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1.
Fish Shellfish Immunol ; 121: 135-141, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34998985

RESUMO

Matrix metalloproteinases (MMPs) are an important family of proteinases involved in various physiological processes and associated with the immune response. However, the role of MMPs in the immune response remains unclear. To explore the possible role of MMPs in innate immunity, this study selected the MMP-16 gene encoding peptidoglycan (PGN) binding domain identified in the sea cucumber Apostichopus japonicus (named AjMMP-16, GenBank accession No. AQT26486) for microbial polysaccharide-induced transcriptional expression analysis by quantitative real-time PCR, correlation analysis with nine representative genes from A. japonicus immune pathways in microbial polysaccharide-induced transcriptional expression by using Pearson's correlation test, and prokaryotic recombinant expression. Next, its recombinant protein was employed for microbial polysaccharide-binding analysis with ELISA and bacterial binding analysis with the indirect immunofluorescence method. The results showed that AjMMP-16 was significantly induced by diaminopimelic acid (DAP)-type PGN, lipopolysaccharide, mannan, and ß-1,3-glucan and was closely correlated with myeloid differentiation factor 88 (MyD88) in microbial polysaccharide-induced transcriptional expression. In addition, recombinant AjMMP-16 bound to lysine-type PGN, DAP-type PGN, lipopolysaccharide, mannan, ß-1,3-glucan, Vibrio splendidus, Pseudoalteromonas nigrifaciens, Shewanella baltica, Bacillus cereus, Escherichia coli, and Staphylococcus aureus. These results suggest that AjMMP-16 might act as a pattern recognition receptor in innate immunity and play an important role in initiating the MyD88-dependent Toll-like receptor signaling pathway.

2.
Parasitol Int ; 87: 102539, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007764

RESUMO

Haemonchus contortus is the most prevalent and pathogenic gastrointestinal nematode infecting sheep and goats. The two CSIRO sheep resource flocks, the Haemonchus-selected flock (HSF) and Trichostrongylus-selected flock (TSF) were developed for research on host resistance or susceptibility to gastrointestinal nematode infection. A recent study focused on the gene expression differences between resistant and susceptible sheep within each flock, with lymphatic and gastrointestinal tissues. To identify features in the host transcriptome and understand the molecular differences underlying host resistance to H. contortus between flocks with different selective breeding and genetic backgrounds, we compared the abomasal transcriptomic responses of the resistant or susceptible animals between HSF and TSF flocks. A total of 11 and 903 differentially expressed genes were identified in the innate infection treatment in HSF and TSF flocks between resistant and susceptible sheep respectively, while 52 and 485 genes were identified to be differentially expressed in the acquired infection treatment, respectively. Among them, 294 genes had significantly different gene expression levels between HSF and TSF flock animals within the susceptible sheep by both the innate and acquired infections. Moreover, similar expression patterns of the 294 genes were observed, with 273 genes more highly expressed in HSF and 21 more highly expressed in the TSF within the abomasal transcriptome of the susceptible animals. Gene ontology enrichment of the differentially expressed genes identified in this study predicted the likely differing function between the two flock's susceptible lines in response to H. contortus infection. Nineteen pathways were significantly enriched in both the innate and adaptive immune responses in susceptible animals, which indicated that these pathways likely contribute to the host resistance development to H. contortus infection in susceptible sheep. Biological networks built for the set of genes differentially abundant in susceptible animals identified hub genes of PRKG1, PRKACB, PRKACA, and ITGB1 for the innate immune response, and CALM2, MYL1, COL1A1, ITGB1 and ITGB3 for the adaptive immune response, respectively. Our results offered a quantitative snapshot of host transcriptomic changes induced by H. contortus infection between flocks with different selective breeding and genetic backgrounds and provided novel insights into molecular mechanisms of host resistance.

