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Biomedical subjects

Min Pan

Publications and source records attributed to Min Pan.

At least 19 recordsLinked to original sources
PubMed2025

Habitat radiomics predicts occult lymph node metastasis and uncovers immune microenvironment of head and neck cancer.

BACKGROUND: Occult lymph node metastasis (LNM) is a key prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). This study was to establish radiomics models derived from intratumoral, peritumoral, and habitat regions for identifying occult LNM in HNSCC. METHODS: Patients with pathologically confirmed HNSCC from three medical Centers (from March 2014 to April 2024) and The Cancer Genome Atlas (TCGA) were enrolled. Center 1 was split into training (n = 330) and internal test sets (n = 154), while Center 2 and Center 3 served as the external test set (n = 183). Genomic set (n = 50) from TCGA and single-cell RNA sequencing set (n = 6) from Center 1 were used for biological analysis. We used the intratumoral, peritumoral, and habitat volumes of interest (VOIs) to extract radiomics features, respectively. Based on Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) classifiers, nine radiomics models were built to confirm the optimal predictive performance. The best-performing model, along with clinical-radiologic data, was combined to develop a hybrid model. The log-rank test was used to evaluate the model's prognostic performance. Additionally, bulk and single-cell RNA sequencing were applied for investigating the biological mechanisms underlying the optimal model. RESULTS: The RF-habitat radiomics model showed the best performance, achieving AUCs of 0.835-0.919 across all datasets. Survival analysis further confirmed the prognostic value of the RF-habitat radiomics model. The RF-habitat radiomics model and the hybrid model notably surpassed the clinical model in predictive performance. Moreover, the RF-habitat radiomics model was associated with the abundance level of exhaustion-associated CD8 + T cells, uncovering the immune microenvironment characteristics contributing to occult LNM in HNSCC. CONCLUSIONS: The RF-habitat radiomics model demonstrated excellent performance for predicting occult LNM in HNSCC across three cohorts, providing a non-invasive solution for occult LNM. Furthermore, radiogenomic analysis further revealed the biological associations of the model, primarily related to T cell dysfunction.

Humans↗
PubMed2006

An integrated systems approach for understanding cellular responses to gamma radiation.

Cellular response to stress entails complex mRNA and protein abundance changes, which translate into physiological adjustments to maintain homeostasis as well as to repair and minimize damage to cellular components. We have characterized the response of the halophilic archaeon Halobacterium salinarum NRC-1 to (60)Co ionizing gamma radiation in an effort to understand the correlation between genetic information processing and physiological change. The physiological response model we have constructed is based on integrated analysis of temporal changes in global mRNA and protein abundance along with protein-DNA interactions and evolutionarily conserved functional associations. This systems view reveals cooperation among several cellular processes including DNA repair, increased protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis and an overall effort to repair oxidative damage. Further, we demonstrate the importance of time dimension while correlating mRNA and protein levels and suggest that steady-state comparisons may be misleading while assessing dynamics of genetic information processing across transcription and translation.

Archaeal Proteins↗
PubMed2006

Inflammation: a possible pathogenic link to atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained dysrhythmia in clinical practice. Despite the extensive studies, the pathophysiological mechanisms in AF, however, remain unclear. More recently, the data has been suggested that inflammatory process has been associated with development of AF. The evidence for the hypotheses included that: (1) Histological studies have demonstrated inflammatory infiltrates in AF patients and in animal models of AF; (2) inflammatory markers are increased in AF patients and is associated with successful cardioversion. And also, Inflammatory markers are not only associated with the presence of AF but also independently predicted increased risk for the development of future AF; (3) treatment with anti-inflammatory agents is associated with a decreased recurrence of AF. Although the studies suggest the existence of an association between inflammation and AF, many aspects remain elusive and require further investigation. Specifically, whether inflammation is an initiator or a perpetuator of AF; the effects of anti-inflammatory drugs on atrial remodeling and their exact role in the recurrence and perpetuation of AF. Inflammation may provide a potential target for pharmacological interruption of AF and may favorably affect atrial remodeling leading to important clinical benefits.

Animals↗
PubMed2006

A systems view of haloarchaeal strategies to withstand stress from transition metals.

Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals, we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sublethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large-scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up-regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down-regulation of Mn(II) uptake and up-regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all of these discoveries into a unified systems-level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals, we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms.

Adenosine Triphosphatases↗
PubMed2006

Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.

Animals↗
PubMed2006

[Expression of E-cadherin and beta-catenin in Bowen's disease and squamous cell carcinoma].

