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1.
Adv Sci (Weinh) ; : e2406228, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962907

ABSTRACT

The transition metal-catalyzed multi-component cross-electrophile sulfonylation, which incorporates SO2 as a linker within organic frameworks, has proven to be a powerful, efficient, and cost-effective means of synthesizing challenging alkyl-alkyl sulfones. Transition metal catalysts play a crucial role in this method by transferring electrons from reductants to electrophilic organohalides, thereby causing undesirable side reactions such as homocoupling, protodehalogenation, ß-hydride elimination, etc. It is worth noting that tertiary alkyl halides have rarely been demonstrated to be compatible with current methods owing to various undesired side reactions. In this work, a zinc-promoted cross-electrophile sulfonylation is developed through a radical-polar crossover pathway. This approach enables the synthesis of various alkyl-alkyl sulfones, including 1°-1°, 2°-1°, 3°-1°, 2°-2°, and 3°-2° types, from inexpensive and readily available alkyl halides. Various functional groups are well tolerated in the work, resulting in yields of up to 93%. Additionally, this protocol has been successfully applied to intramolecular sulfonylation and homo-sulfonylation reactions. The insights gained from this work shall be useful for the further development of cross-electrophile sulfonylation to access alkyl-alkyl sulfones.

2.
Adv Mater ; 36(25): e2402184, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38458150

ABSTRACT

Efficient electrocatalysts are pivotal for advancing green energy conversion technologies. Organic electrocatalysts, as cost-effective alternatives to noble-metal benchmarks, have garnered attention. However, the understanding of the relationships between their properties and electrocatalytic activities remains ambiguous. Plenty of research articles regarding low-cost organic electrocatalysts started to gain momentum in 2010 and have been flourishing recently though, a review article for both entry-level and experienced researchers in this field is still lacking. This review underscores the urgent need to elucidate the structure-activity relationship and design suitable electrode structures, leveraging the unique features of organic electrocatalysts like controllability and compatibility for real-world applications. Organic electrocatalysts are classified into four groups: small molecules, oligomers, polymers, and frameworks, with specific structural and physicochemical properties serving as activity indicators. To unlock the full potential of organic electrocatalysts, five strategies are discussed: integrated structures, surface property modulation, membrane technologies, electrolyte affinity regulation, and addition of anticorrosion species, all aimed at enhancing charge efficiency, mass transfer, and long-term stability during electrocatalytic reactions. The review offers a comprehensive overview of the current state of organic electrocatalysts and their practical applications, bridging the understanding gap and paving the way for future developments of more efficient green energy conversion technologies.

3.
Nat Commun ; 14(1): 4638, 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37532729

ABSTRACT

Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.

4.
Genes Dis ; 10(2): 568-582, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37223530

ABSTRACT

Our previous studies found that Zinc-finger protein 382 (ZNF382) played as a tumor suppressor gene in esophageal and gastric cancers, and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients. However, the biological roles and mechanisms of ZNF382 in breast cancer remains unclear. We detected ZNF382 expression by reverse-transcription PCR (RT-PCR) and real-time quantitative PCR (qRT-PCR) in breast cancer cells and tissues, and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo, respectively. Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues. Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation, viability, migration and invasion, and epithelial-mesenchymal-transition (EMT), but also induced apoptosis and G0/G1 arrest. In conclusion, ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling, and, inhibit cell migration, invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.

5.
Clin Epigenetics ; 15(1): 57, 2023 04 01.
Article in English | MEDLINE | ID: mdl-37005662

ABSTRACT

BACKGROUND: The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC. RESULTS: NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell-cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC. CONCLUSIONS: NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.


