ABSTRACT
Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.
Subject(s)
Acid Sensing Ion Channels , Ganglia, Spinal , Insulin , Receptor, Insulin , Sensory Receptor Cells , Animals , Acid Sensing Ion Channels/metabolism , Insulin/metabolism , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/drug effects , Ganglia, Spinal/metabolism , Ganglia, Spinal/drug effects , Ganglia, Spinal/cytology , Rats , Receptor, Insulin/metabolism , Male , Signal Transduction/drug effects , Action Potentials/drug effects , Rats, Sprague-Dawley , Hyperalgesia/metabolism , Cells, CulturedABSTRACT
Ethylene response factors have been shown to be involved in the effects of plant developmental processes and to regulate stress tolerance. The aim of this study was to recognize the regulatory mechanisms of ethylene response factors on tobacco plant height. In this study, a gene-edited mutant (ERF10-KO) and wild type (WT) were utilized as experimental materials. Transcriptome and metabolome analyses were used to investigate the regulatory mechanism of NtERF10 gene editing on plant height in tobacco. Here, through the analysis of differentially expressed genes (DEGs), 2051 genes were upregulated and 1965 genes were downregulated. We characterized the different ERF10-KO and WT plant heights and identified key genes for photosynthesis, the plant hormone signal transduction pathway and the terpene biosynthesis pathway. NtERF10 was found to affect the growth and development of tobacco by regulating the expression levels of the PSAA, PSBA, GLY17 and GGP3 genes. Amino acid metabolism was analyzed by combining analyses of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). In addition, we found that members of the bHLH, NAC, MYB, and WRKY transcription factor families have vital roles in regulating plant height. This study not only provides important insights into the positive regulation of the ethylene response factor NtERF10 on plant height during plant growth and development but also provides new research ideas for tobacco molecular breeding.
Subject(s)
Gene Expression Regulation, Plant , Nicotiana , Plant Proteins , Transcription Factors , Nicotiana/genetics , Nicotiana/growth & development , Nicotiana/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics , Ethylenes/metabolism , Plants, Genetically Modified/growth & development , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , TranscriptomeABSTRACT
This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.
ABSTRACT
Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Rectal Neoplasms/immunology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Aged , Chemoembolization, Therapeutic/methods , Prognosis , Treatment Outcome , Adult , Chemoradiotherapy/methodsABSTRACT
Both CXCL10/CXCR3 and acid-sensing ion channels (ASICs) are expressed in nociceptive sensory neurons and participate in various pain processes, but it is still unclear whether there is a link between them. Herein, we report that CXCL10 enhances the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. A brief (10 min) application of CXCL10 increased acid-evoked ASIC currents in a concentration-dependent manner. CXCL10 increased the maximum response of ASICs to acidic stimuli without changing their sensitivity. CXCL10 enhanced ASIC currents in DRG cells through CXCR3, as this enhancement was completely blocked by AMG487, a selective CXCR3 antagonist. CXCL10 also increased ASIC3 currents in CHO cells coexpressing ASIC3 and CXCR3 but not in cells expressing ASIC3 alone. The CXCL10-mediated increase in ASIC currents was prevented by the application of either the G protein inhibitor GDP-ß-S or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 but not by the ERK inhibitor U0126 or the JNK inhibitor SP600125. Moreover, CXCL10 increased the number of action potentials triggered by acidic stimuli via CXCR3. CXCL10 dose-dependently exacerbated acid-induced nociceptive behavior in rats through peripheral CXCR3. These results indicated that CXCL10/CXCR3 signaling enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats via a p38 MAPK-dependent pathway, revealing a novel mechanism underlying pain. CXCL10/CXCR3 signaling may be an effective target in the treatment of pain associated with tissue acidification.
ABSTRACT
Introduction: The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern. Methods: A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles. Results: Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%. Conclusion: The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.
ABSTRACT
Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas, Aeromonas, Pseudomonas, and Acinetobacter, accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD5, TN, NH4+-N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.
