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1.
Cell Signal ; 119: 111165, 2024 Jul.
Article En | MEDLINE | ID: mdl-38583746

Emerging evidence suggests that long non-coding RNAs (lncRNAs) play significant roles in renal ischemia reperfusion (RIR) injury. However, the specific mechanisms by which lncRNAs regulate ferroptosis in renal tubular epithelial cells remain largely unknown. The objective of this study was to investigate the biological function of lncRNA heme oxygenase 1 (lnc-HMOX1) in RIR and its potential molecular mechanism. Our findings demonstrated that the expression of HMOX1-related lnc-HMOX1 was reduced in renal tubular epithelial cells treated with hypoxia-reoxygenation (HR). Furthermore, the over-expression of lnc-HMOX1 mitigated ferroptotic injury in renal tubular epithelial cells in vivo and in vitro. Mechanistically, lnc-HMOX1, as a competitive endogenous RNA (ceRNA), promoted the expression of HMOX1 by sponging miR-3587. Furthermore, the inhibition of HMOX1 effectively impeded the aforementioned effects exerted by lnc-HMOX1. Ultimately, the inhibitory or mimic action of miR-3587 reversed the promoting or refraining influence of silenced or over-expressed lnc-HMOX1 on ferroptotic injury during HR. In summary, our findings contribute to a comprehensive comprehension of the mechanism underlying ferroptotic injury mediated by lnc-HMOX1 during RIR. Significantly, we identified a novel lnc-HMOX1-miR-3587-HMOX1 axis, which holds promise as a potential therapeutic target for RIR injury.


Ferroptosis , Heme Oxygenase-1 , MicroRNAs , RNA, Long Noncoding , Reperfusion Injury , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/genetics , Reperfusion Injury/pathology , MicroRNAs/metabolism , MicroRNAs/genetics , Animals , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Ferroptosis/genetics , Mice , Male , Humans , Mice, Inbred C57BL , Kidney/pathology , Kidney/metabolism
2.
Aust Crit Care ; 37(2): 369-379, 2024 Mar.
Article En | MEDLINE | ID: mdl-37734999

OBJECTIVE: The objective of this study was to evaluate the clinical efficacy of early and delayed renal replacement therapy (RRT) in patients with sepsis-associated acute kidney injury (AKI). METHODS: We searched three databases (PubMed, Web of Science, and Cochrane) for randomised controlled trials and cohort studies published up to March 28, 2022, and manually searched for relevant references. We included data from adults older than 18 years of age with sepsis-associated AKI. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool were used for quality assessment. The primary outcome was 28-day mortality. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were used for meta-analysis. RESULTS: There were a total of 3648 patients from four randomised controlled trials and eight cohort studies. The pooled results indicated that compared to delayed RRT, early RRT had a lower 28-day mortality (RR: 0.72; 95% CI: 0.59-0.88; P = 0.001; I2 = 76%), and this result was robust according to sensitivity analysis, and no significant difference in 90-day mortality (RR: 0.80; 95% CI: 0.64-1.00; P = 0.05; I2 = 82%),180-day mortality (RR: 1.07; 95% CI: 0.93-1.23; P = 0.36; I2 = 0%), length of intensive care unit stay (MD - 0.94; 95% CI -2.43-0.55; P = 0.22; I2 = 0%), length of hospital stay (MD - 1.02; 95% CI -4.21-2.17; P = 0.53; I2 = 0%), and RRT dependence was found among survivors at 28 days (RR: 1.21; 95% CI: 0.73-2.00; P = 0.47; I2 = 0%). Subgroup analysis of 28-day mortality showed that patients with sepsis-associated AKI who received early RRT at Kidney Disease: Improving Global Outcomes stage 2 or Sequential Organ Failure Assessment score ≤12 had a better chance of survival. CONCLUSIONS: Early RRT may be beneficial to the 28-day short-term survival rate of patients with sepsis-associated AKI in Kidney Disease: Improving Global Outcomes stage 2 and having Sequential Organ Failure Assessment score less than or equal to 12 but has no significant effect on long-term survival, length of intensive care unit stay, the total length of hospital stay, and 28-day RRT dependence of survivors. These results still need to be confirmed by more large-scale randomised controlled studies.


