Biomedical subjects

Hui Sun

Publications and source records attributed to Hui Sun.

At least 19 recordsLinked to original sources

PubMed2026

Ergothioneine Alleviated the Apoptosis of HK Cells by Regulating Ferroptosis.

INTRODUCTION/OBJECTIVE: Ergothioneine (EGT) is a naturally occurring antioxidant with protective effects on various human cell types. The impact of this substance on HK-2 cells, a human renal proximal tubular epithelial cell line, and the associated molecular mechanisms remain incompletely elucidated. METHODS: The present study aims to elucidate the effects of EGT on apoptosis induced by RAS-selective Lethal Molecule 3 (RSL3) and Erastin in HK-2 cells, as well as the potential mechanisms involved. The renal cortical proximal tubular epithelial HK-2 cells were cultured and exposed to RSL3 and Erastin, with or without EGT treatment. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 (CCK-8) assay, while the detection of ferrous ion content and mitochondrial membrane potential changes was accomplished through the utilisation of flow cytometry and the JC-1 staining method, respectively. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, proteomic analysis, and western blotting were employed to explore the molecular pathways involved. RESULTS: The data demonstrated that RSL3 and Erastin exhibited a substantial inhibitory effect on HK-2 cell proliferation, concomitant with the accumulation of intracellular ferrous ions and a shift in mitochondrial membrane potential. The EGT treatment effectively mitigated RSL3- and Erastin-induced apoptosis in HK-2 cells. GO and KEGG enrichment analysis demonstrated that EGT suppressed pathways and functions associated with oxidative stress during ferroptosis. Proteomics analysis further demonstrated that EGT modulated various biological processes, molecular functions, and cellular components in HK-2 cells. The protective mechanism of EGT against RSL3- and Erastin-induced HK-2 cells was potentially mediated through regulation of ferroptosis. The results of the western blot analysis demonstrated that EGT modulated the expression levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 member 11 (SLC7A11) in HK-2 cells. CONCLUSION: These data demonstrated that EGT exerts an alleviating effect on the apoptosis of HK-2 cells induced by RSL3 and Erastin by modulating ferroptosis. These findings suggest that EGT has the potential to serve as a therapeutic candidate for the treatment of kidney diseases in the future.

Ergothioneine↗

PubMed2026

Integrative multi-omics analysis unravels the metabolic landscape and reveals serum biomarkers for early diagnosis of hyperuricemia.

BACKGROUND: Hyperuricemia (HUA) is a major risk factor for gout and multiple metabolic disorders. Although serum uric acid (UA) is the gold standard for HUA diagnosis, it fails to reflect early metabolic disturbances and shows limited predictive value for asymptomatic HUA. This study sought to elucidate the pathological mechanisms underlying HUA and identify novel diagnostic biomarkers beyond UA. METHODS: This study enrolled 195 patients with HUA and 98 healthy controls. Global metabolomics and proteomics profiling were performed to characterize molecular alterations underlying HUA. Based on the biological relevance of the shared dysregulated pathways, a pathway correlation network was constructed to elucidate the pathological mechanisms driving HUA initiation and progression. Furthermore, diagnostic biomarkers for HUA were identified using machine learning algorithms, and were validated with an external cohort. RESULTS: HUA patients exhibited distinct metabolic and proteomic profiles compared with healthy controls. Integrated multi-omics pathway analysis revealed that peroxisome proliferators-activated receptor signaling pathway, arachidonic acid metabolism, purine metabolism, pyrimidine metabolism and sphingolipid signaling pathway were significantly dysregulated in HUA. Among them, arachidonic acid metabolism was identified as a hub pathway involved in HUA progression. Furthermore, a metabolite panel consisting of cysteine-S-sulfate, glycerophosphocholine and 4-hydroxyphenylpyruvic acid was screened by machine learning and validated in an independent cohort, which showed slightly higher diagnostic performance for HUA than UA. CONCLUSIONS: This study reveals the core metabolic and protein regulatory networks of HUA, and identifies a novel serum metabolite panel for the diagnosis of HUA. These findings provide new insights for improved clinical diagnosis and management.

Humans↗

PubMed2026

Tracing and characterization of a family outbreak of subtype B2 botulism linked to homemade pickled eggs in Jinan, China.

