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Clinica Chimica Acta; International... Jun 2024Breast cancer (BC) remains the most prevalent cancer among women worldwide, despite significant advancements in its prevention and treatment. The escalating incidence of...
Breast cancer (BC) remains the most prevalent cancer among women worldwide, despite significant advancements in its prevention and treatment. The escalating incidence of BC globally necessitates continued research into novel diagnostic and therapeutic strategies. Metabolomics, a burgeoning field, offers a comprehensive analysis of all metabolites within a cell, tissue, system, or organism, providing crucial insights into the dynamic changes occurring during cancer development and progression. This review focuses on the metabolic alterations associated with BC, highlighting the potential of metabolomics in identifying biomarkers for early detection, diagnosis, treatment and prognosis. Metabolomics studies have revealed distinct metabolic signatures in BC, including alterations in lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic changes not only support the rapid proliferation of cancer cells but also influence the tumour microenvironment and therapeutic response. Furthermore, metabolomics holds great promise in personalized medicine, facilitating the development of tailored treatment strategies based on an individual's metabolic profile. By providing a holistic view of the metabolic changes in BC, metabolomics has the potential to revolutionize our understanding of the disease and improve patient outcomes.
PubMed: 38944408
DOI: 10.1016/j.cca.2024.119836 -
Biochemical Pharmacology Jun 2024Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA...
Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA is a fat-soluble active ingredient obtained from Salvia miltiorrhiza, which has an inhibitory effect against various cancers. We designed and synthesized a novel L-shaped ortho-quinone analog TE5 with tanshinone IIA as the lead compound and tested its antitumor activity against GBM. The results indicated that TE5 effectively inhibited the proliferation, migration, and invasion of GBM cells, and demonstrated low toxicity in vitro. We found that TE5 may bind to androgen receptors and promote their degradation through the proteasome. Inhibition of the PI3K/AKT signaling pathway was also observed in TE5 treated GBM cells. Additionally, TE5 arrested the cell cycle at the G2/M phase and induced mitochondria-dependent apoptosis. In vivo experiments further confirmed the anti-tumor activity, safety, and effect on androgen receptor level of TE5 in animal models of GBM. Our results suggest that TE5 may be a potential therapeutic drug to treat GBM.
PubMed: 38944395
DOI: 10.1016/j.bcp.2024.116398 -
Journal of Theoretical Biology Jun 2024The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a...
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing the finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
PubMed: 38944380
DOI: 10.1016/j.jtbi.2024.111893 -
Journal of Theoretical Biology Jun 2024Regulation of cell proliferation is a crucial aspect of tissue development and homeostasis and plays a major role in morphogenesis, wound healing, and tumor invasion. A...
Regulation of cell proliferation is a crucial aspect of tissue development and homeostasis and plays a major role in morphogenesis, wound healing, and tumor invasion. A phenomenon of such regulation is contact inhibition, which describes the dramatic slowing of proliferation, cell migration and individual cell growth when multiple cells are in contact with each other. While many physiological, molecular and genetic factors are known, the mechanism of contact inhibition is still not fully understood. In particular, the relevance of cellular signaling due to interfacial contact for contact inhibition is still debated. Cellular automata (CA) have been employed in the past as numerically efficient mathematical models to study the dynamics of cell ensembles, but they are not suitable to explore the origins of contact inhibition as such agent-based models assume fixed cell sizes. We develop a minimal, data-driven model to simulate the dynamics of planar cell cultures by extending a probabilistic CA to incorporate size changes of individual cells during growth and cell division. We successfully apply this model to previous in-vitro experiments on contact inhibition in epithelial tissue: After a systematic calibration of the model parameters to measurements of single-cell dynamics, our CA model quantitatively reproduces independent measurements of emergent, culture-wide features, like colony size, cell density and collective cell migration. In particular, the dynamics of the CA model also exhibit the transition from a low-density confluent regime to a stationary postconfluent regime with a rapid decrease in cell size and motion. This implies that the volume exclusion principle, a mechanical constraint which is the only inter-cellular interaction incorporated in the model, paired with a size-dependent proliferation rate is sufficient to generate the observed contact inhibition. We discuss how our approach enables the introduction of effective bio-mechanical interactions in a CA framework for future studies.
PubMed: 38944379
DOI: 10.1016/j.jtbi.2024.111882 -
Journal of Ethnopharmacology Jun 2024Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health.... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2,000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice.
AIM OF THE STUDY
To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis.
MATERIALS AND METHODS
In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China.
RESULTS
In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy.
CONCLUSION
Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.
PubMed: 38944361
DOI: 10.1016/j.jep.2024.118501 -
Cellular Signalling Jun 2024Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in...
BACKGROUND AND OBJECTIVES
Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in lungs are linked to silicosis development. Mitochondrial dysfunction plays critical role in some diseases, but how these processes progress and regulated in silicosis, remains limited. Detailed study of silica induced pulmonary fibrosis in mouse model, its progression and severity may be helpful in designing future therapeutic strategies.
METHODS
In present study, mice model of silicosis has been developed after repeated silica exposures which may closely resemble clinical symptoms of silicosis in human. In addition to efficiently mimicking the acute/chronic transformation processes of silicosis, this is practical and efficient in terms of time and output, which avoids mechanical injury to the upper respiratory tract due to surgical interventions. Sonicated sterile silica suspension (120 mg/kg) was administered through intranasal route thrice a week at regular intervals (21, 28 and 35 days).
