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1.
Proc Natl Acad Sci U S A ; 118(15)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33876762

RESUMO

Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP51-486), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP51-486 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.

2.
Med Sci Monit ; 27: e932346, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33820903

RESUMO

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures.Reference:Yong Xiong, Yi-Jia Xiong, Dong-Yang Liu, Rong-Rong Shen: Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest.Med Sci Monit 2019; 25:6015-6022. 10.12659/MSM.916116.

4.
Aging Ment Health ; : 1-9, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818221

RESUMO

Objectives: This study aimed to examine (1) the feasibility of the study procedures (i.e. recruitment, retention, attendance, and assessment completion rates), and (2) the effects of horticultural therapy (HT) on apathy, cognitive ability, quality of life, and functional capacity.Methods: This was a parallel-group, match-paired, randomized controlled trial. Thirty-two participants were allocated to either the experimental or the control group. Data were collected at baseline (T0), immediately postintervention (T1), and 3 months postintervention (T2). The Apathy Evaluation Scale-informant version (AES-I); Mini-Mental State Examination (MMSE); Quality of Life in Alzheimer's disease (QoL-AD) scale; Barthel index (BI) were used to measure apathy, cognitive ability, quality of life, and functional capacity, respectively.Results: The recruitment, retention, attendance and assessment completion rates were 22.7%, 87.5%, 100% and 100%, respectively. The between-group differences in AES-I (p = 0.007) and MMSE (p = 0.034) scores were statistically significant at T1. In the experimental group, the AES-I (p = 0.001), MMSE (p = 0.010), and QoL-AD (p = 0.017) scores were significantly different over time. In the post hoc pair-wise analysis, the AES-I scores of the experimental group observed at T1 were significantly lower than that at T0 (p = 0.032). In the control group, the MMSE scores (p = 0.001) were significantly different over time.Conclusion: HT is feasible for residents with dementia and apathy. The HT program effectively reduced apathy and promoted cognitive function, but its effects on quality of life and functional capacity were not observed.

5.
Mol Cell ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33930332

RESUMO

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.

6.
J Nanosci Nanotechnol ; 21(10): 5120-5130, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875097

RESUMO

Poly(cyclotriphosphazene-co-4,4'-diaminodiphenyl ether) (PPO) microspheres were prepared via a precipitation polymerization method, using hexachlorocyclotriphosphazene (HCCP) and 4,4'-diaminodiphenyl ether (ODA) as monomers. Silver-loaded PPO (PPOA) microspheres were generated by the in situ loading of silver nanoparticles onto the surface by Ag+ reduction. Our results showed that PPOA microspheres were successfully prepared with a relatively uniform distribution of silver nanoparticles on microsphere surfaces. PPOA microspheres had good thermal stability and excellent antibacterial activity towards Escherichia coli and Staphylococcus aureus. Furthermore, PPOA microspheres exhibited lower cytotoxicity when compared to citrate-modified silver nanoparticles (c-Ag), and good sustained release properties. Our data indicated that polyphosphazene-based PPOA microspheres are promising antibacterial agents in the biological materials field.

7.
Tissue Cell ; 72: 101540, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33838353

RESUMO

OBJECTIVE: To investigate whether miR-105 can regulate the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) by targeting SOX9. METHODS: The hADSCs were grouped for subsequent transfection and induction of osteogenic differentiation as follows: control, miR-NC, miR-105 mimics, miR-105 inhibitors, SOX9, SOX9 siRNA, miR-105 mimics + SOX9 and miR-105 inhibitors + SOX9 siRNA groups. Next, hADSCs were stained for alkaline phosphatase (ALP), and Alizarin Red S staining (ARS) was performed. Osteogenic differentiation-related genes and miR-105 expression were assessed by qRT-PCR, while SOX9 protein expression was determined by Western blotting. RESULTS: MiR-105 expression was increased and SOX9 protein expression was decreased during the osteogenic differentiation of hADSCs. A dual-luciferase reporter assay confirmed SOX9 to be a target gene of miR-105. Compared with the control group, the miR-105 mimics and SOX9 siRNA groups had elevated BMP2, OPN, OCN, BSP, Osx and Runx2 mRNA expression with reduced SOX9 expression, as well as increased ARS intensity and ALP activity. After transfection of miR-105 inhibitors/SOX9 into hADSCs, the results were the opposite. Overexpressing SOX9 reversed the effect of miR-105 in promoting the osteogenic differentiation of hADSCs. CONCLUSION: MiR-105 could target SOX9 to improve the expression of osteogenic differentiation genes and thus enhance the osteogenic differentiation of hADSCs.

