Post-stroke depression (PSD) seriously affects the normal life of patients. Based on the previous sequencing results, this study selected miR-129-5p as the research object, which was significantly ...reduced in the PSD model by screening. To clarify the regulatory role of miR-129-5p, this study overexpressed and interfered with miR-129-5p in neuronal cells cultured in vitro, tested its effect on neuronal cell autophagy, and determined expressions of fasciculation and elongation protein zeta-1 (FEZ1), short coiled-coil protein (SCOC), unc-51 like autophagy activating kinase 1 (ULK1) and autophagy cargo receptor (NBR1) autophagy-related proteins. The dual-luciferase reporter system and immunoprecipitation were applied to detect the molecular regulatory mechanism of miR-129-5 and FEZ1, SCOC, ULK1 and NBR1. Findings of the present study revealed that the autophagy of neuronal cells was markedly decreased by overexpressing miR-129-5p (p < 0.05), and expressions of FEZ1, SCOC, ULK1 and NBR1 were substantially reduced (p < 0.05). The dual-luciferase reporter system results indicated that FEZ1, SCOC, ULK1 and NBR1 were all miR-129-5p target genes. Furthermore, immunoprecipitation assay revealed that SCOC, ULK1 and NBR1 could directly bind to the FEZ1 protein. The experiments at an animal level demonstrated that miR-129-5p could effectively alleviate the behavioral indicators of PSD model mice. Taken together, this study testified that SCOC/ULK1/NBR1 proteins could directly bind to FEZ1 to form protein complex, and all of the four proteins FEZ1/SCOC/ULK1/NBR1 were miR-129-5p target genes. miR-129-5p overexpression could effectively restore the behavioral characteristics of model mice, and reduce the autophagy-related proteins FEZ1/SCOC/ULK1/NBR1.
Abstract
Our previous studies have shown adenosine A
2A
R activation markedly promotes the expression of cystatin F (CF) and exacerbates the white matter lesions induced by hypoxic brain injuries. ...Thus, we hypothesized that CF was probably involved in neuroinflammation of activated microglia induced by A
2A
R activation. We transfected the BV2 cells with a CF shRNA vector and examined the production of pro-inflammatory cytokines in hypoxic-BV2 cells in which A
2A
R was activated or inactivated to confirm this hypothesis. Additionally, we also investigated the probable signaling pathways involved in modulation of A
2A
R activation on CF expression in hypoxia-activated BV2 cells. Activation of A
2A
R promoted CF expression, which was significantly increased after the low glucose and hypoxia treatments in BV2 cells. CF gene knockdown markedly inhibited the increase in the expression of pro-inflammatory cytokines induced by A
2A
R activation in hypoxic-BV2 cells. Furthermore, the increased expression of the CF induced by A
2A
R activation was remarkably inhibited in hypoxic-BV2 cells administrated with the PKA inhibitor H-89 and the PKC inhibitor staurosporine. Hence, these results indicate that hypoxia BV2 cells highly express CF, which is involved in A
2A
R activation-mediated neuroinflammation via the PKA/CREB and PKC/CREB or ERK1/2 signaling pathways.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To clarify the differential expressions of microRNAs and mRNAs in a PSD model, this study employed PSD mice for model construction by injecting vasoconstrictor ET-1 (angioendothelin-1) into the ...medial prefrontal cortex (mPFC) of mice. The animals underwent elevated plus maze test, open field test, tail suspension test, and forced swimming test subsequently. Transcriptome sequencing was performed to analyze the differentially expressed mRNAs and microRNAs. The results showed that open arm entries and time of PSD mice were markedly decreased. Times of the entry to center for mice in the model group were apparently decreased. The climbing time of mice in the model group was greatly decreased. The behavior of PSD mice indicated a marked change, and several indicators of the behavioral tests were significantly lower than those of the control group. Transcriptome sequencing analysis demonstrated that expressions of 1 206 genes and 21 microRNAs were markedly upregulated in model group, whereas expressions of 2 113 genes and 32 microRNAs were markedly downregulated. GO analysis revealed that the differentially expressed genes were mainly involved in regulatory pathways of single-multicellular organism process, developmental process, cell periphery, plasma membrane, and neuron projection. Meanwhile, KEGG analysis results indicated that the differentially expressed genes mostly participated in signaling pathways of neuroactive ligand-receptor interaction, calcium signaling pathway, and cytokine-cytokine receptor interaction. In conclusion, differentially expressed microRNAs and mRNAs were screened, which offers a theoretical foundation for further investigation of molecular mechanisms and novel insight for the early identification, prevention, and treatment of PSD.
