Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. ...Epigallocatechin‐3‐gallate (EGCG) is a natural polyphenol that exhibits anti‐inflammatory and anti‐oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re‐epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re‐epithelialization and wound healing in T2D‐induced wounds. Murine models of wound healing in T2D were established via feeding high‐fat high‐fructose diet (HFFD) and the creation of full‐thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2‐related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re‐epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch‐like ECH‐associated protein 1 (KEAP1), thereby inhibiting KEAP1‐mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re‐epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.
In the basal state, Kelch‐like ECH‐associated protein 1 (KEAP1) binds to and constantly degrades the transcription factor NRF2 in the cell. Epigallocatechin‐3‐gallate binds to KEAP1, thereby preventing KEAP1‐mediated binding and sequestration of NRF2. Subsequently, nuclear translocation of NRF2 results in the upregulation of cytokeratin 16 expression, thereby allowing the activation of epidermal keratinocytes and reepithelialization that is critical in promoting the wound healing response in type 2 diabetes.
Myocardial infarction (MI) is one of the leading causes of death worldwide, and due to the widespread and irreversible damage caused, new therapeutic treatments are urgently needed in order to limit ...the degree of ischaemic damage following MI. Aberrant activation of Wnt/β‐catenin signalling pathway often occurs during cardiovascular diseases including MI, which results in excess production of reactive oxygen species (ROS) and further promotes myocardial dysfunction. Huoxin pill (HXP) is a Traditional Chinese Medicine formula that has been widely used in the treatment of coronary heart disease and angina; however, its mechanisms remain unclear. Here, we performed mouse models of MI and examined the effects and mechanisms of HXP in protecting against MI‐induced ischaemic damage. Our study showed that administration with HXP robustly protected against MI‐induced cardiac injuries, decreased infarct size and improved cardiac function. Moreover, HXP attenuated ischaemia‐induced DNA damage occurrence in vivo and H2O2‐induced DNA damage occurrence in vitro, via potent inhibition of adverse Wnt/β‑catenin signalling activation. Our study thus elucidated the role and mechanism of HXP in protecting against MI and oxidative stress‐induced injuries and suggests new therapeutic strategies in ischaemic heart disease via inhibition of Wnt/β‐catenin signalling pathway.
Vascular endothelial growth factor (VEGF) is a well‐known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed ...to investigate whether dual treatment with insulin‐like growth factor binding protein‐4 (IGFBP‐4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP‐4 enhanced VEGF‐induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin‐1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen‐I and collagen‐III following MI. Importantly, while the protective action of IGFBP‐4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post‐ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease.
Sodium‐ion batteries (SIBs) are considered as a low‐cost complementary or alternative system to prestigious lithium‐ion batteries (LIBs) because of their similar working principle to LIBs, ...cost‐effectiveness, and sustainable availability of sodium resources, especially in large‐scale energy storage systems (EESs). Among various cathode candidates for SIBs, Na‐based layered transition metal oxides have received extensive attention for their relatively large specific capacity, high operating potential, facile synthesis, and environmental benignity. However, there are a series of fatal issues in terms of poor air stability, unstable cathode/electrolyte interphase, and irreversible phase transition that lead to unsatisfactory battery performance from the perspective of preparation to application, outside to inside of layered oxide cathodes, which severely limit their practical application. This work is meant to review these critical problems associated with layered oxide cathodes to understand their fundamental roots and degradation mechanisms, and to provide a comprehensive summary of mainstream modification strategies including chemical substitution, surface modification, structure modulation, and so forth, concentrating on how to improve air stability, reduce interfacial side reaction, and suppress phase transition for realizing high structural reversibility, fast Na+ kinetics, and superior comprehensive electrochemical performance. The advantages and disadvantages of different strategies are discussed, and insights into future challenges and opportunities for layered oxide cathodes are also presented.
Recent progress in layered oxide cathodes for sodium‐ion batteries (SIBs) from air stability, interface chemistry, and phase transition are comprehensively summarized. The intrinsic degradation mechanisms behind electrochemical performance and mainstream modification strategies are systematically sorted out and analyzed. The remaining challenges, promising optimization strategies as well as endeavor directions to break current limitations are also presented for the future design of high‐performance layered oxide cathodes for SIBs.
Pathogenic microbial biofilms that readily form on implantable medical devices or human tissues have posed a great threat to worldwide healthcare. Hopes are focused on preventive strategies towards ...biofilms, leaving a thought-provoking question: how to tackle the problem of established biofilms? In this review, we briefly summarize the functionalized biomaterials to combat biofilms and highlight current approaches to eradicate pre-existing biofilms. We believe that all of these strategies, alone or in combination, could represent a blueprint for fighting biofilm-associated infections in the postantibiotic era.
Pathogenic microbial biofilms that readily form on implantable medical devices or human tissues have posed a great threat to worldwide healthcare.
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•Plastomes of Rhodiola are conserved with respect to size, structure, and gene content.•Rhodiola is divided into two clades: dioecious and hermaphrodite.•Four chloroplast genes of ...Rhodiola may be involved in alpine adaptation.
