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1.
Acta Pharmacol Sin ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702500

ABSTRACT

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

2.
Article in English | MEDLINE | ID: mdl-38104474

ABSTRACT

Mercury (Hg), a heavy metal pollutant worldwide, can be transformed into methylmercury (MeHg) by various aquatic microorganisms in water, thus accumulating along the aquatic food chain and posing a particular challenge to human health. Zooplankton plays a crucial role in aquatic ecosystems and serves as a major component of the food chain. To evaluate the effects of MeHg on the rotifer Brachionus plicatilis and reveal the underlying mechanism of these effects, we exposed B. plicatilis to MeHg by either direct immersion or by feeding with MeHg-poisoned Chlorella pyrenoidesa, respectively, and conducted a transcriptomic analysis. The results showed that B. plicatilis directly exposed to MeHg by immersion showed significant enrichment of the glutathione metabolism pathway for detoxification of MeHg. In addition, the exposure to MeHg by feeding induced a significant enrichment of lysosome and notch signaling pathways of rotifers, supporting the hypothesis that MeHg can induce autophagy dysfunction in cells and disturb the nervous system of rotifers. In two different routes of MeHg exposure, the pathway of cytochrome P450 in rotifers showed significant enrichment for resisting MeHg toxicity. Our results suggest further studies on the potential mechanism and biological responses of MeHg toxicity in other links of the aquatic food chain.


Subject(s)
Chlorella , Methylmercury Compounds , Rotifera , Water Pollutants, Chemical , Humans , Animals , Methylmercury Compounds/toxicity , Methylmercury Compounds/metabolism , Transcriptome , Ecosystem , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism
3.
Int J Gen Med ; 16: 4537-4548, 2023.
Article in English | MEDLINE | ID: mdl-37818108

ABSTRACT

Objective: The incidence of cardiogenic shock cases treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been on the rise. Acute kidney injury (AKI) is a significant complication of cardiogenic shock and a frequent serious complication in patients requiring ECMO-supported therapy. AKI is strongly associated with unfavorable patient prognosis. However, there is a paucity of data on the influence of AKI on the prognosis of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who are receiving ECMO support, particularly with regard to long-term outcomes. Methods: This retrospective observational study included 103 patients in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2017 and June 2022. AKI was defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Cox regression and logistic regression were used to identify risk factors. Results: In this study, the incidence of AKI was 63.11%, with AKI stage 1, 2, and 3 accounting for 21.36%, 12.62%, and 29.13%, respectively. Patients with severe AKI had significantly higher in-hospital mortality (43.33% vs 27.40%, P < 0.001), 30-day mortality (60.00% vs 31.51%, P = 0.001), and 1-year mortality (63.67% vs 34.25%, P<0.001) than those without severe AKI. Furthermore, severe AKI significantly increased the risk of one-year mortality (HR 10.816, CI 3.118-37.512, P<0.001). Baseline serum creatinine, baseline platelet, and active cardiopulmonary resuscitation were independent predictors of one-year mortality. In addition, baseline white blood cell count, baseline aspartate aminotransferase, baseline alanine aminotransferase (ALT), baseline serum creatinine, preoperative lactate, and postoperative mean arterial pressure were independent risk factors of severe AKI during hospitalization. Conclusion: In patients with AMI-CS receiving ECMO support, AKI is highly prevalent. Development of severe AKI significantly increased the risk of one-year mortality.