8.
Phys Chem Chem Phys ; 23(10): 5878-5887, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33659975

RESUMO

Molecular magnetic compounds, which combine the advantages of nanoscale behaviors with the properties of bulk magnetic materials, are particularly attractive in the fields of high-density information storage and quantum computing. Before molecular electronic devices can be fabricated, a crucial task is the measurement and understanding of the transport behaviors. Herein, we consider a magnetic molecular trimer sandwiched between two metal electrodes, and, with the aid of the sophisticated full density matrix numerical renormalization group (FDM-NRG) technique, we study the effect of magnetic anisotropy on the charge transport properties, illustrated by the local density of states (LDOS, which is proportional to the differential conductance), the Kondo effect, and the temperature and inter-monomer hopping robustness. Three kinds of energy peaks are clarified in the LDOS: the Coulomb, the Kondo and the Ruderman-Kittel-Kasuya-Yosida (RKKY) peaks. The local magnetic moment and entropy go through four different regimes as the temperature decreases. The Kondo temperature TK could be described by a generalized Haldane's formula, revealing in detail the process where the local moment is partially screened by the itinerant electrons. A relationship between the width of the Kondo resonant peak WK and TK is built, ensuring the extraction of TK from WK in an efficient way. As the inter-monomer hopping integral varies, the ground state of the trimer changes from a spin quadruplet to a magnetically frustrated phase, then to an orbital spin singlet through two first order quantum phase transitions. In the first two phases, the Kondo peak in the transmission coefficient reaches its unitary limit, while in the orbital spin singlet, it is totally suppressed. We demonstrate that magnetic anisotropy may also induce the Kondo effect, even without Coulomb repulsion, hence it is replaceable in the many-body behaviours at low temperature.

9.
Nat Chem ; 13(4): 335-342, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33785892

RESUMO

In cells, myriad membrane-interacting proteins generate and maintain curved membrane domains with radii of curvature around or below 50 nm. To understand how such highly curved membranes modulate specific protein functions, and vice versa, it is imperative to use small liposomes with precisely defined attributes as model membranes. Here, we report a versatile and scalable sorting technique that uses cholesterol-modified DNA 'nanobricks' to differentiate hetero-sized liposomes by their buoyant densities. This method separates milligrams of liposomes, regardless of their origins and chemical compositions, into six to eight homogeneous populations with mean diameters of 30-130 nm. We show that these uniform, leak-resistant liposomes serve as ideal substrates to study, with an unprecedented resolution, how membrane curvature influences peripheral (ATG3) and integral (SNARE) membrane protein activities. Compared with conventional methods, our sorting technique represents a streamlined process to achieve superior liposome size uniformity, which benefits research in membrane biology and the development of liposomal drug-delivery systems.

10.
Front Immunol ; 12: 627844, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679771

RESUMO

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Assuntos
/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , /metabolismo , Adulto , Idoso , China/epidemiologia , Intervalo Livre de Doença , Feminino , Ferritinas/sangue , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
11.
Sci Total Environ ; 777: 146006, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33677283

RESUMO

Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants.

12.
Aging (Albany NY) ; 13(4): 5185-5196, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535185

RESUMO

In this study, we investigated the effect of a short deletion in the DNA-binding domain of STAT3 (STAT3del) on the transcriptional activation of STAT3 target genes and its relationship with colon carcinogenesis. We used the CRISPR-CAS9 gene editing system to delete a short sequence encoding amino acids 400-411 in the DNA-binding domain (amino acid sequence: 317-567) from STAT3 gene in SW480, SW620 and HCT116 colon cancer cells. ChIP sequencing analysis showed that STAT3del occupancy was significantly reduced in 1029 genes and significantly increased in 475 genes compared to wild-type STAT3. The mutation altered the DNA motifs recognized by STAT3del as compared to the wild-type STAT3. We observed a strong correlation between expression of the STAT3 target genes and the loss or gain of STAT3del binding to their promoters. CCK-8, wound healing, and TUNEL assays showed reduced proliferation, migration, and survival of SW480, SW620 and HCT-116 cells expressing STAT3del as compared to the corresponding controls. These findings demonstrate that a short deletion in the DNA-binding domain of STAT3 alters its genome-wide DNA-binding and transcriptional profile of STAT3-target proteins, and suppresses the growth, progression and survival of colon cancer cells.

