Biomedical subjects

Hong Jiang

Publications and source records attributed to Hong Jiang.

At least 19 recordsLinked to original sources

PubMed2026

Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration.

Alzheimer's disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8+ T cells correlating with tau pathology severity. However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear. In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8+ T cells into effector cells. We show that tauopathy mice lacking cDC1s or antigen cross-presentation are protected from neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation. The remaining CD8+ T cells exhibit limited clonal expansion, consistent with impaired priming. We further demonstrate that brain-derived antigens are presented in secondary lymphoid tissues, suggesting a site of T cell activation. Together, these findings establish cDC1-dependent peripheral priming as a key driver of CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration.

Journal Article↗

PubMed2026

Intron editing of RISBZ1 confers thermotolerance for grain filling in rice.

RISBZ1 encodes the transcription factor bZIP58, which regulates grain filling; intron editing of RISBZ1 to eliminate aberrant alternatively spliced transcripts increased grain weight without compromising key agronomic traits under normal conditions, and enhanced grain weight and quality under heat stress conditions.

Oryza↗

PubMed2025

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients as an anesthetic and a neuroprotectant used for treating brain injuries. Xe penetrates the blood-brain barrier, which could make it an effective therapeutic. To assess the effect of Xe on microglia and AD pathology, we designed a custom Xe inhalation chamber and treated several mouse models of AD with Xe gas. Xe treatment induced mouse microglia to adopt an intermediate activation state that we have termed pre-neurodegenerative microglia (pre-MGnD). This microglial phenotypic transition was observed in mouse models of acute neurodegeneration and amyloidosis (APP/PS1 and 5xFAD mice) and tauopathy (P301S mice). This microglial state enhanced amyloid plaque compaction and reduced dystrophic neurites in the APP/PS1 and 5xFAD mouse models. Moreover, Xe inhalation reduced brain atrophy and neuroinflammation and improved nest-building behavior in P301S mice. Mechanistically, Xe inhalation induced homeostatic brain microglia toward a pre-MGnD state through IFN-γ signaling that maintained the microglial phagocytic response in APP/PS1 and 5xFAD mice while suppressing the microglial proinflammatory phenotype in P301S mice. These results support the translation of Xe inhalation as an approach for treating AD.

Animals↗

PubMed2024

Solving the 250-year-old mystery of the origin and global spread of the German cockroach, Blattella germanica.

The origin of the German cockroach, Blattella germanica, is enigmatic, in part because it is ubiquitous worldwide in human-built structures but absent from any natural habitats. The first historical records of this species are from ca. 250 years ago (ya) from central Europe (hence its name). However, recent research suggests that the center of diversity of the genus is Asian, where its closest relatives are found. To solve this paradox, we sampled genome-wide markers of 281 cockroaches from 17 countries across six continents. We confirm that B. germanica evolved from the Asian cockroach Blattella asahinai approximately 2,100 ya, probably by adapting to human settlements in India or Myanmar. Our genomic analyses reconstructed two primary global spread routes, one older, westward route to the Middle East coinciding with various Islamic dynasties (~1,200 ya), and another younger eastward route coinciding with the European colonial period (~390 ya). While Europe was not central to the early domestication and spread of the German cockroach, European advances in long-distance transportation and temperature-controlled housing were likely important for the more recent global spread, increasing chances of successful dispersal to and establishment in new regions. The global genetic structure of German cockroaches further supports our model, as it generally aligns with geopolitical boundaries, suggesting regional bridgehead populations established following the advent of international commerce.

Animals↗

PubMed2007

High glucose promotes the production of collagen types I and III by cardiac fibroblasts through a pathway dependent on extracellular-signal-regulated kinase 1/2.