The amount of plastome sequence data available has soared in the last decade, but the nature of plastome evolution during rapid radiations is largely unknown. Moreover, although there is increasing evidence showing that plastomes may have undergone adaptive evolution in order to allow adaptation to various environments, few studies have systematically investigated the role of the plastome in alpine adaptation. To address these questions, we sequenced and analyzed 12 representative species of Rhodiola, a genus which includes ca. 70 perennial herbs mainly growing in alpine habitats in the Qinghai-Tibet Plateau and the Hengduan Mountains. Rapid radiation in this genus was triggered by the uplift of the Qinghai-Tibet Plateau. We also included nine species of Crassulaceae as the outgroups. All plastomes were conserved with respect to size, structure, and gene content and order, with few variations: each contained 134 genes, including 85 protein-coding genes, 37 tRNAs, 8 rRNAs, and 4 potential pseudogenes. Four types of repeat sequence were detected. Slight contraction and expansion of the inverted repeats were also revealed. Both the genome-wide alignment and sequence polymorphism analyses showed that the inverted repeats and coding regions were more conserved than the single-copy regions and the non-coding regions. Positive selection analyses identified three genes containing sites of positive selection (rpl16, ndhA, ndhH), and one gene with a faster than average rate of evolution (psaA). The products of these genes may be involved in the adaptation of Rhodiola to alpine environments such as low CO2 concentration and high-intensity light.
Pathological cardiac hypertrophy is a hallmark of various cardiovascular diseases (CVD) including chronic heart failure (HF) and an important target for the treatment of these diseases. Aberrant ...activation of Angiotensin II (Ang II)/AT1R signaling pathway is one of the main triggers of cardiac hypertrophy, which further gives rise to excessive inflammation that is mediated by the key transcription factor NF-κB. Resveratrol (REV) is a natural polyphenol with multiple anti-inflammatory and anti-oxidative effects, however the ability of REV in preventing Ang II-induced cardiac hypertrophy in combination with NF-κB signaling activation remains unclear.
Murine models of cardiac hypertrophy was conducted via implantation of Ang II osmotic pumps. Primary neonatal rat cardiomyocyte and heart tissues were examined to determine the effect and underlying mechanism of REV in preventing Ang II-induced cardiac hypertrophy.
Administrations of REV significantly prevented Ang II-induced cardiac hypertrophy, as well as robustly attenuated Ang II-induced cardiac fibrosis, and cardiac dysfunction. Furthermore, REV not only directly prevented Ang II/AT1R signal transductions, but also prevented Ang II-induced expressions of pro-inflammatory cytokines and activation of NF-κB signaling pathway.
Our study provides important new mechanistic insight into the cardioprotective effects of REV in preventing Ang II-induced cardiac hypertrophy via inhibiting adverse NF-κB signaling activation. Our findings further suggest the therapeutic potential of REV as a promising drug for the treatment of cardiac hypertrophy and heart failure.
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•Resveratrol administration robustly inhibited Ang II-induced cardiac hypertrophy.•Resveratrol attenuated Ang II-induced cardiac fibrosis and cardiac dysfunction.•The effects of resveratrol were via inhibiting adverse NF-κB signaling activation.
Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there ...are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored.
We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury.
Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway.
Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases.
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•Resveratrol robustly protects against myocardial ischemic injury in obese mice.•Resveratrol prevents oxidative damage by activating SIRT3/FOXO3a-dependent enzymes.•A SIRT3 specific inhibitor completely prevents cardioprotective effects of resveratrol.•Resveratrol’s beneficial effects are via restoring redox homeostasis post-MI.
Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used ...for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown.
Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/β-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD).
We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of β-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/β-catenin signaling.
BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/β-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness.
Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/β-catenin signaling, and implicate its use in the clinical treatment of cancers.
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•BBD inhibits cancer cell proliferation and stem-like property of cancer stem cells.•BBD attenuates both intrinsic and extrinsic activation of Wnt/β-catenin pathway.•BBD inhibits EpCAM expression, a Wnt target gene and marker of cancer cell stemness.•Robust anti-tumor effects of BBD was via potent inhibition of Wnt/β-catenin signaling.
Myocardial infarction (MI) is the leading cause of deaths worldwide, triggering widespread and irreversible damage to the heart. Currently, there are no drugs that can reverse ischemic damage to the ...myocardium and hence, finding novel therapeutic agents that can limit the extent of myocardial damage following MI is crucial. Liensinine (LSN) is a naturally derived bisbenzylisoquinoline alkaloid that is known to exhibit numerous antioxidative and cardiovascular beneficial effects. However, the role of LSN in MI-induced injury and its underlying mechanisms remain unexplored.
Our study aims to evaluate the cardioprotective effects of LSN following MI and its underlying molecular mechanisms.
We constructed murine models of MI in order to examine the potential cardioprotective effects and mechanisms of LSN in protecting against myocardial ischemic damage both in vivo and in vitro.
Administration with LSN strongly protected against cardiac injuries following MI by decreasing the extent of ischemic damage and improving cardiac function. Additionally, LSN was found to be a potent inhibitor of Wnt/β‑catenin signaling pathway. Hence, the beneficial effects of LSN in preventing oxidative and DNA damage following ischemia was due to its ability to inhibit aberrant activation of Wnt/β‑catenin signaling.
Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases.
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•Liensinine is a natural alkaloid that exhibits strong cardioprotective effects.•Liensinine robustly protects against ischemic injury after myocardial infarction.•Liensinine attenuates ischemia-induced oxidative and DNA damage.•Cardioprotective effects of Liensinine is via inhibiting Wnt/β-catenin signaling.
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