Preclinical animal research plays a crucial role in studying colorectal cancer (CRC). Mouse models allow for testing the efficacy of potential medications and understanding the mechanisms behind CRC development. Carcinogens like DMH and AOM are used to induce CRC in these models, enabling researchers to investigate various treatment approaches. The availability of diverse animal strains facilitates the study of CRC progression and metastasis. By examining literature on animal models, researchers can assess the accuracy of reproducing different stages of CRC, from crypts to polyps and tumors. Animal models are essential for studying the tumour microenvironment and its impact on colorectal cancer (CRC). These models replicate key features of human CRC, including angiogenesis and immune responses. Both immunocompetent and immunocompromised rodents are used to evaluate immunotherapeutic drugs. This review summarizes common murine models for CRC and their applications in translational research. Future trends in this field likely include further advancements in animal models for studying tumour biology.

Kidney diseases, characterized by renal dysfunction, are among the leading causes of death worldwide. Preventing and treating kidney diseases is important for reducing their associated morbidity and mortality. Moderate physical exercise has been recognized to be advantageous for kidney health. Irisin is an exercise-induced myokine identified in 2012. It plays an important role in energy and bone metabolism, oxidative stress reduction, anti-inflammatory processes, prevention of cell death, and cardiovascular protection. However, the relationship between irisin and kidney disease has not been fully elucidated. This review explores the role of irisin as a biomarker in the diagnosis of kidney diseases and their associated complications, elucidating the mechanisms through which it participates in various cell death pathways, such as apoptosis, autophagy, pyroptosis and ferroptosis. Furthermore, the levles of irisin secretion are discussed to provide a basis for the preventing and treating kidney diseases, as well as therapeutic guidance for developing new and promising intervention strategies.

Bone defects are common surgical complications, and stem cell and gene therapies are key strategies for bone repair and regeneration. Transcription factor 7-like 2 (TCF7L2) is a key regulator of the Wnt signaling pathway, with potential applications in gene editing. However, the role of TCF7L2 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) remains poorly understood. We knocked down or overexpressed TCF7L2 to evaluate its effect on erastin-induced ferroptosis in BMSCs. Simultaneously, we assessed the impact of TCF7L2 overexpression on the osteogenic capacity of BMSCs. To confirm the involvement of Glutathione peroxidase 4 (GPX4), we conducted rescue experiments by knocking down GPX4 expression. A mouse cranial defect model was established to analyze the effect of TCF7L2 overexpression on cranial bone healing. The results showed that TCF7L2 knockdown promoted, while TCF7L2 overexpression inhibited, erastin-induced ferroptosis in BMSCs. Mechanistic studies revealed that TCF7L2 knockdown reduced, while TCF7L2 overexpression enhanced GPX4 expression, thereby regulating ferroptosis. Conversely, GPX4 knockdown significantly attenuated the regulatory effects of TCF7L2 overexpression on cell proliferation and ferroptosis inhibition. Furthermore, TCF7L2 overexpression promoted cell proliferation, osteogenic differentiation, and mineralization in vitro, while enhancing cranial defect healing in vivo. This study is the first to reveal the dual role of TCF7L2: regulating ferroptosis in BMSCs via GPX4, while promoting BMSC proliferation and osteogenic differentiation. These findings provide novel molecular targets and theoretical foundations for the treatment of bone defects.

With the increasing aging of the population and the increasing number of patients with cardiovascular diseases, how to improve the damage of myocardial cells caused by acute myocardial infarction (AMI) and improve cardiac function after infarction has attracted widespread attention. Bone marrow mesenchymal stem cells (BMSCs) are easy to obtain and proliferate, naturally lack MHC class II antigens, and have the function of promoting angiogenesis. They have become ideal seed cells for improving the prognosis of myocardial infarction in tissue engineering. This review mainly summarizes the biological characteristics of BMSCs and the chemical, physical, co-culture, and gene transfection methods for inducing BMSCs to differentiate into cardiomyocyte-like cells in vitro, and discusses the protective effects of BMSCs and their exosomes on the heart in myocardial infarction.

Thoracic aortic aneurysms and dissection (TAAD) is a critical, life-threatening cardiovascular condition characterized by immune-mediated inflammatory infiltration and structural degradation of the aorta wall, which are pivotal in its etiology. In recent years, the significance of T lymphocytes in TAAD has increasingly garnered scientific attention. TAAD is a multifaceted vascular disorder characterized by the involvement of many immune cells, with T lymphocytes playing a pivotal role, particularly in the modulation of inflammatory responses, immunological control, and tissue damage. A comprehensive understanding of the T lymphocyte activation process in TAAD is crucial for the advancement of novel preventative and therapy strategies. This article evaluates the recent research advancements on the function of T lymphocytes in TAAD, aiming to offer novel insights for the future prevention and treatment of TAAD.