Subject(s)
Bacteria , Nitrogen , RNA, Ribosomal, 16S , Bacteria/genetics , Phosphorus , SoilABSTRACT
OBJECTIVES: To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy. METHODS: A prospective randomized, controlled, and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021. These infants were divided into a nasal cannula (NC) group and a modified T-piece resuscitator (TPR) group using a random number table. The lowest intraoperative blood oxygen saturation was recorded as the primary outcome, and intraoperative heart rate and respiratory results were recorded as the secondary outcomes. RESULTS: Compared with the NC group, the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia (P<0.05). In the modified TPR group, there were 6 infants with mild hypoxemia, 2 with moderate hypoxemia, and 1 with severe hypoxemia, while in the NC group, there were 3 infants with mild hypoxemia, 5 with moderate hypoxemia, and 9 with severe hypoxemia (P<0.05). The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group (P<0.05), but there was no significant difference in the incidence rate of arrhythmias between the two groups (P>0.05). CONCLUSIONS: Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy, and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.
Subject(s)
Lung Diseases , Oxygen , Infant , Humans , Bronchoscopy/adverse effects , Cannula , Prospective Studies , Electronics , Hypoxia/etiology , Hypoxia/prevention & controlABSTRACT
Vegetation restoration affects the carbon cycle of terrestrial ecosystems by changing the rate of carbon input and conversion. In order to explore the evolution characteristics of soil active organic carbon components and carbon pool management index during vegetation restoration in karst areas, the soil of a grassland sequence(5, 10, 15, and 20 a), shrub sequence(5, 10, 15, and 20 a), and garden sequence(5, 10, and 15 a) in a karst area was taken as the research object, and the adjacent farmland was taken as the control(CK). The effects of different vegetation restoration years on the evolution of soil organic carbon(SOC), readily oxidizable organic carbon(ROC333, ROC167, and ROC33 were all soil active organic carbon that could be oxidized by 333, 167, and 33 mmol·L-1 KMnO4), microbial biomass carbon(MBC), dissolved organic carbon(DOC), and carbon pool management index(CPMI) were analyzed. The results showed that compared with that of CK, the average grassland, shrub, and garden SOC contents in the 0-40 cm soil layer increased by 70.77%, 114.40%, and 50.17%, respectively. In the 0-20 cm soil layer, with the increase in restoration years, the SOC content of the grassland sequence and garden sequence increased first and then decreased, and that of the shrub sequence increased first, then decreased, and then increased again. ROC333, ROC167, and ROC33 were consistent with the SOC change trend of the corresponding sequence. In the 20-40 cm soil layer, the change trend of ROC333, ROC167, and ROC33 of each sequence was inconsistent with the SOC of the corresponding sequence. In the 0-40 cm soil layer, the MBC content of the grassland sequence decreased first, then increased, and then decreased, and the maximum value of MBC in each soil layer was in G15. The shrub sequence in the 0-10 cm soil layer increased first, then decreased, and then increased, and in the 10-40 cm soil layer it increased first and then decreased. The garden sequence increased first and then decreased in the 0-30 cm soil layer and gradually increased in the 30-40 cm soil layer. Kos of the three sequences decreased first, then increased, and then decreased, whereas L and LI showed the opposite of Kos. CPI increased first and then decreased; the CPMI of the grassland and garden sequences increased first and then decreased, whereas the CPMI of the shrub sequence increased first, then decreased, and then increased again. The contents of SOC, ROC333, ROC167, ROC33, and MBC and the annual growth of Kos were shrub>grassland>orchard, and the annual growth of DOC and CPMI were orchard>grassland>shrub. The contents of SOC and its components in the three sequences decreased with the increase in soil layer and had obvious surface aggregation. Redundancy analysis showed that alkali-hydrolyzable nitrogen(AN) was the main environmental factor affecting soil active organic carbon components and soil organic carbon pool under the vegetation restoration in the karst area. In summary, soil active organic carbon components and CPMI evolved with vegetation restoration years. Different vegetation restorations could increase the content of SOC and its components in karst areas to a certain extent, and shrub restoration promotes the accumulation of SOC.
