scholarly journals Antiaging Potential of Peptides from Underused Marine Bioresources

Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 513
Author(s):  
Enqin Xia ◽  
Xuan Zhu ◽  
Xuebin Gao ◽  
Jindong Ni ◽  
Honghui Guo
Keyword(s):  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Biological Process ◽  
Marine Organisms ◽  
Activity Inhibition ◽  
Cosmetic Ingredients ◽  
Effects Of Aging ◽  
Natural Peptides ◽  
Near Future

Aging is a biological process that occurs under normal conditions and in several chronic degenerative diseases. Bioactive natural peptides have been shown to improve the effects of aging in cell and animal models and in clinical trials. However, few reports delve into the enormous diversity of peptides from marine organisms. This review provides recent information on the antiaging potential of bioactive peptides from underused marine resources, including examples that scavenge free radicals in vitro, inhibit cell apoptosis, prolong the lifespan of fruit flies and Caenorhabditis elegans, suppress aging in mice, and exert protective roles in aging humans. The underlying molecular mechanisms involved, such as upregulation of oxidase activity, inhibition of cell apoptosis and MMP-1 expression, restoring mitochondrial function, and regulating intestinal homeostasis, are also summarized. This work will help highlight the antiaging potential of peptides from underused marine organisms which could be used as antiaging foods and cosmetic ingredients in the near future.

scholarly journals Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Sushant Khanal ◽  
Qiyuan Tang ◽  
Dechao Cao ◽  
Juan Zhao ◽  
Lam Nhat Nguyen ◽  
...  
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Molecular Mechanisms ◽  
Cd4 T Cell ◽  
Cell Aging

ABSTRACT CD4 T-cell depletion is a hallmark of HIV/AIDS, but the underlying mechanism is still unclear. We have recently shown that ataxia-telangiectasia-mutated (ATM) deficiency in CD4 T cells accelerates DNA damage, telomere erosion, and cell apoptosis in HIV-infected individuals on antiretroviral therapy (ART). Whether these alterations in ART-treated HIV subjects occur in vitro in HIV-infected CD4 T cells remains unknown. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the telomeric DNA damage response (DDR) and cellular apoptosis in highly permissive SupT1 cells, followed by the validation of our observations in primary CD4 T cells with active or drug-suppressed HIV infection. Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo. We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This in vitro model provides a new tool to investigate HIV pathogenesis, and our results shed new light on the molecular mechanisms of telomeric DDR and CD4 T-cell homeostasis during HIV infection. IMPORTANCE The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection.

scholarly journals Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc

Bone Research ◽  
2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Sheng Chen ◽  
Xiaohao Wu ◽  
Yumei Lai ◽  
Di Chen ◽  
Xiaochun Bai ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Mechanical Stress ◽  
Nucleus Pulposus ◽  
Nlrp3 Inflammasome ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

AbstractIntervertebral disc (IVD) degeneration (IVDD) is the main cause of low back pain with major social and economic burdens; however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus (NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1β in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix (ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD.

scholarly journals An Integrative Pharmacology Based Analysis of Refined Liuweiwuling Against Liver Injury: A Novel Component Combination and Hepaprotective Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Gao ◽  
Wei Shi ◽  
Hongyu Yao ◽  
Yongqiang Ai ◽  
Ruisheng Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Cell Apoptosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Anti Inflammatory

Liver disease is a major cause of illness and death worldwide. In China, liver diseases, primarily alcoholic and nonalcoholic fatty liver disease, and viral hepatitis, affect approximately 300 million people, resulting in a major impact on the global burden of liver diseases. The use of Liuweiwuling (LWWL), a traditional Chinese medicine formula, approved by the Chinese Food and Drug Administration for decreasing aminotransferase levels induced by different liver diseases. Our previous study indicated a part of the material basis and mechanisms of LWWL in the treatment of hepatic fibrosis. However, knowledge of the materials and molecular mechanisms of LWWL in the treatment of liver diseases remains limited. Using pharmacokinetic and network pharmacology methods, this study demonstrated that the active components of LWWL were involved in the treatment mechanism against liver diseases and exerted anti-apoptosis and anti-inflammatory effects. Furthermore, esculetin, luteolin, schisandrin A and schisandrin B may play an important role by exerting anti-inflammatory and hepatoprotective effects in vitro. Esculeti and luteolin dose-dependently inhibited H2O2-induced cell apoptosis, and luteolin also inhibited the NF-κB signaling pathway in bone marrow-derived macrophages. schisandrin A and B inhibited the release of ROS in acetaminophen (APAP)-induced acute liver injury in vitro. Moreover, LWWL active ingredients protect against APAP-induced acute liver injury in mice. The four active ingredients may inhibit oxidative stress or inflammation to exert hepatoprotective effect. In conclusion, our results showed that the novel component combination of LWWL can protect against APAP-induced acute liver injury by inhibiting cell apoptosis and exerting anti-inflammatory effects.

scholarly journals In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1052-1061 ◽  
Author(s):  
GQ Chen ◽  
J Zhu ◽  
XG Shi ◽  
JH Ni ◽  
HJ Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Nuclear Dna ◽  
Staining Pattern ◽  
Promyelocytic Leukemia ◽  
Nb4 Cells