Acute Kidney Injury , Continuous Renal Replacement Therapy , Sepsis , Adult , Humans , Renal Replacement Therapy/adverse effects , Renal Replacement Therapy/methods , Treatment Outcome , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Sepsis/complications , Sepsis/therapy
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(12): 1262-1267, 2023 Dec.
Article Zh | MEDLINE | ID: mdl-38149387

OBJECTIVE: To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10-9 mmol), GLR2 group (4.97×10-9 mmol < GLR < 9.75×10-9 mmol) and GLR3 group (GLR ≥ 9.75×10-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI. RESULTS: A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%. CONCLUSIONS: GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.


Acute Kidney Injury , Sepsis , Male , Female , Humans , Blood Glucose , Glucose , ROC Curve , Prognosis , Sepsis/complications , Sepsis/diagnosis , Retrospective Studies , Intensive Care Units
4.
J Inflamm Res ; 16: 861-877, 2023.
Article En | MEDLINE | ID: mdl-36876152

Background: Uncontrolled inflammation is a typical feature of sepsis-related lung injury. The key event in the progression of lung injury is Caspase-1-dependent alveolar macrophage (AM) pyroptosis. Similarly, neutrophils are stimulated to release neutrophil extracellular traps (NETs) to participate in the innate immune response. This study aims to illustrate the specific mechanisms by which NETs activate AM at the post-translational level and maintain lung inflammation. Methods: We established a septic lung injury model by caecal ligation and puncture. We found elevated NETs and interleukin-1b (IL-1ß) levels in the lung tissues of septic mice. Western blot and immunofluorescence analyses was utilized to determine whether NETs promote AM pyroptosis and whether degrading NETs or targeting the NLRP3 inflammasome had protective effects on AM pyroptosis and lung injury. Flow cytometric and co-immunoprecipitation analyses verified intracellular reactive oxygen species (ROS) levels and the binding of NLRP3 and ubiquitin (UB) molecules, respectively. Results: Increased NETs production and IL-1ß release in septic mice were correlated with the degree of lung injury. NETs upregulated the level of NLRP3, followed by NLRP3 inflammasome assembly and caspase-1 activation, leading to AM pyroptosis executed by the activated fragment of full-length gasdermin D (FH-GSDMD). However, the opposite effect was observed in the context of NETs degradation. Furthermore, NETs markedly elicited an increase in ROS, which facilitated the activation of NLRP3 deubiquitination and the subsequent pyroptosis pathway in AM. Removal of ROS could promote the binding of NLRP3 and ubiquitin, inhibit NLRP3 binding to apoptosis-associated spotted proteins (ASC) and further alleviate the inflammatory changes in the lungs. Conclusion: In summary, these findings indicate that NETs prime ROS generation, which promotes NLRP3 inflammasome activation at the post-translational level to mediate AM pyroptosis and sustain lung injury in septic mice.