ABSTRACT
To investigate the seasonal variation, health risks, and potential sources of polycyclic aromatic hydrocarbons(PAHs) in PM2.5 in the Lüliang area, PM2.5 samples were collected in Lishi District(downtown area) and Xiaoyi City(suburban area) from October 23, 2018 to July 1, 2019, and the concentrations of 14 PAHs were determined using gas chromatography-mass spectrometry(GC-MS). The annual average concentration of PAHs was 95.50 ng·m-3, and the concentration of 5-6 ring PAHs was mainly(49.7%), with 3 ring PAHs accounting for a relatively low proportion(8.3%).The concentration of PAHs in Lüliang City showed a seasonal pattern of winter>autumn>spring>summer. The results of the ILCRs model and Monte Carlo simulation showed that the toxicity of PAHs in Lüliang City followed the rule of adults>youth>children. Except in summer, the ILCRs values in the Lishi area were between 10-6 and 10-4, much higher than those in Xiaoyi City, indicating that there was a high potential risk of polycyclic aromatic hydrocarbons in the urban area. Through the characteristic ratio method and positive matrix factorization(PMF), it was shown that the PAHs in Lüliang City were mainly from the combustion of coal and biomass(61.9%) and vehicle exhaust emissions(38.1%). Based on the backward trajectory and potential source factor contribution analysis model, it was determined that the potential sources of PAHs in Lüliang City were mainly distributed in southern Shanxi, northern Shaanxi, and western Inner Mongolia.
Subject(s)
Air Pollutants , Polycyclic Aromatic Hydrocarbons , Adult , Child , Adolescent , Humans , Air Pollutants/analysis , Particulate Matter/analysis , Environmental Monitoring/methods , Vehicle Emissions/analysis , Seasons , Risk Assessment , China , Polycyclic Aromatic Hydrocarbons/analysis , Coal/analysisABSTRACT
Introduction: Auricular acupressure (AA) has been widely utilized in the management of constipation, with several studies suggesting its efficacy in treating constipation patients. However, the safety and effectiveness of AA in constipation remain uncertain. Hence, the aim of this study was to assess the effectiveness and safety of AA for constipation. Methods and analysis: A total of eight electronic databases and three clinical trial registration platforms were searched from their inception to April 2023 for randomized controlled trials (RCTs) of AA for constipation. The included studies were appraised for quality using the Cochrane Collaboration's Risk of Bias Assessment tool. The quality of evidence was assessed by two independent reviewers employing the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool. Meta-analysis of data and assessment of publication bias were performed using RevMan 5.4 and STATA 13.0 software, respectively. Results: This review included 34 randomized controlled trials conducted between 2007 and 2023, involving 2,465 participants. The findings of the study indicate that overall, AA is significantly associated with improved CSBMs (MD = 1.22, 95% CI [0.68, 1.77], p < 0.0001, I2 = 0%), BSF (MD = 0.72, 95%CI: [0.15,1.28], p = 0.01, I2 = 82%), CAS (MD = -3.28, 95%CI: [-5.95, -0.60], p = 0.02, I2 = 80%), responder rate (RR = 1.27, 95%CI: [1.16, 1.38], p < 0.00001, I2 = 79%), cure rate (RR = 1.84, 95% CI [1.56, 2.15], p < 0.00001, I2 = 0%), and PAC-QOL (MD = -2.73, 95% CI: [-3.41, -2.04], p < 0.00001, I2 = 98%) compared to the control group. However, no difference in PAC-SYM (MD = -0.15, 95%CI: [-0.38,0.07], p = 0.19, I2 = 67%) was found between the two groups. Additionally, there was no significant difference in adverse events (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I2 = 38%). Conclusion: Based on the available evidence, auricular acupressure appears to be a potentially safe and effective intervention for managing constipation in adults. Nonetheless, the overall quality of evidence for the identified outcomes was assessed as low to very low, highlighting the need for additional high-quality randomized controlled trials to further validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023425033.