OBJECTIVE: To investigate the involvement of E-cadherin-catenin adhesion system in Bowen's disease (BD) and cutaneous squamous cell carcinoma (SCC). METHODS: Fifteen normal skin, 28 BD and 18 SCC specimens were stained with monoclonal antibodies against E-cadherin and beta-catenin. Evaluation of the staining results was performed with semi-quantification of the pattern and intensity of staining, percentage of positive cells, and cytoplasmic staining. RESULT: Normal skins strongly expressed membranous E-cadherin and beta-catenin, but their expression was remarkably reduced in BD and SCC. Abnormal staining of beta-catenin was observed in the cytoplasm or cell nuclei of BD and SCC. CONCLUSION: Abnormal expression of the E-cadherin/catenin complex is common in SCC and BD.

Adult↗
PubMed2004

Systems level insights into the stress response to UV radiation in the halophilic archaeon Halobacterium NRC-1.

We report a remarkably high UV-radiation resistance in the extremely halophilic archaeon Halobacterium NRC-1 withstanding up to 110 J/m2 with no loss of viability. Gene knockout analysis in two putative photolyase-like genes (phr1 and phr2) implicated only phr2 in photoreactivation. The UV-response was further characterized by analyzing simultaneously, along with gene function and protein interactions inferred through comparative genomics approaches, mRNA changes for all 2400 genes during light and dark repair. In addition to photoreactivation, three other putative repair mechanisms were identified including d(CTAG) methylation-directed mismatch repair, four oxidative damage repair enzymes, and two proteases for eliminating damaged proteins. Moreover, a UV-induced down-regulation of many important metabolic functions was observed during light repair and seems to be a phenomenon shared by all three domains of life. The systems analysis has facilitated the assignment of putative functions to 26 of 33 key proteins in the UV response through sequence-based methods and/or similarities of their predicted three-dimensional structures to known structures in the PDB. Finally, the systems analysis has raised, through the integration of experimentally determined and computationally inferred data, many experimentally testable hypotheses that describe the metabolic and regulatory networks of Halobacterium NRC-1.

Animals↗
PubMed2004

Low-pass sequencing for microbial comparative genomics.

BACKGROUND: We studied four extremely halophilic archaea by low-pass shotgun sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non-pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand single pass genomic sequences per genome were obtained. The data were analyzed by comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid approach that can readily be performed on any cultured microbe. RESULTS: As expected, the four archaeal halophiles analyzed exhibit both bacterial and eukaryotic characteristics as well as uniquely archaeal traits. All five halophiles exhibit greater than sixty percent GC content and low isoelectric points (pI) for their predicted proteins. Multiple insertion sequence (IS) elements, often involved in genome rearrangements, were identified in H. lacusprofundi and H. marismortui. The core biological functions that govern cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these four other halophiles. Multiple TATA box binding protein (TBP) and transcription factor IIB (TFB) homologs were identified from most of the four shotgunned halophiles. The reconstructed molecular tree of all five halophiles shows a large divergence between these species, but with the closest relationship being between H. sp. NRC-1 and H. lacusprofundi. CONCLUSION: Despite the diverse habitats of these species, all five halophiles share (1) high GC content and (2) low protein isoelectric points, which are characteristics associated with environmental exposure to UV radiation and hypersalinity, respectively. Identification of multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest that genome structure and dynamic genome reorganization might be similar to that previously observed in the IS-element rich genome of H. sp. NRC-1. Identification of multiple TBP and TFB homologs in these four halophiles are consistent with the hypothesis that different types of complex transcriptional regulation may occur through multiple TBP-TFB combinations in response to rapidly changing environmental conditions. Low-pass shotgun sequence analyses of genomes permit extensive and diverse analyses, and should be generally useful for comparative microbial genomics.

Archaea↗
PubMed2004

Detection of left ventricular regional relaxation abnormalities in patients with hypertrophic cardiomyopathy by quantitative tissue velocity imaging.

