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1.
Exp Cell Res ; 412(1): 113009, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34990616

RESUMO

LINC010503 is a novel oncogenic lncRNA in multiple cancers. In this study, we further explored the expression of LINC010503 transcripts and their regulations on the glioblastoma (GBM) stem cell (GSC) properties. LINC01503 transcription patterns in GBM and normal brain tissues were compared using RNA-seq data from Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA)-GBM. GBM cell lines (U251 and U87) were used as in vitro cell models for cellular and molecular studies. The results showed that ENST00000444125 was the dominant transcript of LINC01503 in both normal and tumor tissues. Its expression was significantly elevated in the tumor group and associated with poor survival outcomes. LINC01503 had both cytoplasmic and nuclear distribution. It positively modulated the expression of multiple GSC markers, including CD133, SOX2, NESTIN, ALDH1A1, and MSI1, and tumorsphere formation in U251 and U87 cells. RNA pull-down and RIP-qPCR assay confirmed an interaction between ENST00000444125 and GLI2. ENST00000444125 positively regulated the half-life of the GLI2 protein in GBM cells. ENST00000444125 overexpression reduced GLI2 ubiquitination and partially attenuated FBXW1 overexpression induced GLI2 ubiquitination. ENST00000444125 overexpression could activate Wnt/ß-catenin signaling in GBM cells. However, these activating effects were remarkedly hampered when GLI2 was knocked down. In conclusion, this study revealed that LINC01503 might have isoform-specific dysregulation in GBM. Among the two major transcripts expressed in GBM cells, ENST00000444125 might be the major functional transcript. Its upregulation might enhance the GSC properties of GBM cells via reducing FBXW1-mediated proteasomal degradation of GLI2.

2.
Foodborne Pathog Dis ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35020482

RESUMO

Giardia duodenalis has a wide range of host species and is a common causative agent of diarrheal disease in humans and animals. This study conducted a systematic review and meta-analysis to evaluate the pooled prevalence of Giardia among dogs in China. We extracted 33 studies related to the prevalence of G. duodenalis in dogs, with samples taken from 2001 to 2021. The random-effect model was used to calculate pooled prevalence estimates with 95% confidence intervals, and the analyzed data were from 14 provinces in China. The estimated overall prevalence of G. duodenalis among dogs in China was 11.2%. The prevalence of Giardia was significantly higher in Northwestern China (35.7%) than in other regions. The prevalence in 2010 or later (11.8%) was significantly higher than in 2010 or before (6.9%). The estimated prevalence detected by microscopy (9.3%) was lower than molecular (12.3%) and serological (14.3%) ones. The prevalence was higher in dogs <1 year of age (12.2%) than that >1 year (5.4%). Among the genotype groups, the positive rate of assemblage A (5.2%) was significantly higher than that of other assemblages. Depending on the dog' type, the prevalence of G. duodenalis in stray dogs (3.5%) was lower than that in pet dogs (6.7%) and intensively breeding dogs (11.8%). In addition, no correlation was found between Giardia positive rate and the dogs' gender (p > 0.05). We also analyzed the effects of different geographic factor subgroups (longitude, latitude, precipitation, temperature, humidity, and altitude) on the prevalence of G. duodenalis in dogs in China. The results showed that giardiasis was widespread in dogs in China. It is suggested that corresponding control scheme and effective management measures should be formulated and applied to reduce the transmission of G. duodenalis according to the difference in geographical conditions in different areas.