ABSTRACT
Resolvin D2 (RvD2), an endogenous lipid mediator derived from docosahexaenoic acid, has been demonstrated to have analgesic effects. However, little is known about the mechanism underlying RvD2 in pain relief. Herein, we demonstrate that RvD2 targeted the P2X3 receptor as an analgesic. The electrophysiological activity of P2X3 receptors was suppressed by RvD2 in rat dorsal root ganglia (DRG) neurons. RvD2 pre-application dose-dependently decreased α,ß-methylene-ATP (α,ß-meATP)-induced inward currents. RvD2 remarkably decreased the maximum response to α,ß-meATP, without influencing the affinity of P2X3 receptors. RvD2 also voltage-independently suppressed ATP currents. An antagonist of the G protein receptor 18 (GPR18), O-1918, prevented the RvD2-induced suppression of ATP currents. Additionally, intracellular dialysis of the Gαi/o -protein antagonist pertussis toxin (PTX), the PKA antagonist H89, or the cAMP analog 8-Br-cAMP also blocked the RvD2-induced suppression. Furthermore, α,ß-meATP-triggered depolarization of membrane potential along with the action potential bursts in DRG neurons were inhibited by RvD2. Lastly, RvD2 attenuated spontaneous nociceptive behaviors as well as mechanical allodynia produced by α,ß-meATP in rats via the activation of the peripheral GPR18. These findings indicated that RvD2 inhibited P2X3 receptors in rat primary sensory neurons through GPR18, PTX-sensitive Gαi/o -proteins, and intracellular cAMP/PKA signaling, revealing a novel mechanism that underlies its analgesic effects by targeting P2X3 receptors.
ABSTRACT
In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.
Subject(s)
Aspergillus oryzae , Tobacco Mosaic Virus , Nicotiana , Anthraquinones/pharmacology , Biological Assay , Antiviral Agents/pharmacologyABSTRACT
Cholecystokinin (CCK) is a peptide that has been implicated in pain modulation. Acid sensitive ion channels (ASICs) also play an important role in pain associated with tissue acidification. However, it is still unclear whether there is an interaction between CCK signaling and ASICs during pain process. Herein, we report that a functional link between them in rat dorsal root ganglion (DRG) neurons. Pretreatment with CCK-8 concentration-dependently increased acid-evoked ASIC currents. CCK-8 increased the maximum response of ASICs to acid, but did not changed their acid sensitivity. Enhancement of ASIC currents by CCK-8 was mediated by the stimulation of CCK2 receptor (CCK2R), rather than CCK1R. The enhancement of ASIC currents by CCK-8 was prevented by application of either G-protein inhibitor GDP-ß-S or protein kinase C (PKC) inhibitor GF109203×, but not by protein kinase A (PKA) inhibitor H-89 or JNK inhibitor SP600125. Moreover, CCK-8 increased the number of action potentials triggered by acid stimuli by activating CCK2R. Finally, CCK-8 dose-dependently exacerbated acid-induced nociceptive behavior in rats through local CCK2R. Together, these results indicated that CCK-8/CCK2R activation enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats. The enhancement effect depended on G-proteins and intracellular PKC signaling rather than PKA and JNK signaling pathway. These findings provided that CCK-8/CCK2R is an important therapeutic target for ASIC-mediated pain.