Abstract: Recent research has shown a strong link between Th17 cells and their cytokine IL-17, and various cardiovascular diseases such as myocarditis, myocardial infarction, and atherosclerosis. Moreover, Th17 cell signalling is likely to be a key factor in cardiovascular disease. Here, we summarize recent advances in the source, function, regulation, and the effects of Th17 signaling in cardiovascular disease. Research on Th17 will suggest more specific strategies to manipulate these functions. Thus, effective treatment of cardiovascular disease and future clinical treatment will be possible.

Stem cells have differentiation and regulatory functions. Here, we discuss the effect of cell culture density on stem cell proliferate, adipogenesis and regulation ability. To investigate the effect of the initial culture density of human periodontal ligament stem cells (hPDLSC) on the adipogenic differentiation of autologous cells. We found that the proliferation rate of hPDLSC increased with the initial cell densities (0.5~8 × 10 4 cells/cm 2) increase. After adipogenic differentiation induced by different initial cell densities of hPDLSC, we found that the mean adipose concentration and the expression levels of lipoprotein lipase (LPL), CCAAT/enhancer binding protein α (CEBP-α) and peroxisome proliferator-activated receptor γ (PPAR-γ) genes all increased with increasing cell density. To investigate the regulatory role of hPDLSCs on the adipogenic differentiation of other cells, we used secreted exosomes derived from hPDLSCs cultured at different initial cell densities of 50 μg/mL to induce the adipogenic differentiation of human bone marrow stromal cells (hBMSC). We also found that the mean adipose concentration and the expression of LPL, CEBP-α and PPARγ genes increased with increasing cell density, the optimal culture density was 8 × 10 4 cells/cm 2. This provides a laboratory research basis for the application of adipogenic differentiation of stem cells.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing rapidly due to the obesity epidemic. In the inflammatory stages of MASLD (NASH), activation of hepatic stellate cells (HSCs) leads to initiation and progression of liver fibrosis. Extracellular vesicles (EVs) are released from all cell types and play an important role in intercellular communication. However, the role of EVs released from hepatocytes in the context of MASLD is largely unknown. Therefore, the present study aimed to investigate the role of EVs derived from both normal and steatotic (free fatty acid-treated) hepatocytes on the phenotype of HSCs via the senescence pathway. Primary rat hepatocytes were treated with free fatty acids (FFAs: oleic acid and palmitic acid). EVs were collected by ultracentrifugation. EVs markers and HSCs activation and senescence markers were assessed by Western blot, qPCR and cytochemistry. Reactive oxygen species (ROS) production was assessed by fluorescence assay. RNA profiles of EVs were evaluated by sequencing. We found that EVs from hepatocytes treated with FFAs (FFA-EVs) inhibit collagen type 1 and α-smooth muscle actin expression, increase the production of ROS and the expression of senescence markers (IL-6, IL-1β, p21 and senescence-associated β-galactosidase activity) in early activating HSCs via the AKT-mTOR pathway. Sequencing showed differentially enriched RNA species between the EVs groups. In conclusion, EVs from FFA-treated hepatocytes inhibit HSC activation by inducing senescence via the AKT-mTOR signaling pathway. Determining the components in EVs that induce HSC senescence may lead to the identification of novel targets for the intervention of MASLD.

Cell viability and cytotoxicity assays play a crucial role in drug screening and evaluating the cytotoxic effects of various chemicals. The quantification of cell viability and proliferation serves as the cornerstone for numerous in vitro assays that assess cellular responses to external factors. In the last decade, several studies have developed guidelines for defining and interpreting cell viability and cytotoxicity based on morphological, biochemical, and functional perspectives. As this domain continues to experience ongoing growth, revealing new mechanisms orchestrating diverse cell cytotoxicity pathways, we suggest a revised classification for multiple assays employed in evaluating cell viability and cell death. This classification is rooted in the cellular compartment and/or biochemical element involved, with a specific focus on mechanistic and essential aspects of the process. The assays are founded on diverse cell functions, encompassing metabolic activity, enzyme activity, cell membrane permeability and integrity, ATP content, cell adherence, reduction equivalents, dye inclusion or exclusion, constitutive protease activity, colony formation, DNA fragmentation and nuclear splitting. These assays present straightforward, reliable, sensitive, reproducible, cost-effective, and high-throughput approaches for appraising the effects of newly formulated chemotherapeutic biomolecules on the cell survival during the drug development process.

