Visible Light-driven Metal-free C–H Functionalization: Access to New Bioactive Tetrahydroisoquinoline-Butenolide Hybrids via Domino Amine Oxidation/Vinylogous Mannich Reaction

An efficient metal-free visible light-driven two-step domino reaction towards new bioactive tetrahydroisoquinoline-butenolide hybrid compounds was developed for the first time. Combination of fluorescein as photosensitizer and thiourea as an additive was found to be the most effective way to promote an aerobic amine oxidation/vinylogous Mannich domino reaction sequence with yields up to 97% for a broad substrate scope. While fluorescein without thiourea additive gave product in 84% yield, it was even observed that thiourea in absence of fluorescein is also able to promote formation of product with good yield of 75%, which is explained by a potential role of thiourea as an electron-transfer mediator in light-induced amine oxidation. Both experimental and computational evidence supported the crucial role of singlet oxygen in the developed C–H functionalization reaction. In addition, in vitro studies of tetrahydroisoquinoline-butenolide hybrid compounds demonstrated their high antischistosomal and anti-cancer activities.

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A noble-metal-free photocatalyst system obtained using BODIPY-based MOFs for highly efficient visible-light-driven H2 evolution

Journal of Materials Chemistry A ◽

10.1039/c9ta06989e ◽

2019 ◽

Vol 7 (36) ◽

pp. 20742-20749 ◽

Cited By ~ 8

Author(s):

Heng Yang ◽

Ming Zhao ◽

Jing Zhang ◽

Ji Ma ◽

Pengyan Wu ◽

...

Keyword(s):

Photocatalytic Activity ◽

Visible Light ◽

Noble Metal ◽

H2 Evolution ◽

Metal Free ◽

Highly Efficient ◽

Visible Light Driven

This study provides fundamental insights into the role of porosity in photocatalytic activity and might inform the ongoing efforts toward the noble-metal-free photocatalytic systems via BODIPY-based MOFs for visible-light-promoted H2 evolution.

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Resveratrol: A new potential therapeutic agent for melanoma?

Current Medicinal Chemistry ◽

10.2174/0929867326666191212101225 ◽

2019 ◽

Vol 26 ◽

Cited By ~ 2

Author(s):

Mohamad Hossein Pourhanifeh ◽

Kazem Abbaszadeh-Goudarzi ◽

Mohammad Goodarzi ◽

Sara G.M. Piccirillo ◽

Alimohammad Shafiee ◽

...

Keyword(s):

Quality Of Life ◽

Therapeutic Agent ◽

Current Knowledge ◽

Treatment Resistance ◽

Anti Cancer ◽

Apoptosis Inducer ◽

Life Threatening ◽

First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

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Band-gap-energy-adjustable and noble-metal-free modified NiS-Zn Cd1-S for highly efficient visible-light-driven Cr6+ photoreduction in alkaline wastewater

Journal of Physics and Chemistry of Solids ◽

10.1016/j.jpcs.2020.109893 ◽

2021 ◽

Vol 150 ◽

pp. 109893

Author(s):

Linjuan Wang ◽

Ling Zan

Keyword(s):

Visible Light ◽

Band Gap ◽

Noble Metal ◽

Band Gap Energy ◽

Gap Energy ◽

Metal Free ◽

Highly Efficient ◽

Visible Light Driven

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Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00558-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Miao-Miao Zhao ◽

Wei-Li Yang ◽

Fang-Yuan Yang ◽

Li Zhang ◽

Wei-Jin Huang ◽

...

Keyword(s):

Drug Development ◽

Cathepsin L ◽

Human Cells ◽

New Drugs ◽

Disease Course ◽

Promising Target ◽

First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

Cell Death and Disease ◽

10.1038/s41419-021-03393-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wei Zhang ◽

Guoyu Yin ◽

Heping Zhao ◽

Hanzhi Ling ◽

Zhen Xie ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Hyaluronic Acid ◽

Dependent Manner ◽

Collagen Induced Arthritis ◽

Intracellular Degradation ◽

Main Pathway ◽

First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

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Arginase Activity in Eisenia andrei Coelomocytes: Function in the Earthworm Innate Response

International Journal of Molecular Sciences ◽

10.3390/ijms22073687 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3687

Author(s):

Joanna Homa ◽

Alina Klosowska ◽

Magdalena Chadzinska

Keyword(s):

Immune Response ◽

Wound Healing ◽

Arginase Activity ◽

Eisenia Andrei ◽

Heavy Metals Ions ◽

First Time ◽

Important Marker

Arginase is the manganese metalloenzyme catalyzing the conversion of l-arginine to l-ornithine and urea. In vertebrates, arginase is involved in the immune response, tissue regeneration, and wound healing and is an important marker of alternative anti-inflammatory polarization of macrophages. In invertebrates, data concerning the role of arginase in these processes are very limited. Therefore, in the present study, we focused on the changes in arginase activity in the coelomocytes of Eisenia andrei. We studied the effects of lipopolysaccharide (LPS), hydrogen peroxide (H2O2), heavy metals ions (e.g., Mn2+), parasite infection, wound healing, and short-term fasting (5 days) on arginase activity. For the first time in earthworms, we described arginase activity in the coelomocytes and found that it can be up-regulated upon in vitro stimulation with LPS and H2O2 and in the presence of Mn2+ ions. Moreover, arginase activity was also up-regulated in animals in vivo infected with nematodes or experiencing segment amputation, but not in fasting earthworms. Furthermore, we confirmed that the activity of coelomocyte arginase can be suppressed by l-norvaline. Our studies strongly suggest that similarly to the vertebrates, also in the earthworms, coelomocyte arginase is an important element of the immune response and wound healing processes.

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Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

International Journal of Molecular Sciences ◽

10.3390/ijms22031163 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1163

Author(s):

Gaia Palmini ◽

Cecilia Romagnoli ◽

Simone Donati ◽

Roberto Zonefrati ◽

Gianna Galli ◽

...

Keyword(s):

Cell Line ◽

Molecular Mechanisms ◽

Osteogenic Sarcoma ◽

Cancer Cell Line ◽

Microscopic Features ◽

In Vitro Establishment ◽

Profile Characteristic ◽

First Time

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

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Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

Cancer Cell International ◽

10.1186/s12935-020-01733-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Hang ◽

Shanojie Zhao ◽

Tiejun Wang ◽

Yan Zhang

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Nuclear Accumulation ◽

Migration And Invasion ◽

Ubiquitin Protein Ligase ◽

Novel Target ◽

First Time ◽

Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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