Subject(s)
Acid Sensing Ion Channels , Sincalide , Rats , Animals , Rats, Sprague-Dawley , Sincalide/pharmacology , Sincalide/metabolism , Acid Sensing Ion Channels/metabolism , Sensory Receptor Cells , Pain/metabolism , Ganglia, Spinal/metabolismABSTRACT
AIMS AND OBJECTIVES: To describe dyadic psycho-social intervention measures and to evaluate their influence on stroke survivors and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and coping ability. BACKGROUND: Because of the importance of dyadic intervention and the seriousness of the psycho-social problems of stroke survivors and caregivers, understanding the influence of dyadic psycho-social interventions is vital. DESIGN: A systematic review and meta-analysis based on PRISMA guidelines. DATA SOURCES: Nine databases were systematically searched for randomized controlled trials submitted from 1910 to 4 July 2022. METHODS: The included papers were evaluated for quality, and quantitative data were standardly extracted and analysed by meta-analysis, followed by synthesis. The meta-analysis was carried out using Review Manager 5.4 software. RESULTS: Fifteen randomized controlled trials were included (n = 2190 for patients, and n = 1933 for caregivers). Study results showed that dyadic psycho-social interventions significantly alleviated the depressive symptoms of patients, obviously improved the ability to function independently of patients and more quickly alleviated the care burden of caregivers. CONCLUSIONS: This study provided moderate support for the benefits of dyadic psycho-social intervention in improving survivor and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and care burden. Nevertheless, due to limitations of the study, it was deemed necessary that this topic is studied further. RELEVANCE TO CLINICAL PRACTICE: This review suggests that dyadic psycho-social interventions should be considered as effective strategies for decreasing psycho-social problems of stroke survivors and caregivers, and provides evidence for the formulation of targeted intervention programs. The personalized implementation of such interventions should be the focus of clinical practice. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.
Subject(s)
Quality of Life , Stroke , Humans , Caregivers , Randomized Controlled Trials as Topic , Stroke/therapy , Survivors , Social WorkABSTRACT
Objective: To investigate the correlation between the alteration of intestinal microbiota and disease in children with bronchiolitis. Methods: Fifty seven children diagnosed with bronchiolitis from January 2020 to January 2022 in our pediatric department were included as the case group, and another 36 normal children were included as the control group. Stool and blood were collected from both groups for high-throughput sequencing, untargeted metabolite detection and ELISA. A mouse model of RSV infection was established to validate the results of clinical case detection. Results: Body weight, passive smoking, and a host of other factors were possible as acute bronchiolitis influencing factors in the onset of acute bronchiolitis. The alpha diversity Shannon, Simpson and Pielou's evenness indices were significantly lower in children with acute bronchiolitis than in healthy children with gated levels of Firmicutes, Bacteroidetes and genus levels of Clostridium and other short chain fatty acid-producing bacteria. The relative abundance of short-chain fatty acid (SCFAs)-producing bacteria decreased and the abundance of genus-level sphingolipid-producing bacteria Sphingomonas increased; the progression of acute bronchiolitis is likely to be associated with the abundance of Clostridium and Sphingomonas and higher fecal amino acid concentrations, including FF-MAS, L-aspartic acid, thioinosinic acid, picolinic acid; supplementation with Clostridium butyricum significantly alleviated RSV infection-induced lung inflammation. Conclusion: The progression of bronchiolitis may be associated with altered intestinal microbiota, decreased SCFAs and elevated sphingolipids metabolism in children. Some fecal bacteria and metabolites may predict the onset of bronchiolitis, and oral administration of Clostridium butyricum may alleviate RSV infection-induced pulmonary inflammation.
ABSTRACT
The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.