4.
Int J Med Sci ; 19(1): 152-163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975309

RESUMO

Background and Aims: MicroRNAs (miRNAs) play important roles in hepatocyte differentiation from human bone marrow mesenchymal stem cells (hBMSCs) and the therapeutic application in vivo. However, the mechanisms of miRNA regulation are still unknown. This study aimed to profile the miRNA basis for improving the function of hBMSC-differentiated hepatocyte-like cells (hBMSC-Heps). Methods: Characteristic miRNAs of hBMSC-Heps were identified by transcriptome sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). An in vivo hBMSC transplantation model was used to assess the regulatory effects of miRNAs on liver regeneration during hBMSC therapy in pigs with fulminant hepatic failure (FHF). The biological functions of significant miRNA molecules were confirmed by transfection of miRNA activators or inhibitors into hBMSCs during hepatogenic differentiation. Results: The transcriptome of hBMSC-Heps showed characteristics distinct from those of undifferentiated hBMSCs. A total of 77 miRNAs were significantly differentially expressed in hBMSC-Heps at day 10 and day 20 after hBMSC differentiation that were directly related to the functions of hepatocytes. Among the top 10 significantly differentially expressed and the top 10 most abundant miRNAs, nine miRNAs that exhibited a pattern of gradual change were chosen for further analysis. The expression of nine miRNAs was confirmed by qRT-PCR in vitro and showed the same changing trends in vivo in an hBMSC transplantation model in pigs. Functional experiments with these miRNAs showed that activators of hsa-miR-26b-5p and hsa-miR-148a-3p and an inhibitor of hsa-miR-423-3p were sufficient to improve the differentiation of hBMSCs into hepatocyte-like cells. Conclusions: Transcriptome profiles of miRNA revealed the basis of the differentiation and development of hBMSC-Heps. Manipulation of three miRNAs (hsa-miR-26b-5p, hsa-miR-148a-3p and hsa-miR-423-3p) significantly improved hepatocyte generation and liver regeneration, indicating the potential of these miRNAs for future clinical applications.

5.
Inorg Chem ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985269

RESUMO

The rational design and preparation of monolayer metal-organic framework (MOF) nanosheets remain great challenges. Recently, we found that monolayer MOF nanosheets can be facially exfoliated on a large scale from pristine two-dimensional (2D) MOFs with substantially reduced interlaminar interaction. By employing cage-like bicyclocalix[2]arene[2]triazine tri-imidazole as the building block, a family of cationic two-dimensional metal-organic frameworks (2D MOFs) with steric layer were designed and prepared. The single crystal structures have clearly identified that only very weak and sparse distributed C-H···π interaction exists between adjacent layers.On the basis of density functional theory calculation, the interlayer interaction of these cage-based cationic 2D MOFs was estimated to be 1/46th of that of graphite. Due to the extremely weak interaction, these cationic 2D MOFs tend to degenerate into an "amorphous" state after being soaked in other solvents; they can be readily exfoliated into 1.1 nm thick monolayer nanosheets with a high degree of thickness homogeneity, large lateral size, and significantly enlarged surface area. This work has identified that a cage-like molecule is the ideal building block for 2D cationic MOFs and ultrathin nanosheets; It was futher confirmed that weakening the interlaminar interaction is an effective strategy for facilely producing monolayer nanosheets.

6.
Adv Sci (Weinh) ; : e2103478, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35032111

RESUMO

Phase-change material (PCM) devices are one of the most mature nonvolatile memories. However, their high power consumption remains a bottleneck problem limiting the data storage density. One may drastically reduce the programming power by patterning the PCM volume down to nanometer scale, but that route incurs a stiff penalty from the tremendous cost associated with the complex nanofabrication protocols required. Instead, here a materials solution to resolve this dilemma is offered. The authors work with memory cells of conventional dimensions, but design/exploit a PCM alloy that decomposes into a heterogeneous network of nanoscale crystalline domains intermixed with amorphous ones. The idea is to confine the subsequent phase-change switching in the interface region of the crystalline nanodomain with its amorphous surrounding, forming/breaking "nano-bridges" that link up the crystalline domains into a conductive path. This conductive-bridge switching mechanism thus only involves nanometer-scale volume in programming, despite of the large areas in contact with the electrodes. The pore-like devices based on spontaneously phase-separated Ge13 Sb71 O16 alloy enable a record-low programming energy, down to a few tens of femtojoule. The new PCM/fabrication is fully compatible with the current 3D integration technology, adding no expenses or difficulty in processing.

7.
Bioresour Technol ; 344(Pt A): 126117, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34653631

RESUMO

Fucoxanthin (Fx) has gained a growing attention due to the remarkable biological activities. The limited biomass of was the restrictive factor for Fx production in Phaeodactylum tricornutum. In this study, Laminaria japonica hydrolysate (LPH) with a low addition proportion of 1.5 ml/L, was proved to promote fucoxanthin accumulation and cell growth simultaneously. Fx topped at 27.9 mg/L after 10-d cultivation in the LPH group, with a biomass of 1.59 g/L and a Fx content of 17.55 mg/g. Three key plant hormones in LPH were screened responsible for promoting fucoxanthin accumulation. Transcriptomic analysis and qRT-PCR results showed that genes related to Fx formation were generally up- regulated. The study demonstrated that LPH addition was a feasible and efficient strategy to enhance production of fucoxanthin, facilitating the scale-up production of Fx in autotrophic culture.