5.
Exp Ther Med ; 24(4): 622, 2022 Oct.
Article En | MEDLINE | ID: mdl-36160904

Oxygen-glucose deprivation (OGD) is widely used as an in vitro model for stroke. The present study aimed to explore the mechanisms of action of long non-coding RNA (lncRNA) maternally expressed gene 3 (Meg3) in angiogenesis following OGD. The human brain microvascular endothelial cell line, hCMEC/D3, was used to establish the OGD model. lncRNA Meg3 was highly expressed in hCMEC/D3 cells subjected to OGD. Furthermore, it was found that the overexpression of lncRNA Meg3 decreased the proliferation, migration and angiogenesis of hCMEC/D3 cells subjected to OGD, and increased cell apoptosis. Meg3 silencing exerted the opposite effects. Subsequently, lncRNA Meg3 increased the expression of NDRG family member 3 (NDRG3) by directly binding to miR-122-5p. The overexpression of miR-122-5p and the knockdown of NDRG3 reversed the inhibitory effects of Meg3 overexpression on the proliferation, migration and angiogenesis of hCMEC/D3 cells subjected to OGD, as well as the promoting effects of Meg3 overexpression on cell apoptosis. The present study demonstrated that lncRNA Meg3 functions as a competing endogenous RNA by targeting the miR-122-5p/NDRG3 axis in regulating OGD injury.

6.
J Immunol Res ; 2022: 1709360, 2022.
Article En | MEDLINE | ID: mdl-35846430

Vascular cognitive impairment (VCI) has emerged as the second major disease responsible for dementia, and there is still a lack of effective treatment methods for this disorder to date. Clinical medications have found that Yisui Fuyongtang (YSFYT) Decoction is effective in improving neurological signs and learning-memory functions in patients who develop white matter lesions and whole brain atrophy. To clarify the effect and molecular regulation mechanism of YSFYT Decoction on model rats, this research analyzed the influence of YSFYT Decoction on the learning-memory ability and lipid metabolism of rats based on behavioral and biochemical analysis. Further pathology and protein detection methods were adopted to investigate the action of YSFYT Decoction on the neurons in the hippocampus of model rats and the regulation of the brain derived neurotrophic factor (BDNF)-tyrosine protein kinase receptor B (TrkB) signaling pathway. Compared with the VCI group, after YSFYT Decoction administration, the ratio of swimming time in the platform, number of crossing the platform, number of active avoidance, and proportion of active avoidance of the rats were markedly increased, whereas the response latency was substantially reduced (p < 0.05). Biochemical tests indicated that contents of lipoprotein lipase (LPL), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of the model rats in YSFYT Decoction treatment group were greatly reduced, whereas those of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) were elevated (p < 0.05). Additionally, Bcl-2 expression in YSFYT Decoction treatment group was significantly increased, but neuron apoptosis of the hippocampus tissue was reduced. Meanwhile, neuron number was apparently higher than that in VCI model group. Following Yisui Decoction treatment, expressions of growth-associated protein 43 (GAP43), synaptophysin (SYP), postsynaptic density 95 (PSD95), NMDAR subunit 2B (NR2B), BDNF, TrkB, phospho-mitogen-activated protein kinase (p-MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B (p-AKT) were markedly elevated. Taken together, YSFYT Decoction could activate the BDNF-TrkB signaling pathway, elevate Bcl-2 expression, and minimize neuronal apoptosis in hippocampus, thereby improving the behavioral characteristics and biochemical indicators of the VCI rat model.


Brain-Derived Neurotrophic Factor , Cognitive Dysfunction , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cholesterol/metabolism , Cognition , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Hippocampus , Neuronal Plasticity/physiology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats
7.
Article En | MEDLINE | ID: mdl-35754679

This study clarified the regulatory effect of Yisui multipurpose Soup towards D-galactose-induced cognitive impairment cell model on the molecular level. We first constructed and cultured the cell model of cognitive impairment induced by D-galactose in neurons in vitro and then cultured the cells in the medium supplemented with different doses of drug-containing serum of Yisui multipurpose soup. Expressions of inflammatory cytokine tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), nitric oxide (NO), and interleukin-1ß (IL-1ß) were assessed by the ELISA and western blot, and cell apoptosis was determined by flow cytometry and TUNEL. The expression changes of apoptosis-related proteins Bcl-2 and Bax were estimated by immunofluorescence, qPCR, and western blot. Finally, we analyzed and made the network interaction diagram of Yisui multipurpose soup-components-targets through the network pharmacology method, from which we could learn that there were 1104 gene targets related to vascular cognitive impairment (VCI) and 1071 component targets of Yisui multipurpose soup. And there were 251 overlapping genes, mainly gathering in protein binding, protein modification, MAPK signaling pathway, and calcium signaling pathway. The expressions of TNF-α, iNOS, NO, and IL-1ß were significantly decreased after the culture medium was replaced by medium containing drug serum. We also found that the effect of high-dose drug-containing serum on the expression of inflammatory factors was better than that of low dose. The Yisui multipurpose soup drug serum in the medium not only significantly increased Bcl-2 expression and effectively reduced Bax expression, but also inhibited the apoptosis of neurons induced by D-galactose. In conclusion, Yisui multipurpose soup could effectively protect D-galactose-induced neuronal cell cognitive impairment by orchestrating expressions of the inflammatory factors TNF-α, iNOS, NO, and IL-1ß and the apoptosis-related proteins Bcl-2 and Bax.