Stroke and major depression disorder are common neurological diseases, and a large number of clinical studies have shown that there is a close relationship between the two diseases, but whether the ...two diseases are linked at the genetic level needs to be further explored. The purpose of this study was to explore the comorbidity mechanism of stroke and major depression by using bioinformatics technology and animal experiments. From the GEO database, we gathered transcriptome data of stroke and depression mice (GSE104036, GSE131712, GSE81672, and GSE146845) and identified comorbid gene set through edgR and WGCNA analyses. Further analysis revealed that these genes were enriched in pathways associated with cell death. Programmed cell death gene sets (PCDGs) are generated from genes related to apoptosis, necroptosis, pyroptosis and autophagy. The intersection of PCDGs and comorbid gene set resulted in two hub genes, Mlkl and Nlrp3. Single-cell sequencing analysis indicated that Mlkl and Nlrp3 are mainly influential on endothelial cells and microglia, suggesting that the impairment of these two cell types may be a factor in the relationship between stroke and major depression. This was experimentally confirmed by RT–PCR and immunofluorescence staining. Our research revealed that two specific genes, namely, Mlkl and Nlrp3, play crucial roles in the complex mechanism that links stroke and major depression. Additionally, we have predicted six possible therapeutic agents and the outcomes of docking simulations of target proteins and drug molecules.
•The changes of gene expression in brain tissues of stroke and major depression have some overlap.•Programmed cell death plays an important role in molecular interactions between stroke and major depression.•Mlkl and Nlrp3 are the hub genes involved in the comorbidity mechanism of stroke and major depression.•Necroptosis and pyroptosis of endothelial cells and microglia are common pathological changes of stroke and major depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AbstractObjectiveTo compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and ...tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options.DesignSystematic review and network meta-analysis.Data sourcesOvid Medline, Embase, and Cochrane Central up to 14 October 2022.Eligibility criteria for selecting studiesEligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach.ResultsThe analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference −8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes).ConclusionsThis network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.Systematic review registrationPROSPERO CRD42022325948.
Our previous studies have shown adenosine A
R activation markedly promotes the expression of cystatin F (CF) and exacerbates the white matter lesions induced by hypoxic brain injuries. Thus, we ...hypothesized that CF was probably involved in neuroinflammation of activated microglia induced by A
R activation. We transfected the BV2 cells with a CF shRNA vector and examined the production of pro-inflammatory cytokines in hypoxic-BV2 cells in which A
R was activated or inactivated to confirm this hypothesis. Additionally, we also investigated the probable signaling pathways involved in modulation of A
R activation on CF expression in hypoxia-activated BV2 cells. Activation of A
R promoted CF expression, which was significantly increased after the low glucose and hypoxia treatments in BV2 cells. CF gene knockdown markedly inhibited the increase in the expression of pro-inflammatory cytokines induced by A
R activation in hypoxic-BV2 cells. Furthermore, the increased expression of the CF induced by A
R activation was remarkably inhibited in hypoxic-BV2 cells administrated with the PKA inhibitor H-89 and the PKC inhibitor staurosporine. Hence, these results indicate that hypoxia BV2 cells highly express CF, which is involved in A
R activation-mediated neuroinflammation via the PKA/CREB and PKC/CREB or ERK1/2 signaling pathways.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Intercropping is an important agronomic practice adopted to increase crop production and resource efficiency in areas with intensive agricultural production. Two sequential field trials were ...conducted in 2015-2016 to investigate the effect of shading on the morphological features, leaf structure, and photosynthetic characteristics of soybean in a maize-soybean relay-strip intercropping system. Three treatments were designed on the basis of different row configurations A1 ("50 cm + 50 cm" one row of maize and one row of soybean with a 50 cm spacing between the rows), A2 ("160 cm + 40 cm" two rows of maize by wide-narrow row planting, where two rows of soybean were planted in the wide rows with a width of 40 cm, and with 60 cm row spacing was used between the maize and soybean rows), and CK (sole cropping