economy framework, highlighting their value in enhancing extract efficacy and sustainability. By primarily reviewing in vitro and in vivo preclinical studies, we assess how these extracts modulate angiogenesis across various disease models and explore their potential as adjunctive therapies for cancer and other angiogenesis-driven disorders. This review also identifies existing knowledge gaps and proposes future research directions to fully elucidate the clinical utility of pomegranate extracts in therapeutic applications. Full article

Background: Metastasis is the main cause of cancer-related deaths, but efficient targeted therapies against metastasis are still missing. Major gaps exist in our understanding of the metastatic cascade, as existing methods cannot combine sensitivity, robustness, and practicality to dissect cancer progression. Addressing this issue requires improved strategies to distinguish early metastatic colonization from metastatic outgrowth. Methods: Luciferase-labelled MDA-MB-231, MCF7, and 4T1 breast cancer cells were spiked into samples from tumour-naïve mice to establish the limit of detection for disseminated tumour cells. Luciferase-labelled breast cancer cells (±unlabelled cancer-associated fibroblasts; CAFs) were orthotopically implanted in immunocompromised mice. An ex vivo luciferase assay was used to quantify tumour cell dissemination. Results: In vitro luciferase assay confirmed a linear and positive correlation between cancer cell numbers and the bioluminescence detected at single cell level in blood, brain, lung, liver, and mammary fat pad samples. Remarkably, single luciferase-labelled cancer cells were detectable in all of these sites, as the bioluminescence quantified in the analysed samples was substantially higher than background levels. Ex vivo, circulating tumour cells, metastasis, and tumour self-seeding were detected in all samples from animals implanted with highly metastatic luciferase-labelled MDA-MB-231 cells. In turn, detection of poorly metastatic luciferase-labelled MCF7 cells was scarce but significantly enhanced upon co-implantation with CAFs as early as 20 days after the experiment was initiated. Conclusions: These results demonstrate the feasibility of using an ultrasensitive luciferase-based method to dissect the mechanisms of early metastatic colonization to improving the development of antimetastatic therapies. Full article

Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. Recently reported outcomes demonstrating improvements in patient survival have led to an upsurge in interest in MRT particularly for the treatment of prostate cancer. Unfortunately, between 30% and 40% of patients do not respond. Further normal tissue exposure, especially kidney and salivary gland due to receptor expression, result in toxicity, including dry mouth. Predictive biomarkers to select patients who will benefit from MRT are crucial. Whilst pre-treatment imaging with imaging versions of the therapeutic agents is useful in demonstrating tumour binding and potentially organ toxicity, they do not necessarily predict patient benefit, which is dependent on tumour radiosensitivity. Transcript-based biomarkers have proven useful in tailoring external beam radiotherapy and adjuvant treatment. However, few studies have attempted to derive signatures for MRT response prediction. Here, transcriptomic studies that have identified genes associated with clinical radionuclide exposure have been reviewed. These studies will provide potential features for seeding multi-component biomarkers of MRT response. Full article

As a nutrient-rich multigrain crop, buckwheat is a typical “medicinal food homology” crop that is rich in flavonoids, including rutin and various vitamins. It has positive anti-oxidant and anti-tumour properties and lowers blood pressure. However, due to strict self-crossing characteristics, slow progress has been made in Tartary buckwheat (TB) cross-breeding, resulting in the slow breeding of new varieties of new TB varieties, which has limited the improvement of yield and quality. Therefore, mutant breeding is a rapid and effective technique for broadening and innovating TB breeding. In recent years, improving qualities related to yield, lodging resistance, and stability have become key points in TB breeding. Based on the above findings, excellent, potentially valuable TB lines with rich phenotypes were obtained for the TB mutation library via ethyl methanesulfonate (EMS), laying a foundation for creating new TB germplasms. In this study, we systematically investigated more than 10 agronomic traits of JQ2 and JQ4 mutants, including plant type, leaf colour, grain type, grain colour, grain number per plant, grain length, grain width, grain weight per plant, and 1000-grain weight. The results show that the maximum number of grains per plant was 1956, the weight was 32.84 g, and the 1000-grain weight was 30.89 g. The maximum number of grains per JQ4 plant was 2308, and the weight was 44.82 g. The maximum 1000-grain weight was 24.7 g. Among the 295 JQ2 mutants and 153 JQ4 mutants, 10 flavonoids (orientin, morin, quercetin, kaempferol, luteolin, naringin, hesperetin, myricetin, hesperidin, and rutin) were detected with near infrared spectroscopy (NIR). The mutants were divided into five groups according to the flavonoid content of the JQ2 mutants, of which the first group included 31 individual lines. and the second to fifth groups included 70, 69, 72, and 53 lines, respectively. The JQ4 mutants were divided into four classes, of which 41, 50, 32, and 30 were individual lines, respectively, with the highest rutin content being 82.06 mg/g. In summary, through systematic analysis and screening of the agronomic traits and flavonoid contents of JQ2 and JQ4 mutant seeds, we obtained three lines with a high 1000-grain weight, including two JQ2 mutant lines (30.89 g) and one JQ4 mutant line, which reached 24.70 g and ten lines with high grain weight per plant. This included 8 JQ2 mutants and 2 JQ4 mutants, as well as 72 high-rutin mutants (including 31 lines from JQ2 and 41 lines from JQ4 mutants). These elite lines provide the material basis for creating TB germplasms with excellent qualities and cultivation characteristics. Full article