Subject(s)
Colorectal Neoplasms , DNA Methylation , Humans , Neuroglobin/genetics , Neuroglobin/metabolism , Epigenesis, Genetic , Cell Line, Tumor , Colorectal Neoplasms/pathology , Biomarkers/metabolism , Gene Expression Regulation, Neoplastic , Cell Proliferation , Tumor Microenvironment , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism
6.
J Cancer Res Clin Oncol ; 149(10): 7379-7392, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36939925

ABSTRACT

PURPOSE: Lung adenocarcinoma (LUAD) is a malignant tumor with a high lethality rate. Immunotherapy has become a breakthrough in cancer treatment and improves patient survival and prognosis. Therefore, it is necessary to find new immune-related markers. However, the current research on immune-related markers in LUAD is not sufficient. Therefore, there is a need to find new immune-related biomarkers to help treat LUAD patients. METHODS: In this study, a bioinformatics approach combined with a machine learning approach screened reliable immune-related markers to construct a prognostic model to predict the overall survival (OS) of LUAD patients, thus promoting the clinical application of immunotherapy in LUAD. The experimental data were obtained from The Cancer Genome Atlas (TCGA) database, including 535 LUAD and 59 healthy control samples. Firstly, the Hub gene was screened using a bioinformatics approach combined with the Support Vector Machine Recursive Feature Elimination algorithm; then, a multifactorial Cox regression analysis by constructing an immune prognostic model for LUAD and a nomogram to predict the OS rate of LUAD patients. Finally, the regulatory mechanism of Hub genes in LUAD was analyzed by ceRNA. RESULTS: Five genes, ADM2, CDH17, DKK1, PTX3, and AC145343.1, were screened as potential immune-related genes in LUAD. Among them, ADM2 and AC145343.1 had a good prognosis in LUAD patients (HR < 1) and were novel markers. The remaining three genes screened were associated with poor prognosis in LUAD patients (HR > 1). In addition, the experimental results showed that patients in the low-risk group had better OS rates than those in the high-risk group (P < 0.001). CONCLUSION: In this paper, we propose an immune prognostic model to predict OS rate in LUAD patients and show the correlation between five immune genes and the level of immune-related cell infiltration. It provides new markers and additional ideas for immunotherapy in patients with LUAD.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Peptide Hormones , Humans , Prognosis , Adenocarcinoma of Lung/genetics , Nomograms , Machine Learning , Lung Neoplasms/genetics
7.
Front Nutr ; 9: 1006520, 2022.
Article in English | MEDLINE | ID: mdl-36238460

ABSTRACT

The burden of public health challenges associated with the western dietary and living style is growing. Nutraceuticals have been paid increasing attentions due to their effects in promotion of health. However, in the gastrointestinal (GI) tract, the nutraceuticals suffer from not only the harsh acidic environment of the stomach and a variety of digestive enzymes, but also the antibacterial activity of intestinal bile salts and the action of protease from the gut microbiota. The amount of the nutraceuticals arriving at the sites in GI tract for absorption or exerting the bioactivities is always unfortunately limited, which puts forward high requirements for protection of nutraceuticals in a certain high contents during oral consumption. Hydrogels are three-dimensional polymeric porous networks formed by the cross-linking of polymer chains, which can hold huge amounts of water. Compared with other carries with the size in microscopic scale such as nanoparticle and microcapsules, hydrogels could be considered to be more suitable delivery systems in food due to their macroscopic bulk properties, adjustable viscoelasticity and large spatial structure for embedding nutraceuticals. Regarding to the applications in food, natural polymer-based hydrogels are commonly safe and popular due to their source with the appealing characteristics of affordability, biodegradability and biocompatibility. Although chemical crosslinking has been widely utilized in preparation of hydrogels, it prefers the physical crosslinking in the researches in food. The reasonable design for the structure of natural polymeric hydrogels is essential for seeking the favorable functionalities to apply in the delivery system, and it could be possible to obtain the enhanced adhesive property, acid stability, resistant to bile salt, and the controlled release behavior. The hydrogels prepared with proteins, polysaccharides or the mix of them to deliver the functional ingredients, mainly the phenolic components, vitamins, probiotics are discussed to obtain inspiration for the wide applications in delivery systems. Further efforts might be made in the in situ formation of hydrogels in GI tract through the interaction among food polymers and small-molecular ingredients, elevation of the loading contents of nutraceuticals in hydrogels, development of stomach adhesive hydrogels as well as targeting modification of gut microbiota by the hydrogels.