3.
NPJ Breast Cancer ; 8(1): 7, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027562

RESUMO

Anoikis resistance is an essential prerequisite for tumor metastasis, but the underlying molecular mechanisms remain unknown. Herein, we report that the oncoprotein hepatitis B X-interacting protein (HBXIP) is prominently upregulated in breast cancer cells following ECM detachment. Altering HBXIP expression can impair the anchorage-independent growth ability of tumor cells. Mechanistically, HBXIP, which binds to Kelch-like ECH-associated protein 1 (Keap1) to activate nuclear factor E2-related factor 2 (Nrf2), contains a cis-acting antioxidant response element (ARE) in the gene promoter and is a target gene of Nrf2. The HBXIP/Nrf2 axis forms a reciprocal positive feedback loop that reinforces the expression and tumor-promoting actions of each protein. In response to ECM detachment, Nrf2 reduces reactive oxygen species (ROS) accumulation, protects the mitochondrial membrane potential and increases cellular ATP, GSH and NADPH levels to maintain breast cancer cell survival. Meanwhile, the reinforcement of HBXIP induced by Nrf2 inhibits JNK1 activation by inhibiting ubiquitin-mediated degradation of Prdx1, which also plays an essential role in promoting ECM-detached cell survival. Furthermore, a strong positive correlation was identified between HBXIP expression and Prdx1 expression in clinical breast cancer tissues and TCGA Pan-Cancer Atlas clinical data of breast invasive carcinoma based on the cBioPortal cancer genomics database. Co-expression of HBXIP and Prdx1 predicts a poor prognosis for breast cancer patients. Collectively, our findings reveal a significant mechanism by which the HBXIP/Nrf2 feedback loop contributes to anoikis resistance by maintaining redox homeostasis and inhibiting JNK1 activation and support the likely therapeutic value of the HBXIP/Nrf2 axis in breast cancer patients.

4.
Nat Commun ; 13(1): 305, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027566

RESUMO

Biocatalytic transformations in living organisms, such as multi-enzyme catalytic cascades, proceed in different cellular membrane-compartmentalized organelles with high efficiency. Nevertheless, it remains challenging to mimicking biocatalytic cascade processes in natural systems. Herein, we demonstrate that multi-shelled metal-organic frameworks (MOFs) can be used as a hierarchical scaffold to spatially organize enzymes on nanoscale to enhance cascade catalytic efficiency. Encapsulating multi-enzymes with multi-shelled MOFs by epitaxial shell-by-shell overgrowth leads to 5.8~13.5-fold enhancements in catalytic efficiencies compared with free enzymes in solution. Importantly, multi-shelled MOFs can act as a multi-spatial-compartmental nanoreactor that allows physically compartmentalize multiple enzymes in a single MOF nanoparticle for operating incompatible tandem biocatalytic reaction in one pot. Additionally, we use nanoscale Fourier transform infrared (nano-FTIR) spectroscopy to resolve nanoscale heterogeneity of vibrational activity associated to enzymes encapsulated in multi-shelled MOFs. Furthermore, multi-shelled MOFs enable facile control of multi-enzyme positions according to specific tandem reaction routes, in which close positioning of enzyme-1-loaded and enzyme-2-loaded shells along the inner-to-outer shells could effectively facilitate mass transportation to promote efficient tandem biocatalytic reaction. This work is anticipated to shed new light on designing efficient multi-enzyme catalytic cascades to encourage applications in many chemical and pharmaceutical industrial processes.

5.
Int J Biol Sci ; 18(1): 242-260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975330

RESUMO

The limb-bud and heart (LBH) gene was reported to suppress nasopharyngeal carcinoma (NPC) progression in our previous study. Distant metastasis predominantly accounts for the unsatisfactory prognosis of NPC treatment, in which epithelial-mesenchymal transition (EMT) and tumor angiogenesis are of great significance. The roles of exosomes in mediating NPC progression have been highlighted in recent researches, and attempts have been made to explore the clinical application of NPC exosomes. Here we investigated the function of the LBH gene in NPC exosomes, and its potential mechanism. NPC xenografts were constructed, showing that vascular endothelial growth factor A (VEGFA) expression and neovascularity were attenuated by LBH overexpression, together with diminished EMT progression. NPC-derived exosomes were isolated, identified and applied for in vitro/in vivo experiments, and the exosomal distribution of LBH was elevated in exosomes derived from LBH-upregulated cells. Ectopic LBH, αB-crystallin (CRYAB) and VEGFA expression was induced by lentiviral infection or plasmid transfection to explore their functions in modulating EMT and angiogenesis in NPC. The addition of LBH+ NPC exosomes during a Matrigel plug assay in mice suppressed in vivo angiogenesis, and the treatment of human umbilical vein endothelial cells (HUVECs) with LBH+ NPC exosomes inhibited cellular proliferation, migration and tube formation. The interactions among LBH, CRYAB and VEGFA were confirmed by colocalization and fluorescence resonance energy transfer (FRET) assays, and extracellular VEGFA secretion from both HUVECs and NPC cells under the treatment with LBH+ NPC exosomes was diminished according to ELISA results. We concluded that exosomal LBH inhibits EMT progression and angiogenesis in the NPC microenvironment, and that its effects are partially implemented by modulation of VEGFA expression, secretion and related signaling. Thus, LBH could serve as a promising therapeutic target in VEGFA-focused NPC treatment.