Foodborne botulism (FB) results from the ingestion of food contaminated with botulinum neurotoxin. Here, we report a family outbreak of foodborne botulism caused by Clostridium botulinum subtype B2 linked to homemade pickled eggs. On August 13, 2024, the Jinan Center for Disease Control and Prevention and the Shanghe County Center for Disease Control and Prevention collaborated to investigate an outbreak of botulism poisoning related to a family gathering in Shanghe County, Jinan City. A total of 4 people attended the family gathering, three of whom developed clinical symptoms of botulism after consuming pickled eggs. The diagnosis of botulism was suspected through collaborative efforts by the Qilu Medical Prevention and Control Innovation Integration Mechanism and multidisciplinary consultations across multiple hospitals. We detected the bont gene using real-time quantitative PCR (qPCR) in Jinan CDC, determined the toxin serotype by mouse bioassay (MBA) in China CDC and performed whole-genome sequencing of bacterial strains isolated from patient feces, the homemade pickled eggs and soil in both laboratories. It was shown that the toxin type and bont gene were subtype B2, belonging to the ha gene cluster. The Clostridium botulinum strains isolated from two patients were closely related to the strains from the homemade pickled eggs through whole-genome single nucleotide polymorphism analysis. We also found that Clostridium botulinum strains from soil clustered into one branch with those from patients and food, suggesting that the source of Clostridium botulinum contamination may be from soil, although the contamination pathway was not clear. Importantly, our findings provided a basis for clinical antitoxin treatment, in which one patient successfully gave birth after recovery. These results underscore the importance of strengthening public education about the health risks associated with consuming homemade fermented or preserved foods and enhancing the laboratory detection capabilities.

Botulism↗

PubMed2026

A rare and atypical case of long-distance indirect DNA transfer: Contamination from an investigator never present at the scene.

To maximize the usefulness of DNA obtained from biological samples in forensic genetics, it is crucial to avoid DNA contamination throughout all procedures, from sample collection at crime scenes to STR profile generation in DNA laboratories. This study reports a rare and atypical case of DNA contamination in a forensic setting. During the analysis of biological evidence from a cold case preserved for 18 years, the STR profile obtained from the surface of a plastic bag matched that of an investigator, identified through the DNA elimination database. Case reconstruction confirmed that the investigator-who was located 80 km from the DNA laboratory and had never entered the crime scene or the sample storage room-was not a suspect and that the obtained STR profile originated from contamination. The most plausible explanation for the contamination was indirect transfer: investigator's DNA had adhered to a colleague's clothing and was subsequently dislodged and deposited onto the surface of the plastic bag as the colleague approached the sample pretreatment area. This study integrates trace DNA profiling of challenged samples with rapid contamination investigation and proposes prevention and control measures. This case underscores that, although DNA is widely regarded as the "gold standard" in forensic genetics, its interpretation must be considered within the context of the entire case. Conclusions should not be drawn based solely on a single DNA result.

Humans↗

PubMed2025

Comprehensive clinical and genetic characterization of hyperprogressive biliary tract cancer during PD-1 blockade monotherapy: case report and literature review.

BACKGROUND: Some genetically characterized patients show the rapid disease progression during immune checkpoint inhibitors (ICIs) monotherapy, a phenomenon known as hyperprogressive disease (HPD). CASE PRESENTATION: Herein we report a relevant case of biliary tract cancer (BTC) that initially responded to gemcitabine plus oxaliplatin (GEMOX) and PD-1 blockade but subsequently developed HPD in the process of PD-1 blockade maintenance therapy, leading to death within two weeks. Genomic analysis revealed mutations in CDKN2A, PIK3CA, KRAS and EPHA2 in both baseline and hyperprogressive plasma and tumor samples. Notably, higher KRAS mutation abundance was observed in plasma and ascites after disease progression. CONCLUSIONS: These findings suggest a potential association between these negative genes especially KRAS mutation and HPD. Therefore, administration of PD-1 blockade monotherapy in this subgroup of patients harboring KRAS mutation should be performed with caution. Further studies are warranted to confirm these results and explore the correlation between genomic mutations and HPD.

Humans↗

PubMed2025

HEPARIN AND DNase I TREAT MYOCARDIAL INJURY IN SEPTIC MICE.