8.
Angew Chem Int Ed Engl ; 61(50): e202213431, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36214646

ABSTRACT

Silanes are important in chemistry and material science. The self-redistribution of HSiCl3 is an industrial process to prepare SiH4 , which is widely used in electronics and automobile industries. However, selective silane cross-redistribution to prepare advanced silanes is challenging. We now report an enthalpy-driven silane cross-redistribution to access bis-silanes that contain two different types of Si-H bonds in the same molecule. Compared with entropy-driven reactions, the enthalpy-driven reaction shows high regioselectivity, broad substrate scope (62 examples) and high atom economy. Our combined experimental and computational study indicates that the reaction proceeds through a Ni0 -NiII -NiIV catalytic cycle.

9.
J Agric Food Chem ; 70(30): 9432-9441, 2022 Aug 03.
Article in English | MEDLINE | ID: mdl-35876899

ABSTRACT

Although the synthetic chemistry or synthetic biological systems have already shown the power of biomaterials engineering, natural bioresource matter is still a valuable library of raw ingredients for the production of biomaterials, in particular, the edible ones. However, the influence of upstream isolation and purification of the raw materials on their performance in the downstream processing procedures is still unexplored, which is essential for the engineering of biomaterials. Based on the comparison of conventional techniques, heating-induced precipitation combined with resin-blending ion exchange was developed as a simple and cheap method for the utilization of egg whites to produce the lysozyme that is found to be exclusively feasible for fibrillation. Even with similar purities, only the lysozyme prepared by this method could be utilized to form ordered linear aggregate fibrils. Fibrillation was recently pursued as a new approach to utilize bioresource mass for high-tech end-products. Phytochemicals, totally replacing salts, induced the lysozyme fibrils to form hydrogels spontaneously, which was further demonstrated in an in vivo study to prevent obesity induced by a high-fat diet (HFD) by reducing lipid absorption and lipogenesis, promoting energy expenditure, and inhibiting inflammation. The agri-food bioresource was successfully employed as a proof of concept in edible biomedical materials for the regulation of lipid metabolism.


Subject(s)
Egg White , Muramidase , Antiviral Agents , Biocompatible Materials , Hydrogels , Lipid Metabolism , Phytochemicals
10.
Biomater Sci ; 10(13): 3597-3611, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35642606

ABSTRACT

Innovative precise clinical approaches to protect humans from the alarming global growth of chronic disease epidemics, such as metabolic syndrome (MetS), are urgently needed. Here, we introduce protein hydrogels developed through the self-assembly of flavonoids and protein amyloid fibrils as a possible approach to mitigate obesity. After oral administration of the hydrogels, high-fat diet (HFD)-induced obesity was significantly prevented in mice, accompanied by downregulation of lipogenesis and pro-inflammatory genes in the liver and adipose tissue and upregulation of lipid metabolism genes. Additionally, gut microbiota dysbiosis caused by HFD-induced obesity was markedly ameliorated. Overexpression of the host intestinal lipid absorption genes CD36 and NFIL3 decreased significantly, while the inhibited expression of the gene encoding the tight junction protein Claudin-1 was reversed. Furthermore, transplantation of the gut microbiota educated by the hydrogels to germ-free mice showed a substantial prevention effect on HFD-induced obesity, accompanied by a distinct microbiota structure that resisted HFD-induced divergence in microbiota structure. The flavonoid-amyloid fibril hydrogels inhibited the core molecular links between gut microbes and host intestinal lipid absorption, enhanced intestinal barrier function and reduced the abundance of bacterial taxa generating pro-inflammatory products, providing a general concept to design edible biomaterials for obesity prevention by targeting host-microbiota crosstalk.