8.
Int J Biochem Cell Biol ; 143: 106154, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34990837

RESUMO

Flap endonuclease 1 (FEN1) plays important roles in DNA replication, repair and recombination. Herein, we report biochemical characteristics and catalytic mechanism of a novel FEN1 from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tb-FEN1). As expected, the recombinant Tb-FEN1 can cleave 5'-flap DNA. However, the enzyme has no activity on cleaving pseudo Y DNA, which sharply contrasts with other archaeal and eukaryotic FEN1 homologs. Tb-FEN1 retains 24% relative activity after heating at 100 °C for 20 min, demonstrating that it is the most thermostable among all reported FEN1 proteins. The enzyme displays maximal activity in a wide range of pH from 7.0 to 9.5. The Tb-FEN1 activity is dependent on a divalent metal ion, among which Mg2+ and Mn2+ are optimal. Enzyme activity is inhibited by NaCl. Kinetic analyzes estimated that an activation energy for removal of 5'-flap from DNA by Tb-FEN1 was 35.7 ± 4.3 kcal/mol, which is the first report on energy barrier for excising 5'-flap from DNA by a FEN1 enzyme. Mutational studies demonstrate that the K87A, R94A and E154A amino acid substitutions abolish cleavage activity and reduce 5'-flap DNA binding efficiencies, suggesting that residues K87, R94, and E154 in Tb-FEN1 are essential for catalysis and DNA binding as well. Overall, Tb-FEN1 is an extremely thermostable endonuclease with unusual features.

9.
Fish Shellfish Immunol ; 121: 116-123, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34995768

RESUMO

Molluscan bivalves secrete shell matrices into the extrapallial space (EPS) to guide the precipitation of rigid shells. Meanwhile, immune components are present in the EPS and shell matrices, which are pivotal in resistant to invaded pathogens, thus ensuring the shell formation process. However, the origin of these components remains unclear. In this study, we revealed numerous vesicles were secreted from the outer mantle epithelial cells by using light and electron microscopes. The secreted vesicles were isolated by gradient centrifugation and confirmed by transmission electron microscopy. Proteomics analysis showed that the secreted vesicles were composed of cytoplasmic and immune components, most of which do not have signal peptides, indicating that they were secreted by a non-classical pathway. Moreover, real-time PCR revealed that some immune components were highly expressed in the mantle tissue, compared to the hemocytes. FTIR analysis verified the presence of lipids in the shell matrices, indicating that the vesicles have integrated into the shell layers. Taken together, our results suggested that mantle epithelial cells secreted some important immune components into the EPS via secreted vesicle transportation, thus cooperating with the hemocytes to play a vital role in immunity during shell formation.

10.
BMC Ophthalmol ; 22(1): 8, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983448

RESUMO

BACKGROUND: To longitudinally analyze and compare the accommodative micro-fluctuation (MFs) and accommodative function between myopic patients after implantable collamer lens (ICL) implantation and laser in situ keratomileusis (LASIK). METHODS: Patients with good corrected visual acuity (20/20 or better) and underwent ICL (V4c) and LASIK for myopic-correction (ranging from - 3.50 to - 8.50 D) were recruited. Refraction, amplitude of accommodation (AMP), accommodative lag, higher-order aberration (HOA), and MFs were recorded before surgery and 1 and 3 months after surgery. The ACOMEREF automatic refractor was used to measure the high-frequency component (HFC) of the MFs, which suggested tension of the ciliary muscle. RESULTS: The study comprised 120 eyes. At 3 months after surgery, the manifest refractive spherical equivalent of the ICL and LASIK groups were - 0.11 and - 0.09 D, respectively (p = 0.46). HFC values were significantly higher at 1 month (p = 0.03) and 3 months postoperatively (p = 0.03) in the ICL group compared to that in the LASIK group. The ocular HOA of the ICL group was 1.08 ± 0.43 µm, which was lower than the LASIK group 1.45 ± 0.54 µm (p = 0.01). No significant differences in AMP and accommodative lag between groups were noted at 3 months postoperatively. There was a positive correlation between HFC and vault of the ICL lens (r2 = 0.14, p = 0.005). There were no correlations between HFC and ocular HOA and postoperative MRSE in the two groups (all p>0.05). CONCLUSIONS: The HFC increased significantly after an early period of ICL implantation compared to laser in situ keratomileusis for myopic correction, which indicated increased tension of the ciliary muscle, and had a positive correlation on the vault of the ICL lens; However, studies with longer follow-up time and more structural evaluation are needed.


Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Lentes Intraoculares , Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular , Miopia/cirurgia , Refração Ocular , Resultado do Tratamento , Acuidade Visual
11.
PLoS Negl Trop Dis ; 16(1): e0010048, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34986169

RESUMO

BACKGROUND: The first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak. METHODOLOGY/PRINCIPAL FINDINGS: Guangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (Rt) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42-6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29-6.11) to 3.78 (95% CI: 2.74-4.81) days. The incubation period increased with age (P<0.001). A hierarchical prevention and control strategy against COVID-19 was implemented in Guangzhou, with Rt decreasing from 6.83 (95% credible interval [CrI]: 3.98-10.44) for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Individuals with partial or full vaccination schedules with BBIBP-CorV or CoronaVac accounted for 15.3% of the COVID-19 cases. Clinical symptoms were milder in partially or fully vaccinated cases than in unvaccinated cases (odds ratio [OR] = 0.26 [95% CI: 0.07-0.94]). CONCLUSIONS/SIGNIFICANCE: The hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19.

12.
Huan Jing Ke Xue ; 43(1): 230-238, 2022 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-34989507

RESUMO

Based on the flow direction of the Fuhe River into Baiyangdian Lake, the impacted area of the Fuhe River was divided into 6 subareas, and sediments from 48 sites were collected in November 2020. The characteristics and risks of sediment nutrients and heavy metal pollution in these six subareas were investigated. The results showed that the average ω(TN), ω(TP), and ω(TOC) were 1841 mg·kg-1, 769 mg·kg-1, and 1.77%, respectively. The major heavy metals were Cd, Cu, Zn, Hg, and Pb, which were 3.73, 1.50, 1.42, 1.31, and 1.31 times the soil background values for Hebei Province, respectively. The TP and heavy metal (Cd, Cu, Zn, Hg, and Pb) content showed a decreasing trend from the Fuhe River estuary to the downstream Zaolinzhuang, whereas the TN and TOC content showed no marked trends. TN, TP, TOC, and heavy metals (Cd, Cu, Zn, Hg, and Pb) were enriched in surface sediments (0-10 cm). The TP content in the surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were heavily polluted; the Wangjiazhai and Guangdian subareas were moderately polluted; and the Zaolinzhuang subarea was slightly polluted. Cd and Hg were the major contributors to heavy metal pollution, which were at considerable risk and moderate risk levels, respectively. The heavy metals in surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were at a considerable risk level, and the sediments below 30 cm presented a low risk level. The leaching concentrations of heavy metals in sediments from the subarea of severe ecological risk level were far less than the identification standard values of leaching toxicity, suggesting that the sediments can be treated as general waste after dredging.


Assuntos
Metais Pesados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Metais Pesados/análise , Nutrientes , Medição de Risco , Poluentes Químicos da Água/análise
13.
Quant Imaging Med Surg ; 12(1): 481-492, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993095