Background: Sepsis is a life-threatening clinical condition often seen in intensive care units, leading to multi-organ dysfunction. Myocardial injury is a prevalent complication, significantly increasing mortality among sepsis patients. Although heparin is used in sepsis management, its specific effects on myocardial injury and the role of neutrophil extracellular traps (NETs) in this context remain insufficiently understood. Aim: This study investigates the role of unfractionated heparin (UFH) combined with DNase I in reducing myocardial injury in a septic mouse model. Methods: A cecal ligation and puncture (CLP)-induced sepsis model was established in C57BL/6 mice to study myocardial injury. The experimental groups included treatments with UFH, UFH with DNase I, and NETs introduction. Myocardial injury was assessed using hematoxylin and eosin staining, enzyme linked immunosorbent assay for injury markers (creatine kinase MB [CK-MB] and lactate dehydrogenase [LDH]), and Western blotting for inflammatory proteins (TNF-α and IL-6). Differential proteomic analysis using data independent acquisition mass spectrometry and pathway enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were conducted to identify molecular pathways and key proteins affected by the treatments. Results: Single UFH treatment increased the formation of NETs, upregulated TNF-α and IL-6, and increased CK-MB and LDH, worsening myocardial injury. The combination of UFH and DNase I significantly reduced myocardial injury, suppressing NETs formation and inflammation. Proteomic analysis identified crucial pathways related to NETs, metabolism, and complement and coagulation cascades, with proteins Ccn1 and Tagln highlighted as potential therapeutic targets. Conclusion: UFH combined with DNase I effectively alleviates myocardial injury in septic mice by modulating NETs formation and associated inflammatory processes. This study may provide new insights and options for the early use of heparin in the treatment of septic patients, particularly in cases with a higher risk of myocardial injury.

Animals↗

PubMed2025

Natural variation in the cytokinin oxidase gene ZmCKX6 influences leaf morphology and yield-related traits in maize.

Leaf width (LW) is a critical determinant of maize architecture and yield. To uncover its genetic basis, we performed a genome-wide association study (GWAS) on 348 maize inbred lines and identified ZmCKX6, encoding cytokinin oxidase/dehydrogenase, as a key gene associated with LW. Natural variation in the ZmCKX6 promoter significantly influenced its expression levels, leading to differences in LW across various haplotypes. Functional validation using CRISPR/Cas9 revealed that ZmCKX6 knockout results in pleiotropic effects, including narrower leaves, reduced plant height, and decreased grain yield components. These phenotypes were accompanied by elevated levels of active cytokinins but reduced levels of auxin, gibberellins, and salicylic acid. Transcriptome analysis revealed a significant downregulation of photosynthesis-related genes, corresponding to reduced photosynthetic rates in knockout lines. Evolutionary analysis demonstrated that the allele associated with narrower leaves were preferentially selected during maize domestication and breeding. This study highlights the role of ZmCKX6 in modulating cytokinin homeostasis and its subsequent impact on multiple agronomic traits in maize, providing insights into the complex genetic control of plant architecture and yield. The identified natural variations could be valuable for marker-assisted selection aimed at optimizing plant architecture and improving yield.

Zea mays↗

PubMed2006

A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a strong genetic predisposition. A locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) have not been identified. We genotyped 581 AMD cases and 309 normal controls in a Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients revealed that the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein. We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis.

Aged↗

PubMed2006

The pi-pi stacked geometries and association thermodynamics of quinacridone derivatives studied by 1H NMR.

The pi-pi stacked associations of three N,N'-di(n-butyl) quinacridone derivatives, widely used dopants in organic light-emitting diodes, with different sizes of substituents were investigated in solution at various temperatures by (1)H NMR spectroscopy. The pi-pi stacked geometries were estimated by both the magnitudes of peak shifts with concentration and the directions of peak shifts induced by polar solvents. Two patterns of geometries with different pi-pi interaction strengths were found to coexist in solution for all the three samples. In both of the patterns, the preferential orientation of the stacking is the approach of the carbonyl groups on one molecule to the nitrogen atoms on the stacked partner, which makes the pi-deficient aromatic atoms interact with both pi-rich and pi-deficient aromatic atoms of the stacked partner to maximize the electrostatic complementarity. Differently, whereas the molecules in one pattern are face-to-face stacked in a parallel fashion and slip two rings relative to one another along with the long axis of the conjugated ring systems, the molecules in the other are either face-to-face stacked in an antiparallel fashion with slight slipping between layers or stacked in a turning fashion. Both association constants obtained by fitting the dilution curves and thermodynamic parameters obtained from van't Hoff analyses revealed unexpectedly three thermodynamic processes of aggregations for all the three samples in the temperature region of 298-213 K. The size of substituents on the outer aromatic rings significantly influences the pi-pi stacked structures and association thermodynamics.

