Antitumor Properties Research Articles

Chondroitin sulfate-based universal nanoparticle delivers angiogenic inhibitor and paclitaxel to exhibit a combination of chemotherapy and anti-angiogenic therapy

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.

Evaluation of in vitro antioxidative and protective effects of kefir on cyclophosphamide-upon oxidative stress and lung damage in rats

Purpose: Kefir, a natural probiotic, has antioxidative and antitumor properties, as well as potential beneficial properties resulting from microbial species and fermentation. Cyclophosphamide (CYP) is a cytotoxic drug that is highly preferred in cancer therapy but can suppress both humoral and cellular immunity. The use of effective doses is limited because CYP has an immunosuppressive effect and causes multiple organ toxicity such as the lungs, and the use of effective high doses is restricted. Methods: Wistar albino rats were divided into 6 groups. As; control, 150 mg/kg CYP, 5 mg/kg kefir, 5 mg/kg kefir +150 CYP, l0 mg/kg kefir, l0 mg/kg kefir+150 CYP. Fermented kefirs from the 1st, 2nd and 3rd days were mixed and given to the rats for 12 days, while CYP was given as a single dose and ip on the 12th day of the experiment. The received parameters were evaluated. Results: It was observed that the OSI value, which indicates oxidative stress, increased in the CYP-administered group, and this level approached control in the CYP+kefir groups. In addition, while degeneration, intense inflammation in the interalveolar area, collapse of the alveoli, and intense inflammation around the bronchioles were observed in the lung parenchyma of CYP-administered rats, it was observed that these effects were effectively improved in the groups given kefir+CYP. Conclusion: In conclusion, in our study, it was observed that kefir showed antioxidative and protective effects on CYP-induced oxidative stress, congestion, alveolar damage and inflammation.

Genome-wide analysis of bZIP transcription factors and their expression patterns in response to methyl jasmonate and low-temperature stresses in Platycodon grandiflorus.

Platycodon grandiflorus belongs to the genus Platycodon and has many pharmacological effects, such as expectorant, antitussive, and anti-tumor properties. Among transcription factor families peculiar to eukaryotes, the basic leucine zipper (bZIP) family is one of the most important, which exists widely in plants and participates in many biological processes, such as plant growth, development, and stress responses. However, genomic analysis of the bZIP gene family and related stress response genes has not yet been reported in P. grandiflorus. P. grandiflorus bZIP (PgbZIP) genes were first identified here, and the phylogenetic relationships and conserved motifs in the PgbZIPs were also performed. Meanwhile, gene structures, conserved domains, and the possible protein subcellular localizations of these PgbZIPs were characterized. Most importantly, the cis-regulatory elements and expression patterns of selected genes exposed to two different stresses were analyzed to provide further information on PgbZIPs potential biological roles in P. grandiflorus upon exposure to environmental stresses. Forty-six PgbZIPs were identified in P. grandiflorus and divided into nine groups, as displayed in the phylogenetic tree. The results of the chromosomal location and the collinearity analysis showed that forty-six PgbZIP genes were distributed on eight chromosomes, with one tandem duplication event and eleven segmental duplication events identified. Most PgbZIPs in the same phylogenetic group have similar conserved motifs, domains, and gene structures. There are cis-regulatory elements related to the methyl jasmonate (MeJA) response, low-temperature response, abscisic acid response, auxin response, and gibberellin response. Ten PgbZIP genes were selected to study their expression patterns upon exposure to low-temperature and MeJA treatments, and all ten genes responded to these stresses. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that the expression levels of most PgbZIPs decreased significantly within 6 h and then gradually increased to normal or above normal levels over the 90 h following MeJA treatment. The expression levels of all PgbZIPs were significantly reduced after 3 h of the low-temperature treatment. These results reveal the characteristics of the PgbZIP family genes and provide valuable information for improving P. grandiflorus's ability to cope with environmental stresses during growth and development.

