Novel Antioxidant Tripeptide “ACQ” Can Prevent UV-Induced Cell Death and Preserve the Number of Epidermal Stem Cells

We found that tripeptide “ACQ: alanine-cysteine-glutamine” has significant DPPH scavenging activity compared to that of glutathione. Antioxidant effects of ACQ were tested inin vitroandin vivomodels. When treated with H2O2, mock treated fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed good protective effects against hydrogen peroxide treatment. When mice were fed for 2 or 4 weeks, similar protective effects were observed. In the control group, epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were observed. There were also numerous TUNEL positive cells. But in the ACQ group, epidermis became thicker and there was no sign of severe damage. Interestingly, the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell rescuing effects of ACQ, three-dimensional skin samples were constructed. Results showed that ACQ increased the expression of integrinα6 and the number of p63 positive cells. These findings showed that ACQ has good antioxidant activity and may increase stem cell activities by the regulation of integrinα6.

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In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽

10.3390/molecules25030478 ◽

2020 ◽

Vol 25 (3) ◽

pp. 478 ◽

Cited By ~ 6

Author(s):

Rasha Al-Rikabi ◽

Hanady Al-Shmgani ◽

Yaser Hassan Dewir ◽

Salah El-Hendawy

Keyword(s):

Breast Cancer ◽

Chromatin Condensation ◽

Control Group ◽

Potential Candidate ◽

Dependent Manner ◽

Protective Effects ◽

Mcf7 Cells ◽

Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

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An Explanation of the Underlying Mechanisms for the In Vitro and In Vivo Antiurolithic Activity of Glechoma longituba

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3134919 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Qiang Liang ◽

Xiaoran Li ◽

Wangning Zhou ◽

Yu Su ◽

Shenbao He ◽

...

Keyword(s):

Kidney Injury ◽

Positive Control ◽

Potassium Citrate ◽

Positive Control Group ◽

Control Group ◽

Protective Effects ◽

In Vivo Models ◽

Glechoma Longituba

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract’s antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule-1 (KIM-1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis-related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate- (CaOx-) induced OPN expression, KIM-1 expression, and OS compared with the positive control group (P<0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P<0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P<0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone-forming constituents and urolithiasis-related protein expression, and elevating urinary citrate levels.

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Protective Effects of Millettia Pulchra Flavonoids on Myocardial Ischemia In Vitro and In Vivo

Cellular Physiology and Biochemistry ◽

10.1159/000369716 ◽

2015 ◽

Vol 35 (2) ◽

pp. 516-528 ◽

Cited By ~ 8

Author(s):

Jianchun Huang ◽

Xudong Zhang ◽

Feizhang Qin ◽

Yingxin Li ◽

Xiaoqun Duan ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Myocardial Ischemia ◽

Ischemia Reperfusion ◽

Control Group ◽

Protective Effects ◽

Bax Protein ◽

Oxide Synthase

Background: Previous studies have demonstrated that Millettia pulchra flavonoids (MPF) exhibit protective effects on myocardial ischemia reperfusion injury (MI/RI) in isolated rat hearts and show anti-oxidative, anti-hypoxic and anti-stress properties. Methods: In this study, the cardioprotective effects of MPF on myocardial ischemia and its underlying mechanisms were investigated by a hypoxia/ reoxygenation (H/R) injury model in vitro and a rat MI/RI model in vivo. Results: We found that the lactate dehydrogenase (LDH) and inducible nitric oxide synthase (iNOS) activities were decreased in the MPF pretreatment group, whereas the activities of constructional nitric oxide synthase (cNOS), total nitric oxide synthase (tNOS), Na+-K+-ATPase and Ca2+-Mg2+-ATPase were significantly increased. In addition, the cardiocytes were denser in the MPF groups than in the control group. The mortality rate and apoptosis rate of cardiocytes were significantly decreased. Furthermore, pretreatment with MPF in vivo significantly improved the hemodynamics, decreased malondialdehyde (MDA) abundance, increased the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the expression of the Bax protein and ratio Bax/Bc1-2 ration. Conclusions: These results suggest that MPF is an attractive protective substance in myocardial ischemia due to its negative effects on heart rate and ionotropy, reduction of myocardial oxidative damage and modulation of gene expression associated with apoptosis.

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Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

10.1101/2020.03.10.975482 ◽

2020 ◽

Author(s):

Yunki Lee ◽

Jeongmoon J. Choi ◽

Song Ih Ahn ◽

Nan Hee Leea ◽

Woojin M. Han ◽

...