Journal Article↗

PubMed2006

Flow analysis coupled with PQC/DNA biosensor for assay of E. coli based on detecting DNA products from PCR amplification.

A flow-through PQC/DNA biosensor system is developed by combining sequential flow polymerase chain reaction (PCR) products denaturing prior to piezoelectric quartz crystal (PQC) detection via hybridization of ssDNA. The PQC/DNA biosensor is fabricated based on complex formation of neutravidin/biotinylated probe in 0.2M NaCl in TE buffer (10mM Tris, 1mM EDTA, pH 7.5). Results show that the coating fabricated provides a desirable quality with satisfactory performance. Its application for Escherichia coli detection under controlled flow at 0.02 mL/min for denaturing PCR products and 10 mL/min for transferring solution between reactors and delivering samples to detector to reduce rehybridization leads to significant improvement in repeatability (R.S.D.<6%, n=5) and sensitivity (DeltaF=34 Hz/1000 E. coli cells) as compared to existing manual method (R.S.D.=19%, n=5 and DeltaF=26 Hz/1000 E. coli cells, respectively). Down to 23 E. coli cells are detected, satisfying the HKEPD requirements for E. coli count in beach water.

Biosensing Techniques↗

PubMed2006

Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones.

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

Adenocarcinoma↗

PubMed2006

An interaction involving an arginine residue in the cytoplasmic domain of the 5-HT3A receptor contributes to receptor desensitization mechanism.

A large cytoplasmic domain accounts for approximately one-third of the entire protein of one superfamily of ligand-gated membrane ion channels, which includes nicotinic acetylcholine (nACh), gamma-aminobutyric acid type A (GABA(A)), serotonin type 3 (5-HT3), and glycine receptors. Desensitization is one functional feature shared by these receptors. Because most molecular studies of receptor desensitization have focused on the agonist binding and channel pore domains, relatively little is known about the role of the large cytoplasmic domain (LCD) in this process. To address this issue, we sequentially deleted segments of the LCD of the 5-HT3A receptor and examined the function of the mutant receptors. Deletion of a small segment that contains three amino acid residues (425-427) significantly slowed the desensitization kinetics of the 5-HT3A receptor. Both deletion and point mutation of arginine 427 altered desensitization kinetics in a manner similar to that of the (425-427) deletion without significantly changing the apparent agonist affinity. The extent of receptor desensitization was positively correlated with the polarity of the amino acid residue at 427: the desensitization accelerates with increasing polarity. Whereas the R427L mutation produced the slowest desensitization, it did not significantly alter single channel conductance of 5-HT3A receptor. Thus, the arginine 427 residue in the LCD contributes to 5-HT3A receptor desensitization, possibly through forming an electrostatic interaction with its neighboring residues. Because the polarity of the amino acid residue at 427 is highly conserved, such a desensitization mechanism may occur in other members of the Cys-loop family of ligand-gated ion channels.

Amino Acids↗

PubMed2006

[Association of baseline cholesterol level and its 10-year change with carotid atherosclerosis in the population of Peking University community].

