-
MBio Mar 2020Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. Despite its great abundance on earth, the accessibility for...
Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. Despite its great abundance on earth, the accessibility for microorganisms is often limited, because poorly soluble ferric iron (Fe) is the predominant oxidation state in an aerobic environment. Hence, the reduction of Fe is of essential importance to meet the cellular demand of ferrous iron (Fe) but might become detrimental as excessive amounts of intracellular Fe tend to undergo the cytotoxic Fenton reaction in the presence of hydrogen peroxide. We demonstrate that the complex formation rate of Fe and phenolic compounds like protocatechuic acid was increased by 46% in the presence of HCO and thus accelerated the subsequent redox reaction, yielding reduced Fe Consequently, elevated CO/HCO levels increased the intracellular Fe availability, which resulted in at least 50% higher biomass-specific fluorescence of a DtxR-based reporter strain, and stimulated growth. Since the increased Fe availability was attributed to the interaction of HCO and chemical iron reduction, the abiotic effect postulated in this study is of general relevance in geochemical and biological environments. In an oxygenic environment, poorly soluble Fe must be reduced to meet the cellular Fe demand. This study demonstrates that elevated CO/HCO levels accelerate chemical Fe reduction through phenolic compounds, thus increasing intracellular Fe availability. A number of biological environments are characterized by the presence of phenolic compounds and elevated HCO levels and include soil habitats and the human body. Fe availability is of particular interest in the latter, as it controls the infectiousness of pathogens. Since the effect postulated here is abiotic, it generally affects the Fe distribution in nature.
Topics: Bicarbonates; Biomass; Carbon Dioxide; Corynebacterium glutamicum; Ferric Compounds; Ferrous Compounds; Hydrogen Peroxide; Iron; Oxidation-Reduction; Phenols; Soil
PubMed: 32156807
DOI: 10.1128/mBio.00085-20 -
American Journal of Physiology.... Apr 2020Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection...
Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection without terminating pregnancy in some cases. However, how pregnancy affects maternal liver regeneration remains elusive. We performed 70% partial hepatectomy (PH) in nonpregnant mice and gestation mice, and histologically and molecularly compared their liver regrowth during the next 4 days. We found that compared with the nonpregnant state, pregnancy altered the molecular programs driving hepatocyte replication, indicated by enhanced activities of epidermal growth factor receptor and STAT5A, reduced activities of cMet and p70S6K, decreased production of IL-6, TNFα, and hepatocyte growth factor, suppressed cyclin D1 expression, increased cyclin A1 expression, and early activated cyclin A2 expression. As a result, pregnancy allowed the remnant hepatocytes to enter the cell cycle at least 12 h earlier, increased hepatic fat accumulation, and enhanced hepatocyte mitosis. Consequently, pregnancy ameliorated maternal liver regeneration following PH. In addition, a report showed that maternal liver regrowth after PH is driven mainly by hepatocyte hypertrophy rather than hyperplasia during the second half of gestation in young adult mice. In contrast, we demonstrate that maternal liver relies mainly on hepatocyte hyperplasia instead of hypertrophy to restore the lost mass after PH. Overall, we demonstrate that pregnancy facilitates maternal liver regeneration likely via triggering an early onset of hepatocyte replication, accumulating excessive liver fat, and promoting hepatocyte mitosis. The results from our current studies enable us to gain more insights into how maternal liver regeneration progresses during gestation. We demonstrate that pregnancy may generate positive effects on maternal liver regeneration following partial hepatectomy, which are manifested by early entry of the cell cycle of remnant hepatocytes, increased hepatic fat accumulation, enhanced hepatocyte mitosis, and overall accelerated liver regrowth.
Topics: Animals; Body Weight; Female; Hepatectomy; Liver; Liver Regeneration; Mice; Mice, Inbred C57BL; Mitosis; Organ Size; Pregnancy
PubMed: 32003603
DOI: 10.1152/ajpgi.00125.2019 -
Frontiers in Immunology 2023Like telomere shortening, global DNA hypomethylation occurs progressively with cellular divisions or aging and functions as a mitotic clock to restrain malignant...