Conventional treatment methods are not effective enough to fight the rapid increase in cancer cases. The interest is increasing in the investigation of herbal sources for the development of new anticancer therapeutics. Particularly, much attention is given to finding combined phytochemical/chemotherapeutic treatment models to overcome drug resistance and decrease side effects. The aim was to investigate the antitumor capacity of Hypericum alpestre herb extract in vitro and in vivo, either alone or combined with the inhibitors of the L-arginine/polyamine/nitric oxide pathway and characterize its active phytochemicals using advanced chromatographic techniques. The antioxidant capacity of H. alpestre extract was assessed through chemical spectrophotometric tests (DPPH and ABTS) and in biological systems using Cellular Antioxidant Activity assay. The inhibitory effect of H. alpestre extract on the growth of human colorectal (HT29) and breast cancer (MCF-7) cell cultures was explored by the MTT test. The genotoxicity of the tested extract was studied using a comet assay. In vivo, the antitumor properties of H. alpestre and its combinations were explored in a rat mammary gland carcinogenesis model induced by subcutaneous injection of 7,12-dimethylbenz[a]anthracene. The polyphenolic substances present in H. alpestre extract have been characterized using the LC-Q-Orbitrap HRMS system. The H. alpestre extract expressed promising antiproliferative effects on MCF-7 and HT29 cells. The extract did not exhibit genotoxic activity nor possessed antigenotoxic properties. The in vivo rat mammary carcinogenesis model data showed that the H. alpestre extract stimulated the activity of antioxidant enzymes in the liver, brain, and tumors of rats in the experimental groups, demonstrating its antioxidant protective effects. The herb alone and in combination with N ω-OH-nor-L-arginine and N ω-nitro-L-arginine methyl ester exhibited pro-/antioxidant, antiproliferative, anti-angiogenic, and cytotoxic effects.

Langerhans cells(LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling(YXL) is a representative herbal medicine formula for the treatment of psoriasis in South China. It was confirmed to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod(IMQ)-induced psoriasis-like C57BL/6 mouse model in vivo, and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL to regulate the differentiation, migration, mature and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections. Although there was not any effect on the proportion of total DCs in the skin draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 was significantly inhibited, and its migration to draining lymph nodes and maturation were also inhibited. Further data showed that the number of antigen-carrying LC in the epidermis increased, indicating that YXL could effectively inhibit the antigen presentation of LCs. YXL also significantly inhibited the differentiation of LC in vitro. Further data showed that YXL decreaded the relatve expression of TGFβmRNA and IL-23 mRNA. Thus, YXL allievates psoriasis by regualting differentiation, migration, maturation and antigen presentation via TGFβ/ PU.1/IL-23 signal axis.

Non-coding RNA species play important roles in biological mechanisms that regulate glioma initiation and progression. Recently, evidence suggests that ZNFX1 antisense RNA 1 ( ZFAS1) has the ability to act as an oncogene or tumour suppressor, and so plays critical regulatory functions in the development and progression of many types of cancers such as lung, renal and hepatocarcinoma. The roles of ZFAS1 in glioma cancer are still unclear, and there are numerous potential pathways to explore. The current work provides a scoping review of studies on ZFAS1’s functions and underlying molecular mechanisms in the initiation and progression of glioma, as well as a possible field of research to be examined further. A literature search was carried out using Scopus, PubMed, and Web of Science (WoS) using a specified search string, and the data gathered was discussed and reported. This scoping review comprised five original research papers that study ZFAS1 and its roles in gliomagenesis. ZFAS1 was found to be highly upregulated in glioma. Tumour-node-metastasis (TNM) stage, lymph node metastases, and overall survival were revealed to be significantly associated with ZFAS1 status and regulated via several pathways and interactions, such as miRNA signalling, Epithelial-to-Mesenchymal Transition (EMT) and Notch signalling pathway. Furthermore, ZFAS1 knockdown decreased cell proliferation, migration, and invasion while promoting cell death, implying that ZFAS1 is involved in the glioma cancer progression. The evaluation of their diagnostic importance and therapeutic potential may aid in the development of novel therapies for glioma cancer.

As the field of stem cell-based therapies continues to evolve, the ability to monitor the regenerative capacity of stem cell following delivery to target tissues has become increasingly relevant. While Bromodeoxyuridine (BrdU) and green-fluorescent protein (GFP) labeling techniques are often used, limited knowledge exists regarding their effects on the regeneration capacity of stem cells. In order to further understand the impact of these techniques in a clinical scenario, porcine adipose stem cells (ASCs) were derived, cultured and subsequently labeled with BrdU or GFP using transfection (GFP-t) or infection (GFP-i) by lentivirus, followed by investigation of downstream labeling effects on ASCs proliferation, differentiation, colony formation, secretion of regenerative cytokines, growth factors and healing ability. Neither BrdU nor GFP labeling led to gross morphological changes in adipose stem cells. Both groups of GFP labeled cells maintained a high percentage of signal intensity for at least 28 days, with a decrease in cell proliferation ability in the GFP-i group. In contrast, BrdU labelling began displaying weaker signal strength after 7-days of experiments. Both tracers negatively affected osteogenic and adipogenic differentiation of ASCs, causing decrease in the secretion of the regeneration markers VEGF and TNF-α. In contrast, in-vitro wound healing ability of labeled ASCs and secretion of IL-8, IL-10, and TGF-β was not affected by either method. Our results demonstrate that BrdU labelling may be more effective for short-term in-vitro studies due to the relative ease of preparation and shorter lifespan of the tracer signal. Contrarily, for studies with a longer duration, GFP labeling of cells by transfection provides more durable and stable signal. While further studies are needed, our results indicate that labelling mode can alter regeneration capacity of stem cells and should, therefore, be optimized prior to clinical translation experiments.