Post-surgery statin use contributes to favorable outcomes in patients with early breast cancer

BackgroundStatins are a group of lipid-lowering drugs with pleiotropic effects that include, but are not limited to the inhibition of cholesterol synthesis resulting in a wide range of anti-inflammatory, anti-tumor, immunomodulatory, and anti-thrombotic properties. This study aimed to determine the impact of the prior to- or after- breast surgery usage of statins on the tumor prognosis in breast cancer (BC) patients. MethodsA cohort of patients diagnosed with early invasive ductal BC (n=301) at the Hospital Italiano de Buenos Aires, Argentina, with a minimum follow-up period of 10 years after the surgical procedure were included and stratified according to the time of use of statins and type of statin used. Then, local relapse-free survival (RFS), metastasis-free survival (MFS), bone metastasis-free survival (BMFS), visceral metastasis-free (VMFS), mixed metastasis (bone and visceral)-free survival (mix-MFS) and overall survival (OS) were analyzed. ResultsStatins usage after breast surgery was related with lesser metastatic occurrence (p=0.017), lower number of metastatic foci (p=0.034) and fewer dead events (p=0.041), as well as longer MFS (p=0.013) and OS (p=0.027). When stratified by the nature of statins (hydrophilic or lipophilic), only the relatively hydrophilic statin rosuvastatin (ROSU) had an impact on the increase of MFS and OS (p=0.018 and p=0.030, respectively). ConclusionPost-surgery statins usage was associated with increased MFS and OS, with increased benefits of ROSU over simvastatin (SIM) or atorvastatin (ATOR). These results set the rationale for additional studies addressing the use of statins, and particularly, rosuvastatin, to improve the outcome of BC patients.

PD-L1 targeted peptide demonstrates potent antitumor and immunomodulatory activity in cancer immunotherapy.

In recent years, immunotherapy has been emerging as a promising alternative therapeutic method for cancer patients, offering potential benefits. The expression of PD-L1 by tumors can inhibit the T-cell response to the tumor and allow the tumor to evade immune surveillance. To address this issue, cancer immunotherapy has shown promise in disrupting the interaction between PD-L1 and its ligand PD-1. We used mirror-image phage display technology in our experiment to screen and determine PD-L1 specific affinity peptides (PPL-C). Using CT26 cells, we established a transplanted mouse tumor model to evaluate the inhibitory effects of PPL-C on tumor growth in vivo. We also demonstrated that PPL-C inhibited the differentiation of T regulatory cells (Tregs) and regulated the production of cytokines. In vitro, PPL-C has a strong affinity for PD-L1, with a binding rate of 0.75 μM. An activation assay using T cells and mixed lymphocytes demonstrated that PPL-C inhibits the interaction between PD-1 and PD-L1. PPL-C or an anti-PD-L1 antibody significantly reduced the rate of tumor mass development in mice compared to those given a control peptide (78% versus 77%, respectively). The results of this study demonstrate that PPL-C prevents or retards tumor growth. Further, immunotherapy with PPL-C enhances lymphocyte cytotoxicity and promotes proliferation in CT26-bearing mice. PPL-C exhibited antitumor and immunoregulatory properties in the colon cancer. Therefore, PPL-C peptides of low molecular weight could serve as effective cancer immunotherapy.

Polysaccharides from Russula: a review on extraction, purification, and bioactivities.

Russula, a renowned edible fungus, has gained popularity as a functional food among diverse populations due to the abundant presence of amino acids, proteins, and polysaccharides. As the primary constituents of Russula, polysaccharides exhibit a wide range of biological properties, making them an exceptional choice for incorporation into food, medicines, and diverse biotechnological applications. This review provides a summary of the recent research on the extraction, purification, and biological applications of polysaccharides from various Russula spp. Currently, there are many advanced extraction technologies, such as hot water-based extraction, alkali-based extraction, ultrasonic-assisted extraction and microwave-assisted extraction. Hence, the latest progress of extraction technologies, as well as their advantages and limitations will be discusses and summarizes in this review. The separation and purification methods of polysaccharide from Russula were introduced, including ethanol precipitation, deproteinization and gel filtration chromatography. It also focuses on exploring the diverse bioactive capabilities of Russula, including anti-oxidant, anti-tumor, immunomodulatory, anti-inflammation, and anti-bacterial properties. Hence, this review aims to foster a comprehensive understanding of the polysaccharides from various Russula spp. and pave the way for their promising and potential future applications in the medical and functional fields.