Assuntos
Diatomáceas , Laminaria , Biomassa , Diatomáceas/genética , Xantofilas
8.
Gut ; 71(1): 163-175, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33431576

RESUMO

OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.


Assuntos
Insuficiência Hepática Crônica Agudizada/patologia , Hepatite B Crônica/complicações , Leucócitos Mononucleares/imunologia , Insuficiência Hepática Crônica Agudizada/virologia , Imunidade Adaptativa , Adulto , Animais , Estudos de Casos e Controles , DNA Viral/sangue , Feminino , Vírus da Hepatite B , Humanos , Imunidade Inata , Masculino , Metaboloma , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos , Transcriptoma
9.
Life Sci Alliance ; 5(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34853163

RESUMO

Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis-based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune-related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune-related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them THBS1, IL-10, and NR4A3 expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.

10.
Chem Pharm Bull (Tokyo) ; 69(12): 1200-1205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853287

RESUMO

A protocol for the ruthenium-on-carbon (Ru/C)-catalyzed solvent-free oxidation of alcohols, which proceeds efficiently under solid-solid (liquid)-gas conditions, was developed. Various primary and secondary alcohols were transformed to corresponding aldehydes and ketones in moderate to excellent isolated yields by simply stirring in the presence of 10% Ru/C under air or oxygen conditions. The solvent-free oxidation reactions proceeded efficiently regardless of the solid or liquid state of the substrates and reagents and could be applied to gram-scale synthesis without loss of the reaction efficiency. Furthermore, the catalytic activity of Ru/C was maintained after five reuse cycles.

11.
Diabetes Metab Syndr Obes ; 14: 4599-4608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34848984

RESUMO

Purpose: Nonalcoholic fatty liver disease (NAFLD) is closely related to lipid metabolism and insulin resistance. The current research mainly attempted to verify the clinical value of LncRNA plasmacytoma variant translocation 1 (PVT1), and whether microRNA regulates lipid metabolism and insulin resistance to participate in NAFLD. Patients and Methods: 81 patients with NAFLD and 78 healthy individuals were enrolled in this study. In addition, C57BL/6 mice were fed a high-fat diet to establish NAFLD model in vivo. Serum PVT1 and miR-20a-5p expression in NAFLD patients and mice were assessed by RT-qPCR. ROC curves determine the diagnostic value of PVT1 and miR-20a-5p. NAFLD mice were subjected to IPGTT to detect changes in insulin sensitivity, and the common indicators of lipid metabolism and insulin resistance were also evaluated. Dual-luciferase reporter assay verified the regulation mechanism of PVT1 and miR-20a-5p. Results: PVT1 was upregulated in NAFLD patients and mice, while miR-20a-5p was decreased. Their expression trends were similar in patients with HOMA-IR ≥2.5. What's more, miR-20a-5p, FBG, ALT, and HOMA-IR were independently correlated with PVT1. And PVT1 and miR-20a-5p show high clinical diagnostic value. Bodyweight, insulin sensitivity, lipid metabolism inductors were increased in NAFLD mice, but these increases were attenuated by PVT1 elimination. Finally, miR-20a-5p might function as the possible miRNA target of PVT1 via the binding sites at 3'-UTR and negatively regulated by it. Conclusion: PVT1 and miR-20a-5p are potential clinical biomarkers of NAFLD, and PVT1 promotes the occurrence of NAFLD by regulating insulin sensitivity and lipid metabolism, which may be achieved by targeting miR-20a-5p.

12.
Front Pharmacol ; 12: 726158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867329

RESUMO

Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand-receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.

13.
Physiol Genomics ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859688

RESUMO

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10×Genomics). Detailed t-Distributed Stochastic Neighbor Embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2 and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits>2, p<0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included five subtypes, fibroblasts comprised of seven subtypes and macrophages contained eleven subtypes. The key representative DEGs (p<0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, as well as Clec4e and Trem-1 in in cluster 3 of marcophages perhaps involved in the occur of atherosclerosis, heart failure and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.