4.
Sci Total Environ ; 905: 167063, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37709075

ABSTRACT

Methylmercury (MeHg) readily accumulates in aquatic organisms while transferring and amplifying in the aquatic food chains. This study firstly explores the in vivo accumulation sites and metabolic regulation of MeHg in the rotifer Brachionus plicatilis by aggregation-induced emission fluorogen (AIEgen) and metabolomics. Fluorescent image analysis by AIEgen showed that MeHg in B. plicatilis mainly occured in the ciliary corona, esophagus, mastax, stomach and intestine in the direct absorption group. In the other group, where B. plicatilis were indirectly supplied with MeHg via food intake, the accumulation of MeHg in the rotifer occurred in the ciliary corona, various digestive organs, and the pedal gland. However, the MeHg accumulated in the rotifer is difficult to metabolize outside the body. Metabolomics analysis showed that the significant enrichment of ABC transporters was induced by the direct exposure of rotifers to dissolved MeHg. In contrast, exposure of rotifers to MeHg via food intake appeared to influence carbon, galactose, alanine, aspartate and glutamate metabolisms. Besides, the disturbed biological pathways such as histidine metabolism, beta-alanine metabolism and pantothenate and CoA biosynthesis in rotifers may be associated with L-aspartic acid upregulation in the feeding group. The significant enrichment of ABC transporters and carbon metabolism in rotifers may be related to the accumulation of MeHg in the intestine of rotifers. In both pathways of MeHg exposure, the arginine biosynthesis and metabolism of rotifers were disturbed, which may support the hypothesis that rotifers produce more energy to resist MeHg toxicity. This study provides new insight into the accumulation and toxicity mechanisms of MeHg on marine invertebrates from the macro and micro perspectives.


Subject(s)
Methylmercury Compounds , Rotifera , Animals , Methylmercury Compounds/metabolism , Rotifera/physiology , Metabolic Networks and Pathways , ATP-Binding Cassette Transporters/metabolism , Carbon/metabolism
5.
Stem Cells Int ; 2023: 8282961, 2023.
Article in English | MEDLINE | ID: mdl-37197688

ABSTRACT

Chronic refractory wounds (CRW) are one of the most serious clinical challenges for surgeons to address. Stromal vascular fraction gels (SVFG), including human adipose stem cells (hASCs), have excellent vascular regenerative and tissue repair properties. Here, we combined single-cell RNA sequencing (scRNA-seq) of leg subcutaneous adipose tissue samples with scRNA-seq data from abdominal subcutaneous adipose tissue, leg subcutaneous adipose tissue, and visceral adipose tissue samples from public databases. The results showed specific differences in cellular levels in adipose tissue from different anatomical site sources. We identified cells including CD4+ T cells, hASCs, adipocyte (APC), epithelial (Ep) cells, and preadipocyte. In particular, the dynamics between groups of hASCs, epithelial cells, APCs, and precursor cells in adipose tissue of different anatomical site origins were more significant. Furthermore, our analysis reveals alterations at the cellular level and molecular level, as well as the biological signaling pathways involved in these subpopulations of cells with specific alterations. In particular, certain subpopulations of hASCs have higher cell stemness, which may be related to lipogenic differentiation capacity and may be beneficial in promoting CRW treatment and healing. In general, our study captures a human single-cell transcriptome profile across adipose depots, the cell type identification and analysis of which may help dissect the function and role of cells with specific alterations present in adipose tissue and may provide new ideas and approaches for the treatment of CRW in the clinical setting.

6.
PeerJ ; 11: e14954, 2023.
Article in English | MEDLINE | ID: mdl-37009154

ABSTRACT

Emerging evidence indicates that N6-methyladenosine (m6A) plays a critical role in vascular biological characteristic. In diabetes mellitus pathophysiology, high glucose (HG)-induced vascular endothelial dysfunction is associated with diabetes vascular complications. Nevertheless, the underlying mechanism of high glucose (HG)-related m6A regulation on vascular endothelial cells is still unclear. Results indicated that m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was up-regulated in HG-treated human umbilical vascular endothelium cells (HUVECs) comparing to normal group. Functionally, results indicated that IGF2BP1 knockdown recovered the proliferation of HUVECs inhibited by HG-administration. Besides, IGF2BP1 knockdown reduced the apoptosis induced by HG-administration. Mechanistically, IGF2BP1 interacted with HMGB1 mRNA and stabilized its expression of m6A-modified RNA. Therefore, these findings provided compelling evidence demonstrating that m6A reader IGF2BP1 contributes to the proliferation and apoptosis of vascular endothelial cells in hyperglycaemia, serving as a target for development of diabetic angiopathy therapeutics.