8.
Int J Gen Med ; 15: 4837-4847, 2022.
Article En | MEDLINE | ID: mdl-35585999

Purpose: To investigate the correlation and prognostic significance of low triiodothyronine (T3) syndrome and norepinephrine dosage in patients with sepsis and septic shock. Methods: This single-center, retrospective, cohort study enrolled 169 patients with sepsis and septic shock that were admitted to the intensive care unit of First Hospital of Nanchang, Nanchang, China from June 2017 to July 2019. All included patients were followed up for 28 days or died, whichever was earlier. Patients with free T3 (FT3) of <3.1 pmol/L were considered with low T3 syndrome. The correlation and prognostic significance of the FT3 and maximum dosage of norepinephrine (MDN) within 72 h, as well as other clinical indicators, were analyzed by using correlation analysis, principal component analysis, receiver operating characteristic curve, Youden index, and logistic regression. Results: A total of 138 patients were allocated to the low T3 group. FT3 inversely correlated with the Sequential Organ Failure Assessment (SOFA) score within 24 h, fluid resuscitation volume within 24 h, and lactic acid levels, and positively correlated with the mean arterial pressure. The critical values of age, SOFA, and MDN for predicting the 28-day mortality were 79.5 years, 8.5 points, and 0.61 µg/kg/min, respectively. The mortality of the low T3 and normal T3 groups was similar. Considering the MDN of 0.61 µg/kg/min as the cutoff value, the mortality between the two groups was significantly different. Conclusion: Among patients with sepsis and septic shock, FT3 was inversely correlated with the disease severity. An MDN ≥ 0.61 µg/kg/min within 72 h may be an important prognostic indicator.

9.
Int J Exp Pathol ; 102(3): 157-162, 2021 06.
Article En | MEDLINE | ID: mdl-33993564

Xeroderma Pigmentosum group D (XPD) gene has been shown to suppress hepatocellular carcinoma (HCC) progression, but its mechanism remains not fully understood. ETS-related gene (ERG) is generally known as an oncogenic gene. This study aimed to explore whether XPD regulated HCC cell proliferation, apoptosis and cell cycle by inhibiting ERG expression via the PPARγ pathway. The human hepatoma cells (HepG2) were transfected with the XPD overexpression vector (pEGFP-N2/XPD) or empty vector (pEGFP-N2). The PPARγ inhibitor GW9662 was used to determine whether XPD effects were mediated by activation of PPARγ pathway. Cell cycle and apoptosis were ascertained by flow cytometry, and cell viability was measured by MTT assay. Reverse transcription-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels. Overexpression of XPD significantly enhanced the expression of PPARγ and p-PPARγ, whereas it downregulated that of ERG and cdk7. Furthermore, XPD overexpression notably inhibited proliferation, promoted apoptosis and decreased the percentage of cells in the S + G2 phase of HepG2 cells. However, these effects of XPD overexpression were abrogated by GW9662. Collectively, XPD suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via activation of the PPARγ pathway.


Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , PPAR gamma/metabolism , Xeroderma Pigmentosum Group D Protein/metabolism , Apoptosis/physiology , Carcinoma, Hepatocellular/metabolism , Cell Proliferation/physiology , Down-Regulation , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Signal Transduction/physiology , Transcriptional Regulator ERG/metabolism
10.
Paediatr Anaesth ; 31(7): 755-762, 2021 07.
Article En | MEDLINE | ID: mdl-33882623

BACKGROUND: Stroke volume variation appears to be reliable for predicting fluid responsiveness in adults, and its predictive value in pediatric patients has been recently reported. However, its predictive value in children undergoing cardiac surgery is unclear. METHODS: A review and meta-analysis were performed on the diagnostic utility of stroke volume variation for predicting fluid responsiveness in children undergoing cardiac surgery. All relevant articles for prospective research assessing the value of stroke volume variation were searched in the Embase, MEDLINE (PubMed), and Cochrane databases through March 2020. The primary outcome was the accuracy of stroke volume variation for predicting fluid responsiveness in children. The combined data were analyzed by a meta-analysis. Publication quality was assessed using the QUADAS (quality assessment for studies of diagnostic accuracy, maximum score) standard guidelines. RESULTS: Six articles were included in the meta-analysis, following the search strategy. A total of 251 children were included from 6 prospective studies. Fluid therapy for all patients used crystalloids or colloids. The results of the analysis revealed a pooled diagnostic odds ratio of 8.23 (95% CI: 3.07-22.11), pooled sensitivity of 0.73 (95% CI: 0.64-0.80), and pooled specificity of 0.66 (95% CI: 0.58-0.74). Additionally, the overall area of the summary receiver operating characteristic curve was 0.78. There was significant moderate heterogeneity in these studies (p < .05, I2  = 42.1%) due to thresholds. CONCLUSIONS: There was some heterogeneity due to thresholds in the included studies. An evaluation of stroke volume variation may represent a reliable predictor of fluid responsiveness in children undergoing cardiac surgery. After operative cardiac output optimization, the possible impact of goal-directed fluid treatment depending on stroke volume variation on the perioperative outcome in the children population should subsequently be assessed.


Cardiac Surgical Procedures , Fluid Therapy , Adult , Cardiac Output , Child , Crystalloid Solutions , Hemodynamics , Humans , Prospective Studies , Stroke Volume
11.
J Inflamm Res ; 14: 413-428, 2021.
Article En | MEDLINE | ID: mdl-33628043

PURPOSE: To explore the molecular mechanism and search for candidate lncRNA and mRNA associated with pyroptosis in the gene expression profile of LPS-induced acute lung injury (ALI). METHODS: We investigated lncRNA and mRNA expression in lipopolysaccharide (LPS)-induced ALI at an early stage. RNA sequencing (RNA-Seq) was carried out to analyze lncRNA and mRNA expression profiles between the LPS-induced and control groups. We used bioinformatics analysis to predict target genes of early differential lncRNAs among obtained the differential mRNAs. RESULTS: A total of 78 lncRNAs and 248 mRNAs were upregulated at 2 hours and downregulated at 9 hours, and 21 lncRNAs and 107 mRNAs were downregulated at 2 and upregulated at 9 hours in early ALI models. We predicted 7 cis-and trans-regulated target genes of the top 20 lncRNAs. Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS. Additionally, target genes of lncRNAs were the top three enriched in pertussis, osteoclast differentiation, and cAMP signaling pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also identified vital mRNAs and lncRNAs. Protein-protein interaction (PPI) network analysis suggested that Tnf, Jun, and Atf3 were the top three key genes. Hub lncRNA4344 (NONRATT004344.2) and cis-regulated target mRNA (NLRP3) were validated in vitro. Finally, luciferase assay results confirmed that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses to LPS-induced acute lung injury by targeting NLRP3. CONCLUSION: Based on analysis of lncRNA and mRNA expression profiles by RNA-Seq and experimental verification, this study is the first to reveal that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses of LPS-induced acute lung injury by targeting NLRP3. These newly identified lncRNA, miRNA, and mRNA might be novel potential targets for early treatment and prevention in early ALI.