It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.

scholarly journals ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Lejian Jiang ◽  
Jiachen Lin ◽  
Sen Zhao ◽  
Jiaqian Wu ◽  
Yongming Jin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Biological Process ◽  
Therapeutic Strategies ◽  
Molecular Signaling ◽  
Biological Functions ◽  
Fundamental Understanding

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both in vitro and in vivo. Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway–based modulations showed great potential in future therapeutic strategies for OA.

scholarly journals A Novel Tanshinone Analog Exerts Anti-Cancer Effects in Prostate Cancer by Inducing Cell Apoptosis, Arresting Cell Cycle at G2 Phase and Blocking Metastatic Ability

2019 ◽  
Vol 20 (18) ◽  
pp. 4459 ◽  
Author(s):  
Mengling Wang ◽  
Xueyi Zeng ◽  
Shengyou Li ◽  
Zekun Sun ◽  
Jia Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Salvia Miltiorrhiza ◽  
Cyclin B1 ◽  
Migration And Invasion ◽  
Caspase 8

Prostate cancer (PCa), an epithelial malignant tumor, is the second common cause of cancer death among males in western countries. Thus, the development of new strategies is urgently needed. Tanshinones isolated from Salvia miltiorrhiza and its synthetic analogs show various biological activities including anticancer effects. Among them, the tanshinone analog 2-((Glycine methyl ester)methyl)-naphtho (TC7) is the most effective, with better selectivity and lower toxicity. Therefore, in this work, the effect of TC7 against PCa was investigated through assessing the molecular mechanisms regulating the growth, metastasis, and invasion of PCa cells. Human PCa cells, PC3 and LNCAP, were used to evaluate TC7 mechanisms of action in vitro, while male BALB/c nude mice were used for in vivo experiments by subjecting each mouse to a subcutaneous injection of PC3 cells into the right flank to evaluate TC7 effects on tumor volume. Our in vitro results showed that TC7 inhibited cell proliferation by arresting the cell cycle at G2/M through the regulation of cyclin b1, p53, GADD45A, PLK1, and CDC2/cyclin b1. In addition, TC7 induced cell apoptosis by regulating apoptosis-associated genes such as p53, ERK1, BAX, p38, BCL-2, caspase-8, cleaved-caspase-8, PARP1, and the phosphorylation level of ERK1 and p38. Furthermore, it decreased DNA synthesis and inhibited the migration and invasion ability by regulating VEGF-1 and MMP-9 protein expression. Our in vivo evidence supports the conclusion that TC7 could be considered as a potential promising chemotherapeutic candidate in the treatment of PCa.

scholarly journals In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1052-1061 ◽  
Author(s):  
GQ Chen ◽  
J Zhu ◽  
XG Shi ◽  
JH Ni ◽  
HJ Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Nuclear Dna ◽  
Staining Pattern ◽  
Promyelocytic Leukemia ◽  
Nb4 Cells

Abstract It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.

scholarly journals Curcumin Ameliorates Palmitic Acid-Induced Saos-2 Cell Apoptosis Via Inhibiting Oxidative Stress and Autophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Baicheng Ma ◽  
Gaopeng Guan ◽  
Qizhuang Lv ◽  
Lei Yang
Keyword(s):  
Oxidative Stress ◽  
Flow Cytometry ◽  
Palmitic Acid ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Human Osteoblast ◽  
Flow Cytometry Assay ◽  
Obvious Effect ◽  
Anti Oxidant

Objectives. We aimed to determine the effects of curcumin on palmitic acid- (PA-) induced human osteoblast-like Saos-2 cell apoptosis and to explore the potential molecular mechanisms in vitro level. Methods. Saos-2 cell were cultured with PA with or without curcumin, N-acetylcysteine (NAC, anti-oxidant), 3-methyladenine (3-MA, autophagy inhibitor) AY-22989 (autophagy agonist) or H2O2. Then, the effects of PA alone or combined with curcumin on viability, apoptosis, oxidative stress, and autophagy in were detected by CCK-8, flow cytometry assay and western blot. Results. We found that autophagy was induced, oxidative stress was activated, and apoptosis was promoted in PA-induced Saos-2 cells. Curcumin inhibited PA-induced oxidative stress, autophagy, and apoptosis in Saos-2 cells. NAC successfully attenuated oxidative stress and apoptosis, and 3-MA attenuated oxidative stress and apoptosis in palmitate-induced Saos-2 cells. Interestingly, NAC inhibited PA-induced autophagy, but 3-MA had no obvious effects on oxidative stress in PA-treated Saos-2 cells. In addition, curcumin inhibited H2O2 (oxidative stress agonist)-induced oxidative stress, autophagy, and apoptosis, but curcumin had no obvious effect on AY-22989 (autophagy agonist)-induced autophagy and apoptosis. Conclusion. The present study demonstrated that oxidative stress is an inducer of autophagy and that curcumin can attenuate excess autophagy and cell apoptosis by inhibiting oxidative stress in PA-induced Saos-2 cells.

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

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