14.
Zhen Ci Yan Jiu ; 46(11): 942-7, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34865331

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) on the survival rate and serum inflammatory cytokine levels in rats with lethal endotoxemia, and to explore its parasympathetic mechanism in suppressing severe systemic inflammation. METHODS: A total of 82 male SD rats were used in the present study. In the first part of this study, 40 rats were randomized into model and EA-BL32 groups (n=20/group). The endotoxemia model was established by intraperitoneal injection of lethal amount of lipopolysaccharide (LPS, 10 mg/kg). EA (30 Hz, 6 mA) was applied to bilateral BL32 for 30 min before and after LPS injection. The survival rate in 7 days was then recorded. In the second part of this study, 42 rats were randomized into normal control, model, EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal (subdiagrammatical) vagotomy and EA-BL32+pelvic neurectomy groups (n=7/group). The endotoxemia model was established by intraperitoneal injection of LPS (6 mg/kg) 30 min after the neurectomy. Rats of the control group received intraperitoneal injection of 6 mg/kg saline. EA with the same parameters mentioned above was applied to bilateral BL32 for 30 min before and after LPS injection. Blood sample was collected from the abdominal aorta 3 h after LPS injection for detecting the levels of TNF-α, IL-1ß and IL-6 by ELISA. RESULTS: ① The EA survival rate was 25% in the model group and 60% in the EA -BL32group, being significantly improved after EA (P<0.05). ② The contents of serum TNF-α, IL-1ß and IL-6 were significantly higher in the model group than those in the control group (P<0.000 1). After EA intervention, and compared with the model group, the levels of TNF-α, IL-1ß and IL-6 were significantly decreased in the EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal vagotomy and EA-BL32+pelvic neurectomy groups (P<0.000 1,P<0.01). After neurectomy and compared to the EA-BL32 group, the contents of TNF-α and IL-6 in the EA+cervical vagotomy and EA+pelvic neurectomy groups, IL-1ß in the EA+pelvic neurotomy group were significantly higher (P<0.0000 1, P<0.05), suggesting an elimination of EA effects after neurectomy. No significant differences were found among the 3 neurectomy groups in the levels of TNF-α, IL-1ß and IL-6 (P>0.05). CONCLUSION: EA of BL32 can improve the survival rate and attenuate the level of inflammatory cytokines in rats with lethal endotoxemia, which is closely related to the intact of parasympathetic pathway including the vagus nerve and pelvic nerve.

15.
Int J Ophthalmol ; 14(12): 1915-1920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926208

RESUMO

AIM: To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). METHODS: In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. RESULTS: Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. CONCLUSION: The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34939348

RESUMO

Nanozymes are nanomaterials with enzyme-like characteristics, which catalyze the conversion of enzyme substrates and follow enzymatic kinetics under physiological conditions. As a new generation of artificial enzymes, nanozymes provide alternative approaches for those upon enzymatic catalysis. Compared with natural enzymes, nanozymes have the advantages of simple preparation, good stability and low cost, which makes nanozymes promising for application in many fields, such as antimicrobial infection treatment. Many studies have reported that nanozymes are capable of killing a number of pathogenic bacteria with resistance, fungi as well as viruses, and have shown great curative effects for diseases caused by these pathogens. Herein, we summarize the application of nanozymes for antibacterial, antiviral, and antifungal therapies and outline the issues needing resolution in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

17.
Front Plant Sci ; 12: 758785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938306

RESUMO

The adjustment of stomatal density and clustered ratio on the epidermis is the important strategy for plants to respond to drought, because the stoma-based water loss is directly related to plant growth and survival under drought conditions. But the relevant adjustment mechanism still needs to be explored. 1-Aminocyclopropane-1-carboxylate (ACC) is disclosed to promote stomatal development, while in vivo ACC levels depend on activation of ACC synthase (ACS) family members. Based on the findings of ACS expression involving in drought response and several ACS activity inhibitors reducing stomatal density and cluster in drought response, here we examined how ACS activation is involved in the establishment of stomatal density and cluster on the epidermis under drought conditions. Preliminary data indicated that activation of ACS2 and/or ACS6 (ACS2/6) increased stomatal density and clustered ratio on the Arabidopsis leaf epidermis by accumulating ACC under moderate drought, and raised the survival risk of seedlings under escalated drought. Further exploration indicated that, in Arabidopsis seedlings stressed by drought, the transcription factor SPEECHLESS (SPCH), the initiator of stomatal development, activates ACS2/6 expression and ACC production; and that ACC accumulation induces Ca2+ deficiency in stomatal lineage; this deficiency inactivates a subtilisin-like protease STOMATAL DENSITY AND DISTRIBUTION 1 (SDD1) by stabilizing the inhibition of the transcription factor GT-2 Like 1 (GTL1) on SDD1 expression, resulting in an increases of stomatal density and cluster ratio on the leaf epidermis. This work provides a novel evidence that ACS2/6 activation plays a key role in the establishment of stomatal density and cluster on the leaf epidermis of Arabidopsis in response to drought.