12.
Mol Immunol ; 131: 191-200, 2021 03.
Article En | MEDLINE | ID: mdl-33446392

Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are involved in various pathophysiological processes of disease, such as cancer occurrence, viral invasion, and inflammatory damage. The main inflammatory body component, nod-like receptor protein 3 (NLRP3), is the trigger point of inflammatory reactions and inflammation-related diseases and coordinates the body's response to inflammation. At present, increasing evidence shows that the interaction of lncRNAs and the NLRP3 inflammasome plays an important role in the inflammatory response and different diseases. This may be involved in the development and progression of various diseases by activating signalling pathways and a variety of molecular regulatory mechanisms-this article reviews progress in research on the relationship between lncRNAs and the NLRP3 inflammasome under different conditions.


Inflammasomes/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , RNA, Long Noncoding/genetics , Animals , Humans , Inflammation/genetics , Signal Transduction/genetics
13.
Front Mol Biosci ; 8: 789927, 2021.
Article En | MEDLINE | ID: mdl-35047556

Renal ischemia-reperfusion (IR) is frequently observed in patients who are critically ill, yet there are no reliable or effective approaches for the treatment of this condition. Ferroptosis, a form of programmed cell death, is regulated by key genes such as glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) and participates in the injury of renal tubular epithelial cells during IR. This study aimed to investigate the miRNA-mRNA regulatory networks involved in ferroptosis following renal IR. Using bioinformatics analysis, HMOX1 was found to be significantly upregulated during the early stages of renal IR injury, and microRNA-3587 (miR-3587) was identified as a putative regulator of HMOX1. When a miR-3587 inhibitor was applied in a hypoxia-reoxygenation (HR) model system using renal tubular epithelial cells, HO-1 protein (encoded by HMOX1) expression was significantly increased relative to that observed in the HR group, with concomitant increases in GPX4 protein levels, enhanced cell viability, a reduction in malondialdehyde content, decreased Fe2+ level, and the restoration of normal mitochondrial membrane potential. Transmission electron microscopy showed a reduced or absent mitochondrial crest and a damaged mitochondrial outer membrane. Targeting of HMOX1 by miR-3587 was confirmed by luciferase reporter gene assay. In conclusion, these preliminary results indicate that inhibition of miR-3587 promotes HO-1 upregulation, thereby protecting renal tissues from IR-induced ferroptosis.

14.
Transl Cancer Res ; 10(5): 2044-2054, 2021 May.
Article En | MEDLINE | ID: mdl-35116526

BACKGROUND: With the advent of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) treatment has become considered the appropriate chemotherapy treatment for aggressive or advanced-stage indolent B-cell non-Hodgkins lymphoma (NHL). In recent years, RCHOP-14 seems to have achieved better outcomes in patients with aggressive or advanced-stage indolent B-cell NHL than RCHOP-21. METHODS: To verify the befitting chemotherapy regimens for patients with B-cell NHL, we searched the electronic databases for relevant English-language literature published in January 2020. The primary outcomes were complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Six eligible Phase II and III randomized controlled clinical trials (RCTs) and two high-quality observational comparative studies (OCSs) were extracted, with 5,565 patients with B-cell NHL involved in the evaluation. RESULTS: The analysis demonstrated no significant difference in RCHOP-14 and RCHOP-21 CR rates [odds ratio (OR) =0.98, 95% CI: 0.77-1.24, P=0.85]. Compared with RCHOP-21, the merged hazard ratio (HR) after treatment with RCHOP-14 for PFS and OS was 0.94 (95% CI: 0.84-1.06, P=0.32) and 0.91 (95% CI: 0.83-1.01, P=0.08), respectively. A subgroup analysis based on the international prognostic index (IPI) score showed that both chemotherapy regimens were applicable in B-cell NHL patients with different prognoses. The frequency of toxic side-effects was similar between schemes. CONCLUSIONS: The data presented suggest that the efficacy and safety of both regimens are comparable and that RCHOP-14 remains a viable plan in patients with B-cell NHL who prefer a shorter therapy course.