Keyword(s):

Stem Cell ◽

Cell Function ◽

Three Dimensional ◽

Muscle Stem Cell ◽

Organ Systems ◽

Systemic Factors ◽

Underlying Mechanisms ◽

On Chip

AbstractExposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young- and old-muscle stem cell vascular niche on a three-dimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

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Neuroprotective Effects of Ginsenosides against Cerebral Ischemia

Molecules ◽

10.3390/molecules24061102 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1102 ◽

Cited By ~ 15

Author(s):

Zhekang Cheng ◽

Meng Zhang ◽

Chengli Ling ◽

Ying Zhu ◽

Hongwei Ren ◽

...

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Ischemic Injury ◽

Neurological Dysfunction ◽

Control Group ◽

Protective Effects ◽

Ginsenoside Rb1 ◽

Neuroprotective Effects

Ginseng has been used worldwide as traditional medicine for thousands of years, and ginsenosides have been proved to be the main active components for their various pharmacological activities. Based on their structures, ginsenosides can be divided into ginseng diol-type A and ginseng triol-type B with different pharmacological effects. In this study, six ginsenosides, namely ginsenoside Rb1, Rh2, Rg3, Rg5 as diol-type ginseng saponins, and Rg1 and Re as triol-type ginseng saponins, which were reported to be effective for ischemia-reperfusion (I/R) treatment, were chosen to compare their protective effects on cerebral I/R injury, and their mechanisms were studied by in vitro and in vivo experiments. It was found that all ginsenosides could reduce reactive oxygen species (ROS), inhibit apoptosis and increase mitochondrial membrane potential in cobalt chloride-induced (CoCl2-induced) PC12 cells injury model, and they could reduce cerebral infarction volume, brain neurological dysfunction of I/R rats in vivo. The results of immunohistochemistry and western blot showed that the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), silencing information regulator (SIRT1) and nuclear transcription factor P65 (NF-κB) in hippocampal CA1 region of some ginsenoside groups were also reduced. In general, the effect on cerebral ischemia of Rb1 and Rg3 was significantly improved compared with the control group, and was the strongest among all the ginsenosides. The effect on SIRT1 activation of ginsenoside Rb1 and the inhibition effect of TLR4/MyD88 protein expression of ginsenoside Rb1 and Rg3 were significantly stronger than that of other groups. The results indicated that ginsenoside Rg1, Rb1, Rh2, Rg3, Rg5 and Re were effective in protecting the brain against ischemic injury, and ginsenoside Rb1 and Rg3 have the strongest therapeutic activities in all the tested ginsenosides. Their neuroprotective mechanism is associated with TLR4/MyD88 and SIRT1 activation signaling pathways, and they can reduce cerebral ischemic injury by inhibiting NF-κB transcriptional activity and the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

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Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02023-9 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Chunjie Xu ◽

Jing Zhao ◽

Qiuyue Li ◽

Lin Hou ◽

Yan Wang ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Pulmonary Fibrosis ◽

Umbilical Cord ◽

Three Dimensional ◽

Control Group ◽

Human Umbilical Cord ◽

Promising Alternative ◽

Cell Based Therapy

Abstract Background Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages. Methods and results In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica. Conclusions Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.

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Ononin Alleviates Doxorubicin-Induced Cardiotoxicity by Inhibiting ER Stress Through Activation of SIRT3

10.21203/rs.3.rs-813164/v2 ◽

2021 ◽

Author(s):

Shimin Sun ◽

Jingfan Weng ◽

Qi Yang ◽

Xingxiao Huang ◽

Hanlin Zhang ◽

...

Keyword(s):

Er Stress ◽

Myocardial Injury ◽

Molecular Mechanisms ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Protective Effects ◽