Subject(s)
Gastrointestinal Microbiome , Amyloid , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , Gastrointestinal Microbiome/physiology , Hydrogels/pharmacology , Lipids , Mice , Mice, Inbred C57BL , Obesity
11.
Food Res Int ; 156: 111187, 2022 06.
Article in English | MEDLINE | ID: mdl-35651045

ABSTRACT

Globally, 800 million are undernourished and 2 billion are deficient in micronutrients. A regular dietary intake of meat is one of effective strategies to fight against undernourishment and deficiency of micronutrients. However, meat is a typical perishable food; proper handling to extend the shelf life of meat is required. In the present study, homogenous hydrogels composed with high contents of lysozyme amyloid fibrils, zein and green tea polyphenol epigallocatechin gallate (EGCG) were developed via the orchestration of protein-protein interaction and polyphenol-protein interaction for coating of beef. The protein-protein interaction between amyloid fibrils and zein showed higher affinity than that of the polyphenol-protein interactions. In addition, polyphenol EGCG was found to be more inclined to bind with zein than to the amyloid fibrils. Thus, the amyloid fibrils performed as the scaffold, in which EGCG on one hand induced the zein aggregate nanoparticles and on the other hand deposited on the surface of amyloid fibrils, leading to the dense multi-pore network with the nanoparticle-embed wall. It served as the microstructure mechanism for the enhanced gel strength. Coating of fresh chilling beef with the amyloid fibril-zein-EGCG hybrid hydrogels effectively protected the freshness and tenderness through inhibiting the over-growth of microorganisms and oxidation of lipid. This study paves the way to develop functional edible biomaterials via polyphenol induced coordination of the protein-protein interaction and polyphenol-protein interaction, where polyphenol acts as the molecular glue. This strategy shows high application potentials in health promotion related fields, including edible coating to extend the shelf-life of fresh meat.


Subject(s)
Nanoparticles , Zein , Amyloid/chemistry , Animals , Catechin/analogs & derivatives , Cattle , Hydrogels , Micronutrients , Polyphenols/chemistry
12.
Nat Commun ; 13(1): 3691, 2022 Jun 27.
Article in English | MEDLINE | ID: mdl-35760931

ABSTRACT

Regioselectivity and stereoselectivity control in hydrosilylation of terminal allenes is challeging. Although the selective synthesis of vinylsilanes, branched allylsilanes or linear (Z)-allylsilanes have been achieved, transition-metal catalyzed hydrosilylation of terminal allenes to access (E)-allylsilane is difficult. Herein, we report a copper-catalyzed selective hydrosilylation reaction of terminal allenes to access (E)-allylsilanes under mild reaction conditions. The reaction shows broad substrate scope, representing an efficient method to prepare trisubstituted (E)-allylsilanes through hydrosilylation reaction of allenes and can also be applied in the synthesis of disubstituted (E)-allylsilanes. The mechanism study reveals that the E-selectivity is kinetically controlled by the catalyst but not by the thermodynamically isomerization of the (Z)-isomer.

13.
Front Pharmacol ; 13: 875149, 2022.
Article in English | MEDLINE | ID: mdl-35600862

ABSTRACT

Background: Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy. Methods: Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients. Results: Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy (p = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) (p = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP). Conclusion: We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics.

14.
Sci Total Environ ; 838(Pt 1): 155857, 2022 Sep 10.
Article in English | MEDLINE | ID: mdl-35561920

ABSTRACT

Biological nitrification inhibitors are exudates from plant roots that can inhibit nitrification, and have advantages over traditional synthetic nitrification inhibitors. However, our understanding of the effects of biological nitrification inhibitors on nitrogen (N) loss and fertilizer N recovery efficiency in staple food crops is limited. In this study, acidic and calcareous soils were selected, and rice growth pot experiments were conducted to investigate the effects of the biological nitrification inhibitor, methyl 3-(4-hydroxyphenyl) propionate (MHPP) and/or a urease inhibitor (N-[n-butyl], thiophosphoric triamide [NBPT]) on NH3 volatilization, N leaching, fertilizer N recovery efficiency under a 20% reduction of the conventional N application rate. Our results show that rice yield and fertilizer N recovery efficiency were more sensitive to reduced N application in the calcareous soil than in the acidic soil. MHPP stimulated NH3 volatilization by 13.2% in acidic soil and 9.06% in calcareous soil but these results were not significant. In the calcareous soil, fertilizer N recovery efficiency significantly increased by 19.3% and 44.4% in the MHPP and NBPT+MHPP groups, respectively, relative to the reduced N treatment, and the rice yield increased by 16.7% in the NBPT+MHPP treatment (P < 0.05). However, such effects were not significant in the acidic soil. MHPP exerted a significant effect on soil ammonia oxidizers, and the response of abundance and community structure of ammonia-oxidizing archaea, ammonia-oxidizing bacteria, and total bacteria to MHPP depended on the soil type. MHPP+NBPT reduced NH3 volatilization, N leaching, and maintaining rice yield for a 20% reduction in conventional N fertilizer application rate. This could represent a viable strategy for more sustainable rice production, despite the inevitable increase in cost for famers.