Hyperglycemia promotes fibrosis by increasing collagen synthesis, a process involving mitogen activated protein kinases (MAPKs). Several studies of diabetic cardiomyopathy have demonstrated an accumulation of collagen, including collagen types I and III, in the myocardium, leading to interstitial fibrosis, which is related to left-ventricular diastolic dysfunction. However, the mechanisms of hyperglycemia-induced collagen production in cardiac fibroblasts are poorly defined. In the present study, neonatal rat cardiac fibroblasts treated with high glucose (25 mM) were assessed by real time PCR and enzyme linked immunosorbent assay (ELISA) showed an increase in both the mRNA and protein level of collagen types I and III. These effects were not due to changes in osmotic pressure. Extracellular signal regulated kinase 1/2 (ERK1/2) was activated by high glucose level (25 mM), and treatment with PD98059 to block ERK phosphorylation significantly inhibited the mRNA and protein expression of collagen types I and III. These results suggest that high glucose accelerates the synthesis of collagen types I and III, and an ERK1/2 cascade in cardiac fibroblasts play an essential role in the control of collagen deposition by high glucose.

Animals↗

PubMed2006

Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation.

Telomere shortening limits the proliferative lifespan of human cells by activation of DNA damage pathways, including upregulation of the cell cycle inhibitor p21 (encoded by Cdkn1a, also known as Cip1 and Waf1)) (refs. 1-5). Telomere shortening in response to mutation of the gene encoding telomerase is associated with impaired organ maintenance and shortened lifespan in humans and in mice. The in vivo function of p21 in the context of telomere dysfunction is unknown. Here we show that deletion of p21 prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres. p21 deletion improved hematolymphopoiesis and the maintenance of intestinal epithelia without rescuing telomere function. Moreover, deletion of p21 rescued proliferation of intestinal progenitor cells and improved the repopulation capacity and self-renewal of hematopoietic stem cells from mice with dysfunctional telomeres. In these mice, apoptotic responses remained intact, and p21 deletion did not accelerate chromosomal instability or cancer formation. This study provides experimental evidence that telomere dysfunction induces p21-dependent checkpoints in vivo that can limit longevity at the organismal level.

Animals↗

PubMed2006

Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks.

BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study.

Adolescent↗

PubMed2006

Structure of a NADH-insensitive hexameric citrate synthase that resists acid inactivation.

Acetobacter aceti converts ethanol to acetic acid, and strains highly resistant to both are used to make vinegar. A. aceti survives acetic acid exposure by tolerating cytoplasmic acidification, which implies an unusual adaptation of cytoplasmic components to acidic conditions. A. aceti citrate synthase (AaCS), a hexameric type II citrate synthase, is required for acetic acid resistance and, therefore, would be expected to function at low pH. Recombinant AaCS has intrinsic acid stability that may be a consequence of strong selective pressure to function at low pH, and unexpectedly high thermal stability for a protein that has evolved to function at approximately 30 degrees C. The crystal structure of AaCS, complexed with oxaloacetate (OAA) and the inhibitor carboxymethyldethia-coenzyme A (CMX), was determined to 1.85 A resolution using protein purified by a tandem affinity purification procedure. This is the first crystal structure of a "closed" type II CS, and its active site residues interact with OAA and CMX in the same manner observed in the corresponding type I chicken CS.OAA.CMX complex. While AaCS is not regulated by NADH, it retains many of the residues used by Escherichia coli CS (EcCS) for NADH binding. The surface of AaCS is abundantly decorated with basic side chains and has many fewer uncompensated acidic charges than EcCS; this constellation of charged residues is stable in varied pH environments and may be advantageous in the A. aceti cytoplasm.

Acetobacter↗

PubMed2006

Kohn-Sham perturbation theory: simple solution to variational instability of second order correlation energy functional.

The orbital-dependent correlation energy functional resulting from second order Kohn-Sham perturbation theory leads to atomic correlation potentials with correct shell structure and asymptotic behavior. The absolute magnitude of the exact correlation potential, however, is greatly overestimated. In addition, this functional is variationally instable, which shows up for systems with nearly degenerate highest occupied and lowest unoccupied levels like Be. In this contribution we examine the simplest resummation of the Kohn-Sham perturbation series which has the potential to resolve both the inaccuracy and the instability problem of the second order expression. This resummation includes only the hole-hole terms of the Epstein-Nesbet series of diagrams, which has the advantage that the resulting functional is computationally as efficient as the pure second order expression. The hole-hole Epstein-Nesbet functional is tested for a number of atoms and ions. It is found to reproduce correlation and ground state energies with an accuracy comparable to that of state-of-the-art generalized gradient approximations. The correlation potential, on the other hand, is dramatically improved compared to that obtained from generalized gradient approximations. The same applies to all quantities directly related to the potential, as, for instance, Kohn-Sham eigenvalues and excitation energies. Most importantly, however, the hole-hole Epstein-Nesbet functional turned out to be variationally stable for all neutral as well as all singly and doubly ionized atoms considered so far, including the case of Be.