Subject(s)
Diabetic Angiopathies , HMGB1 Protein , Humans , Human Umbilical Vein Endothelial Cells , Glucose/pharmacology , HMGB1 Protein/metabolism , Apoptosis/genetics , Diabetic Angiopathies/metabolism , RNA, Messenger/genetics
7.
Sensors (Basel) ; 22(16)2022 Aug 13.
Article in English | MEDLINE | ID: mdl-36015825

ABSTRACT

Mildew of maize seeds may affect their germination rates and reduce crop quality. It is crucial to classify maize seeds efficiently and without destroying their original structure. This study aimed to establish hyperspectral datasets using hyperspectral imaging (HSI) of maize seeds with different degrees of mildew and then classify them using spectral characteristics and machine learning algorithms. Initially, the images were processed with Otus and morphological operations. Each seed's spectral features were extracted based on its coding, its edge, region of interest (ROI), and original pixel coding. Random forest (RF) models were optimized using the sparrow search algorithm (SSA), which is incapable of escaping the local optimum; hence, it was optimized using a modified reverse sparrow search algorithm (JYSSA) strategy. This reverse strategy selects the top 10% as the elite group, allowing us to escape from local optima while simultaneously expanding the range of the sparrow search algorithm's optimal solution. Finally, the JYSSA-RF algorithm was applied to the validation set, with 96% classification accuracy, 100% precision, and a 93% recall rate. This study provides novel ideas for future nondestructive detection of seeds and moldy seed selection by combining hyperspectral imaging and JYSSA algorithms based on optimized RF.


Subject(s)
Hyperspectral Imaging , Zea mays , Algorithms , Fungi , Machine Learning , Seeds/chemistry , Support Vector Machine , Zea mays/chemistry
8.
Ultrastruct Pathol ; 46(4): 303-312, 2022 Jul 04.
Article in English | MEDLINE | ID: mdl-35686365

ABSTRACT

Macrophages serve an active role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been verified as an effective treatment for COPD. However, there are few studies on the effect of EM on the ultrastructure of macrophages exposed to cigarette smoke extract (CSE). In the present study, human macrophages were randomly divided into three groups: The control, CSE and the CSE+EM group, using electron microscopy, the effect of EM was evaluated by comparing the ultrastructural changes between these groups. The macrophages were additionally divided into a further four groups: The control, CSE, CSE+EM 24 h and CSE+EM 48 h groups. The generation of reactive oxygen species (ROS) in each group was evaluated by detecting fluorescence intensity. It was observed that the cellular ultrastructure of the CSE group exhibited abnormal changes, though this effect was reversed back to the level of the control in the CSE+EM group. Compared with the control group, the ROS expression level was significantly increased in the CSE group (P < .05); however, compared with the CSE group, the ROS concentration was decreased in the CSE+EM 24 h (P < .05) and CSE+EM 48 h groups (P < .05), though this was more apparent in the EM 48 h group. It was concluded that EM protects human macrophages against CSE. Moreover, it was hypothesized that EM may reduce the symptoms of patients with COPD by protecting the macrophage ultrastructure from the effects of CSE, resulting in the decreased generation of ROS, inhibiting autophagy and reducing endoplasmic reticulum stress.


Subject(s)
Cigarette Smoking , Pulmonary Disease, Chronic Obstructive , Cigarette Smoking/adverse effects , Erythromycin/metabolism , Erythromycin/pharmacology , Humans , Macrophages/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/pharmacology , Nicotiana/metabolism
9.
Sensors (Basel) ; 20(23)2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33297289