Like telomere shortening, global DNA hypomethylation occurs progressively with cellular divisions or aging and functions as a mitotic clock to restrain malignant transformation/progression. Several DNA-methylation (DNAm) age clocks have been established to precisely predict chronological age using normal tissues, but show DNAm age drift in tumors, which suggests disruption of this mitotic clock during carcinogenesis. Little is known about DNAm age alterations and biological/clinical implications in endometrial cancer (EC). Here we address these issues by analyzing TCGA and GSE67116 cohorts of ECs. Horvath clock analysis of these tumors unexpectedly revealed that almost 90% of them exhibited DNAm age deceleration (DNAmad) compared to patient chronological age. Combined with an additional clock named Phenoage, we identified a subset of tumors (82/429) with high DNAmad (hDNAmad+) as assessed by both clocks. Clinically, hDNAmad+ tumors were associated with advanced diseases and shorter patient survival, compared to hDNAmad- ones. Genetically, hDNAmad+ tumors were characterized by higher copy number alterations (CNAs) whereas lower tumor mutation burden. Functionally, hDNAmad+ tumors were enriched with cell cycle and DNA mismatch repair pathways. Increased PIK3CA alterations and downregulation of SCGB2A1, the inhibitor of PI3K kinase, in hDNAmad+ tumors, might promote tumor growth/proliferation and stemness. In addition, the inactivation of aging drivers/tumor suppressors (TP53, RB1, and CDKN2A) while enhanced telomere maintenance occurred more frequently in hDNAmad+ tumors, which supports sustained tumor growth. Prominently, hDNAmad+ tumors were featured with immunoexclusion microenvironments, accompanied by significantly higher levels of VTCN1 expression while lower PD-L1 and CTLA4 expression, which indicates their poor response to immune checkpoint inhibitor (ICI)-based immunotherapy. We further showed significantly higher levels of DNMT3A and 3B expression in hDNAmad+ than in hDNAmad- tumors. Thus, the tumor suppressive function of aging-like DNA hypomethylation is severely impaired in hDNAmad+ tumors, likely due to enhanced expression of DNMT3A/3B and dysregulated aging regulators. Our findings not only enrich biological knowledge of EC pathogenesis but also help improve EC risk stratification and precision ICI immunotherapy.
Topics: Female; Humans; DNA Methylation; Deceleration; Endometrial Neoplasms; Carcinogenesis; DNA Modification Methylases; DNA; Tumor Microenvironment
PubMed: 37388735
DOI: 10.3389/fimmu.2023.1208223 -
Biophysical Journal Jun 2022Contrasting most known bacterial motility mechanisms, a bacterial sliding motility discovered in at least two gram-positive bacterial families does not depend on...
Contrasting most known bacterial motility mechanisms, a bacterial sliding motility discovered in at least two gram-positive bacterial families does not depend on designated motors. Instead, the cells maintain end-to-end connections following cell divisions to form long chains and exploit cell growth and division to push the cells forward. To investigate the dynamics of this motility mechanism, we constructed a mechanical model that depicts the interplay of the forces acting on and between the cells comprising the chain. Due to the exponential growth of individual cells, the tips of the chains can, in principle, accelerate to speeds faster than any known single-cell motility mechanism can achieve. However, analysis of the mechanical model shows that the exponential acceleration comes at the cost of an exponential buildup in mechanical stress in the chain, making overly long chains prone to breakage. Additionally, the mechanical model reveals that the dynamics of the chain expansion hinges on a single non-dimensional parameter. Perturbation analysis of the mechanical model further predicts the critical stress leading to chain breakage and its dependence on the non-dimensional parameter. Finally, we developed a simplistic population-expansion model that uses the predicted breaking behavior to estimate the physical limit of chain-mediated population expansion. Predictions from the models provide critical insights into how this motility depends on key physical properties of the cell and the substrate. Overall, our models present a generically applicable theoretical framework for cell-chain-mediated bacterial sliding motility and provide guidance for future experimental studies on such motility.