18.
Front Pharmacol ; 12: 783317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955854

RESUMO

Ovarian cancer is the second most common gynecological malignancy, and one of the most deadly. The bottleneck restricting the treatment of ovarian cancer is its multi-drug resistance to chemotherapy. Cajanol is an isoflavone from pigeon pea (Cajanus cajan) that has been reported to have anti-tumor activity. In this work, we evaluate the effect of cajanol in reversing paclitaxel resistance of the A2780/Taxol ovarian cancer cell line in vitro and in vivo, and we discuss its mechanism of action. We found that 8 µM cajanol significantly restored the sensitivity of A2780/Taxol cells to paclitaxel, and in vivo experiments demonstrated that the combination of 0.5 mM/kg paclitaxel and 2 mM/kg cajanol significantly inhibited the growth of A2780/Taxol metastatic tumors in mice. Flow cytometry, fluorescence quantitative PCR, western blotting and immunohistochemical staining methods were used to study the mechanism of reversing paclitaxel resistance with cajanol. First, we determined that cajanol inhibits paclitaxel efflux in A2780/Taxol cells by down-regulating permeability glycoprotein (P-gp) expression, and further found that cajanol can inhibit P-gp transcription and translation through the PI3K/Akt/NF-κB pathway. The results of this work are expected to provide a new candidate compound for the development of paclitaxel sensitizers.

19.
Front Cardiovasc Med ; 8: 753072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966794

RESUMO

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure worldwide. The Z-line protein Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is closely associated with DCM, both clinically and in animal models. Our earlier work revealed Cypher/ZASP as a PKA-anchoring protein (AKAP) that tethers PKA to phosphorylate target substrates. However, the downstream PKA effectors regulated by AKAP Cypher/ZASP and their relevance to DCM remain largely unknown. Methods and Results: For the identification of candidate PKA substrates, global quantitative phosphoproteomics was performed on cardiac tissue from wild-type and Cypher-knockout mice with PKA activation. A total of 216 phosphopeptides were differentially expressed in the Cypher-knockout mice; 31 phosphorylation sites were selected as candidates using the PKA consensus motifs. Bioinformatic analysis indicated that differentially expressed proteins were enriched mostly in cell adhesion and mRNA processing. Furthermore, the phosphorylation of ß-catenin Ser675 was verified to be facilitated by Cypher. This phosphorylation promoted the transcriptional activity of ß-catenin, and also the proliferative capacity of cardiomyocytes. Immunofluorescence staining demonstrated that Cypher colocalised with ß-catenin in the intercalated discs (ICD) and altered the cytoplasmic distribution of ß-catenin. Moreover, the phosphorylation of two other PKA substrates, vimentin Ser72 and troponin I Ser23/24, was suppressed by Cypher deletion. Conclusions: Cypher/ZASP plays an essential role in ß-catenin activation via Ser675 phosphorylation, which modulates cardiomyocyte proliferation. Additionally, Cypher/ZASP regulates other PKA effectors, such as vimentin Ser72 and troponin I Ser23/24. These findings establish the AKAP Cypher/ZASP as a signalling hub in the progression of DCM.

20.
Comput Math Methods Med ; 2021: 7850281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34961823

RESUMO

Objective: The study was to explore the roles of personality characteristics of different genders and analyze the risk factors of quality of life (QOL) analysis in suicide among depressive patients. Methods: One hundred and eighty-six depressive patients from January 2018 to March 2019 in the Department of Psychiatry of our hospital were enrolled and divided into Groups A and B considering whether they had a suicidal tendency or not. Among them, 90 in Group A had a suicidal tendency and consisted of 42 males and 48 females, while 96 in Group B had no suicidal tendency and consisted of 44 males and 52 females. Forward and backward selection and then backward selection were performed on all the variables of gender characteristic factors and QOL factors that may cause suicide, on which stepwise regression was finally conducted. Next, univariate logistic regression analysis was first performed to select important variables from the related risk factors that may cause suicide, and then, the multivariate logistic regression model was used to select important independent risk factors. Results and Conclusion. The age of onset, degree of anxiety, moral support, positive mental attitude, and family independence were the independent risk factors that may cause a suicidal tendency for male depressive patients. The age of onset, degree of anxiety, negative life events, moral support, positive mental attitude, family intimacy, psychoticism, and neuroticism were the independent risk factors for female depressive patients. Physiological function, role physical, bodily pain, social function, and emotional role in QOL may be the independent risk factors for a suicidal tendency.

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