OBJECTIVE: To explore the association of baseline cholesterol level in 1992 and its 10-year change from 1992 to 2002 with the prevalence of carotid atherosclerosis. METHODS: In 1992, 1985 subjects of the community of Peking University, aged 35 - 64, underwent physical examination and blood-lipid test to study the cardio-vascular disease (CVD) risk factors. In 2002, the second survey on CVD risk factors was conducted among the existing 1932 subjects, now aged 45 - 74. In addition, B-mode ultrasonography of the carotid artery was performed too. The complete data of 1331 subjects were analyzed. RESULTS: (1) In 2002, the prevalence rates of intimal medial thickening (IMT) and carotid plaque in the study population were 47.8% and 29.9% respectively. (2) The post-10-year prevalence rate of carotid plaque was 19.7% in the subjects with the baseline cholesterol < 3.64 mmol/L, and was 46.8% in those with the baseline cholesterol 6.24 mmol/L, with a thickening rate 3.1 times that of the subjects with the baseline cholesterol < 3.64 mmol/L. The higher the baseline TV level, the higher the prevalence rates of carotid plaque and IMT. (3) The prevalence rate of carotid plaque was 32.0% in the subjects with normal TC in both 1992 and 2002, and 50.0% in those with hypercholesterolemia in both 1992 and 2002. CONCLUSION: Carotid atherosclerosis is a prevalent disorder in the people aged 45 - 74 in Beijing. The prevalence rates of carotid plaque and IMT increase with the elevation of baseline cholesterol level.

Adult↗

PubMed2006

Insulin-like growth factor-1 and PTEN deletion enhance cardiac L-type Ca2+ currents via increased PI3Kalpha/PKB signaling.

Ca2+ influx through the L-type Ca2+ channel (I(Ca,L)) is a key determinant of cardiac contractility and is modulated by multiple signaling pathways. Because the regulation of I(Ca,L) by phosphoinositide-3-kinases (PI3Ks) and phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in the regulation of myocardial growth and contractility, I(Ca,L) was recorded in myocytes isolated from mice overexpressing a dominant-negative p110alpha mutant (DN-p110alpha) in the heart, lacking the PI3Kgamma gene (PI3Kgamma(-/-)) or with muscle-specific ablation of PTEN (PTEN(-/-)). Combinations of these genetically altered mice were also examined. Although there were no differences in the expression level of CaV1.2 proteins, basal I(Ca,L) densities were larger (P<0.01) in PTEN(-/-) myocytes compared with littermate controls, PI3Kgamma(-/-), or DN-p110alpha myocytes and showed negative shifts in voltage dependence of current activation. The I(Ca,L) differences seen in PTEN(-/-) mice were eliminated by pharmacological inhibition of either PI3Ks or protein kinase B (PKB) as well as in PTEN(-/-)/DN-p110alpha double mutant mice but not in PTEN(-/-)/PI3Kgamma(-/-) mice. On the other hand, application of insulin-like growth factor-1 (IGF-1), an activator of PKB, increased I(Ca,L) in control and PI3Kgamma(-/-), while having no effects on I(Ca,L) in DN-p110alpha or PTEN(-/-) mice. The I(Ca,L) increases induced by IGF-1 were abolished by PKB inhibition. Our results demonstrate that IGF-1 treatment or inactivation of PTEN enhances I(Ca,L) via PI3Kalpha-dependent increase in PKB activation.

Animals↗

PubMed2006

Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction.

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na(+)/Ca(2+) exchanger, beta-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca(2+) cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload.

Animals↗

PubMed2006

[Mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy by valsartan].