of soybean, with 70 cm rows spacing). Results showed that the photosynthetically active radiation transmittances of soybean canopy at V5 stage under A2 treatment (31.1%) were considerably higher than those under A1 (8.7%) treatment, and the red-to-far-red ratio was reduced significantly under A1 (0.7) and A2 (1.0) treatments compared with those under CK (1.2). By contrast with CK, stem diameter, total aboveground biomass, chlorophyll content and net photosynthetic rate decreased significantly except plant height under A1 and A2. The thickness of palisade tissue and spongy tissue of soybean leaf under A1 and A2 were significantly reduced at V5 stage compared with CK. The leaf thicknesses under A1 and A2 were lower than those in CK by 39.5% and 18.2%, respectively. At the R1 stage of soybean (after maize harvest), the soybean plant height, stem biomass, leaf biomass and petiole biomass under A1 and A2 treatments were still significantly lower than those under CK, but no significant differences were observed in Chl a/b, Pn, epidermis thickness and spongy tissue thickness of soybean leaves in A2 compared with CK. In addition, the soybean yields (g plant-1) under A1 and A2 were 54.69% and 16.83% lower than those in CK, respectively. These findings suggested that soybean plants can regulate its morphological characteristics and leaf anatomical structures under different light environments.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Light intensity and light quality affect photosynthesis of soybean.•Higher far-red light can improve the photosynthetic capacity of soybean.•iTRAQ approach can be used to investigate the response of ...photosynthetic proteins to light environment change.
Photosynthesis is dependent on the density and quality of light that reaches chloroplasts. Shade conditions are characterized by changes in light density and quality. These changes, which are represented by the red to far-red (R/Fr) ratio of light, directly affect the photosynthetic capacity of soybean in close-planting and intercropping systems. We postulated that high far-red light under shade conditions would improve crop photosynthesis. Herein, we conducted a quantitative proteomic analysis through the isobaric tagging for relative and absolute quantification approach to investigate the response of photosynthetic proteins to the interaction between light intensity and quality. We identified 7834 proteins (P value < 0.05, FC > 1.3) from soybean leaves. Among these proteins, 98 are associated with differential chloroplast accumulation under shade (S, low light intensity and low R/Fr ratio) and normal light (N, normal light intensity and normal R/Fr ratio) conditions. Additionally, 134 are associated with differential chloroplast accumulation under low light (L, low light intensity and normal R/Fr ratio) and N conditions. Eight representative proteins that are involved in photosynthesis were differentially regulated under L and S treatments. These proteins included one protein involved in porphyrin and chlorophyll metabolism, three proteins involved in light-harvesting chlorophyll protein complex, and four proteins involved in photosynthesis. Among the eight differentially regulated proteins under L and S treatments, five up-regulated proteins (protochlorophyllide reductase; light-harvesting complex II chlorophyll a/b binding protein Lhcb1; Lhcb2; photosystem I subunit II; and plastocyanin PetE) and three down-regulated proteins (Lhcb4; Ferredoxin-1; and NADPH:quinone oxidoreductase NQO) were validated through quantitative reverse-transcription polymerase chain reaction and Western blot methods L and S treatments decreased net photosynthesis rate (Pn) but increased chlorophyll content; thylakoid stacking; and photosystem II (PSII), PSI, and electron transport associated protein levels. Likewise, N and S treatments decreased PetE and NQO protein expression levels. This effect, in turn, decreased P700 oxidation. In addition, the higher far-red light of the S treatment than that of the L treatment increased Pn by up-regulating the gene expressions of differential proteins. We conclude that light intensity directly affects photosynthesis by regulating the expression of photosynthetic proteins. High far-red light, however, can improve the photosynthetic capacity of plants under shade conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Shading includes low light intensity and varying quality. However, a low red/far-red (R/Fr) ratio of light is a signal that affects plant growth in intercropping and close- planting systems. Thus, ...the low R/Fr ratio uncoupling from shading conditions was assessed to identify the effect of light quality on photosynthesis and CO
assimilation. Soybean plants were grown in a growth chamber with natural solar radiation under four treatments, that is, normal (N, sunlight), N + Fr, Low (L) + Fr, and L light.
