-
International Journal of Molecular... Jun 2024The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases,...
The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases, ultimately contributing to a decreased lifespan and quality of life. Much effort has been made to surmise the molecular mechanisms underlying muscle atrophy and develop tools for improving muscle function. Enhancing mitochondrial function is considered critical for increasing muscle function and health. This study is aimed at evaluating the effect of an aqueous extract of (GTAE) on myogenesis and muscle atrophy caused by dexamethasone (DEX). The GTAE promoted myogenic differentiation, accompanied by an increase in peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) expression and mitochondrial content in myoblast cell culture. In addition, the GTAE alleviated the DEX-mediated myotube atrophy that is attributable to the Akt-mediated inhibition of the Atrogin/MuRF1 pathway. Furthermore, an in vivo study using a DEX-induced muscle atrophy mouse model demonstrated the efficacy of GTAE in protecting muscles from atrophy and enhancing mitochondrial biogenesis and function, even under conditions of atrophy. Taken together, this study suggests that the GTAE shows propitious potential as a nutraceutical for enhancing muscle function and preventing muscle wasting.
Topics: Animals; Muscular Atrophy; Dexamethasone; Muscle Development; Mice; Plant Extracts; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Cell Differentiation; Myoblasts; Cell Line; Muscle Proteins; Male; Muscle, Skeletal; Muscle Fibers, Skeletal; Mice, Inbred C57BL; Tripartite Motif Proteins; Rhodophyta
PubMed: 38928510
DOI: 10.3390/ijms25126806 -
International Journal of Molecular... Jun 2024Our skeleton is an essential part of our body consisting of 206 pieces made of a specialized form of connective tissue, with a matrix containing collagen fibers and a...
Our skeleton is an essential part of our body consisting of 206 pieces made of a specialized form of connective tissue, with a matrix containing collagen fibers and a large amount of minerals [...].
Topics: Humans; Bone Development; Animals; Bone and Bones; Osteogenesis
PubMed: 38928471
DOI: 10.3390/ijms25126767 -
International Journal of Molecular... Jun 2024Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables,...
Onion ( L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.
Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Topics: Animals; Osteoblasts; RANK Ligand; Osteoporosis; Flavonoids; Mice; Onions; Cell Differentiation; Plant Extracts; Rats; Cell Proliferation; RAW 264.7 Cells; Osteogenesis; Humans; Female; Osteoclasts; Bone Density; Ovariectomy; Rats, Sprague-Dawley; Osteoprotegerin
PubMed: 38928460
DOI: 10.3390/ijms25126754 -
International Journal of Molecular... Jun 2024Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural...
Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in () on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel- seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without seed oil, under osteogenic conditions, seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells ( < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with seed oil were nearly doubled compared to control defects ( < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.
Topics: Animals; Rabbits; Plant Oils; Seeds; Mesenchymal Stem Cells; Osteogenesis; Bone Regeneration; Sapindus; Cell Differentiation; X-Ray Microtomography; Tissue Engineering; Humans; Cells, Cultured
PubMed: 38928455
DOI: 10.3390/ijms25126749 -
International Journal of Molecular... Jun 2024Renal cell carcinoma (RCC) is a significant oncological challenge due to its heterogeneous nature and limited treatment options. The developmental gene family encodes... (Review)
Review
Renal cell carcinoma (RCC) is a significant oncological challenge due to its heterogeneous nature and limited treatment options. The developmental gene family encodes nine highly conserved transcription factors that play crucial roles in embryonic development and organogenesis, which have been implicated in the occurrence and development of RCC. This review explores the molecular landscape of RCC, with a specific focus on the role of the gene family in RCC tumorigenesis and disease progression. Of the various RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most prevalent, characterized by the loss of the von Hippel-Lindau () tumor suppressor gene. Here, we review the published literature on the expression patterns and functional implications of genes, particularly and , in the three most common RCC subtypes, including ccRCC, papillary RCC (PRCC), and chromophobe RCC (ChRCC). Further, we review the interactions and potential biological mechanisms involving genes and loss in driving the pathogenesis of RCC, including the key signaling pathways mediated by in ccRCC and associated mechanisms implicating . Lastly, concurrent with our update regarding gene research in RCC, we review and comment on the targeting of towards the development of novel RCC therapies.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Paired Box Transcription Factors; Gene Expression Regulation, Neoplastic; PAX2 Transcription Factor; Von Hippel-Lindau Tumor Suppressor Protein; Animals; PAX8 Transcription Factor; Signal Transduction
PubMed: 38928435
DOI: 10.3390/ijms25126730 -
International Journal of Molecular... Jun 2024Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with... (Review)
Review
Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.