ABSTRACT

During the processing and planting of soybeans, it is greatly significant that a reliable, rapid, and accurate technique is used to detect soybean varieties. Traditional chemical analysis methods of soybean variety sampling (e.g., mass spectrometry and high-performance liquid chromatography) are destructive and time-consuming. In this paper, a robust and accurate method for nondestructive soybean classification is developed through hyperspectral imaging and ensemble machine learning algorithms. Image acquisition, preprocessing, and feature selection are used to obtain different types of soybean hyperspectral features. Based on these features, one of ensemble classifiers-random subspace linear discriminant (RSLD) algorithm is used to classify soybean seeds. Compared with the linear discrimination (LD) and linear support vector machine (LSVM) methods, the results show that the RSLD algorithm in this paper is more stable and reliable. In classifying soybeans in 10, 15, 20, and 25 categories, the RSLD method achieves the highest classification accuracy. When 155 features are used to classify 15 types of soybeans, the classification accuracy of the RSLD method reaches 99.2%, while the classification accuracies of the LD and LSVM methods are only 98.6% and 69.7%, respectively. Therefore, the ensemble classification algorithm RSLD can maintain high classification accuracy when different types and different classification features are used.


Subject(s)
Glycine max , Hyperspectral Imaging , Machine Learning , Algorithms , Seeds , Support Vector Machine
10.
Rice (N Y) ; 13(1): 54, 2020 Aug 06.
Article in English | MEDLINE | ID: mdl-32761436

ABSTRACT

BACKGROUND: The chloroplast signal recognition particle 54 (cpSRP54) is known for targeting the light-harvesting complex proteins to thylakoids and plays a critical role for chloroplast development in Arabidopsis, but little is known in rice. Here, we reported two homologous cpSRP54s that affect chloroplast development and plant survival in rice. RESULTS: Two rice cpSRP54 homologues, OscpSRP54a and OscpSRP54b, were identified in present study. The defective OscpSRP54a (LOC_Os11g05552) was responsible for the pale green leaf phenotype of the viable pale green leaf 14 (pgl14) mutant. A single nucleotide substitution from G to A at the position 278, the first intron splicing site, was detected in LOC_Os11g05552 in pgl14. The wild type allele could rescue the mutant phenotype. Knockout lines of OscpSRP54b (LOC_Os11g05556) exhibited similar pale green phenotype to pgl14 with reduced chlorophyll contents and impaired chloroplast development, but showed apparently arrested-growth and died within 3 weeks. Both OscpSRP54a and OscpSRP54b were constitutively expressed mainly in shoots and leaves at the vegetative growth stage. Subcellular location indicated that both OscpSRP54a and OscpSRP54b were chloroplast-localized. Both OscpSRP54a and OscpSRP54b were able to interact with OscpSRP43, respectively. The transcript level of OscpSRP43 was significantly reduced while the transcript level of OscpSRP54b was apparently increased in pgl14. In contrast, the transcript levels of OscpSRP54a, OscpSRP43 and OscpSRP54b were all significantly decreased in OscpSRP54b knockout lines. CONCLUSION: Our study demonstrated that both OscpSRP54a and OscpSRP54b were essential for normal chloroplast development by interacting with OscpSRP43 in rice. OscpSRP54a and OscpSRP54b might play distinct roles in transporting different chloroplast proteins into thylakoids through cpSRP-mediated pathway.