A review of recent research on the antimicrobial activities of thiosemicarbazone-based compounds

Thiosemicarbazones can be synthesized by condensation of thiosemicarbazides with ketones or aldehydes and play a role as precursors in the synthesis of many compounds such as thiazoles. They can exhibit many biological activities such as anti-inflammatory, antitumor, and antimicrobial properties. The discovery of antibiotics was an important milestone in the treatment of bacterial infections. However, antimicrobial resistance developed by microorganisms has created the need to discover new antimicrobial agents. Thiosemicarbazones and thiosemicarbazone-based compounds show significant antimicrobial potential. This review investigates the antimicrobial activity results of 244 Thiosemicarbazones and Thiosemicarbazone-based compounds over the last five years. We summarized some articles on thiosemicarbazones and their hybrids showing only antibacterial and antifungal activity in Web of Science (WOS) between 2019 and 2024.

Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

Structural clarification of mannoglucan GSBP-2 from Ganoderma sinense and its effects on triple-negative breast cancer migration and invasion

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, β-d-Glcp-(1→, β-d-GlcpA-(1→, →3)-β-d-Glcp-(1→, →3)-β-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-β-d-Manp-(1→, and →3,6)-β-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial–mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial–mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.

The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy

BackgroundAnaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. ObjectiveIn this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. MethodsA series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. ResultsHF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-β-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. ConclusionThis study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.

Natural deep eutectic solvents: promising agents for extracting substances from plant materials

There is a growing trend to replace synthetic products or additives with natural alternatives. Historical experience and developments in human health science demonstrate the adverse effects of xenobiotics on human health and metabolism. The shift toward natural products is essential for enhancing vitality, social activity, and overall quality of life, while preventing adverse events and diseases. Industries such as pharmaceutical, cosmetic, and food are increasingly turning to natural and biologically active chemicals isolated from plants or microorganisms. However, the primary challenge lies in developing effective and eco-friendly methods for their isolation. Deep eutectic solvents are a mixture of two or more components with unique properties like low volatility, low melting points, ease of preparation, cost-effective starting materials, and minimal toxicity to humans. They have gained popularity as environmentally friendly agents for extracting biologically active substances from medicinal plants and as safe alternatives for various industries, including food and pharmaceuticals. Traditional organic solvent extraction methods have several drawbacks, including long extraction times, safety concerns, environmental damage, high cost, and the need for large solvent volumes. This review summarizes research progress on the benefits of using deep eutectic solvents for extracting bioactive compounds, including phenolic acid, flavonoids, isoflavones, catechins, polysaccharides, curcuminoids, proanthocyanidin, phycocyanin, gingerols, ginsenosides, anthocyanins, rutin, and chlorogenic acids. Additionally, it examines the biological activity of these extracts, including antioxidant, antibacterial, and antitumor properties.

Effect of per os administration of fucoxanthin alcoholic and oil extracts to Balb/c mice on biochemical parameters and serum cytokine level

Microalgae are a source of various biologically active substances, including carotenoids. One of the carotenoids of diatom microalgae is fucoxanthin, which has antioxidant, antimicrobial, antitumour and anti-inflammatory properties that can be used in the treatment of a wide range of human and animal pathologies. The aim of the study was to investigate the effect of alcohol and oil extract of fucoxanthin on biochemical parameters and levels of serum cytokines in mice during intragastric administration. Material and methods. Fucoxanthin extracts from the microalga Nanofrustulum shiloi were used. Mice of Balb/c strain were intragastrically administrated with 0.5 ml of oil (500 μg/ml) or alcoholic extract of fucoxanthin (187.5 μg/ml), mice in the comparison group were given 0.5 ml of olive oil or 45% ethyl alcohol once a day within 5 days. On the 8th day, blood serum was obtained and the level of albumin, triglycerides, cholesterol, low (LDL) and high density lipoproteins (HDL), urea, uric acid, creatinine, aspartate (AST) and alanine aminotransferases (ALT), lactate, stable nitric oxide (NO) metabolites (nitrites), cytokines (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) was determined using ELISA with photometric detection. Results and discussion. In the comparison group, ethyl alcohol promoted an increase in serum triglyceride, cholesterol, LDL, HDL, ALT, AST, nitrite, IL-10, IFN-γ and TNF-α content compared to intact animals. Fucoxanthin alcoholic extract administration increased the level of LDL, HDL, uric acid, TNF-α and decreased albumin, cholesterol, uric acid, creatinine, ALT, AST, IL-6 content compared to control. The olive oil group showed a decrease in serum triglycerides, cholesterol, urea, uric acid, ALT and AST content but an increase in LDL, HDL, nitrite level compared to the control. Administration of fucoxanthin oil extract to animals decreased albumin, triglycerides, cholesterol, HDL, uric acid, ALT, AST, lactate, IL-6, IL-10 compared to control. Conclusions. Thus, it was discovered that fucoxanthin in Balb/c mice contributes to a decrease in hepatic synthetic function, as evidenced by the change in the concentration of albumin, triglycerides, uric acid), influences energy metabolism (creatinine, lactate), cell membrane stability (cholesterol, LDL, HDL), serum transaminase activity, pro- and anti-inflammatory cytokines content.

