miR-429 Acts as a Tumor Suppressor in Multiple Myeloma by Regulating Cell Proliferation

Background/Objectives: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of abnormal plasma cells in bone marrow, predominantly affecting individuals over 65 years of age. Despite recent therapeutic advances, MM remains largely incurable due to frequent relapses and the emergence of drug resistance. MicroRNAs have emerged as key post-transcriptional regulators implicated in cancer progression, with miR-429 exhibiting context-dependent oncogenic or tumor-suppressive roles in various cancers. However, its function in MM has not been thoroughly investigated. Methods: miR-429 expression was evaluated in MM cells and patient samples by qRT-PCR. Functional effects were assessed through inhibition studies, proliferation/apoptosis assays, and co-culture with stromal cells. Results: In this study, we found that miR-429 expression is significantly downregulated in MM cell lines and primary malignant plasma cells compared to normal plasma cells. The functional inhibition of miR-429 in U266 cells led to a significant increase in cell proliferation without affecting spontaneous apoptosis, as confirmed in both MM cell lines and patient-derived plasma cells. Additionally, the inhibition of miR-429 in HS-5 stromal cells enhanced the proliferation of co-cultured MM cells, highlighting the role of the bone marrow microenvironment in disease progression. Conclusions: These findings suggest that miR-429 may act as a tumor suppressor by modulating MM cell proliferation. Although preliminary, our results support the need for further investigation into miR-429 as a potential biomarker or therapeutic target

Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility

Endometriosis, a chronic estrogen-dependent disorder defined by ectopic endometrial-like tissue growth, causes pelvic pain and infertility in reproductive-age women. Despite its prevalence, the underlying mechanisms driving lesion persistence and reproductive impairment remain unclear. This review synthesizes recent pathophysiological advances, highlighting how hormonal dysregulation, immune dysfunction, epigenetic alterations, and oxidative stress collectively foster lesion persistence and treatment resistance. Critically, these molecular disturbances disrupt critical reproductive functions—including oocyte quality, endometrial receptivity, and embryo implantation. We further explore emerging non-hormonal therapeutic strategies, including MAPK and PI3K/AKT inhibitors as well as epigenetic agents targeting HOXA10 methylation and microRNA modulation, which offer fertility-sparing alternatives to conventional hormonal suppression. To enhance clinical translation, we propose a multi-level prevention framework—encompassing at the primary level, risk reduction; at the secondary level, biomarker-guided intervention; and at the tertiary level, fertility preservation—to anticipate disease progression and personalize reproductive care. By delineating shared pathways between endometriosis and infertility, this work advances precision medicine approaches for affected patients

5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells

Multiple myeloma (MM) is an incurable plasma cell malignancy with frequent patient relapse due to innate or acquired drug resistance. Cholesterol metabolism is reported to be altered in MM; therefore, we investigated the potential anti-myeloma activity of two cholesterol derivatives: the 5,6 α- and 5,6 β-epoxycholesterol (EC) isomers. To this end, viability assays were used, and isomers were shown to exhibit important anti-tumor activity in vitro in JJN3 and U266 human myeloma cell lines (HMCLs) and ex vivo in myeloma patients’ sorted CD138+ malignant cells. Moreover, we confirmed that 5,6 α-EC and 5,6 β-EC induced oxiapoptophagy through concomitant oxidative stress and caspase-3-mediated apoptosis and autophagy. Interestingly, in combination treatment a synergistic interaction was observed between 5,6 α-EC and 5,6 β-EC on myeloma cells. These data highlight a striking anti-tumor activity of 5,6 α-EC and 5,6 β-EC bioactive molecules against human myeloma cells, paving the way for their potential role in future therapeutic strategies in MM.</jats:p

LC-MS profiling and antioxidant, antifungal, and anticancer potentials of Tunisian Allium sativum L. extracts.

Despite Garlic's (Allium. sativum) long-standing reputation for therapeutic properties, comprehensive studies on Tunisian garlic are lacking. This study aims to evaluate different Tunisian A. sativum extracts rich in bioactive compounds (phenolic acids, flavonoids, and vitamins), exploring their potential bioactivities (antifungal, antioxidant, and cytotoxic). A. sativum samples underwent hexane, ethyl acetate, methanol, and water-based extractions. LC-MS quantification assessed bioactive compounds. Antioxidant activity was determined via the DPPH assay, antifungal effects were evaluated against Aspergillus spp., and cytotoxic effects were assessed using the MTT assay on U266 human multiple myeloma and MDA-MB-231 metastatic breast cancer cell lines. The aqueous extract exhibited the highest phenolic acid content (96.25 mg/kg fw) and the most water-soluble vitamins (14.69 mg/kg fw). In contrast, the methanol extract was richest in flavonoids, while the ethyl acetate extract had the highest concentration of fat-soluble vitamins (20.21 mg/kg fw). Both aqueous and methanolic extracts demonstrated potent antioxidant activity. The aqueous extract exhibited the strongest antifungal activity (MIC: 1.5 mg/mL for A. flavus and 3 mg/mL for A. niger). Furthermore, the ethyl acetate extract showed remarkable cytotoxic effects against cancer cell lines, indicating its potential as an effective agent against metastatic breast cancer and refractory multiple myeloma. A. sativum emerges as a functional food source with antioxidant, antifungal, and cytotoxic activities, particularly against multiple myeloma. While this study provides a strong foundation for further exploration, additional research is needed to identify active compounds, elucidate mechanisms, and assess therapeutic potential

