Although there is growing evidence that cellular senescence influences wound healing, a clear understanding of how senescence can be beneficial and/or detrimental to wound healing is unknown. Wound ...healing may also be influenced by the baseline tissue senescence, which is elevated in aging and chronic wounds, both of which have significant healing delays. To study the effects of skin senescence on wound healing, we developed an elevated skin senescence model based on the subcutaneous transfer of irradiated fibroblasts into young 8-week-old wild-type C57BL/6 male mice. This senescent cell transfer significantly increased skin senescence levels compared to control transfers of non-irradiated fibroblasts. There was an increased presence of SA-β-Gal- and p21-positive senescent cells throughout the skin. Furthermore, the entire skin showed significantly elevated gene expression of senescence (p16, p21) and SASP markers (IL-6, MCP-1, MMP-3, MMP-9, and TGF-β). Subsequent wound healing in the skin with elevated senescence was markedly delayed and had similar kinetics to naturally aged 2-year-old mice. After the wounds had healed, the skin developed persistently elevated senescence. Our results demonstrate that states of elevated skin senescence can delay wound healing and result in sustained senescence after healing. Therefore, the accumulation of senescent cells in aged skin or chronic wounds may be a driver of delayed healing and can be considered a potential target to improve healing.
Society and our healthcare system are facing unprecedented challenges due to the expansion of the older population. As plastic surgeons, we can improve care of our older patients through ...understanding the mechanisms of aging that inevitably impact their outcomes and well-being. One of the major hallmarks of aging, cellular senescence, has recently become the focus of vigorous research in academia and industry. Senescent cells, which are metabolically active but in a state of stable cell cycle arrest, are implicated in causing aging and numerous age-related diseases. Further characterization of the biology of senescence revealed that it can be both detrimental and beneficial to organisms depending on tissue context and senescence chronicity. Here, we review the role of cellular senescence in aging, wound healing, tissue regeneration, and other domains relevant to plastic surgery. We also review the current state of research on therapeutics that modulate senescence to improve conditions of aging.
Senescence is a complex cellular stress response that abolishes proliferative capacity and generates a unique secretory pattern that is implicated in organismal aging and age-related disease. How a ...cell transitions to a senescent state is multifactorial and often requires transcriptional regulation of multiple genes. Epigenetic alterations to DNA and chromatin are powerful regulators of genome architecture and gene expression, and they play a crucial role in mediating the induction and maintenance of senescence. This review will highlight the changes in chromatin, DNA methylation, and histone alterations that establish and maintain cellular senescence, alongside the specific epigenetic regulation of the senescence-associated secretory phenotype (SASP).
Magnetic ferrite nanoparticles (MNPs) coated with biocompatible polymers capable of drug loading and release are fascinating nanostructures for delivering anti-cancer drugs. Herein, we report the ...synthesis and characterization of a novel β-cyclodextrin-folate-tethered dextran polymer. Nickel-zinc ferrite nanoparticles are prepared and coated with the polymer to form a biocompatible hybrid magnetic nanocarrier. To establish the significance of folate unit of the polymer in anticancer activity, a similar derivatized polymer, i.e. β-cyclodextrin-dextran conjugate without folate tether is used for comparison. The size of the hybrid MNPs is ∼20 nm, which is a size suitable for cancer drug targeting. The polymer-coated magnetic nanocarriers are soft ferromagnets as suggested by their narrow magnetic hysteresis loops. The anticancer drug camptothecin (CPT) is loaded on the magnetic nanocarriers. The drug loading efficiency is observed to be above 92%. The nanocarriers show sustained in vitro drug release for above 45 h. The in vitro cytotoxicity studies reveal that the loaded CPT retains its potency in the nanocarrier and the folate-tethered nanocarrier shows better anticancer activity than the one which does not carry a folate unit. The magnetic nanocarrier is suitable for magnetic field-guided drug transport, enhanced drug loading and release and folate receptor-mediated endocytotic uptake of drugs by cancer cells.
Mucorales species cause debilitating, life-threatening sinopulmonary diseases in immunocompromised patients and penetrating wounds in trauma victims. Common antifungal agents against mucormycosis ...have significant toxicity and are often ineffective. To evaluate treatments against mucormycosis, sporangiospores are typically used for in vitro assays and in pre-clinical animal models of pulmonary infections. However, in clinical cases of wound mucormycosis caused by traumatic inoculation, hyphal elements found in soil are likely the form of the inoculated organism. In this study, Galleria mellonella larvae were infected with either sporangiospores or hyphae of Rhizopus arrhizus and Lichtheimia corymbifera. Hyphal infections resulted in greater and more rapid larval lethality than sporangiospores, with an approximate 10–16-fold decrease in LD50 of hyphae for R. arrhizus (p = 0.03) and L. corymbifera (p = 0.001). Liposomal amphotericin B, 10 mg/kg, was ineffective against hyphal infection, while the same dosage was effective against infections produced by sporangiospores. Furthermore, in vitro, antifungal susceptibility studies show that minimum inhibitory concentrations of several antifungal agents against hyphae were higher when compared to those of sporangiospores. These findings support using hyphal elements of Mucorales species for virulence testing and antifungal drug screening in vitro and in G. mellonella for studies of wound mucormycosis.
