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Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642 -
International Journal of Molecular... Jun 2024Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical...
Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.
Topics: Animals; Berberine; Quercetin; Constipation; Gastrointestinal Microbiome; Mice; Male; Disease Models, Animal; Motilin
PubMed: 38892414
DOI: 10.3390/ijms25116228 -
International Journal of Molecular... Jun 2024The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was...
The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.
Topics: Animals; Female; Epithelial-Mesenchymal Transition; Fibrosis; Tissue Adhesions; Mice; Glucagon-Like Peptides; Humans; Disease Models, Animal; Endometrium; Transforming Growth Factor beta1; Uterus
PubMed: 38892384
DOI: 10.3390/ijms25116196 -
International Journal of Molecular... Jun 2024Blackberries (), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess...
Blackberries (), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess multiple health beneficial effects, including anti-inflammation, anti-atherosclerosis, anti-tumor and immunomodulatory activity. However, the potential biological effects and precise molecular mechanisms of the fermented extracts remain largely unexplored. In this research, we demonstrate the effect of blackberries fermented with for addressing obesity. We investigated the effect of blackberries fermented by on mice fed a high-fat (60% kcal) diet for 12 weeks. Fermented blackberry administration reduced the body weight and epididymal fat caused by a high-fat diet compared to the obese group. The triglyceride and total cholesterol, which are blood lipid indicators, and the levels of leptin, which is an insulin resistance indicator, were significantly increased in the obese group but were significantly decreased in the fermented blackberries-treated group. Additionally, the expression of adipogenesis marker proteins, such as CEBPα, PPAR-γ and SREBP-1, was significantly increased in the obese group, whereas it was decreased in the fermented blackberries-treated group. These results suggest that fermented blackberries have a protective effect against high-fat-diet-induced obesity by inhibiting adipogenesis and are a potential candidate for the treatment of obesity.
Topics: Animals; Adipogenesis; Rubus; Mice; Obesity; Anti-Obesity Agents; Male; Diet, High-Fat; PPAR gamma; Fermentation; Signal Transduction; Lactobacillus plantarum; Plant Extracts; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Leptin; CCAAT-Enhancer-Binding Proteins; Triglycerides; Body Weight
PubMed: 38892352
DOI: 10.3390/ijms25116164 -
International Journal of Molecular... Jun 2024Mitochondria-targeted antioxidants (MTAs) have been studied quite intensively in recent years as potential therapeutic agents and vectors for the delivery of other...
Mitochondria-targeted antioxidants (MTAs) have been studied quite intensively in recent years as potential therapeutic agents and vectors for the delivery of other active substances to mitochondria and bacteria. Their most studied representatives are MitoQ and SkQ1, with its fluorescent rhodamine analog SkQR1, a decyl ester of rhodamine 19 carrying plastoquinone. In the present work, we observed a pronounced antibacterial action of SkQR1 against Gram-positive bacteria, but virtually no effect on Gram-negative bacteria. The MDR pump AcrAB-TolC, known to expel SkQ1, did not recognize and did not pump out SkQR1 and dodecyl ester of rhodamine 19 (C12R1). Rhodamine 19 butyl (C4R1) and ethyl (C2R1) esters more effectively suppressed the growth of Δ, but lost their potency with the wild-type pumping them out. The mechanism of the antibacterial action of SkQR1 may differ from that of SkQ1. The rhodamine derivatives also proved to be effective antibacterial agents against various Gram-positive species, including and . By using fluorescence correlation spectroscopy and fluorescence microscopy, SkQR1 was shown to accumulate in the bacterial membrane. Thus, the presentation of SkQR1 as a fluorescent analogue of SkQ1 and its use for visualization should be performed with caution.
Topics: Anti-Bacterial Agents; Rhodamines; Esters; Microbial Sensitivity Tests; Plastoquinone; Gram-Positive Bacteria; Escherichia coli; Mitochondria; Staphylococcus aureus; Fluorescent Dyes
PubMed: 38892325
DOI: 10.3390/ijms25116137 -
International Journal of Molecular... Jun 2024The sodium pump, or Na/K-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na) and... (Review)
Review
The sodium pump, or Na/K-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na) and potassium (K) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA's role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell-cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells.
Topics: Sodium-Potassium-Exchanging ATPase; Animals; Humans; Cell Membrane; Signal Transduction; Ouabain; Cardiac Glycosides; Sodium
PubMed: 38892309
DOI: 10.3390/ijms25116122 -
International Journal of Molecular... May 2024The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz)...
The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz) technology, the biological effects of this emerging nonionizing radiation, particularly its influence on immune function, remain insufficiently explored but are progressively attracting attention. Here, we demonstrated that 0.1 sub-THz radiation can modulate the immune system and alleviate symptoms of arthritis in collagen-induced arthritis (CIA) mice through a nonthermal manner. The application of 0.1 sub-THz irradiation led to a decrease in proinflammatory factors within the joints and serum, reducing the levels of blood immune cells and the quantity of splenic CD4 T cells. Notably, 0.1 sub-THz irradiation restored depleted Treg cells in CIA mice and re-established the Th17/Treg equilibrium. These findings suggested that sub-THz irradiation plays a crucial role in systemic immunoregulation. Further exploration of its immune modulation mechanisms revealed the anti-inflammatory properties of 0.1 sub-THz on LPS-stimulated skin keratinocytes. Through the reduction in NF-κB signaling and NLRP3 inflammasome activation, 0.1 sub-THz irradiation effectively decreased the production of inflammatory factors and immune-active substances, including IL-1β and PGE, in HaCaT cells. Consequently, 0.1 sub-THz irradiation mitigated the inflammatory response and contributed to the maintenance of immune tolerance in CIA mice. This research provided significant new evidence supporting the systemic impacts of 0.1 sub-THz radiation, particularly on the immune system. It also enhanced the field of photoimmunology and offered valuable insights into the potential biomedical applications of 0.1 sub-THz radiation for treating autoimmune diseases.
Topics: Animals; Arthritis, Experimental; Mice; Terahertz Radiation; Anti-Inflammatory Agents; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; NF-kappa B; Mice, Inbred DBA; T-Lymphocytes, Regulatory; Humans; Signal Transduction; Keratinocytes
PubMed: 38892148
DOI: 10.3390/ijms25115963 -
International Journal of Molecular... May 2024Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and...
Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.
Topics: Hydrogels; Cannabidiol; Skin; Humans; Cyclohexane Monoterpenes; Antioxidants; Regeneration; Polymers; Biocompatible Materials; Keratinocytes; HaCaT Cells; Drug Carriers; Drug Delivery Systems; Anti-Infective Agents
PubMed: 38892121
DOI: 10.3390/ijms25115934 -
International Journal of Molecular... May 2024Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators...
Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.
Topics: Animals; Mast Cells; Dermatitis, Atopic; Mice; Disease Models, Animal; Skin; alpha7 Nicotinic Acetylcholine Receptor; Inflammation; Peptide Hydrolases; Urokinase-Type Plasminogen Activator; Substance P; Stress, Physiological; Mice, Inbred C57BL; Nerve Growth Factor
PubMed: 38891925
DOI: 10.3390/ijms25115738 -
International Journal of Molecular... May 2024According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With... (Review)
Review
According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin's possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.
Topics: Glioblastoma; Humans; Metformin; Angiogenesis Inhibitors; Animals; Brain Neoplasms; Antineoplastic Agents; Drug Development; Neovascularization, Pathologic; Neoplastic Stem Cells
PubMed: 38891882
DOI: 10.3390/ijms25115694