Topics: Bacteria; Cell Proliferation; Humans; Stress, Mechanical
PubMed: 35591787
DOI: 10.1016/j.bpj.2022.05.012 -
Recent Patents on Biotechnology Apr 2013This paper presents the design and test of a dual-mode electric and magnetic biological stimulator (EM-Stim). The stimulator generates pulsing electric and magnetic... (Review)
Review
This paper presents the design and test of a dual-mode electric and magnetic biological stimulator (EM-Stim). The stimulator generates pulsing electric and magnetic fields at programmable rates and intensities. While electric and magnetic stimulators have been reported before, this is the first device that combines both modalities. The ability of the dual stimulation to target bone and muscle tissue simultaneously has the potential to improve the therapeutic treatment of osteoporosis and sarcopenia. The device is fully programmable, portable and easy to use, and can run from a battery or a power supply. The device can generate magnetic fields of up to 1.6 mT and output voltages of +/- 40 V. The EM-Stim accelerated myogenic differentiation of myoblasts into myotubes as evidenced by morphometric, gene expression, and protein content analyses. Currently, there are many patents concerned with the application of single electrical or magnetic stimulation, but none that combine both simultaneously. However, we applied for and obtained a provisional patent for new device to fully explore its therapeutic potential in pre-clinical models.
Topics: Animals; Cell Differentiation; Cell Growth Processes; Cell Line; Cytological Techniques; Electric Stimulation; Electromagnetic Fields; Humans; Mice; Muscle Development; Myoblasts; Patents as Topic
PubMed: 23445453
DOI: 10.2174/1872208311307010007 -
Postepy Higieny I Medycyny... Aug 2011Until recently it was thought that aging is a characteristic feature only of cells and organisms of eukaryotic origin. Recent studies on Caulobacter crescentus showed... (Review)
Review
Until recently it was thought that aging is a characteristic feature only of cells and organisms of eukaryotic origin. Recent studies on Caulobacter crescentus showed that their dimorphic life cycle associated with asymmetric cell division leads to a gradual increase in the time needed for the development of new bacteria generations, which may reflect aging of this organism. Moreover, as shown in Escherichia coli, accelerated exhaustion of proliferative capacity and bacteria death are caused by inheritance of certain structures from the mother cell during cell division. A similar phenomenon, called 'conditional senescence', has been observed during the stationary phase of growth in liquid cultures. The aim of this paper is to present the current state of knowledge on the causes, mechanisms and evolutionary significance of aging in bacteria. Some issues associated with bacterial aging will be discussed in the context of similar phenomena occurring in eukaryotic cells.
Topics: Aging; Asymmetric Cell Division; Bacteria; Biological Evolution; Models, Biological; Prokaryotic Cells; Time Factors
PubMed: 21918253
DOI: 10.5604/17322693.955129 -
Communications Biology Jun 2022Cell-cultured meat offers the potential for a more sustainable, ethical, resilient, and healthy food system. However, research and development has been hindered by the...
Cell-cultured meat offers the potential for a more sustainable, ethical, resilient, and healthy food system. However, research and development has been hindered by the lack of serum-free media that enable the robust expansion of relevant cells (e.g., muscle satellite cells) over multiple passages. Recently, a low-cost serum-free media (B8) was described for pluripotent stem cells. Here, B8 is adapted for bovine satellite cells through the addition of a single component, recombinant albumin, which renders it suitable for long-term satellite cell expansion without sacrificing myogenicity. This new media (Beefy-9) maintains cell growth over the entire period tested (seven passages), with an average doubling time of 39 h. Along with demonstrated efficacy for bovine cells, Beefy-9 offers a promising starting-point for developing serum-free media for other meat-relevant species. Ultimately, this work offers a foundation for escaping cultured meat research's reliance on serum, thereby accelerating the field.