To assess the left ventricular regional relaxation abnormalities in patients with hypertrophic cardiomyopathy (HCM) by quantitative tissue velocity imaging (QTVI), Doppler echocardiography and QTVI were performed in HCM (n=10) and healthy subjects (n=11) at apical long-axis, two-chamber and four-chamber views. Regional early diastolic velocity (rVe) and regional atrial contraction (rVa) were measured at each segment of ventricular middle, basal and annular levels. Mean rVe and mean rVa at three levels as well as mean rVe/rVa ratio were calculated. Our results showed that transmitral inflow peak velocities during early diastole (E) and atrial contraction (A) were also measured and E/A ratio was calculated. The rVe of all left ventricular segments in HCM were lower than those in healthy subjects (P<0.05), but compared with healthy subjects majority of rVa in HCM were not different except inferior wall and anterior wall. E between HCM and healthy subjects was different (P=0.036), while mean rVe between them was significantly different (P<0.0001). Mean rVa and mean rVe/rVa of three levels were lower in HCM than in healthy subjects (P<0.05), but there were no differences in A and E/A between them (P=0.22, P=0.101). Left ventricular regional myocardial relaxation is reduced in HCM. Transmitral inflow E and A are influenced by preload, relaxation of myocardium and atrial contraction, etc., while rVe and rVa reflect myocardial relaxation function independently. QTVI is more sensitive and more accurate than conventional Doppler imaging for characterizingregional diastolic properties in HCM.

Adolescent↗
PubMed2004

Nitric oxide formation contributes to beta-adrenergic dilation of epicardial coronary arteries in response to intravenous administration of dobutamine in dogs.

To examine the role of nitric oxide in the beta-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transthoracic echocardiography before and after dobutamine (5 microg/kg/min IV) with and without intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) (1 mg/kg). In all 12 dogs, the diameter of left anterior descending coronary artery increased significantly from 2.35 +/- 0.25 mm to 2.59 +/- 0.24 mm (P<0.001) after dobutamine administration. In 6 of the 12 dogs, the percent change in left anterior descending coronary artery diameter induced by dobutamine decreased significantly from 12.5% +/- 8.6% to -1.5% +/- 5.4% (P<0.05) after the administration of intracoronary L-NMMA (1 mg/kg for 5 min) to block nitric oxide synthesis from L-arginine. The study demonstrated that nitric oxide formation contributes to the beta-adrenergic dilatory response of epicardial coronary arteries to dobutamine in dogs.

Adrenergic beta-Agonists↗
PubMed2004

Genome sequence of Haloarcula marismortui: a halophilic archaeon from the Dead Sea.

We report the complete sequence of the 4,274,642-bp genome of Haloarcula marismortui, a halophilic archaeal isolate from the Dead Sea. The genome is organized into nine circular replicons of varying G+C compositions ranging from 54% to 62%. Comparison of the genome architectures of Halobacterium sp. NRC-1 and H. marismortui suggests a common ancestor for the two organisms and a genome of significantly reduced size in the former. Both of these halophilic archaea use the same strategy of high surface negative charge of folded proteins as means to circumvent the salting-out phenomenon in a hypersaline cytoplasm. A multitiered annotation approach, including primary sequence similarities, protein family signatures, structure prediction, and a protein function association network, has assigned putative functions for at least 58% of the 4242 predicted proteins, a far larger number than is usually achieved in most newly sequenced microorganisms. Among these assigned functions were genes encoding six opsins, 19 MCP and/or HAMP domain signal transducers, and an unusually large number of environmental response regulators-nearly five times as many as those encoded in Halobacterium sp. NRC-1--suggesting H. marismortui is significantly more physiologically capable of exploiting diverse environments. In comparing the physiologies of the two halophilic archaea, in addition to the expected extensive similarity, we discovered several differences in their metabolic strategies and physiological responses such as distinct pathways for arginine breakdown in each halophile. Finally, as expected from the larger genome, H. marismortui encodes many more functions and seems to have fewer nutritional requirements for survival than does Halobacterium sp. NRC-1.

Archaeal Proteins↗
PubMed2004

[Studies on safety of cordocentesis guided by transabdominal ultrasound for prenatal diagnosis].

OBJECTIVE: To assess the safety and efficacy of diagnostic cordocentesis during pregnancy. METHODS: During March 1990 to June 2003, 2403 consecutive cordocenteses were performed under transabdominal ultrasound guidance at Guangzhou Women and Children's Hospital. The results of each procedure was prospectively collected and subsequently analysed in terms of operational complications and pregnancy outcomes. RESULTS: Success rate of cordocentesis: totally 2368 procedures (98.5%) were done successfully at the first attempt, and 35(1.5%) required repeated cordocentesis, 16 of which were performed successfully at second attempt. Duration of cordocentesis: In 75.5% cases, the procedure was completed in less than 5 min, and in 93.0% cases in less than 10 min. COMPLICATIONS: Transient bleeding at puncture site was observed in 315 cases (13.1%), transient fetal bradycardia in 125 cases (5.2%), and chorioamnionitis in 2 cases (0.1%). Pregnancy outcomes: The total fetal loss rate was 0.8% (18 cases of abortions). The rate of premature birth after cordocentesis was 0.2% (4 cases). CONCLUSION: Cordocentesis during pregnancy is a useful, relatively safe, and effective procedure for prenatal diagnosis.