OBJECTIVE: To investigate the mechanism of reversion of myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) by valsartan. METHODS: Forty male wistar rats were randomly divided into 3 groups: DCM group, n = 16, fed with high-fat diet for 4 weeks and injected intraperitoneally with streptozocin (STZ) once to induce hyperglycemia so as to construct a DCM model, and then perfused into the stomach with normal saline; valsartan group, n = 16, to be constructed into DCM model and then perfused into the stomach with valsartan once daily; and control group (n = 8, fed with normal food and perfused into the stomach with normal saline. Four weeks after feeding (i.e., before injection of STZ), 1 week after STZ injection, and by the end of experiment after 12-hour fasting samples of venous blood were collected to detect the contents of triglyceride and fasting blood-glucose and insulin; by the end of experiment miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by Masson staining, real-time RT-PCR was used to detect the mRNA expression of thrombospondin (TSP)-1 and tumor growth factor (TGF)-beta(1) mRNA, expression, and Western blotting was used to detect the protein expression of TSP-1, active TGF-beta(1) (A-TGF-beta(1)) and latent TGF-beta(1) (L-TGF-beta(1)). RESULTS: By the end of the experiment, the body weights, and insulin sensitivity index were significantly lower and fasting blood-glucose, and serum triglyceride and cholesterol were significantly higher in the DCM group and valsartan group in comparison with those in the control group (all P < 0.01), however, there was no significant differences in fasting insulin among these 3 groups. The values of left ventricular systolic pressure (LVSP) and +/- dp/dt(max) were significantly lower and left ventricular end diastolic pressure were significantly higher in the DCM group in comparison with the control group (all P < 0.01). The LVSP and -dp/dt(max) were significantly higher and LVEDP was significantly lower in the valsartan group than in the DCM group (all P < 0.05). The LVEDP was significantly higher and -dp/dt(max) was significantly lower in the valsartan group than in the control group. Electron microscopy showed the distribution of a great amount of collagen in the myocardial interstitial tissue. The collagen content of the DCM group was 17 +/- 3, significantly higher than that of the control group (11 +/- 3, P < 0.05), and the collagen content of the valsartan group was 13 +/- 3, significantly lower than that of the DCM group (P < 0.05). The mRNA expression of TSP-1 and that of TGF-beta(1) were significant higher in the DCM group than in the control group (both P < 0.05), and were significantly lower in the valsartan group than in the DCM group (both P < 0.05); however, the TGF-beta(1) mRNA expression in the valsartan group was significantly higher in the valsartan group than in the control group (P < 0.05). The values of protein expression of TSP-1, A-TGF-beta(1) and L-TGF-beta(1) were all significantly higher in the DCM group than in the control group (all P < 0.05), and the values of protein expression of TSP-1 and A-TGF-beta(1) in the valsartan group were both significantly lower than those in the DCM group (both P < 0.05), however, there was no significant difference in the protein expression of L-TGF-beta(1) between the valsartan group and DCM group. CONCLUSION: Valsartan amelioorates myocardial interstitial fibrosis in DCM via TSP-1/TGF-beta(1) signaling pathway.

Animals↗

PubMed2006

Purification and properties of a beta-1,3-glucanase from Chaetomium sp. that is involved in mycoparasitism.

A beta-1,3-glucanase was detected, using laminarin as substrate, in the culture broth of Chaetomium sp. Major activity was associated with a 70 kDa protein band visualized on a polyacrylamide gel. beta-1,3-Glucanase was purified by a one-step, native gel purification procedure. Optimal activity was observed at pH 6.0 and 30 degrees C (over 30 min). It could degrade cell walls of plant pathogens including Rhizoctonia solani, Gibberella zeae, Fusarium sp., Colletotrichum gloeosporioides and Phoma sp. The N-terminal amino acid residues of the purified beta-1,3-glucanase are PYQLQTP, which do not exhibit homology to other fungal beta-1,3-glucanases suggesting it may be a novel enzyme.

Chaetomium↗

PubMed2006

Phosphoinositide 3-kinase gamma regulates cardiac contractility by locally controlling cyclic adenosine monophosphate levels.

Class I phosphoinositide 3-kinases (PI3Ks) are enzymes with both protein and lipid kinase activities that regulate important cellular functions in many tissues. In the heart, subclass IA PI3Ks (mainly PI3Kalpha) regulate cell growth, apoptosis, cell division and cell size, whereas PI3Kgamma, the only member of subclass IB, has been shown to regulate cardiac contractility. We have shown that the loss of PI3Kgamma (PI3Kgamma(-/-) mice) enhances cardiac excitation-contraction coupling by modulating cyclic adenosine monophosphate (cAMP) levels in subcellular domains containing the sarcoplasmic reticulum. Specifically, PI3Kgamma(-/-) mice show enhanced sarcoplasmic reticulum Ca(2+) cycling in association with increased cAMP. Surprisingly, L-type Ca(2+) current, a prototypic target of cAMP-dependent protein kinase A phosphorylation, is largely unchanged in PI3Kgamma(-/-) mice. In this article, we discuss the consequences and implications of cAMP compartmentation in cardiomyocytes. We also review the different roles of PI3Kgamma in the heart, particularly as they relate to cardiac contractility, intracellular cAMP levels, and the regulation of beta-adrenergic receptor signaling in physiologic and pathologic states.

Animals↗