Topics: Animals; Cattle; Cell Differentiation; Cell Proliferation; Culture Media, Serum-Free; Meat; Myoblasts
PubMed: 35654948
DOI: 10.1038/s42003-022-03423-8 -
Current Biology : CB Feb 2020Although developmental mechanisms driving an increase in brain size during vertebrate evolution are actively studied, we know less about evolutionary strategies allowing...
Although developmental mechanisms driving an increase in brain size during vertebrate evolution are actively studied, we know less about evolutionary strategies allowing accelerated brain growth. In zebrafish and other vertebrates studied to date, apical radial glia (RG) constitute the primary neurogenic progenitor population throughout life [1]; thus, RG activity is a determining factor of growth speed. Here, we ask whether enhanced RG activity is the mechanism selected to drive explosive growth, in adaptation to an ephemeral habitat. In post-hatching larvae of the turquoise killifish, which display drastic developmental acceleration, we show that the dorsal telencephalon (pallium) grows three times faster than in zebrafish. Rather than resulting from enhanced RG activity, we demonstrate that pallial growth is the product of a second type of progenitors (that we term NGPs for non-glial progenitors) that actively sustains neurogenesis and germinal zone self-renewal. Intriguingly, NGPs appear to retain, at larval stages, features of early embryonic progenitors. In parallel, RGs enter premature quiescence and express markers of astroglial function. Altogether, we propose that mosaic heterochrony within the neural progenitor population might permit rapid pallial growth by safeguarding both continued neurogenesis and astroglial function.
Topics: Animals; Cyprinodontiformes; Neural Stem Cells; Neurogenesis; Telencephalon
PubMed: 32004451
DOI: 10.1016/j.cub.2019.12.046 -
Biomedicine & Pharmacotherapy =... May 2024Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are...
Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.
Topics: Animals; Antlers; Alopecia; Hair Follicle; Mice; Male; Bone Morphogenetic Protein 4; Hair; Hedgehog Proteins; Zinc Finger Protein GLI1; Cell Proliferation; Signal Transduction; Tissue Extracts; Mice, Inbred C57BL; Disease Models, Animal; Regeneration; Deer; Smad5 Protein
PubMed: 38565060
DOI: 10.1016/j.biopha.2024.116503 -
International Journal of Molecular... Feb 2019Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To...
Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To investigate the effect of Activin B on vibrissae follicles, the anagen induction assay and an in vitro vibrissae culture system were constructed. Hematoxylin and eosin staining were performed to determine the hair cycle stages. The 5-ethynyl-2'-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays were used to examine the cell proliferation. Flow cytometry was used to detect the cell cycle phase. Inhibitors and Western blot analysis were used to investigate the signaling pathway induced by Activin B. As a result, we found that the vibrissae follicle growth was accelerated by 10 ng/mL Activin B in the anagen induction assay and in an organ culture model. 10 ng/mL Activin B promoted hair matrix cell proliferation in vivo and in vitro. Moreover, Activin B modulates hair matrix cell growth through the ERK⁻Elk1 signaling pathway, and Activin B accelerates hair matrix cell transition from the G1/G0 phase to the S phase through the ERK⁻Cyclin D1 signaling pathway. Taken together, these results demonstrated that Activin B may promote mouse vibrissae growth by stimulating hair matrix cell proliferation and cell cycle progression through ERK signaling.
Topics: Activins; Animals; Cell Cycle; Cell Proliferation; Cyclin D1; Hair Follicle; Humans; MAP Kinase Signaling System; Male; Mice, Inbred C57BL; Models, Biological; Organ Culture Techniques; Phosphorylation; Vibrissae; ets-Domain Protein Elk-1
PubMed: 30781441
DOI: 10.3390/ijms20040853