RESUMO

Background: Children with Kawasaki disease (KD) and coronary artery lesions (CALs) can develop myocardial ischemia, fibrosis, and abnormal contractility. We aimed to assess the association between myocardial mechanical deformation with myocardial fibrosis, ischemia, and CALs. Methods: In total, 76 KD and 20 healthy volunteers received cardiac magnetic resonance (CMR). Peak systolic left ventricular (LV) longitudinal, radial, and circumferential strain and strain rate [LV strain longitudinal (LVSL), LV strain radial (LVSR), LV strain circumferential (LVSC), LV strain rate longitudinal (LVSRL), LV strain rate radial (LVSRR), and LV strain rate circumferential (LVSRC)], along with late gadolinium enhancement (LGE), perfusion deficit, and CALs in related segments were analyzed. The KD group was subdivided by CALs, perfusion, and LGE results, and strain results were compared with controls and in subgroups. Results: Cardiac fibrosis and ischemia were not confined to the territory of CALs. In a global analysis, strain and strain rates were lower in the KD group, especially in the subgroup with LGE and perfusion deficit. In segmental analysis, LVSR, LVSC, LVSL, and LVSRR decreased in the giant aneurysm group, and a lower LVSR (20.369%±10.603% vs. 26.071%±12.349%) and LVSC (-13.37%±5.365% vs. -15.847%±5.778%) were observed in thrombosed segments. The strain and strain rate were all lower in segments with LGE and perfusion deficit, and no obvious difference was found between groups with and without stenosis. LVSR had a better ability to identify giant aneurysm, thrombosis, stenosis, perfusion deficit, and LGE. Conclusions: We detected lower strain values in KD patients, which was more pronounced in segments with aneurysm, thrombi, LGE, and perfusion deficit. LVSR is useful to discern patients with higher risk.

14.
J Clin Oncol ; : JCO2101636, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995125

RESUMO

PURPOSE: Although financial toxicity is a growing cancer survivorship issue, no studies have used credit data to estimate the relative risk of financial hardship in patients with cancer versus individuals without cancer. We conducted a population-based retrospective matched cohort study using credit reports to investigate the impact of a cancer diagnosis on the risk of adverse financial events (AFEs). METHODS: Western Washington SEER cancer registry (cases) and voter registry (controls) records from 2013 to 2018 were linked to quarterly credit records from TransUnion. Controls were age-, sex-, and zip code-matched to cancer cases and assigned an index date corresponding to the case's diagnosis date. Cases and controls experiencing past-due credit card payments and any of the following AFEs at 24 months from diagnosis or index were compared, using two-sample z tests: third-party collections, charge-offs, tax liens, delinquent mortgage payments, foreclosures, and repossessions. Multivariate logistic regression models were used to evaluate the association of cancer diagnosis with AFEs and past-due credit payments. RESULTS: A total of 190,722 individuals (63,574 cases and 127,148 controls, mean age 66 years) were included. AFEs (4.3% v 2.4%, P < .0001) and past-due credit payments (2.6% v 1.9%, P < .0001) were more common in cases than in controls. After adjusting for age, sex, average baseline credit line, area deprivation index, and index/diagnosis year, patients with cancer had a higher risk of AFEs (odds ratio 1.71; 95% CI, 1.61 to 1.81; P < .0001) and past-due credit payments (odds ratio 1.28; 95% CI, 1.19 to 1.37; P < .0001) than controls. CONCLUSION: Patients with cancer were at significantly increased risk of experiencing AFEs and past-due credit card payments relative to controls. Studies are needed to investigate the impact of these events on treatment decisions, quality of life, and clinical outcomes.

15.
Mol Cancer ; 21(1): 11, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983546

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common forms of cancer and is associated with poor patient outcomes. The emergence of therapeutic resistance has hampered the efficacy of targeted treatments employed to treat HCC patients to date. In this study, we conducted a series of CRISPR/Cas9 screens to identify genes associated with synthetic lethality capable of improving HCC patient clinical responses. METHODS: CRISPR-based loss-of-function genetic screens were used to target 18,053 protein-coding genes in HCC cells to identify chemotherapy-related synthetic lethal genes in these cells. Synergistic effects were analyzed through in vitro and in vivo analyses, while related mechanisms were explored through RNA-seq and metabolomics analyses. Potential inhibitors of identified genetic targets were selected through high-throughput virtual screening. RESULTS: The inhibition of phosphoseryl-tRNA kinase (PSTK) was found to increase HCC cell sensitivity to chemotherapeutic treatment. PSTK was associated with the suppression of chemotherapy-induced ferroptosis in HCC cells, and the depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat HCC in vitro and in vivo. CONCLUSIONS: These results highlight a key role for PSTK as a mediator of resistance to targeted therapeutic treatment in HCC cells that functions by suppressing ferroptotic induction. PSTK inhibitors may thus represent ideal candidates for overcoming drug resistance in HCC.