Subject(s)
Fertilizers , Oryza , Ammonia/analysis , Fertilizers/analysis , Nitrification , Nitrogen , Oxidation-Reduction , Soil/chemistry , Soil Microbiology , Volatilization
16.
Br J Pharmacol ; 179(12): 2969-2985, 2022 06.
Article in English | MEDLINE | ID: mdl-34997582

ABSTRACT

BACKGROUND AND PURPOSE: As the only ionotropic receptor in the 5-HT receptor family, the 5-HT3 receptor (5-HT3 R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5-HT3 Rs shape synaptic plasticity for memory function. EXPERIMENTAL APPROACH: Extracellular as well as whole-cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5-HT3 AR knockout or 5-HT3 AR-GFP mice. Immunocytochemistry, qRT-PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition. KEY RESULTS: We found that 5-HT3 R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)-CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5-HT3 Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1 R) co-localized with 5-HT3 Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1 Rs. Inhibition of CB1 Rs mimicked the facilitation of GABAergic transmission by 5-HT3 R disruption. Consequently, mice with hippocampal 5-HT3 R disruption exhibited impaired spatial memory in MWM tasks. CONCLUSION AND IMPLICATIONS: These results suggest that 5-HT3 Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1 R-GABAA -dependent pathway to regulate spatial memory.


Subject(s)
Long-Term Potentiation , Spatial Memory , Animals , CA1 Region, Hippocampal/metabolism , Hippocampus/metabolism , Humans , Long-Term Potentiation/physiology , Memory Disorders/metabolism , Mice , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Receptors, GABA-A/metabolism , Serotonin/metabolism , gamma-Aminobutyric Acid/metabolism
17.
Mol Ther Oncolytics ; 22: 604-616, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34589579

ABSTRACT

Hepatocellular carcinoma (HCC) is a highly vascularized, inflammatory, and abnormally proliferating tumor. Monotherapy is often unable to effectively and comprehensively inhibit the progress of HCC. In present study, we selected ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin as the combined therapy. These three plant monomers play important roles in anti-angiogenesis, immunological activation, and apoptosis promotion, respectively. However, the low solubility and poor bioavailability seriously hinder their clinical application. To resolve these problems, we constructed a new drug, Rg3, GLP, and oridonin self-microemulsifying drug delivery system (RGO-SMEDDS). We found that this drug effectively inhibits the progression of HCC by simultaneously targeting multiple signaling pathways. RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by downregulation of vascular endothelial growth factor and its receptor, and retarded proliferation by inhibiting the epidermal growth factor receptor EGFR/AKT/epidermal growth factor receptor/protein kinase B/glycogen synthase kinase-3 (GSK3) signaling pathway. In addition, RGO-SMEDDS showed considerable safety in acute toxicity tests. Results from this study show that RGO-SMEDDS is a promising therapy for the treatment of HCC.