Journal Article↗

PubMed2006

Abnormal intracellular calcium handling underlying T-wave alternans and its hysteresis.

AIMS: To investigate the mechanism underlying T-wave alternans (TWA) and its hysteresis under ischemia conditions. METHODS: Transmembrane action potential (AP) from endocardial, M, and epicardial cells and monophasic AP (MAP) from four epicardial sites were recorded in ventricular wedge preparation and in isolated intact rabbit heart, respectively. The AP/MAP duration (APD/ MAPD), effective refractory period (ERP), activation time, and APD/MAPD restitution were determined under control and ischemia conditions. The effects of ryanodine (0.01 and 1 micromol x l(-1)) on TWA, and the effects of low extracellular Ca2+ and 4-aminopyridine on its hysteresis were studied. RESULTS: Ischemia shortened the APD/MAPD and effective refractory period of all recording sites symmetrically, except the APD of M cells, which shortened markedly. In the ischemia group, TWA was induced within a cycle length (CL) range from 160 to 250 ms, which corresponded to a diastolic interval region of 0-70 ms. In this diastolic interval region, the repolarization restitution curve was the steepest (slope > 1.0). All TWA were accompanied by repolarization alternations. Low concentration ryanodine (0.01 micromol x l(-1)) facilitated TWA, high concentration (1 micromol x l(-1)) abolished it. Alternans of calcium transient were observed in myocytes purfused with ischemia solution during rapid stimulation. Ryanodine (0.1 micromol x l(-1)) abolished alternans of calcium transient, and ryanodine (0.01 micromol x l(-1)) facilitated them. After 60 min pacing at a CL of 200 ms, TWA persisted until the initial several beats at a CL of 300 ms at which a TWA was exceptional. The suppression of hysteresis by low extracellular Ca2+ and 4-aminopyridine indicated an underlying role of the intracellular Ca2+ overload and transient outward current (I(to)). CONCLUSION: TWA is principally due to repolarization alternans, which is secondary to steep APD/MAPD restitution, and relates to intracellular calcium cycling. Hysteresis relates to intracellular Ca2+ overload and I(to).

4-Aminopyridine↗

PubMed2006

Effects of metoprolol on sympathetic remodeling and electrical remodeling at infarcted border zone after myocardial infarction in rabbits.

BACKGROUND: The findings of sympathetic remodeling and its electrophysiological implications force us to rerecognize the drugs presently used. The aim of this study was to investigate the effects of metoprolol on sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) after myocardial infarction (MI). METHODS: Forty rabbits were randomly assigned into two groups: MI group (n = 20), ligation of the anterior descending coronary; Metoprolol group (n = 20), ligation of the anterior descending coronary and administration of oral metoprolol 5 mg/kg/day. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, TDR and difference of TDR (deltaTDR) during sympathetic nerve stimulation were measured at the IBZ. The distribution and densities of growth associated protein 43 and tyrosine hydroxylase positive nerves at the IBZ were detected with immunohistochemical techniques. RESULTS: The study was completed in the 36 surviving animals (18 rabbits in each group). The densities of growth associated protein 43 and tyrosine hydroxylase positive nerves in the Metoprolol group (2,550 +/- 554 and 1,779 +/- 458 microm2/mm2, respectively) were lower than in the MI group (3,217 +/- 589 and 2,616 +/- 528 microm2/mm2, respectively; both p < 0.01). TDR at baseline, TDR and deltaTDR during sympathetic nerve stimulation were shorter in the Metoprolol group than in the MI group (p < 0.01 for all). CONCLUSION: Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. The association of metoprolol with improved electrical remodeling may be partly related to the inhibition of sympathetic remodeling.

Action Potentials↗

PubMed2006

A novel CRM1-dependent nuclear export signal in adenoviral E1A protein regulated by phosphorylation.