11.
Inflammopharmacology ; 28(2): 463-473, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31562605

ABSTRACT

Ferulic acid (FA), a hydroxycinnamic acid, is an organic compound found in several plant species. Previous studies have shown that FA contains anti-inflammatory and anti-arthritic properties. This study aimed to investigate the anti-arthritic activity and possible mechanism(s) of action of FA in complete Freund's adjuvant (CFA)-induced arthritis. The progression of rheumatoid arthritis (RA) involves the activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway by proinflammatory cytokines. Molecular docking of FA showed promising Janus kinase 2 (JAK2) inhibition with a docking score of - 6.7, which is comparable with that of ruxolitinib, a standard inhibitor. However, in vitro JAK2 inhibition assay showed a half maximal inhibitory concentration (IC50) of 6.67 ± 0.88 µg/ml. Both doses of FA (25 and 50 mg/kg) significantly attenuated primary (volume of paw edema) and secondary lesions. CFA-induced arthritic rats showed a significant decrease in body weight, A/G ratio, and Hb but showed a greater arthritic index, ESR levels, and percentage of lymphocytes. These alterations were significantly reduced in rats treated with FA and prednisolone. FA also reversed changes to biochemical parameters and inflammatory markers, such as C-reactive protein (CRP) and rhematoid factor (RF). Additionally, we found CFA-induced arthritis triggered the secretion of TNF- α, increased JAK2 levels, and reduced TGF-ß levels in tissue homogenates. However, in rats treated with FA, such alterations significantly improved. Thus, our results reveal that FA contains anti-arthritic activity, which is possibly mediated by the inhibition of the JAK/STAT pathway.


Subject(s)
Antirheumatic Agents/pharmacology , Arthritis, Experimental/drug therapy , Coumaric Acids/pharmacology , Janus Kinase Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Antirheumatic Agents/administration & dosage , Arthritis, Experimental/physiopathology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/physiopathology , Coumaric Acids/administration & dosage , Cytokines/metabolism , Dose-Response Relationship, Drug , Female , Freund's Adjuvant , Janus Kinase 2/antagonists & inhibitors , Janus Kinase Inhibitors/administration & dosage , Male , Molecular Docking Simulation , Rats , Rats, Wistar
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1297-1304, 2019 Aug.
Article in Chinese | MEDLINE | ID: mdl-31418396

ABSTRACT

OBJECTIVE: To explore the clinical feature of liver injury in patients with hemophagocytic syndrome (HPS). METHODS: The clinical data of 92 patients with HPS in our hospital were analyzed retrospectively, and the characteristics of hepatic lesion and its relationship with prognosis in HPS patients were explored. RESULT: 92 cases of HPS showed different degrees of liver dysfunction from mild to moderate. The clinical parameters of liver dysfunction included the increased level of LDH (89.13%), AST (64.13%), TBIL (59.78%) and decreased level of ALB (90.22%). Moreover, 76.09% and 67.39% of the patients had the prolonging of APTT and PT respectively. The ALB level of patients in rheumatoid immune group were higher than that in infection, maglinancy and unexplained groups, all with statistically and significant difference (P<0.05, P<0.05 and P<0.01), the ALB level of patients in infection group were statistically and significantly higher than that in unexplained group (P<0.01). The Fbg level of patients in infection group were lower than that in maglinancy group, unexplained group and rheumatoid immune group, all the differences were statistically significant (P<0.05, P<0.01 and P<0.05). Child-Pugh grading was further carried out in HPS patients with liver disfunction. Survival time of the patients grade A was significantly higher than that of grade B and C of patients. Univariate analysis showed that the patients with LDH≥2000 U/L, ALB<30 g/L and PT≥15.1 s had a survival time inferior to control patients (P<0.05, P<0.01 and P<0.01, respectively). Multivariate analysis showed that ALB<30 g/L was an independent adverse prognostic factor for these patients (P<0.01). CONCLUSION: Patients with HPS generally have impaired liver function mainly manifested with elevated LDH and AST levels, and declined ALB level, which may correlate with the disease cause and prognosis. Patients with LDH≥2000 U/L, ALB<30 g/L and PT≥15.1 s have a poorer prognosis and should be treated as soon as possible.


Subject(s)
Liver Diseases , Lymphohistiocytosis, Hemophagocytic , Humans , Prognosis , Retrospective Studies
13.
Joint Bone Spine ; 86(3): 335-341, 2019 05.
Article in English | MEDLINE | ID: mdl-30025962

ABSTRACT

OBJECTIVE: Retinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA. METHODS: In this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40. RESULTS: In those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36-52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05-1.11, P < 0.001) and 5% (1.05; 1.02-1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02). CONCLUSION: Elevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients.


Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/physiopathology , Insulin Resistance , Retinol-Binding Proteins, Plasma/metabolism , Adult , Aged , Biomarkers/blood , Case-Control Studies , China , Early Diagnosis , Female , Hospitals, University , Humans , Incidence , Male , Middle Aged , Reference Values , Retrospective Studies , Risk Assessment , Severity of Illness Index , Statistics, Nonparametric
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1696-1701, 2017 Dec.
Article in Chinese | MEDLINE | ID: mdl-29262900

ABSTRACT

OBJECTIVE: To explore the amplification rate, clinical correlation and prognostic significance of 1q21 amplification in newly diagnosed patients with multiple myeloma (MM). METHODS: I-FISH was performed on purified 138+ plasma cells from 72 newly diagnosed MM patients from February 2013 to February 2016 receiving bortezomib-based chemotherapy by using probe covered 1q21 region. Cut off value is 20%. Amplification rate, clinical relevance and prognostic significance were analysed in MM patients. RESULTS: Among 72 patients, male 52, femail 20, the median age was 58(33-80).The amplification rate of 1q21 was 45.8%, the 1q21 amplification was positivly correlated with 13q14 deletion(P=0.041)and ISS III stage (P=0.002). With a median follow-up time of 17.0(3.0-40.0)months, the estimated median progression-free survival(PFS) time and overall survival(OS) time for patients with 1q21 amplification were 17.0 and 22.0 months, however, they did not reach in patients without 1q21 amplification(P=0.000, P=0.001). The multivariate analysis showed that del(17p13), 1q21 amplification and LDH≥220 U/L remained as independent risk factors for PFS and OS. CONCLUSION: 1q21 amplification is an important genetics prognosis indicator in newly diagnosed multiple myeloma patients receiving bortezomib-based first-line treatment. Bortezomib-based treatment can not improve the poor survival in patients with 1q21 amplification.


Subject(s)
Antineoplastic Agents/therapeutic use , Bortezomib/therapeutic use , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Multiple Myeloma/genetics , Adult , Aged , Aged, 80 and over , Chromosome Deletion , Disease-Free Survival , Female , Gene Amplification , Humans , Male , Middle Aged , Multiple Myeloma/drug therapy , Prognosis
15.
Tumour Biol ; 37(5): 6027-34, 2016 May.
Article in English | MEDLINE | ID: mdl-26596840

ABSTRACT

Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment.


Subject(s)
Leukemia, Myeloid, Acute/metabolism , Pentose Phosphate Pathway , 6-Aminonicotinamide/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Computational Biology/methods , Gene Expression Profiling , Gene Expression Regulation, Leukemic , Genetic Variation , Glucose/metabolism , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Oxidation-Reduction/drug effects , Prognosis
16.
PLoS One ; 10(11): e0143249, 2015.
Article in English | MEDLINE | ID: mdl-26600124

ABSTRACT

A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS)-induced IR64 (Oryza sativa L. ssp. indica) mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43) with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43) was required for the normal development of chloroplasts and photosynthesis in rice.


Subject(s)
Chloroplasts/metabolism , Oryza/metabolism , Oryza/physiology , Photosynthesis/physiology , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Oryza/genetics , Photosynthesis/genetics , Plant Proteins/genetics
17.
Biomed Res Int ; 2015: 876040, 2015.
Article in English | MEDLINE | ID: mdl-26273654

ABSTRACT

OBJECTIVES: To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. METHODS: Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. RESULTS: Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ(2) = 6.87, P = 0.009, and wald χ(2) = 5.171, P = 0.023). CONCLUSIONS: Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.