Low R/Fr ratio significantly increased the total biomass, leaf area, starch and sucrose contents, chlorophyll content, net photosynthetic rate, and quantum efficiency of the photosystem II compared with normal R/Fr ratio under the same light level (P < 0.05). Proteomic analysis of soybean leaves under different treatments was performed to quantify the changes in photosynthesis and CO
assimilation in the chloroplast. Among the 7834 proteins quantified, 12 showed a > 1.3-fold change in abundance, of which 1 was related to porphyrin and chlorophyll metabolism, 2 were involved in photosystem I (PS I), 4 were associated with PS II, 3 proteins participated in photosynthetic electron transport, and 2 were involved in starch and sucrose metabolism. The dynamic change in these proteins indicates that photosynthesis and CO
assimilation were maintained in the L treatment by up-regulating the component protein levels compared with those in N treatment. Although low R/Fr ratio increased the photosynthetic CO
assimilation parameters, the differences in most protein expression levels in N + Fr and L + Fr treatments compared with those in N treatment were insignificant. Similar trends were found in gene expression through quantitative reverse transcription polymerase chain reaction excluding the gene expression of sucrose synthase possible because light environment is one of the factors affecting carbon assimilation.
Low R/Fr ratio (high Fr light) can increase the photosynthetic CO
assimilation in the same light intensity by improving the photosynthetic efficiency of the photosystems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•The changing rules of soybean leaf carbon and nitrogen content under shade environment were clarified.•The most sensitive bands to soybean leaf carbon and nitrogen content were extracted by wavelet ...analysis.•The efficacious models based on the wavelet analysis for monitoring the leaf nitrogen and carbon content were established.
Changes in leaf carbon and nitrogen traits are effective parameters for evaluating whether plants are growing normally and for guiding field management measures. Therefore, a nondestructive estimation of soybean leaf carbon content (LCC) and leaf nitrogen content (LNC) is important for managing soybean production. This study aims to investigate the properties of soybean LCC, LNC and leaf carbon and nitrogen ratio (LCNR) under different light conditions and to construct the estimation models for soybean LCC, LNC and LCNR on the basis of hyperspectral reflectance. A 3-year field trial was conducted from 2013 to 2015 to investigate the effect of five shade treatments (from 57% to 18% of normal photosynthetic active radiation) by regulating the distance between maize and soybean rows in an intercropping system.
Results showed that the LNC is increased, and the LCC is decreased with the increase in shading level. A typical leaf hyperspectral reflectance showed that the changes in near infrared and around the green peak are approximately proportional to the LCC and analogously inverse to the LNC. The corresponding first-order derivative presented the changes in the red-edge positions as a ‘blue shift’ with the increase in shading level. General vegetation indices (VIs), uninformative variable elimination-partial least squares (UVE-PLS) and continuous wavelet transform (CWT) were used to develop the models. The linear models constructed using the CWT, compared with the VIs and UVE-PLS, had the highest determination coefficient and the lowest root mean square error (RMSE). The models were validated using independent data from 2015 with RMSE values of 1.9789, 0.6132 and 2.1587 for the LCC, LNC and LCNR, respectively. Moreover, these models obtained relative errors of 4.5%, 13.2% and 20% for the LCC, LNC and LCNR, respectively. Results indicated that soybean LNC and LCC can be accurately estimated using the CWT for assessing the physiological situation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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