H9c2 Cells ◽

Rat Cardiomyocytes

Abstract Introduction Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug, but the clinical application of DOX is seriously limited by its dose-dependent cardiotoxicity. Ononin is a natural isoflavone glycoside and plays a key role in modulating apoptosis related signaling pathways. The aim of this study was to assess the possible cardioprotective effects of Ononin in DOX-induced cardiotoxicity and the underlying molecular mechanisms. Materials and methods Wistar rats were treated with normal saline, DOX with or without Ononin. After the last administration, cardiac function was evaluated by echocardiography. Rats were then sacrificed for histological and TUNEL analyses, with immunological detection for β-actinin, Bax, Bcl-2, GRP78, CHOP and SIRT3. An enzyme-linked immunosorbent assay was performed to assess the myocardial injury markers. H9C2 cells were treated with vehicle, DOX with or without Ononin. Then, 3-TYP was used to find out the relationship between ER stress and SIRT3. Results Ononin treatment ameliorated DOX-induced myocardial injury as demonstrated by echocardiography. Ononin partially restored DOX-induced cardiac dysfunction, both LVEF and LVFS were increased under the cotreatment of Ononin. Ononin also inhibited DOX-induced ER stress and apoptosis in rat cardiomyocytes and H9C2 cells. DOX group had a higher Bax/Bcl-2 ratio, GRP78 and CHOP expression then control group, but Ononin treatment improved these results. This effect was associated with SIRT3 activity, moreover, selective inhibition of SIRT3 blocked the protective effects of Ononin. Conclusion In the present study, we tested the hypothesis that Ononin may protect against DOX-induced cardiomyopathy through ER stress both in vitro and in vivo. Ononin is able to protect against DOX-induced cardiotoxicity by inhibiting ER stress and apoptosis, this effect may via stimulation of the SIRT3 pathway.

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Biofunctional Activities ofEquisetum ramosissimumExtract: Protective Effects against Oxidation, Melanoma, and Melanogenesis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/2853543 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Pin-Hui Li ◽

Yu-Pin Chiu ◽

Chieh-Chih Shih ◽

Zhi-Hong Wen ◽

Laura Kaodichi Ibeto ◽

...

Keyword(s):

Metal Ion ◽

Opposite Effect ◽

Reducing Power ◽

Protective Effects ◽

Related Protein ◽

Melanin Production ◽

Dpph Scavenging Activity ◽

Dpph Scavenging ◽

Tyrosinase Related Protein

Equisetum ramosissimum,a genus of Equisetaceae, is a medicinal plant that can be separated into ethyl acetate (EA), dichloromethane (DM),n-hexane (Hex), methanol (MeOH), and water extracts. EA extract was known to have potent antioxidative properties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared these five extracts in terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058. MTT assay presented the notion that both EA and DM extracts inhibited melanoma growth but did not affect the viabilities of normal dermal keratinocytes (HaCaT) or fibroblasts. Western blot analyses showed that both EA and DM extracts induced overexpression of caspase proteins in all three melanomas. To determine their roles in melanogenesis, this study analyzed theirin vitrosuppressive effects on mushroom tyrosinase. All extracts except for water revealed moderate suppressive effects. None of the extracts affected B16-F10 cells proliferation. EA extract inhibited cellular melanin production whereas DM extract unexpectedly enhanced cellular pigmentation in B16-F10 cells. Data for modulations of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 showed that EA extract inhibited protein expression mentioned above whereas DM extract had the opposite effect. Overall, the experiments indicated that the biofunctional activities of EA extract contained in food and cosmetics protect against oxidation, melanoma, and melanin production.

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The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration

Cells ◽

10.3390/cells9061339 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1339

Author(s):

Ching-Chi Chang ◽

Hsin-Hua Li ◽

Sing-Hua Tsou ◽

Hui-Chih Hung ◽

Guang-Yaw Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Stem Cell ◽

Amyloid Β ◽

Protective Effects ◽

Mitochondrial Superoxide ◽

Nanog Expression ◽

Pluripotency Factor

Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aβ-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aβ-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog—both in vitro and in vivo—and investigated the protective effects and underlying mechanisms against Aβ. We found that overexpression of Nanog is responsible for attenuating Aβ-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aβ neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aβ, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aβ neurotoxicity in the AD brain.

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The Application of Mesenchymal Stem Cells on Wound Repair and Regeneration

Applied Sciences ◽

10.3390/app11073000 ◽

2021 ◽

Vol 11 (7) ◽

pp. 3000

Author(s):

Bruna Lopes ◽

Patrícia Sousa ◽

Rui Alvites ◽

Mariana Branquinho ◽

Ana Sousa ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Wound Repair ◽

Three Dimensional ◽

Skin Lesions ◽

Skin Regeneration ◽

Cell Therapies ◽

Cell Sources

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk-aggravating factors for the development of chronic skin lesions. Stem cells’ regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of three-dimensional (3D) bioprinted scaffolds. With this review, we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, in terms of their relevance in the skin regeneration field.

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