16.
Biomaterials ; 281: 121361, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991034

RESUMO

Efficient and non-invasive drug delivery to the fundus has always been a medical difficulty. Here, a co-assembled glycopeptide nanotransforrs (GPNTs) named MRP@DOX as a drug delivery system is reported. The MRP@DOX co-assemble nanoparticles consisting of glycopeptide, cationic peptide, and doxorubicin (DOX). The nanoparticles are positively charged with the nano-size, which can be induced transformation by legumain cleavage. Once administrate to the eyes, MRP@DOX has a high penetration through the ocular surface to specifically targets M2 macrophages in the fundus. Then, the mannose receptor mediates phagocytosis and intracellular highly expressed legumain induces its nanofibrous transformation, which contributes to a 44.7% DOX retention in cells at 24 h than that of the non-transformed controls (MAP@DOX: 5.1%). The nanofiber transformation provides an inhibition of exocytosis, which explains the higher retention of the delivered drug. In the mouse OIR model, MRP@DOX completely restores the physiological angiogenesis and reduces pathological neovascularization. Pathological neovascularization branches and cell nuclei that break through the inner limiting membrane are reduced by 55% and 72%, respectively, which are 25% and 20% less than those in the non-transformed controls. In addition, MRP@DOX also has good histocompatibility, which provides a possible strategy for non-invasive treatment of fundus diseases in the future.

17.
Molecules ; 27(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35011513

RESUMO

Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.

18.
J Org Chem ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020395

RESUMO

The C-S activation and sulfur removal from native thiols is challenging, which limits their application as feedstock materials in organic synthesis despite their natural abundance. Herein, we introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into sp3-hybridized thiols to activate the C-S bond. Using a Ni catalyst with MgBr2 as an additive, the S group can be removed to yield an aliphatic radical that can react with an aryl halide in a reductive cross-coupling.

19.
Plant Dis ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35021874

RESUMO

Southwest China has the most complex rice-growing regions in China. With great differences in topography, mainly consisting of basins and plateaus, ecological factors in above region differ greatly. In this study, bulk paddy soils collected from a long-term rice field in Chengdu (basins) and in Guiyang (plateaus) were used to study the correlation between microbial diversity and the incidence of rice bacterial diseases. Results showed that the microbial community composition in paddy soils and the microbial functional categories differed significantly between basins and plateaus. They shared more than 70% of the dominant genera (abundance > 1%), but the abundance of the dominant genera differed significantly. Functional analysis found that bulk paddy soils from Chengdu were significantly enriched in virulence factor-related genes; soils from Guiyang were enriched in biosynthesis of secondary metabolites especially antibiotics. Correspondingly, Chengdu was significantly enriched in leaf bacterial pathogens Acidovorax, Xanthomonas, and Pseudomonas. Greenhouse experiments and correlation analysis showed that soil chemical properties had a greater effect on microbial community composition and positively related with the higher incidence of rice bacterial foot rot in Guiyang, while temperature had a greater effect on soil microbial functions and positively related with the higher severity index of leaf bacterial diseases in Chengdu. Our results provide a new perspective on how differences in microbial communities in paddy soils can influence the incidence of rice bacterial diseases in areas with different topographies.

20.
Cell Death Dis ; 13(1): 52, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022391

RESUMO

SMYD2 is a histone methyltransferase, which methylates both histone H3K4 as well as a number of non-histone proteins. Dysregulation of SMYD2 has been associated with several diseases including cancer. In the present study, we investigated whether and how SMYD2 might contribute to colorectal cancer. Increased expression levels of SMYD2 were detected in human and murine colon tumor tissues compared to tumor-free tissues. SMYD2 deficiency in colonic tumor cells strongly decreased tumor growth in two independent experimental cancer models. On a molecular level, SMYD2 deficiency sensitized colonic tumor cells to TNF-induced apoptosis and necroptosis without affecting cell proliferation. Moreover, we found that SMYD2 targeted RIPK1 and inhibited the phosphorylation of RIPK1. Finally, in a translational approach, pharmacological inhibition of SMYD2 attenuated colonic tumor growth. Collectively, our data show that SMYD2 is crucial for colon tumor growth and inhibits TNF-induced apoptosis and necroptosis.

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