In this article, we report Mn(II), Fe(II) and Cu(I) complexes (BIP-Mn, BIP-Fe and BIP-Cu) bearing a non-innocent, NNN pincer ligand, 4-aminoantipyrine tethered 2,6-bis(iminoantipyrine)pyridine (BIP) ...and structural diversity. The complexes were characterized by different spectroscopic and single-crystal X-ray analysis. Superoxide dismutase (SOD) activity has been evaluated for BIP and complexes BIP-Mn, BIP-Fe and BIP-Cu. It was observed that the seven-coordinate BIP-Mn complex showed preeminent SOD activity on comparing to BIP-Fe and BIP-Cu complexes. Besides, preliminary in vitro anticancer properties of BIP-Mn, BIP-Fe and BIP-Cu have been studied. Again, BIP-Mn complex showed stronger anticancer activity compared to ligand, BIP-Fe and BIP-Cu complexes.
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•Untapped biological significance of acyclic diiminodipyrromethane Schiff’s bases.•Biological significance of two structurally diversified four coordinated Zn(II) complexes.•DFT and ...Molecular docking studies to support the experimental results.
Two new self-adjustable acyclic diiminodipyrromethane Schiff‘s bases of composition (Ph)(CH3)C(2,6-iPr2C6H3-N = CH-C4H2NH)2 (L1) and (Ph)(CH3)C(Ph3C-N = CH-C4H2NH)2 (L2) their zinc complexes of chemical composition Zn{(Ph)(CH3)C(2,6-iPr2C6H3-N = CH-C4H2N)(2,6-iPr2C6H3-N = CH-C4H2NH)}2 (1) and ZnCl2{(Ph)(CH3)C(Ph3C-NH = CH-C4H2N)2} (2) are screened for their biological activity such as in-vitro cytotoxicity, antibacterial and antifungal activity by using various cancer cell lines, bacterial and fungal strains respectively. Density Functional Theory (DFT) calculations are made to understand more insight of the self-adjustable coordination behavior of the both ligands (L1 and L2) and structural stability of the zinc complexes (1 and 2). The experimental biological importance of zinc complexes (1 and 2) further investigated by using molecular docking simulations with human breast cancer (2ING and 3PXC), cervical cancer (5J6R), and lung cancer (5WD6) protein strains. Molecular docking studies showed both zinc complexes have significant amount of hydrogen bonding interactions with binding energy from −6.80 to −8.20 kcal/mol (for1) and −8.30 to −10.30 kcal/mol (for 2). In addition to strong hydrogen bonding interactions, significant amount of non-covalent interactions such as pi-pi stacked, pi-piT-shaped, pi-alkyl, pi-cation, pi-anion, pi-sigma and pi-donor interactions have also been observed in the case of zinc complexes (1 and 2) which make them unique and useful anticancer agents.
Mucorales species cause debilitating, life-threatening sinopulmonary diseases in immunocompromised patients and penetrating wounds in trauma victims. Common antifungal agents against mucormycosis ...have significant toxicity and are often ineffective. To evaluate treatments against mucormycosis, sporangiospores are typically used for in vitro assays and in pre-clinical animal models of pulmonary infections. However, in clinical cases of wound mucormycosis caused by traumatic inoculation, hyphal elements found in soil are likely the form of the inoculated organism. In this study, Galleria mellonella larvae were infected with either sporangiospores or hyphae of Rhizopus arrhizus and Lichtheimia corymbifera. Hyphal infections resulted in greater and more rapid larval lethality than sporangiospores, with an approximate 10–16-fold decrease in LDsub.50 of hyphae for R. arrhizus (p = 0.03) and L. corymbifera (p = 0.001). Liposomal amphotericin B, 10 mg/kg, was ineffective against hyphal infection, while the same dosage was effective against infections produced by sporangiospores. Furthermore, in vitro, antifungal susceptibility studies show that minimum inhibitory concentrations of several antifungal agents against hyphae were higher when compared to those of sporangiospores. These findings support using hyphal elements of Mucorales species for virulence testing and antifungal drug screening in vitro and in G. mellonella for studies of wound mucormycosis.
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