RESULTS
Presence of minute to larger silicotic nodules in H&E-stained lung sections were observed in all silica induced model groups. Enhanced ECM deposition was noted in MT stained lung sections of silica exposure groups as compared to control which were confirmed by significantly higher MMP9 expression levels and hydroxyproline content in silica 35 days group. Increase in Reactive oxygen species (ROS), inflammatory cell recruitment mainly, neutrophils and macrophage were observed in all three silica exposure groups. Transmission electron microscopic analysis has confirmed presence of many aberrant shaped mitochondria (swollen, round shape) in 35 days model where autophagosomes were minimum. Western blot analysis of mitophagy and autophagy markers such as Pink1, Parkin, Cytochrome c, SQSTM1/p62, the ratio of light chain LC3B II/LC3B I was found higher in 21 and 28 days which were significantly reduced in 35 days silica model.
CONCLUSIONS
Higher MMP9 activity and MMP9 /TIMP1 ratio demonstrate excessive extracellular matrix damage and deposition in 35 days model. Significantly reduced expressions of autophagy and mitophagy markers have also confirmed progression in fibrosis severity and its association with repeated silica exposures in 35 days model group.
PubMed: 38944258
DOI: 10.1016/j.cellsig.2024.111272 -
Cellular Signalling Jun 2024Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, apoptosis, senescence and cellular metabolism. Here, we...
Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, apoptosis, senescence and cellular metabolism. Here, we report that PML promotes apoptosis and ferroptosis. Our data showed that PML over-expression inhibited cell proliferation and migration. PML over-expression increased apoptotic cells, nuclear condensation and the loss of mitochondrial membrane potential, accompanied by regulation of Bcl-2 family proteins and reactive oxygen species (ROS) level, suggesting that PML enhanced apoptosis. Meanwhile, PML over-expression not only increased lipid ROS accumulation and Malondialdehyde (MDA) content but also downregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, indicating that PML enhanced ferroptosis. Additionally, knockdown of p53 attenuated the effect of PML on SLC7A11 and GPX4, and inhibited the increase of lipid ROS and ROS by PML over-expression. Moreover, translocation of PML from nucleus to cytoplasm not only promoted apoptosis and ferroptosis, but also inhibited cell proliferation. Taken together, PML promotes apoptosis and ferroptosis, in which the mediation of p53 and the nuclear export of PML play important roles.
PubMed: 38944257
DOI: 10.1016/j.cellsig.2024.111278 -
Cellular Signalling Jun 2024The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key...
The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.
PubMed: 38944255
DOI: 10.1016/j.cellsig.2024.111279 -
Fish & Shellfish Immunology Jun 2024The immune system of bony fish closely resembles that of mammals, comprising both specific (adaptive) and non-specific (innate) components. Notably, the...
The immune system of bony fish closely resembles that of mammals, comprising both specific (adaptive) and non-specific (innate) components. Notably, the mucosa-associated lymphoid tissue (MALT) serves as the first line of defense within the non-specific immune system, playing a critical role in protecting these aquatic organisms against invading pathogens. MALT encompasses a network of immune cells strategically distributed throughout the gills and intestines, forming an integral part of the mucosal barrier that interfaces directly with the surrounding aquatic environment. Spring Viremia of Carp Virus(SVCV), a highly pathogenic agent causing substantial harm to common carp populations, has been designated as a Class 2 animal disease by the Ministry of Agriculture and Rural Affairs of China. Utilizing a comprehensive array of research techniques, including Hematoxylin and Eosin (HE)、Alcian Blue Periodic Acid-Schiff (AB-PAS)、transcriptome analysis for global gene expression profiling and Reverse Transcription-Polymerase Chain Reaction (RT-qPCR), this study uncovered several key findings: SVCV is capable of compromising the mucosal architecture in the gill and intestinal tissues of carp, and stimulate the proliferation of mucous cells both in gill and intestinal tissues. Critically, the study revealed that SVCV's invasion elicits a robust response from the carp's mucosal immune system, demonstrating the organism's capacity to resist SVCV invasion despite the challenges posed by the pathogen.
PubMed: 38944254
DOI: 10.1016/j.fsi.2024.109726 -
The International Journal of... Jun 2024The human body is commonly exposed to bisphenol A (BPA), which is widely used in consumer and industrial products. BPA is an endocrine-disrupting chemical that has...
The human body is commonly exposed to bisphenol A (BPA), which is widely used in consumer and industrial products. BPA is an endocrine-disrupting chemical that has adverse effects on human health. In particular, many studies have shown that BPA can cause various neurological disorders by affecting brain development and neural function during prenatal, infancy, childhood, and adulthood exposure. In this review, we discussed the correlation between BPA and neurological disorders based on molecular cell biology, neurophysiology, and behavioral studies of the effects of BPA on brain development and function. Recent studies, both animal and epidemiological, strongly indicate that BPA significantly impacts brain development and function. It hinders neural processes, such as proliferation, migration, and differentiation during development, affecting synaptic formation and activity. As a result, BPA is implicated in neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia.
PubMed: 38944234
DOI: 10.1016/j.biocel.2024.106614