Abortion, Spontaneous↗
PubMed2003

Proteomic analysis of an extreme halophilic archaeon, Halobacterium sp. NRC-1.

Halobacterium sp. NRC-1 insoluble membrane and soluble cytoplasmic proteins were isolated by ultracentrifugation of whole cell lysate. Using an ion trap mass spectrometer equipped with a C18 trap electrospray ionization emitter/micro-liquid chromatography column, a number of trypsin-generated peptide tags from 426 unique proteins were identified. This represents approximately one-fifth of the theoretical proteome of Halobacterium. Of these, 232 proteins were found only in the soluble fraction, 165 were only in the insoluble membrane fraction, and 29 were in both fractions. There were 72 and 61% previously annotated proteins identified in the soluble and membrane protein fractions, respectively. Interestingly, 57 of previously unannotated proteins found only in Halobacterium NRC-1 were identified. Such proteins could be interesting targets for understanding unique physiology of Halobacterium NRC-1. A group of proteins involved in various metabolic pathways were identified among the expressed proteins, suggesting these pathways were active at the time the cells were collected. This data containing a list of expressed proteins, their cellular locations, and biological functions could be used in future studies to investigate the interaction of the genes and proteins in relation to genetic or environmental perturbations.

Archaeal Proteins↗
PubMed2002

Coordinate regulation of energy transduction modules in Halobacterium sp. analyzed by a global systems approach.

The extremely halophilic archaeon Halobacterium NRC-1 can switch from aerobic energy production (energy from organic compounds) to anaerobic phototrophy (energy from light) by induction of purple membrane biogenesis. The purple membrane is made up of multiple copies of a 1:1 complex of bacterioopsin (Bop) and retinal called bacteriorhodopsin that functions as a light-driven proton pump. A light- and redox-sensing transcription regulator, Bat, regulates critical genes encoding the biogenesis of the purple membrane. To better understand the regulatory network underlying this physiological state, we report a systems approach using global mRNA and protein analyses of four strains of Halobacterium sp.: the wild-type, NRC-1; and three genetically perturbed strains: S9 (bat+), a purple membrane overproducer, and two purple membrane deficient strains, SD23 (a bop knockout) and SD20 (a bat knockout). The integrated DNA microarray and proteomic data reveal the coordinated coregulation of several interconnected biochemical pathways for phototrophy: isoprenoid synthesis, carotenoid synthesis, and bacteriorhodopsin assembly. In phototrophy, the second major biomodule for ATP production, arginine fermentation, is repressed. The primary systems level insight provided by this study is that two major energy production pathways in Halobacterium sp., phototrophy and arginine fermentation, are inversely regulated, presumably to achieve a balance in ATP production under anaerobic conditions.

Adenosine Triphosphate↗
PubMed2002

Influence of contractility on myocardial ultrasonic integrated backscatter and cyclic variation in integrated backscatter.

To evaluate the effects of left ventricular contractility on the changes of average image intensity (AII) of the myocardial integrated backscatter (IB) and cyclic variation in IB (CVIB), 7 adult mongrel dogs were studied. The magnitude of AII and CVIB were measured from myocardial IB carves before and after dobatamine or propranolol infusion. Dobutamine or propranolol did not affect the magnitude of AII (13.8 +/- 0.7 vs 14.7 +/- 0.5, P > 0.05 or 14.3 +/- 0.5 vs 14.2 +/- 0.4, P > 0.05). However, dobutamine produced a significant increase in the magnitude of CVIB (6.8 +/- 0.3 vs 9.5 +/- 0.6, P < 0.001) and propranolol induced significant decrease in the magnitude of CVIB (7.1 +/- 0.2 vs 5.2 +/- 0.3, P < 0.001). The changes of the magnitude of AII and CVIB in the myocardium have been demonstrated to reflect different myocardial physiological and pathological changes respectively. The alteration of contractility did not affect the magnitude of AII but induced significant change in CVIB. The increase of left ventricular contractility resulted in a significant rise of the magnitude of CVIB and the decrease of left ventricular contractility resulted in a significant fall of the magnitude of CVIB.

Adrenergic beta-Agonists↗