Explore the vast range of titles available.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by epithelial damage, excessive cytokine release, and dysregulated inflammasome activation. Herein, we report the design, synthesis, and multi-targeted biological evaluation of three novel mesalamine–NSAID hybrid derivatives (D1, D3, and D4) as potential therapeutic agents for UC. Structural hybridization was employed to enhance colonic targeting, suppress NLRP3 inflammasome signaling, and reduce systemic toxicity. All compounds were characterized and screened for anti-inflammatory efficacy via qRT-PCR analysis of key inflammasome-related genes (NLRP3, IL1B, IL-18, Caspase-1) in LPS-activated macrophages. Compound D3 exhibited the most potent downregulation profile, supported by molecular docking studies showing favorable interactions with NLRP3 and caspase-1. Antioxidant activity was evaluated using the DPPH assay, with D3 demonstrating the lowest IC 50 (19.20 µg/mL). Antimicrobial and brine shrimp lethality assays confirmed the moderate cytotoxicity profiles and pathogen-inhibitory potential of all compounds. Collectively, these results highlight D3 as a dual-action anti-inflammatory and antioxidant agent capable of modulating key immune and redox pathways implicated in UC pathogenesis. The study supports mesalamine–NSAID hybridization as a promising strategy for developing next-generation UC therapeutics with improved efficacy and safety profiles.

Glioblastoma, the most aggressive and fatal form of brain tumor, is characterized by rapid growth, extensive invasion of surrounding tissues, and significant angiogenesis. These and other types of cancer remain a leading cause of mortality worldwide, with conventional treatments such as chemotherapy, radiation, and surgery often limited by significant side effects. This has led to the pursuit of novel therapeutic approaches, including bacterial therapy, which utilizes bacteria’s unique ability to target tumor microenvironments and deliver therapeutic agents. This research examines the antitumor effects of Streptomyces sp. M12 extract on the U87_MG glioblastoma cell line. The cytotoxicity of the extract was assessed using the MTT assay. Additionally, flow cytometry and scratch assays were conducted to evaluate cell migration. Furthermore, gene expression analysis for Bax , Bcl-2 , Caspase-8 , and Caspase-9 was performed to determine apoptotic effects. The MTT assay indicated strong anticancer activity with an IC 50 value of 17.72 after 96 h of treatment. In vitro studies showed that the extract significantly promotes apoptosis, as evidenced by an 83.6% increase in apoptosis rates via flow cytometry. Moreover, the scratch assay demonstrated that the extract inhibited U87_MG cell migration, indicating antimetastatic potential. Real‐time PCR analysis results revealed a 1.972‐fold increase in Caspase-8 expression and a 0.468‐fold decrease in Caspase-9 expression ( p ≤ 0.001), suggesting that apoptosis is triggered through the extrinsic pathway. These findings emphasize the dual cytotoxic and antimigratory effects of the strain M12 extract, making it a promising candidate for glioblastoma treatment. Further investigation is necessary to clarify the molecular mechanisms involved and confirm its therapeutic potential in preclinical and clinical settings. This study highlights the significance of natural products, particularly those derived from Streptomyces sp. M12, an innovative cancer treatment strategy.

Triple‐negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by the absence of estrogen and progesterone receptors and minimal HER2 expression, restricting the available treatment options. Actinobacteria have emerged as promising sources of anticancer compounds because of their remarkable ability to produce beneficial compounds. This study aimed to evaluate the antitumor effects of the halophilic Streptomyces violaceorubidus M4 extract on TNBC both in vitro and in vivo. The extracted compounds were analyzed by LC‐MS. MTT and annexin‐PI assays were used to assess the apoptosis‐inducing effects of the compounds on MDA‐MB‐231 and MCF‐10A cells. The expression of apoptosis‐related BAX, BCL2, P53, CASPASE‐8, and CASPASE‐9 genes was analyzed using Real‐time PCR. A TNBC mouse model was established using 4T1 cell transplantation, and the animals received the extract intravenously for 21 days. S. violaceorubidus M4 contained bioactive compounds, including amino acids, carboxylic acids, coumarins, isoflavones, phosphatidylcholine, tetrahydroxyanthraquinone, and flavonoids. The extract demonstrated selective cytotoxicity against MDA‐MB‐231 cells, with an IC50 of 48.04 μg/mL after 48 h, while the IC50 for MCF‐10A cells was 132 μg/mL. The reduction in Cas‐9 expression alongside the elevation of Cas‐8 and P53 expression suggests the participation of the extrinsic pathway in the process of apoptosis. Histopathological evaluation of tumor tissues from mouse models showed that the extract injection reduced the number of mitotic cells, nuclear pleomorphism, and angiogenesis in tumor tissue. This study suggests that S. violaceorubidus M4 has a pronounced anticancer effect on TNBC and can be considered for the production of anticancer substances. The antitumor effects of the halophilic Streptomyces violaceorubidus M4 extract on triple‐negative breast cancer, highlighting its selective cytotoxicity and apoptosis‐inducing properties. Key findings include the identification of bioactive compounds and their impact on apoptosis‐related gene expression, as well as significant reductions in tumor cell proliferation in a mouse model.