15.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6558-6567, 2021 Dec.
Article Zh | MEDLINE | ID: mdl-34994149

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.


Drugs, Chinese Herbal , Medicine, East Asian Traditional , Tension-Type Headache , Asian People , Female , Humans , Medicine, Chinese Traditional , Nonprescription Drugs , Pregnancy
16.
Aging (Albany NY) ; 12(11): 10059-10069, 2020 06 01.
Article En | MEDLINE | ID: mdl-32484453

AIM: To evaluate the clinical value of abnormal laboratory results of multiple organs in patients with coronavirus disease 2019 (COVID-2019) and to help clinicians perform correct treatment. RESULTS: Elevated neutrophil-to-LYM ratio (NLR), D-dimer(D-D), interleukin (IL)-6, IL-10, IL-2, interferon-Y, and age were significantly associated with the severity of illness. However, significant and sustained decreases were observed in the LYM subset (p<0.05). D-D, T cell counts, and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of mild cases. Second, D-D increased from 0.5 to 8, and the risk ratio increased from 2.75 to 55, eventually leading to disseminated intravascular coagulation. Moreover, the acute renal function damage occurred earlier than abnormal heart and liver functions (p<0.05). CONCLUSIONS: The degrees of lymphopenia and proinflammatory cytokine storm were higher in severe COVID-19 patients than in mild cases. The degree was associated with the disease severity. Advanced age, NLR, D-D, and cytokine levels may serve as useful prognostic factors for the early identification of severe COVID-19 cases. METHODS: Peripheral blood samples were collected from 93 confirmed COVID-19 patients. The samples were examined for lymphocyte (LYM) subsets by flow cytometry and cytokine profiles by specific immunoassays. The receiver operating characteristic curve was applied to determine the best diagnostic thresholds for laboratory results, and principal component analysis was used to screen the major risk factors. The prognostic values were assessed using the Kaplan-Meier curve and univariate and multivariate COX regression models.


Betacoronavirus/physiology , Coronavirus Infections/blood , Cytokines/blood , Host-Pathogen Interactions , Pneumonia, Viral/blood , Adult , Aged , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Prognosis , Retrospective Studies , SARS-CoV-2
17.
Int Immunopharmacol ; 84: 106504, 2020 Jul.
Article En | MEDLINE | ID: mdl-32304994

AIM: To accumulate evidence that indicated the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China. METHODS: Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte (MON) ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan-Meier curve and multivariate COX regression models. RESULTS: The median age was 46.4 years old, and 37cases were females. A total of 27.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk [HR] 2.46, 95% confidence interval [CI] 1.98-4.57) and age (HR 2.52, 95% CI 1.65-4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%). CONCLUSIONS: Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.


Betacoronavirus , Blood Platelets/physiology , Coronavirus Infections/diagnosis , Lymphocytes/physiology , Monocytes/physiology , Neutrophils/physiology , Pneumonia, Viral/diagnosis , Adult , C-Reactive Protein/analysis , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Epidemics , Female , Humans , Lymphocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Prognosis , ROC Curve , SARS-CoV-2
18.
Zhongguo Zhen Jiu ; 34(5): 426-30, 2014 May.
Article Zh | MEDLINE | ID: mdl-25022108