Topics: Humans; MicroRNAs; Breast Neoplasms; Female; Muscular Atrophy; Muscle, Skeletal; Animals; Muscle Development
PubMed: 38928418
DOI: 10.3390/ijms25126714 -
International Journal of Molecular... Jun 2024We fabricated a microfluidic chip (osteoblast [OB]-osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of...
We fabricated a microfluidic chip (osteoblast [OB]-osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB-OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB-OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB-OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB-OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB-OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB-OC supernatant at a ratio of 75:25.
Topics: Animals; Osteogenesis; Osteoblasts; Osteoclasts; Mice; Rats; Cell Differentiation; Lab-On-A-Chip Devices; Culture Media, Conditioned; Cell Line; Skull; X-Ray Microtomography; Male
PubMed: 38928310
DOI: 10.3390/ijms25126605 -
International Journal of Molecular... Jun 2024Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators...
Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine-pulp complex during dentinogenesis. The aim of this study was to investigate post-translational histone modulation and HDAC expression during DPC mineralisation and the expression of Class I/II HDACs during tooth development and in adult teeth. HDAC expression (isoforms -1 to -6) was analysed in mineralising primary rat DPCs using qRT-PCR and Western blot with mass spectrometry being used to analyse post-translational histone modifications. Maxillary molar teeth from postnatal and adult rats were analysed using immunohistochemical (IHC) staining for HDACs (1-6). HDAC-1, -2, and -4 protein expression increased until days 7 and 11, but decreased at days 14 and 21, while other HDAC expression increased continuously for 21 days. The Class II mineralisation-associated HDAC-4 was strongly expressed in postnatal sample odontoblasts and DPCs, but weakly in adult teeth, while other Class II HDACs (-5, -6) were relatively strongly expressed in postnatal DPCs and adult odontoblasts. Among Class I HDACs, HDAC-1 showed high expression in postnatal teeth, notably in ameloblasts and odontoblasts. HDAC-2 and -3 had extremely low expression in the rat dentine-pulp complex. Significant increases in acetylation were noted during DPC mineralisation processes, while trimethylation H3K9 and H3K27 marks decreased, and the HDAC-inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced H3K27me3. These results highlight a dynamic alteration in histone acetylation during mineralisation and indicate the relevance of Class II HDAC expression in tooth development and regenerative processes.
Topics: Animals; Acetylation; Rats; Histone Deacetylases; Dentinogenesis; Dentin; Dental Pulp; Protein Processing, Post-Translational; Histones; Molar; Odontoblasts; Male
PubMed: 38928274
DOI: 10.3390/ijms25126569 -
International Journal of Molecular... Jun 2024Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim... (Review)
Review
Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aβ pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.
Topics: Fluoxetine; Alzheimer Disease; Humans; Animals; Cognitive Dysfunction; Disease Models, Animal; Neurogenesis; Neuronal Plasticity
PubMed: 38928248
DOI: 10.3390/ijms25126542 -
International Journal of Molecular... Jun 2024Neurogenesis is the process by which new brain cells are formed. This crucial event emerges during embryonic life and proceeds in adulthood, and it could be influenced...
Neurogenesis is the process by which new brain cells are formed. This crucial event emerges during embryonic life and proceeds in adulthood, and it could be influenced by environmental pollution. Non-combustion-derived magnetite represents a portion of the coarse particulate matter (PM) contributing to air and water pollution in urban settings. Studies on humans have reported that magnetite and other iron oxides have significant damaging effects at a central level, where these particles accumulate and promote oxidative stress. Similarly, magnetite nanoparticles can cross the placenta and damage the embryo brain during development, but the impact on neurogenesis is still unknown. Furthermore, an abnormal Fe cation concentration in cells and tissues might promote reactive oxygen species (ROS) generation and has been associated with multiple neurodegenerative conditions. In the present study, we used zebrafish as an in vivo system to analyze the specific effects of magnetite on embryonic neurogenesis. First, we characterized magnetite using mineralogical and spectroscopic analyses. Embryos treated with magnetite at sub-lethal concentrations showed a dose-response increase in ROS in the brain, which was accompanied by a massive decrease in antioxidant genes (, , , and ). In addition, a higher number of apoptotic cells was observed in embryos treated with magnetite. Next, interestingly, embryos exposed to magnetite displayed a decrease in neural staminal progenitors (, , and markers) and a neuronal marker (). Finally, we observed significative increases in (specific microglia marker) and interleukin-1b (), confirming a status of inflammation in the brain embryos treated with magnetite. Our study represents the very first in vivo evidence concerning the effects of magnetite on brain development.
Topics: Animals; Zebrafish; Neurogenesis; Ferrosoferric Oxide; Embryo, Nonmammalian; Reactive Oxygen Species; Oxidative Stress; Brain; Apoptosis; Magnetite Nanoparticles
PubMed: 38928164
DOI: 10.3390/ijms25126459