First Report of the Biosynthesis and Characterization of Silver Nanoparticles Using <i>Scabiosa atropurpurea</i> subsp. <i>maritima</i> Fruit Extracts and Their Antioxidant, Antimicrobial and Cytotoxic Properties

Candida and dermatophyte infections are difficult to treat due to increasing antifungal drugs resistance such as fluconazole, as well as the emergence of multi-resistance in clinical bacteria. Here, we first synthesized silver nanoparticles using aqueous fruit extracts from Scabiosa atropurpurea subsp. maritima (L.). The characterization of the AgNPs by means of UV, XRD, FTIR, and TEM showed that the AgNPs had a uniform spherical shape with average sizes of 40–50 nm. The biosynthesized AgNPs showed high antioxidant activity when investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The AgNPs displayed strong antibacterial potential expressed by the maximum zone inhibition and the lowest MIC and MBC values. The AgNPs revealed a significant antifungal effect against the growth and biofilm of Candida species. In fact, the AgNPs were efficient against Trichophyton rubrum, Trichophyton interdigitale, and Microsporum canis. The antifungal mechanisms of action of the AgNPs seem to be due to the disruption of membrane integrity and a reduction in virulence factors (biofilm and hyphae formation and a reduction in germination). Finally, the silver nanoparticles also showed important cytotoxic activity against the human multiple myeloma U266 cell line and the human breast cancer cell line MDA-MB-231. Therefore, we describe new silver nanoparticles with promising biomedical application in the development of novel antimicrobial and anticancer agents

First Report of the Biosynthesis and Characterization of Silver Nanoparticles Using Scabiosa atropurpurea subsp. maritima Fruit Extracts and Their Antioxidant, Antimicrobial and Cytotoxic Properties

Candida and dermatophyte infections are difficult to treat due to increasing antifungal drugs resistance such as fluconazole, as well as the emergence of multi-resistance in clinical bacteria. Here, we first synthesized silver nanoparticles using aqueous fruit extracts from Scabiosa atropurpurea subsp. maritima (L.). The characterization of the AgNPs by means of UV, XRD, FTIR, and TEM showed that the AgNPs had a uniform spherical shape with average sizes of 40–50 nm. The biosynthesized AgNPs showed high antioxidant activity when investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The AgNPs displayed strong antibacterial potential expressed by the maximum zone inhibition and the lowest MIC and MBC values. The AgNPs revealed a significant antifungal effect against the growth and biofilm of Candida species. In fact, the AgNPs were efficient against Trichophyton rubrum, Trichophyton interdigitale, and Microsporum canis. The antifungal mechanisms of action of the AgNPs seem to be due to the disruption of membrane integrity and a reduction in virulence factors (biofilm and hyphae formation and a reduction in germination). Finally, the silver nanoparticles also showed important cytotoxic activity against the human multiple myeloma U266 cell line and the human breast cancer cell line MDA-MB-231. Therefore, we describe new silver nanoparticles with promising biomedical application in the development of novel antimicrobial and anticancer agents.</jats:p

Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion.

International audienceLeberagin-C, a new member of the disintegrin-like/cysteine-rich (D/C) family, was purified to homogeneity from the venom of Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric protein with a molecular mass of 25,787 Da. Its complete sequence of 205 amino acid residues was established by cDNA cloning. The leberagin-C shows many conserved sequences with other known D/C proteins, like the SECD binding sites and a pattern of 28 cysteines. It is the first purified protein from M. lebetina transmediterranea with only two disintegrin-like/cysteine-rich domains. Leberagin-C is able to inhibit platelet aggregation induced by thrombin and arachidonic acid with IC(50) of 40 and 50 nM respectively. It was also able to inhibit the adhesion of melanoma tumour cells on fibrinogen and fibronectin, by interfering with the function of alphavbeta3 and, to a lesser extent, with alphavbeta6 and alpha5beta1 integrins. To our knowledge, leberagin-C is the sole described D/C protein that does not specifically interact with the alpha2beta1 integrin. Structure-activity relationship study of leberagin-C suggested that there are some important amino acid differences with jararhagin, the most studied PIII metalloprotease from Bothrops jararaca, notably around the SECD motif in its disintegrin-like domain. Other regions implicated in leberagin-C specificities could not be excluded

Additional file 1 of Tunisian Artemisia campestris L.: a potential therapeutic agent against myeloma - phytochemical and pharmacological insights

Supplementary Material