13.
Eur Neurol ; 84(1): 6-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33477142

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss and cognitive impairment. In 2011, the National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework has proposed to use biomarkers to diagnose AD in living persons. AD core biomarkers show high diagnostic specificity in distinguishing AD from healthy control subjects, but have little additional value for prognosis or stage of disease. SUMMARY: With the update of detection methods and techniques, other AD biomarkers have been discovered. Neurofilament light (NFL) is currently recognized as a biomarker of nerve axonal injury and one of the candidate markers in AD neurodegeneration, and the relationship between NFL and AD pathophysiology has attracted widespread attention. More and more studies have shown that NFL plays an important role in predicting the clinical progress and prognosis of AD. Recently, the genome-wide association study also found that multiple single-nucleotide polymorphisms are associated with NFL levels and AD risk. Key Messages: In this review, we discuss the relationship between the genetic characteristics of NFL and AD, the NFL levels in AD, and the relationship between NFL and AD core biomarkers, neuroimaging, and cognitive performance.

14.
Redox Biol ; 40: 101854, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33454563

RESUMO

Gestational exposure to environmental stress induces fetal growth restriction (FGR), and thereby increasing the risk of infant death and chronic noncommunicable diseases in adults. However, the mechanism by which environmental stress induces FGR remains unclear. Based on case-control study, we found that the reduced level of melatonin (MT), a major secretory product from the pineal gland, was observed in placentae of FGR. This work was to investigate the protective effect of MT on environmental stress-caused FGR and its mechanisms. We used cadmium (Cd) as an environmental stressor to stimulate pregnant mice and thereby establishing a FGR model. The data showed that maternal Cd exposure lowered the P4 concentration in maternal sera, placentae and amniotic fluid, and caused FGR. Correspondingly, the expression of CYP11A1, a critical P4 synthase, was markedly downregulated in Cd-treated placentae. Simultaneously, Cd triggered BNIP3-dependent mitophagy in placental trophoblasts, as determined by the degradation of mitochondrial proteins, including HSP60 and COX IV, and the accumulation of puncta representing co-localization of TOM20 with LC3B or BNIP3 with LC3B. Based on our case-control study, we also found that activated BNIP3-dependent mitophagy and P4 synthesis inhibition occurred in SGA placentae. Most importantly, BNIP3 siRNA reversed Cd-induced P4 synthesis suppression in human placental trophoblasts. It is noteworthy that MT alleviated Cd-caused P4 synthesis suppression and FGR via antagonizing BNIP3-dependent mitophagy in placental trophoblasts. Further results confirmed that MT attenuated Cd-triggered BNIP3-dependent mitophagy via blocking GCN2/ATF4 signaling. Amusingly, Cd triggered oxidative stress and then activating GCN2/ATF4 signaling in placental trophoblasts. As expected, MT obviously suppressed Cd-caused reactive oxygen species (ROS) release. In the present study, we propose a neoteric mechanism by which MT protects against environmental stress-impaired P4 synthesis and fetal growth via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts. As above, MT is a potential therapeutic agent antagonizing environmental stress-induced developmental toxicity.

15.
J Hazard Mater ; 401: 123438, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32763717

RESUMO

Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress.

16.
Environ Int ; 147: 106319, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33348103

RESUMO

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.


Assuntos
Retardo do Crescimento Fetal , Trofoblastos , Animais , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Mitofagia , Placenta , Gravidez
17.
Environ Pollut ; 270: 116241, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33321432

RESUMO

Cadmium (Cd) was an environmental pollutant, which could result in germ cell apoptosis in testes. Sertoli-germ cell communication was vital for germ cell development and maturity. However, little was known about the effect of Sertoli cell autophagy on Cd-induced germ cell apoptosis. Here, we used male Amh-Cre+/Atg5flox/flox (Atg5-/-) mice, loss of autophagy-related gene 5 (Atg5) in testicular Sertoli cells, to explore the obscure effects. Atg5-/- and Wild-type (WT) mice were given with cadmium chloride (CdCl2, 2.0 mg/kg) for 0-24 h. Our results showed that Cd triggered testicular germ cell apoptosis, as evidenced by the increment of TUNEL-labeled germ cells, cleaved caspase3 and cleaved poly (ADP-ribose) polymerase protein level. Additionally, Cd induced testicular autophagy, as determined by elevating the level of autophagy-related proteins, including Atg5, Atg7, LC3B-II, and the gathering of LC3 puncta. 3-methyladenine, a specific autophagy inhibitor, exacerbated Cd-caused germ cell apoptosis. Inversely, rapamycin, an autophagy inducer, relieved Cd-stimulated germ cell apoptosis. Interestingly, we found that autophagy in Sertoli cells was activated in Cd-treated WT mouse testes as evidenced by the increment of LC3 puncta surrounding SOX9, a specific Sertoli cell marker. More importantly, loss of autophagy in Sertoli cells aggravated Cd-triggered germ cell apoptosis. Taken together, these data indicate that autophagy in Sertoli cells alleviates Cd-triggered germ cell apoptosis in mouse testes.