Subject(s)
DNA-Binding Proteins , Ovarian Neoplasms , Humans , Animals , Mice , Female , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Apoptosis , Cell Line, Tumor , Ovarian Neoplasms/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic/genetics , Cell Proliferation/genetics , RNA-Binding Proteins/genetics , TEA Domain Transcription FactorsABSTRACT
This study investigated the growth, SPAD value, chlorophyll fluorescence and transcriptome response of endophyte uninoculated and inoculated rice seedlings under Pb stress after treatment of 1 d and 5 d. Inoculation of endophytes significantly improved the plant height, SPAD value, Fv/F0, Fv/Fm and PIABS by 1.29, 1.73, 0.16, 1.25 and 1.90 times on the 1 d, by 1.07, 2.45, 0.11, 1.59 and 7.90 times on the 5 d, respectively, however, decreased the root length by 1.11 and 1.65 times on the 1 d and 5 d, respectively under Pb stress. Analysis of rice seedlings leaves by RNA-seq, there were 574 down-regulated and 918 up-regulated genes after treatment of 1 d, 205 down-regulated and 127 up-regulated genes after treatment of 5 d, of which 20 genes (11 up-regulated and 9 down-regulated) exhibited the same changing pattern after treatment of 1 d and 5 d. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to annotate these DEGs, and it was found that many of DEGs involved in photosynthesis, oxidative detoxification, hormone synthesis and signal transduction, protein phosphorylation/kinase and transcription factors. These findings provide new insights into the molecular mechanism of interaction between endophyte and plants under heavy metal stress, and contribute to agricultural production in limited environments.
Subject(s)
Oryza , Transcriptome , Seedlings/genetics , Seedlings/metabolism , Endophytes/genetics , Endophytes/metabolism , Gene Expression Profiling , Oryza/metabolism , Lead/toxicity , Lead/metabolism , Gene Expression Regulation, PlantABSTRACT
Two unusual polyketide-sesquiterpene metabolites, craterodoratins T (1) and U (2), along with the known compound craterellin A (3), were isolated from the higher fungus Craterellus odoratus. The structures of isolated compounds were characterized based on nuclear magnetic resonance (NMR) and mass spectrum (MS) spectroscopic analysis, while the absolute configuration of the compounds was determined by theoretical NMR and electronic circular dichroism (ECD) calculations. Compound 1 possessed a rare structure with two aromatic groups. Compounds 1 and 3 showed immunosuppressive activity with IC50 values ranging from 5.516 to 19.953 µM.
Subject(s)
Basidiomycota , Molecular Structure , Basidiomycota/chemistry , Fungi , Magnetic Resonance Spectroscopy/methods , Circular Dichroism , Immunosuppressive AgentsABSTRACT
BACKGROUND: There are controversies surrounding the effects of lung function decline on cognitive impairment and dementia. OBJECTIVE: We conducted a meta-analysis and systematic review to explore the associations of lung function decline with the risks of cognitive impairment and dementia. METHODS: The PubMed, EMBASE, and the Cochrane Library were searched to identify prospective studies published from database inception through January 10, 2023. We pooled relative risk (RR) and 95% confidence intervals (CI) using random-effects models. The Egger test, funnel plots, meta-regression, sensitivity, and subgroup analyses were conducted to detect publication bias and investigate the source of heterogeneity. RESULTS: Thirty-three articles with a total of 8,816,992 participants were subjected to meta-analysis. Poorer pulmonary function was associated with an increased risk of dementia (FEV: RRâ=â1.25 [95% CI, 1.17-1.33]; FVC: RRâ=â1.40 [95% CI, 1.16-1.69]; PEF: RRâ=â1.84 [95% CI, 1.37-2.46]). The results of the subgroup analyses were similar to the primary results. Individuals with lung diseases had a higher combined risk of dementia and cognitive impairment (RRâ=â1.39 [95% CI, 1.20-1.61]). Lung disease conferred an elevated risk of cognitive impairment (RRâ=â1.37 [95% CI, 1.14-1.65]). The relationship between lung disease and an increased risk of dementia was only shown in total study participants (RRâ=â1.32 [95% CI, 1.11-1.57]), but not in the participants with Alzheimer's disease (RRâ=â1.39 [95% CI, 1.00-1.93]) or vascular dementia (RRâ=â2.11 [95% CI, 0.57-7.83]). CONCLUSION: Lung function decline was significantly associated with higher risks of cognitive impairment and dementia. These findings might provide implications for the prevention of cognitive disorders and the promotion of brain health.