Correlations between preoperative statin treatment with short- and long-term survival following colorectal cancer surgery: a propensity score-matched national cohort study

IntroductionThe pleiotropic effects of statins have attracted considerable attention in oncological treatment. Several preclinical and epidemiological studies have highlighted their potential anti-tumor properties in patients with colorectal cancer, although results have been conflicting. This study aimed to examine the association between statin exposure before colorectal cancer surgery with long and short-term survival outcomes.MethodsThis retrospective propensity score-adjusted study was conducted on a Danish cohort of patients who underwent elective curative-intended surgery for stage I–III colorectal cancer in 2008–2020, using four national patient databases. The primary and secondary outcomes were overall, 90-day, and disease-free survival. Propensity scores were calculated using all available data to match patients with and without statin exposure in a 1:1 ratio.ResultsFollowing propensity score matching, 7120 patients were included in the primary analysis. The median follow-up time was 5 years. A Cox proportional hazards model showed no statistically significant difference in overall survival between patients with or without statin exposure 365 days before surgery (HR 0.93, 95% CI 0.85–1.02) and no association with 90-day survival (OR 0.91, 95% CI 0.76–1.10). However, a subgroup analysis examining a 90-day exposure before surgery found a statistically significant association with increased overall survival (HR 0.85, 95% CI 0.77–0.93).ConclusionAlthough a subgroup of patients with a preoperative exposure time of 90 days showed statistically significant better overall survival, we found no statistically significant association between statin exposure 1 year before colorectal cancer surgery and overall survival.

Sesamin ameliorates nonalcoholic hepatic steatosis by inhibiting CD36-mediated hepatocyte lipid accumulation in vitro and in vivo

Hepatic steatosis is a critical factor in the development of nonalcoholic steatohepatitis (NASH). Sesamin (Ses), a functional lignan isolated from Sesamum indicum, possesses hypolipidemic, liver-protective, anti-hypertensive, and anti-tumor properties. Ses has been found to improve hepatic steatosis, but the exact mechanisms through which Ses achieves this are not well understood. In this study, we observed the anti-hepatic steatosis effects of Ses in palmitate/oleate (PA/OA)-incubated primary mouse hepatocytes, AML12 hepatocytes, and HepG2 cells, as well as in high-fat, high-cholesterol diet-induced NASH mice. RNA sequencing analysis revealed that cluster of differentiation 36 (CD36), a free fatty acid (FA) transport protein, was involved in the Ses-mediated inhibition of hepatic fat accumulation. Moreover, the overexpression of CD36 significantly increased hepatic steatosis in both Ses-treated PA/OA-incubated HepG2 cells and NASH mice. Furthermore, Ses treatment suppressed insulin-induced de novo lipogenesis in HepG2 cells, which was reversed by CD36 overexpression. Mechanistically, we found that Ses ameliorated NASH by inhibiting CD36-mediated FA uptake and upregulation of lipogenic genes, including FA synthase, stearoyl-CoA desaturase 1, and sterol regulatory element-binding protein 1. The findings of our study provide novel insights into the potential therapeutic applications of Ses in the treatment of NASH.

Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease.