Adenoviral E1A is a versatile protein that can reprogram host cells for efficient viral replication. The nuclear import of E1A is mediated by a nuclear localization signal; however, whether E1A can be actively exported from the nucleus is unknown. We first reported a CRM1-dependent nuclear export signal (NES) in E1A that is conserved in the group C adenoviruses. We showed that CRM1 and E1A coimmunoprecipitated and that blockage of CRM1 function by leptomycin B or small interfering RNA resulted in the nuclear localization of E1A. Through mutational analyses, we identified an active canonical NES element within the E1A protein spanning amino acids 70-80. We further demonstrated that phosphorylation of adjacent serine (S)89 resulted in the cytoplasmic accumulation of E1A. Interestingly, coincident with the accumulation of cells in the S/G2/M phase and histone H1 phosphorylation, E1A was relocated to the cytoplasm at the late stage of the viral cycle, which was blocked by the CDC2/CDK2 inhibitor roscovitine. Importantly, titration of the progenies of the viruses in infected cells showed that the replication efficiency of the NES mutant adenovirus was up to 500-fold lower than that of the wild-type adenovirus. Collectively, our data demonstrate the existence of a NES in E1A that is modulated by the phosphorylation of the S89 residue and the NES plays a role for an efficient viral replication in the host cells.

Active Transport, Cell Nucleus↗

PubMed2006

Expression and characterization of RNA-dependent RNA polymerase of Dendrolimus punctatus tetravirus.

Dendrolimus punctatus tetravirus (DpTV) has been identified as a new member of the genus Omegatetravirus of the family Tetraviridae that may be related serologically to Nudaurelia capensis virus (NomegaV). To establish the function of DpTV RNA genome and to better understand the mechanism of viral replication, the putative RNA-dependent RNA polymerase (RdRp) domain has been cloned and expressed in Escherichia coli. The recombinant protein was purified on a Ni-chelating HisTrap affinity column and demonstrated to initiate viral RNA synthesis in a primer-independent manner but not by terminal nucleotidyle transferase activity in the presence of Mg2+ and RNA template. Mutation of the GDD to GAA interferes with the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive.

Amino Acid Sequence↗

PubMed2006

Predictors of early recurrence and delayed cure after segmental pulmonary vein isolation for paroxysmal atrial fibrillation without structural heart disease.

BACKGROUND: Early recurrence of atrial fibrillation (ERAF) and delayed cure are commonly observed after atrial fibrillation (AF) ablation. The purpose of this study was to determine the predictors of ERAF and delayed cure after a single pulmonary vein isolation (PVI) performed in paroxysmal AF patients without structural heart disease. METHODS AND RESULTS: In 108 consecutive patients (93 men, 15 women; mean age 51 +/- 8 years) with paroxysmal AF and no structural heart disease, segmental PVI guided by a Lasso catheter was performed. Forty-one percent (44/108) AF patients had ERAF after a single PVI. Univariate analysis revealed that left atrial diameter (p = 0.004), age (p = 0.024) and P-wave dispersion (p = 0.045) were significantly related to ERAF. Logistic regression analysis revealed that left atrial enlargement was the only independent predictor of ERAF (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.04-1.30, p = 0.006). Delayed cure occurred in 32% (14/44) patients with ERAF. P-wave dispersion (p = 0.001), left atrial diameter (p = 0.008) were significantly related to delayed cure. P-wave dispersion was the only independent predictive factor of delayed cure (OR 0.91; 95% CI 0.85-0.97, p = 0.004). CONCLUSIONS: Elderly patients with left atrial enlargement and a high dispersion of P wave are susceptible to ERAF after a single PVI. Left atrial enlargement is the only independent predictor of ERAF. Among patients with ERAF, those with less P-wave dispersion and less left atrial diameter have a higher probability of delayed cure. P-wave dispersion can independently predict delayed cure.

Adult↗

PubMed2006

Saliva cortisol and response to dexamethasone in children of depressed parents.