Subject(s)
Infliximab/administration & dosage , Outcome Assessment, Health Care/methods , Severity of Illness Index , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/drug therapy , Antirheumatic Agents/administration & dosage , Drug Administration Schedule , False Negative Reactions , Female , Humans , Male , Prognosis , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome , Young Adult
18.
Clin Rheumatol ; 34(3): 503-10, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24946723

ABSTRACT

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a standard instrument regularly used to assess disease activity of patients with ankylosing spondylitis (AS). However, the well-being of a patient is also affected by impairment of function as well as psychological status and other factors. The objective of this study was to evaluate if psychological status, stressful life events, and sleep quality contribute significantly to BASDAI. Six hundred eighty-three AS patients satisfying the Modified New York Criteria for AS were recruited from the rheumatology clinics of seven hospitals in China. Patients with other concomitant disorders were excluded. Participants were requested to complete a set of clinical examinations and the following questionnaires: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), Pittsburgh Sleep Quality Index Questionnaire (PSQI), Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and Social Readjustment Rating Scale (SRRS). Spearman correlation analysis showed that BASDAI was highly associated with degree and duration of morning stiffness, overall pain, nocturnal back pain, overall back pain, anxiety, and BASFI (all P < 0.001), but were not associated with education, HAQ-S, and sleep medication in PSQI (P > 0.05). Multiple stepwise regression analysis indicated that overall pain was the maximal statistical contribution in predicting disease activity (standardized coefficient, 0.335). In hierarchic multiple regression analysis, psychological variables added an only additional 2.7% to the overall R(2) beyond that accounted for by demographic and medical variables, resulting in a final R(2) of 53.5%. Although BASDAI is a very good measurement of pain and stiffness and to a certain extent effect of functional impairment in AS, it barely takes into account psychological status, stress life events, and sleep quality These factors should be evaluated by other modalities.


Subject(s)
Severity of Illness Index , Spondylitis, Ankylosing/psychology , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Sleep , Stress, Psychological , Young Adult
19.
Med Oncol ; 31(4): 902, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24610542

ABSTRACT

To identify the clinical features of lymphoma-associated hemophagocytic syndrome (LAHS), we retrospectively analyzed the clinical characteristics, laboratory findings and survival data of 16 LAHS patients from 69 adult hemophagocytic syndrome (HPS) patients. The results showed that the most common clinical manifestations and laboratory parameters were fever (100%), ferritin ≥ 500 g/L (100%), peripheral cytopenia in two or more lineages (100%), fibrinogen (Fbg) < 1.5 g/L (93.8%) and splenomegaly (81.3%) in LAHS patients. The percentages of patients with Fbg < 1.5 g/L, PLT < 40 × 10(9)/L and LDH ≥ 1,000 U/L in the LAHS group were significantly higher than those in non-LAHS patients (P = 0.010, 0.000, and 0.001, respectively). Survival analysis showed that HLH patients with rheumatological reasons had better prognosis (OS; median not reached), followed by patients in the infection group (350 days) and those with unexplained causes (140 days). LAHS had the worst prognosis (only 37 days). The symptoms of LAHS patients are usually confused with other HPS. Patients with LAHS had higher probabilities to have Fbg < 1.5 g/L, PLT < 40 × 10(9)/L, LDH ≥ 1,000 U/L and poor prognosis, so early diagnosis and systemic treatments are required.


Subject(s)
Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphoma/diagnosis , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Blood Cell Count , China , Female , Ferritins/blood , Fibrinogen/metabolism , Gene Rearrangement , Geography , Humans , Lymphohistiocytosis, Hemophagocytic/epidemiology , Male , Middle Aged , Positron-Emission Tomography , Prognosis , Splenomegaly/complications , Treatment Outcome , Young Adult
20.
Asia Pac J Public Health ; 25(4 Suppl): 22S-9S, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23966601

ABSTRACT

In this meta-analysis of the association between PTPN22 gene polymorphisms and susceptibility to systemic lupus erythematosus, 4 case-control studies, including one from China, were included. The studies included 1864 participants: 772 cases and 1092 controls. The meta-analysis showed that the 1858C/T polymorphism of the PTPN22 gene is correlated with systemic lupus erythematosus susceptibility, when assessed by distribution characteristics such as nationality, race, and region. A large sample size from the Chinese population is required for a further prospective study before causality can be established.


Subject(s)
Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Case-Control Studies , China , Humans
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