Assuntos
Cádmio , Células de Sertoli , Animais , Apoptose , Autofagia , Cádmio/toxicidade , Células Germinativas , Masculino , Camundongos , Testículo
18.
Acta Pharmacol Sin ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268823

RESUMO

Endoplasmic reticulum (ER) homeostasis is regulated by ER-resident E3 ubiquitin ligase Hrd1, which has been implicated in inflammatory bowel disease (IBD). Ginsenoside Rb1 (GRb1) is the major ginsenoside in ginseng with multiple pharmacological activities. In this study we investigated the role of Hrd1 in IBD and its regulation by GRb1. Two mouse colitis models were established to mimic human IBD: drinking water containing dextran sodium sulfate (DSS) as well as intra-colonic infusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Colitis mice were treated with GRb1 (20, 40 mg·kg-1·d-1, ig) or a positive control drug sulfasalazine (500 mg·kg-1·d-1, ig) for 7 days. The model mice showed typical colitis symptoms and pathological changes in colon tissue. In addition to significant inflammatory responses and cell apoptosis in colon tissue, colon epithelial expression of Hrd1 was significantly decreased, the expression of ER stress markers GRP78, PERK, CHOP, and caspase 12 was increased, and the expression of Fas was increased (Fas was removed by Hrd1-induced ubiquitination). These changes were partially, or completely, reversed by GRb1 administration, whereas injection of Hrd1 inhibitor LS102 (50 mg·kg-1· d-1, ip, for 6 days) exacerbated colitis symptoms in colitis mice. GRb1 administration not only normalized Hrd1 expression at both the mRNA and protein levels, but also alleviated the ER stress response, Fas-related apoptosis, and other colitis symptoms. In intestinal cell line IEC-6, the expression of Hrd1 was significantly decreased by LPS treatment, but was normalized by GRb1 (200 µM). GRb1 alleviated LPS-induced ER stress and cell apoptosis in IEC-6 cells, and GRb1 action was inhibited by knockdown of Hrd1 using small interfering RNA. In summary, these results reveal a pathological role of Hrd1 in colitis, and provide a novel insight into alternative treatment of colitis using GRb1 activating Hrd1 signaling pathway.

20.
Ying Yong Sheng Tai Xue Bao ; 31(10): 3349-3356, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33314824

RESUMO

We investigated soil total organic carbon (TOC), recalcitrant organic carbon (ROC), and labile organic carbon (LOC) of evergreen broadleaved forests at different altitudes (400, 600, 800, 1000 and 1200 m) in Guanshan National Nature Reserve, Jiangxi Province, with the aim to understand their altitudinal distribution. The results showed that soil TOC, ROC and LOC contents were the highest in the surface layer and decreased with soil depth. With the increases of altitude, contents of soil TOC, ROC, readily oxidizable organic carbon (ROOC), microbial biomass carbon (MBC), and particulate organic carbon (POC, 0-20 cm depth) increased with a peak at 1000 m and then decreased, whereas soil water-soluble organic carbon (WSOC) contents and POC contents in 20-40 cm layer did not change. In 0-10 cm soil layer, the proportions of ROC to TOC at 800 and 1200 m were significantly higher than those at 400 and 1000 m, while the proportions of LOC to TOC were the highest at 400 m. The proportions of ROC and LOC to TOC in 10-40 cm layer showed a low-high-low tendency along the altitude, with peaks at 1000 and 600 m, respectively. Soil organic carbon fractions were positively correlated with soil moisture, microbial biomass nitrogen, and soluble organic nitrogen. A positive correlation was observed between LOC and ammonium concentration. Our results suggested that altitude significantly affected the distribution of soil organic fractions, with soil ROC, ROOC and MBC being more sensitive to altitudinal changes. Soil ROC and LOC at high altitude were prone to decomposition and transformation under conditions with sufficient water and nitrogen, which reduced soil carbon stability. It was essential to study the dyna-mics of soil organic carbon in high altitude forests under global warming scenarios.


Assuntos
Carbono , Solo , Carbono/análise , China , Florestas , Nitrogênio/análise
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