BACKGROUND: Major depression (MDD) is heritable, and children of depressed parents are at higher risk for the development of depression. However, depression in a parent might also act as a stressor leading to increased activation of neuroendocrine stress circuits. To address this question we examined saliva cortisol in children whose parents have a history of MDD. METHODS: We recruited 15 families with one parent with MDD (26 prepubertal children) and 16 control families without history of parental MDD (32 prepubertal children). All parents and children underwent Structured Clinical Interview for DSM-IV and Kiddie Schedule For Affective Disorders And Schizophrenia interviews, respectively. Families were asked to collect morning, afternoon, and bedtime saliva samples for 4 days for 2 weeks. At bedtime of the 3rd day, dexamethasone was administered. Two doses, standard and low, were used in each family. RESULTS: The majority of children demonstrated no psychiatric diagnosis. Children with MDD parents showed higher cortisol basally and higher cortisol after both 25 mg and 5 mg dexamethasone. However, this effect occurred predominantly in children whose parents were currently depressed. There were strong correlations for cortisol between parents and children (r = 52 in depressed; r = 499 in control). CONCLUSIONS: Elevated cortisol and impaired feedback seemed to reflect an environmental effect of MDD in a parent.

Adult↗

PubMed2006

Comparison of cerebral blood volume and permeability in preoperative grading of intracranial glioma using CT perfusion imaging.

INTRODUCTION: Regional cerebral blood volume (rCBV) and permeability surfaces (rPS) permit in vivo assessment of glioma microvasculature, which provides quite important pathophysiological information in grading gliomas. The aim of our study was to simultaneously examine rCBV and rPS in glioma patients to determine their correlation with histological grade using CT perfusion imaging. METHODS: A total of 22 patients with gliomas underwent multislice CT perfusion imaging preoperatively. Low-grade and high-grade groups were categorized corresponding to WHO grade II gliomas and WHO grade III or IV gliomas, respectively, as determined by histopathological examination. rCBVs and rPSs were obtained from regions of maximal abnormality in tumor parenchyma on CBV and PS color perfusion maps. Perfusion parameters were compared using the Kruskal-Wallis test in order to evaluate the differences in relation to tumor grade. The Pearson coefficients of rCBV and rPS for each tumor grade were assessed using SPSS 13.0 software. RESULTS: rCBV and rPS provided significant P-value in differentiating glioma grade (low-grade gliomas 3.28+/-2.01 vs 2.12+/-3.19 ml/100 g/min, high-grade gliomas 8.87+/-4.63 vs 12.11+/-3.18 ml/100 g/min, P<0.05). Receiver operating characteristic (ROC) curves revealed better specificity and sensitivity in PS than in CBV for glioma grade. A significant correlation between rCBV and rPS was observed in high-grade gliomas (r=0.684). rCBVs in oligodendrogliomas were higher than in other low-grade gliomas, whereas their rPS values did not show a parallel difference. CONCLUSION: Perfusion CT provides useful information for glioma grading and might have the potential to significantly impact clinical management and follow-up of cerebral gliomas.

Adolescent↗

PubMed2006

The research of molecular and ionic mechanisms in vagally mediated atrial fibrillation in canine.

BACKGROUND: The reentrant mechanism of vagally mediated AF is not clearly elucidated. METHODS AND RESULTS: After vagal stimulation, thirty dogs were divided AF group (AF could be induced) and control group (AF could not be induced). Western blot and patch clamp were used to determine M(2) receptor and I(K,ACh) in left atrial appendage (LAA), right atrial appendage (RAA), left atrium (LA), right atrium (RA), pulmonary veins (PVs) and superior vena cava (SVC). In control group, the densities of M(2) receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PVs and SVC. However, there was no significant difference in LAA, RAA and LA. In AF group, the densities of M(2) receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PVs and SVC. Furthermore, the densities of the M(2) and I(K,ACh) in LAA and RAA were higher than that in LA. CONCLUSIONS: Atrial appendage perhaps play an important role in initiation of cholinergic AF. However, PVs and SVC less often play an important role in vagotonic paroxysmal AF.

Animals↗

PubMed2006

Detection of H. pylori antibody profile in serum by protein array.

AIM: To detect multiple H. pylori antibodies in serum samples of individuals who carry H. pylori by protein array. METHODS: Recombinant H. pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal. RESULTS: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H. pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min. CONCLUSION: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H. pylori.

Antibodies, Bacterial↗