18.
Microcirculation ; 28(7): e12722, 2021 10.
Article in English | MEDLINE | ID: mdl-34242445

ABSTRACT

BACKGROUND: Pulsatile flow protects vital organ function and improves microcirculatory perfusion during extracorporeal membrane oxygenation (ECMO). Studies revealed that pulsatile shear stress plays a vital role in microcirculatory function and integrity. The objective of this study was to investigate how pulsatility affects wall shear stress and endothelial glycocalyx components during ECMO. METHODS: Using the i-Cor system, sixteen canine ECMO models were randomly allocated into the pulsatile or the non-pulsatile group (eight canines for each). Hemodynamic parameters, peak wall shear stress (PWSS), serum concentration of syndecan-1, and heparan sulfate were measured at different time points during ECMO. Pulsatile shear stress experiments were also performed in endothelial cells exposed to different magnitudes of pulsatility (five plates for each condition), with cell viability, the expressions of syndecan-1, and endothelial-to-mesenchymal transformation (EndMT) markers analyzed. RESULTS: The pulsatile flow generated more surplus hemodynamic energy and preserved higher PWSS during ECMO. Serum concentrations of both syndecan-1 and heparan sulfate were negatively correlated with PWSS, and significantly lower levels were observed in the pulsatile group. Besides, non-pulsatility triggered EndMT and endothelial cells exposed to low pulsatility had the lowest possibility of EndMT. CONCLUSION: The maintenance of the PWSS by pulsatility during ECMO possesses beneficial effects on glycocalyx integrity. Moreover, pulsatility prevents EndMT in endothelial cells, and low pulsatility exhibits the best protective effects. The augmentation of pulsatility may be a plausible future direction to improve the clinical outcome in ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation , Animals , Dogs , Endothelial Cells , Glycocalyx/metabolism , Microcirculation , Pulsatile Flow
19.
Chem Commun (Camb) ; 57(67): 8316-8319, 2021 Aug 28.
Article in English | MEDLINE | ID: mdl-34319338

ABSTRACT

Enynones are powerful synthons for constructing furan derivatives in the presence of transition metal catalysts. Unlike the conventional intramolecular nucleophilic attack with the activation of coinage metals, we propose that enynones undergo an oxidative cyclization process with a Pd(0) species. The full catalytic cycle involves oxidative cyclization, isocyanide insertion, and reductive elimination, which was supported by DFT calculations. Geometric and electronic analyses confirmed the oxidative cyclization process, which proceeds via a Pd(ii) intermediate.

20.
Zhen Ci Yan Jiu ; 46(5): 411-5, 2021 May 25.
Article in Chinese | MEDLINE | ID: mdl-34085465

ABSTRACT

OBJECTIVE: To observe the effect of application at Back-Shu with Front-Mu acupoints on serum uric acid (SUA) and kidney uric acid transport related proteins in hyperuricemia rats, so as to explore the mechanism of Shu-Mu acupoint application on treatment of hyperuricemia. METHODS: SD rats were randomly divided into blank control, model, vaseline application and medication application groups, with 8 rats in each group. The hyperuricemia rat model was established by gavage of potassium oxonate. Rats in the vaseline application group received application of vaseline at bilateral "Ganshu"(BL18) and "Qimen"(LI14), "Pishu"(BL20) and "Zhangmen"(LR13), "Shenshu" (BL23) and "Jingmen"(GB25). Rats in the medication application group received application of traditional Chinese medicine at the same acupoints. The contents of SUA and creatinine (SCr) were detected by automatic biochemical analyzer. H.E. staining was used to observe the pathological changes of kidney. And the protein expression levels of organic anion transporter 1(OAT1) and adenosine triphosphate binding cassette transporter G2(ABCG2) were detected by immunohistochemistry. RESULTS: Rats in the model group showed symptoms such as polydipsia, polyuria, loose stools, fatigue, weakness, etc. The renal tubules atrophied, and urate crystals can be seen in the lumen. Compared with the control group. the SUA content in the model group increased (P<0.01)and the expressions of OAT1 and ABCG2 protein in kidney decreased (P<0.01). After intervention and in comparison with the model group showed that, the diet, excretion function, and mental state of the rats in the medication application group returned to normal, and the pathological changes of the kidney tissue were alleviated, the SUA content was down-regulated(P<0.01)and the expression levels of OAT1 and ABCG2 in the kidney up-regulated (P<0.01). There was no statistically significant difference in the SCr content among the 4 groups (P>0.05). CONCLUSION: Medication application at Shu-Mu points can effectively reduce the SUA level of hyperuricemia rats, which may be related to its effects in up-regulating the protein expressions of OAT1 and ABCG2 in the kidney and reducing the damage to the kidneys.


Subject(s)
Hyperuricemia , Acupuncture Points , Animals , Hyperuricemia/drug therapy , Hyperuricemia/genetics , Kidney , Rats , Rats, Sprague-Dawley , Uric Acid
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