(1) Background: In the last decade, the number of detected renal cancer cases has increased, with the highest incidence in Western countries. Although renal biopsy is reported as a safe procedure, it is not adopted in all centres. As it is not possible to accurately distinguish benign tumours using imaging, this may lead to overtreatment. Most of the cancer detected on imaging is treated by surgery, radiofrequency ablation (RFA), or cryotherapy. (2) Methods: This was a single-centre retrospective study of 225 patients studied preoperatively with ultrasound (US)/CT-guided renal biopsy, with the aim of supporting clinical management. Decisions regarding the biopsy were based on either MDT indication or physician preference. US-guided renal biopsy was the first option for all patients; CT-guided biopsy was used when US-guided biopsy was not feasible. The efficacy of renal biopsy in terms of diagnostic performance and the concordance between biopsy results and definitive pathology were investigated. Additionally, adverse events related to the biopsy were recorded and analysed. Data collected throughout the study were analysed using binary logistic regression, Fisher’s exact test, and Pearson’s chi-square test to investigate possible correlations between post-procedural complications and the size of the lesion. (3) Results: Renal biopsy was not diagnostic in 23/225 (10.2%) patients. A CT-guided approach was necessary in 20/225 patients after failure of US-guided biopsy. The complication rate of renal biopsy was 4.8% overall—all Clavien grade I and without any serious sequelae. Interestingly, complications occurred in patients with very different sizes of renal cell carcinoma. No correlation between complications and anticoagulant/antiplatelet drugs was found. No seeding was reported among the patients who underwent partial/radical nephrectomy. (4) Conclusions: Renal biopsy was shown to be safe and effective, with a high concordance between biopsy results and definitive pathology and a low rate of complications. The use of a CT-guided approach whenever the US-guided approach failed improved the diagnostic performance of renal biopsy. Full article

The management of bone defects is complicated by the presence of clinical conditions, such as critical-sized defects created by high-energy trauma, tumour resection, infection, and skeletal abnormalities, whereby the bone regeneration capacity is compromised. A bone scaffold is a three-dimensional structure matrix serving as a template to be implanted into the defects to promote vascularisation, growth factor recruitment, osteogenesis, osteoconduction, and mechanical support. This review aims to summarise the types and applications of natural and synthetic scaffolds currently adopted in bone tissue engineering. The merits and caveats of natural and synthetic scaffolds will be discussed. A naturally derived bone scaffold offers a microenvironment closer to in vivo conditions after decellularisation and demineralisation, exhibiting excellent bioactivity, biocompatibility, and osteogenic properties. Meanwhile, an artificially produced bone scaffold allows for scalability and consistency with minimal risk of disease transmission. The combination of different materials to form scaffolds, along with bone cell seeding, biochemical cue incorporation, and bioactive molecule functionalisation, can provide additional or improved scaffold properties, allowing for a faster bone repair rate in bone injuries. This is the direction for future research in the field of bone growth and repair. Full article

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2–1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects. Full article

Aesculus hippocastanum L., also known as horse chestnut, is an ornamental tree whose seeds are mostly discarded in landfills in the regions where they are grown. However, recent studies have shown that these seeds can be a source of interesting compounds for several industries. This work aimed to chemically characterize horse chestnut seeds at the level of compounds recognized for their wide bioactivity, i.e., organic acids, including phenolic compounds, using chromatographic methodologies (UFLC-DAD and LC-DAD-ESI/MSn). In addition, the bioactivity of these seeds was evaluated by in vitro methodologies, seeking to relate the respective (bio)activity to the compounds present in the endocarp (husk), seed coat (skin), and peeled seed (pulp). The antioxidant activity (lipid peroxidation inhibition and oxidative haemolysis inhibition), antibacterial potential (against Gram-positive and Gram-negative bacteria) and cytotoxicity (in human tumour cell lines and porcine liver primary cells) were evaluated. Kaempferol-O-pentoside-O-hexoside-O-hexoside was the main phenolic identified in the pulp. At the same time, (-)-epicatechin and β-type (epi)catechin dimer were the major phenolics present in husk and skin, respectively. In general, A. hippocastanum extracts presented antioxidant and antibacterial potential, without toxicity up to the maximal tested dose. Overall, these findings anticipate potential applications of A. hippocastanum seeds in food- or pharmaceutical-related uses. Full article

Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient’s clinical management. Full article

Momordica cochinchinensis is a herbal medicine used throughout Asia and this study investigated the antimelanoma potentials and molecular mechanisms of M. cochinchinensis seed with emphasis on extraction to optimise bioactivity. Overall, the aqueous extract was superior, with a wider diversity and higher concentration of proteins and peptides that was more cytotoxic to the melanoma cells than other extraction solvents. The IC50 of the aqueous extract on melanoma cells were similar to treatment with current anticancer drugs, vemurafenib and cisplatin. This cytotoxicity was cancer-specific with lower cytotoxic effects on HaCaT epidermal keratinocytes. Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma. Full article

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy. Full article

A meta-analysis of 1470 isolated pancreatic metastases of renal cell carcinoma revealed, that, in addition to the unusual exclusive occurrence of pancreatic metastases and the favourable treatment results, the isPMRCC is characterised by further peculiarities of the clinical course: The lack of prognostic significance of volume and growth rate dependent risk factors and the independence of treatment results from standard or local resections. As an explanation for all these peculiarities, according to today’s knowledge, a strong acting seed and soil mechanism can serve, which allows embolized tumour cells to grow to metastases only in the pancreas, and prevents them definitively or for years in all other organs. The good prognosis affects not only isolated PM, but also multi-organ metastases of the RCC, in which the additional occurrence of PM is also associated with a better prognosis. Genetic studies revealed specific changes in cases of PM of RCC: Lack of loss of 9p21.3 and 14q31.2, which are otherwise specific gene mutations at the onset of generalization, a low weight genome instability index, i.e., high genetic stability, and a low rate of PAB1 and a high rate of BPRM1 alterations, which signal a more favourable course. The cause of pancreatic organotropism in isPMRCC is still unclear, so only those factors that have been identified as promoting organotropism in other, more frequent tumour entities can be presented: Formation of the pre-metastatic niche, chemokine receptor–ligand mechanism, ability to metabolic adaptation, and immune surveillance. Full article

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a cell–cell adhesion protein conferring heterotypic and homotypic interactions between cells of the same type and different types. It is aberrantly expressed in various cancer types and has been shown to be a regulator of cancer metastasis. In the present study, we investigated potential roles of ALCAM in the peritoneal transcoelomic metastasis in gastrointestinal cancers, a metastatic type commonly occurred in gastro-intestinal and gynaecological malignancies and resulting in poor clinical outcomes. Specifically, we studied whether ALCAM acts as both a ‘seed’ receptor in these tumour cells and a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. Gastric cancer and pancreatic cancer tissues with or without peritoneal metastasis were compared for their levels of ALCAM expression. The impact of ALCAM expression in these tumours was also correlated to the patients’ clinical outcomes, namely peritoneal metastasis-free survival. In addition, cancer cells of gastric and pancreatic origins were used to create cell models with decreased or increased levels of ALCAM expression by genetic knocking down or overexpression, respectively. Human peritoneal mesothelial cells were also genetically transfected to generate cell models with different profiles of ALCAM expression. These cell models were used in the tumour-mesothelial interaction assay to assess if and how the interaction was influenced by ALCAM. Both gastric and pancreatic tumour tissues from patients who developed peritoneal metastases had higher levels of ALCAM transcript than those without. Patients who had tumours with high levels of ALCAM had a much shorter peritoneal metastasis free survival compared with those who had low ALCAM expression (p = 0.006). ALCAM knockdown of the mesothelial cell line MET5A rendered the cells with reduced interaction with both gastric cancer cells and pancreatic cancer cells. Likewise, levels of ALCAM in both human gastric and pancreatic cancer cells were also a determining factor for their adhesiveness to mesothelial cells, a process that was likely to be triggered the phosphorylation of the SRC kinase. A soluble ALCAM (sALCAM) was found to be able to inhibit the adhesiveness between cancer cells and mesothelial cells, mechanistically behaving like a SRC kinase inhibitor. ALCAM is an indicator of peritoneal metastasis in both gastric and pancreatic cancer patients. It acts as not only a potential peritoneal ‘soil’ receptor of tumour seeding but also a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. These findings have an important therapeutic implication for treating peritoneal transcoelomic metastases. Full article