Semiconductor polymeric graphitic carbon nitride (g-C
3
N
4
) photocatalysts have attracted dramatically growing attention in the field of the visible-light-induced hydrogen evolution reaction (HER) ...because of their facile synthesis, easy functionalization, attractive electronic band structure, high physicochemical stability and photocatalytic activity. This review article presents a panorama of the latest advancements in the rational design and development of g-C
3
N
4
and g-C
3
N
4
-based composite photocatalysts for HER application. Concretely, the review starts with the development history, synthetic strategy, electronic structure and physicochemical characteristics of g-C
3
N
4
materials, followed by the rational design and engineering of various nanostructured g-C
3
N
4
(
e.g.
thinner, highly crystalline, doped, and porous g-C
3
N
4
) photocatalysts for HER application. Then a series of highly efficient g-C
3
N
4
(
e.g.
, metal/g-C
3
N
4
, semiconductor/g-C
3
N
4
, metal organic framework/g-C
3
N
4
, carbon/g-C
3
N
4
, conducting polymer/g-C
3
N
4
, sensitizer/g-C
3
N
4
) composite photocatalysts are exemplified. Lastly, this review provides a comprehensive summary and outlook on the major challenges, opportunities, and inspiring perspectives for future research in this hot area on the basis of pioneering works. It is believed that the emerging g-C
3
N
4
-based photocatalysts will act as the "holy grail" for highly efficient photocatalytic HER under visible-light irradiation.
Graphitic carbon nitrides and their composites with various morphologies and bandgaps engineered for the hydrogen evolution reaction under visible light are reviewed.
Impaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a ...as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL-HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.
Thermally sprayed coatings are essentially layered materials and contain large numbers of lamellar pores. It is thus quite necessary to clarify the formation mechanism of lamellar pores which ...significantly influence coating performances. In the present study, to elaborate the formation mechanism of lamellar pores, the yttria-stabilized zirconia (ZrO
2
–7 wt% Y
2
O
3
, 7YSZ) splats, which have high fracture toughness and tetragonal phase stability, were employed. Interestingly, anomalous epitaxial growth occurred for all deposition temperatures in spite of the extremely high cooling rate, which clearly indicated chemical bonding and complete contact at splat/substrate interface before splat cooling. However, transverse spallation substantially occurred for all deposition temperatures in spite of the high fracture toughness of 7YSZ, which revealed that the lamellar pores were from transverse cracking/spallation due to the large stress during splat cooling. Additionally, fracture mechanics analysis was carried out, and it was found that the stress arose from the constraint effect of the shrinkage of the splat by locally heated substrate with the value about 1.97 GPa. This clearly demonstrated that the stress was indeed large enough to drive transverse cracking/spallation forming lamellar pores during splat cooling. All of these contribute to understanding the essential features of lamellar bonding and further tailoring the coating structures and performance.
Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it ...impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.
Lysine‐specific demethylase 5A (KDM5A) has recently become a promising target for epigenetic therapy. In this study, we designed and synthesized metal complexes bearing ligands with reported ...demethylase and p27 modulating activities. The Rh(III) complex 1 was identified as a direct, selective and potent inhibitor of KDM5A that directly abrogate KDM5A demethylase activity via antagonizing the KDM5A‐tri‐/di‐methylated histone 3 protein–protein interaction (PPI) in vitro and in cellulo. Complex 1 induced accumulation of H3K4me3 and H3K4me2 levels in cells, causing growth arrest at G1 phase in the triple‐negative breast cancer (TNBC) cell lines, MDA‐MB‐231 and 4T1. Finally, 1 exhibited potent anti‐tumor activity against TNBC xenografts in an in vivo mouse model, presumably via targeting of KDM5A and hence upregulating p27. Moreover, complex 1 was less toxic compared with two clinical drugs, cisplatin and doxorubicin. To our knowledge, complex 1 is the first metal‐based KDM5A inhibitor reported in the literature. We anticipate that complex 1 may be used as a novel scaffold for the further development of more potent epigenetic agents against cancers, including TNBC.
A rhodium(III)‐based complex has been discovered as an inhibitor of KDM5A, an epigenetic target for triple‐negative breast cancer. The complex inhibited the KDM5A–H3K4me3 interaction and suppressed proliferation of triple‐negative breast cancer (TNBC) tumors in mice and may be used as a novel scaffold for further development of more potent epigenetic agents against cancers, including TNBC.
The emerging role of KDM5A in human cancer Yang, Guan-Jun; Zhu, Ming-Hui; Lu, Xin-Jiang ...
Journal of hematology & oncology,
02/2021, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, ...transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.
Alzheimer’s disease (AD) is a type of neurodegenerative malady that is associated with the accumulation of amyloid plaques. Metal ions are critical for the development and upkeep of brain activity, ...but metal dyshomeostasis can contribute to the development of neurodegenerative diseases, including AD. This review highlights the association between metal dyshomeostasis and AD pathology, the feasibility of rebalancing metal homeostasis as a therapeutic strategy for AD, and a survey of current drugs that action via rebalancing metal homeostasis. Finally, we discuss the challenges that should be overcome by researchers in the future to enable the practical use of metal homeostasis rebalancing agents for clinical application.
Protein-protein interactions (PPIs) are central to a variety of biological processes, and their dysfunction is implicated in the pathogenesis of a range of human diseases, including cancer. Hence, ...the inhibition of PPIs has attracted significant attention in drug discovery. Covalent inhibitors have been reported to achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic residues in the target protein. Evidence suggests that there is a reduced risk for the development of drug resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious diseases. Recent improvements in structural biology and chemical reactivity have enabled the design and development of potent and selective covalent PPI inhibitors. In this review, we will highlight the design and development of therapeutic agents targeting PPIs for cancer therapy.
Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed ...in human diseases, especially cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues. Currently, drug resistance is a main impediment for cancer therapy. KDMs have been found to mediate drug tolerance of many cancers via altering the metabolic profile of cancer cells, upregulating the ratio of cancer stem cells and drug‐tolerant genes, and promoting the epithelial‐mesenchymal transition and metastatic ability. Moreover, different cancers show distinct oncogenic addictions for KDMs. The abnormal activation or overexpression of KDMs can alter gene expression signatures to enhance cell survival and drug resistance in cancer cells. In this review, we describe the structural features and functions of KDMs, the KDMs preferences of different cancers, and the mechanisms of drug resistance resulting from KDMs. We then survey KDM inhibitors that have been used for combating drug resistance in cancer, and discuss the opportunities and challenges of KDMs as therapeutic targets for cancer drug resistance.
Due to role of the Keap1-Nrf2 protein-protein interaction (PPI) in protecting cells from oxidative stress, the development of small molecule inhibitors that inhibit this interaction has arisen as a ...viable approach to combat maladies caused by oxidative stress, such as cancers, neurodegenerative disease and diabetes. To obtain specific and genuine Keap1-Nrf2 inhibitors, many efforts have been made towards developing new screening approaches. However, there is no inhibitor for this target entering the clinic for the treatment of human diseases. New strategies to identify novel bioactive compounds from large molecular databases and accelerate the developmental process of the clinical application of Keap1-Nrf2 protein-protein interaction inhibitors are greatly needed. In this review, we have summarized virtual screening and other methods for discovering new lead compounds against the Keap1-Nrf2 protein-protein interaction. We also discuss the advantages and limitations of different strategies, and the potential of this PPI as a drug target in disease therapy.
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