OBJECTIVE: To explore the therapeutic effect of acupuncture for hypertensive cerebral hemorrhage at the early stage. METHODS: Fifty-four cases of small-amount cerebral hemorrhage were randomized into an acupuncture group and a conventional treatment group, 27 cases in each one. In the conventional treatment group, special care, oxygen therapy, nerve nutrition and symptomatic support were applied. In necessary, dehydrant and hypotensive drugs were prescribed for antihypertension, or surgery was given. In the acupuncture group, on the basis of the treatment as the control group, acupuncture was applied at Quchi (LI 11), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). Acupuncture was given at the admission, 4 h, 6 h and 12 h after disease onset respectively. Blood pressure was monitored in the whole procedure. 6 h and 24 h after disease onset, the cranial CT was re-examined. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), hematoma volume and neurological deficit score were compared at different time points between the two groups. RESULTS: (1) Blood pressure: from the admission to 12 h after disease onset, SBP, DBP and MAP were increased apparently in the conventional treatment group and increased slightly in the acupuncture group. The differences in SBP [(164.3 +/- 21.6) mmHg vs (158.6 +/- 21.5) mmHg] and MAP [(113.4 +/- 4.9) mmHg vs (106.7 +/- 6.1) mmHg] were significant between the two groups (both P < 0.05). From 12 h to 24 h after disease onset, compared with the conventional treatment group, SBP and MAP were decreased apparently in the acupuncture group [(147.3 +/- 21.6) mmHg vs (158.4 +/- 23.5) mmHg, (97.2 +/- 5.3) mmHg vs (106.6 +/- 5.1) mmHg, both P < 0.05)]. (2) Hematoma volume: from the admission to 6 h after disease onset, the volume was increased by (4.15 +/- 0.73) mL in the convertional treatment group and (2.67 +/- 0.33) mL in the acupuncture group, indicating the significant difference in comparison (P < 0.05). From the admission to 24 h after disease onset, it was increased by (5.57 +/- 1.26) mL in the convertional treatment group and (3.14 +/- 1.18) mL in the acupuncture group, indicating the significant difference in comparison (P < 0.05). (3) Neurological deficit score: the score was increasing gradually in first 3 days after disease onset in the two groups. The score (38.39 +/- 6.84) in the acupuncture group on the first day was different significantly as compared with that (42.37 +/- 7.46) in the conventional treatment group (P < 0.05). On the 10th days, the score (24.68 +/- 5.42) in the acupuncture group was different significantly from that (29.74 +/- 7.36) in the convertional treatment group (P < 0.05). CONCLUSION: There is no peak of blood pressure rising, and the continuous hemorrhagic volume is less in 24 h and neurological deficit score is improved in the acupuncture group. Acupuncture brings the positive significance in the treatment of cerebral hemorrhage at the early stage.


Acupuncture Therapy , Blood Pressure , Cerebral Hemorrhage/therapy , Hematoma/therapy , Adult , Aged , Cerebral Hemorrhage/physiopathology , Female , Hematoma/physiopathology , Humans , Male , Middle Aged
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(1): 121-4, 2011 Jan.
Article Zh | MEDLINE | ID: mdl-21269973

OBJECTIVE: To investigate the three-dimensional reconstruction methods of the portal vein using 64-slice spiral CT data and the anatomical variation of the portal vein. METHODS: Three-dimensional reconstruction of the portal vein was performed using Mimics software based on the 64-slice spiral CT data of 64 cases. Each model of the portal vein and its branches was evaluated according to the presentation rate, depiction quality and anatomic variation. RESULTS: The reconstructed model showed a depiction rates of 100% for the 4-grade branches of the portal vein. The stem of the portal vein and the left and right branches of the level III or above were all displayed, but in 2 cases the superior mesenteric vein and in 1 case the spleen vein was displayed only to the level IV. Of the 64 cases, 50 (78.1%) had normal portal vein and 14 (21.9%) showed anatomical variations. CONCLUSION: The 3D model vividly mimics the anatomic variations of the portal vein to provide valuable information for surgical plans.


Imaging, Three-Dimensional/methods , Portal Vein/anatomy & histology , Portal Vein/diagnostic imaging , Tomography, Spiral Computed/methods , Adult , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Young Adult
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