Isoliquiritigenin (ISL) is a chalcone-type flavonoid derived from the root of licorice with antioxidant, anti-inflammatory, anti-tumour and neuroprotective properties. ISL has been proven to downregulate the productions of IL-1β, TNF-α and IL-6 by macrophages. However, detailed molecular mechanisms of this modulation remain elusive. Here, ISL suppressed Syk phosphorylation and CD80, CD86, IL-1β, TNF-α and IL-6 expressions in lipopolysaccharide-stimulated macrophages exvivo. ApoC3-transgenic (ApoC3TG) mice had more activated macrophages. ISL was also able to downregulate the inflammatory activities of macrophages from ApoC3TG mice. Administration of ISL inhibited Syk activation and inflammatory activities of macrophages in ApoC3TG mice invivo. The treatment of ISL further alleviated MCD-induced non-alcoholic fatty liver disease (NAFLD) in wild-type and ApoC3TG mice, accompanied by less recruitment and activation of liver macrophages. Due to the inhibition of Syk phosphorylation, ISL-treated macrophages displayed less production of cytoplasmic ROS, NLRP3, cleaved-GSDMD and cleaved-IL-1β, suggesting less inflammasome activation. Finally, the molecular docking study demonstrated that ISL bound to Syk directly with the Kd of 1.273 × 10-8 M. When the Syk expression was knocked down by its shRNA, the inhibitory effects of ISL on activated macrophages disappeared, indicating that Syk was at least one of key docking-molecules of ISL. Collectively, ISL could alleviate MCD-induced NAFLD in mice involved with the inhibition of macrophage inflammatory activity by the blockade of Syk-induced inflammasome activation.

Production, Characterization Purification, and Antitumor Activity of L-Asparaginase from Aspergillus niger

Cervical cancer is caused by a persistent and high-grade infection. It is caused by the Human Papillomavirus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. It is known that L-asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers. Due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions, and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization, and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50 °C, resistance to surfactants and metallic ions, and an increase in enzymatic activity with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from A. niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity, and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

Anti-Cancer, Anti-Angiogenic, and Anti-Atherogenic Potential of Key Phenolic Compounds from Virgin Olive Oil.

The Mediterranean diet, renowned for its health benefits, especially in reducing cardiovascular risks and protecting against diseases like diabetes and cancer, emphasizes virgin olive oil as a key contributor to these advantages. Despite being a minor fraction, the phenolic compounds in olive oil significantly contribute to its bioactive effects. This review examines the bioactive properties of hydroxytyrosol and related molecules, including naturally occurring compounds (-)-oleocanthal and (-)-oleacein, as well as semisynthetic derivatives like hydroxytyrosyl esters and alkyl ethers. (-)-Oleocanthal and (-)-oleacein show promising anti-tumor and anti-inflammatory properties, which are particularly underexplored in the case of (-)-oleacein. Additionally, hydroxytyrosyl esters exhibit similar effectiveness to hydroxytyrosol, while certain alkyl ethers surpass their precursor's properties. Remarkably, the emerging research field of the effects of phenolic molecules related to virgin olive oil on cell autophagy presents significant opportunities for underscoring the anti-cancer and neuroprotective properties of these molecules. Furthermore, promising clinical data from studies on hydroxytyrosol, (-)-oleacein, and (-)-oleocanthal urge further investigation and support the initiation of clinical trials with semisynthetic hydroxytyrosol derivatives. This review provides valuable insights into the potential applications of olive oil-derived phenolics in preventing and managing diseases associated with cancer, angiogenesis, and atherosclerosis.

Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Drug repurposing-based nanoplatform via modulating autophagy to enhance chemo-phototherapy against colorectal cancer

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.

Anti-cancer potential of zerumbone in cancer and glioma: current trends and future perspectives.

Plant-derived immunomodulators and antitumor factors have appealed lots of attention from natural product scientists for their efficiency and safety and their important contribution to well-designed targeted drug action and delivery mechanisms. Zerumbone (ZER), the chief component of Zingiber zerumbet rhizomes, has been examined for its wide-spectrum in the treatment of multi-targeted diseases. The rhizomes have been used as food flavoring agents in numerous cuisines and in flora medication. Numerous in vivo and in vitro experiments have prepared confirmation of ZER as a potent immunomodulator as well as a potential anti-tumor agent. This review is an interesting compilation of all the important results of the research carried out to date to investigate the immunomodulatory and anticancer properties of ZER. The ultimate goal of this comprehensive review is to supply updated information and a crucial evaluation on ZER, including its chemistry and immunomodulating and antitumour properties, which may be of principal importance to supply a novel pathway for subsequent investigation to discover new agents to treat cancers and immune-related sickness. In addition, updated information on the toxicology of ZER has been summarized to support its safety profile.