Background Dual-functional antibacterial and osteogenic substitutes are advanced tools for treating bone infections while facilitating bone regeneration. These systems incorporate drug delivery mechanisms that allow for the local release of antibiotics and increased treatment efficacy. Decellularized bone extracellular matrix (dECM) offers key advantages for bone xenografts and local drug delivery due to its biocompatibility and low immunogenicity. This study developed a novel scaffold by loading linezolid-poly (lactic-co-glycolic acid) (PLGA-Lin) microparticles onto dECM derived from bovine tibia. The antibacterial activity, cytocompatibility, and osteoconductive properties of the resulting Lin-PLGA/dECM scaffold were assessed in vitro . Results The results revealed that the dECM had a porous structure and the Lin-PLGA microparticles infiltrated the scaffold. None of the dECM, PLGA/dECM, or Lin-PLGA/dECM scaffolds had toxic effects on adipose tissue-derived mesenchymal stem cells (ADSCs), while the inhibitory effect of Lin-PLGA/dECM on the Staphylococcus aureus strain was significant. All scaffolds—dECM, PLGA/dECM, and Lin-PLGA/dECM—promoted the bone differentiation of ADSCs, as confirmed by alkaline phosphatase (ALP) and calcium content assays, as well as by the expression of the Runt-related transcription factor 2 (Runx2), osteopontin, osteocalcin, and collagen Iα genes. Conclusions The Lin-PLGA/dECM scaffold developed in this study can be considered a biocompatible bone xenograft substitute, as it possesses excellent antibacterial properties and substantial osteogenic potential. Graphical Abstract

Small extracellular vesicles (sEVs) have been recognized as a promising therapeutic modality due to their low immunogenicity, and the ability to penetrate biological barriers. They contain significant amounts of lipids, proteins, and microRNAs, effectively participating in intra- and inter-cellular communications. sEVs derived from mesenchymal stem cells (MSCs) are being explored as a potential therapeutic option due to their immunomodulatory, anti-inflammatory, antioxidant, and regenerative properties, offering advantages over stem cell transplantationbased treatments. Chemotherapy induces side effects on various organs, particularly those with high proliferative capacity, such as testicular tissue. Exposure to some groups of chemotherapeutic agents, such as cyclophosphamide, cisplatin, and doxorubicin can cause DNA damage and induce apoptosis in spermatogonia and primary spermatocytes. Chemotherapy has been shown to induce cellular stress in testicles, leading to testicular dysfunction and the activation of apoptotic pathways in response to external and internal stress. The current research aims to review the potential therapeutic advantages of sEVs derived from MSCs in addressing sperm abnormalities and male infertility resulting from chemotherapy. Several lines of evidence indicate that treatment with sEVs can reduce testicular tissue damage caused by chemotherapy by decreasing oxidative stress and inflammatory responses. sEVs boost the growth and motility of spermatogenic cells and protect them from apoptosis by activating internal pathways. Therefore, as a non-invasive approach, they have shown promising results in regenerating damaged spermatozoa and restoring spermatogenesis.

Scaffolds derived from decellularized tissues provide a natural microenvironment for cell culture. Embryonic cerebrospinal fluid (e-CSF) contains factors which play vital roles in the development of the nervous system. This research was aimed to survey the effect of Wistar rat e-CSF on neural differentiation of bone marrow derived mesenchymal stem cells (BM-MSCs) cultured on the human amniotic membrane (AM). BM-MSCs were collected from femurs and tibias, and were cultured in Dulbecco's Modified Eagle's Medium. The placenta was harvested from healthy women during cesarean section and AM was acellularized using EDTA and physical scrubbing. e- CSF was harvested from rat fetuses at E17. Adequate numbers of BM-MSCs were cultured on acellularized membrane, and were treated with E17 CSF for 7 days. MTT (3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide) assay confirmed the survival and proliferation of BM-MSCs cultured on AM derived scaffold. Hematoxylin/eosin staining and scanning electron microscopy showed the morphological and the structural changes of BM-MSCs throughout the culture and treatment with e-CSF. The results of immunocytochemistry showed that microtubule associated protein 2 and beta-III tubulin were expressed in BM-MSCs cultured on acellular amnion scaffold and treated with e-CSF. Our results showed for the first time that the combination of acellular AM as a natural scaffold and e-CSF as a source of neurological factors could effectively improve the BM-MSCs cultivation and differentiation.

The miR‐34 family is recognized for its crucial role as tumor suppressors, particularly through its interactions with oncogenic regulators such as Tumor Protein 53 (TP53). Bromodomain‐containing Protein 4 (BRD4) functions as a transcriptional regulator that enhances the expression of oncogenes. In triple‐negative breast cancer (TNBC), BRD4 is often found to be overexpressed and linked to poor clinical outcomes. This study is aimed at exploring the impact of miR‐34b on the sensitivity of TNBC cells to BRD4 inhibition, which may also affect TP53 expression. miR‐34b‐5p mimics and scrambled oligonucleotides were transfected into TP53‐mutant MDA‐MB‐231 and nonmutant MCF‐7 cell lines. The expression levels of miR‐34b, TP53, and BRD4 genes, along with the migration rates and sensitivity to the BRD4‐specific inhibitor JQ1, were compared between the miR‐34b overexpressing cells. The results showed that miR‐34b overexpression led to increased TP53 expression in MDA‐MB‐231 cells, while a reduction was observed in MCF‐7 cells. Consequently, BRD4 expression was significantly elevated in MDA‐MB‐231 cells, resulting in resistance to JQ1. The increase in BRD4 expression also correlated with higher migration rates compared to MCF‐7 cells. In conclusion, miR‐34b may have an oncogenic role by promoting the expression of BRD4 in TNBC cells. This finding aligns with prior reports indicating a negative correlation between miR‐34b levels and survival rates in patients with TNBC. These insights may provide new perspectives on the role of miR‐34b in the development and progression of TNBC.

Nowadays, many organizations use Process Aware Information Systems (PAISs) to automate their business process. As any other information systems, security plays a major role in PAIS to provide a secure state and maintain the system in it. In order to provide security in a PAIS, a Process Aware Host-based Intrusion Detection (PAHID) model is proposed in this paper. The model detects host-based intrusions in a PAIS using process mining techniques.The proposed model uses both anomaly detection and misuse detection techniques for more efficiency, and organizational perspective of process mining is considered (rather than control-flow perspective) to detect more attack types. The model is automated and can deal with large logs and is suitable for flexible application domains. The PAHID model is implemented by the use of ProM framework and Java programming. It is evaluated by using a simulated log based on a real-world organization information system. Results demonstrate that the model provides high accuracy and low false positive rate.

Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs. Graphical Abstract Inspired by the positive effects of exosomes on peripheral nerve regeneration, the figure illustrates the rejuvenating effect of exosomes on the peripheral nervous system

Background: Breast cancer accounts for one-third of cancer cases in women. Doxorubicin (Dox) is one of the chemotherapeutical compounds widely used to treat breast cancer. Chemical drugs have several side effects and their continuous administration leads to drug resistance in patients. To decrease such side effects in cancer treatment, combination therapy as well as application of natural and herbal compounds has been taken into consideration. The aim of this study was to investigate the cytotoxic effect of Viola odorata (Vo) extract on T47-D human breast cancer cells, alone and in combination with Dox. Materials and Methods: The cytotoxic effects of V. odorata and Dox were studied by morphological examination and 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flowcytometric analysis was performed to determine the type of cell death. Moreover, scratch healing assay was conducted to investigate antimigration effect of V. odorata. Results: The results of MTT assay showed that V. odorata and Dox-induced cell death in T47-D cells in a dose- and time-dependent manner. Morphological analysis revealed that V. odorata and Dox-induced features of apoptotic cell death in T47-D cells. These results were confirmed by flow cytometry analysis. Scratch healing assay revealed that migration rate was reduced in the V. odorata- treated cells. Conclusions: Our findings suggest that components of V. odorata exert antitumor effects on human breast cancer and could be administered with lower doses of antitumor agent Dox, in combination therapy, to decrease its side effects.