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Biomedical subjects

Song Zhang

Publications and source records attributed to Song Zhang.

At least 19 recordsLinked to original sources

PIEZO1 Mediates Myoblast Proliferation Under Simulated Microgravity.

Skeletal muscle atrophy is a major health risk of prolonged spaceflight, yet how microgravity reshapes muscle cells through mechanotransduction remains poorly understood. Here, we examined the mechanosensitive cation channel PIEZO1 in myoblast proliferation under simulated microgravity. Using a two-dimensional clinostat combined with Hi-C-based 3D genomics, transcriptomics, and functional assays, we found that simulated microgravity promotes C2C12 myoblast proliferation and upregulates Piezo1. Piezo1 mRNA knockdown reduced both proliferation and depolarization-induced Ca2 + influx, each partially restored under simulated microgravity, consistent with PIEZO1 being a central mediator of the response. Simulated microgravity also drove extensive 3D genome reorganization alongside changes in proliferation-related gene expression. Integrating chromatin architecture with transcriptomics, we found that PIEZO1 inhibition increased Elavl2 mRNA expression, PIEZO1 activation suppressed Elavl2 mRNA expression, and Elavl2 mRNA knockdown enhanced cell proliferation. These findings define a PIEZO1-ELAVL2 mechanotransduction axis, coupled to 3D chromatin remodeling, that regulates myoblast proliferation under simulated microgravity, and thus may be a target for countering spaceflight-associated muscle dysfunction.

Cell Proliferation↗

Expression of orexin receptors in the brain and peripheral tissues of the male sheep.

Orexins exert their effects through two specific receptors (OX1R and OX2R) that have been found mainly in the brain and also in peripheral tissues of rats and humans. Here, we demonstrate expression of mRNA encoding for ovine OX1R and OX2R in central and peripheral tissues of sheep. Gene expression for orexin receptors in the hypothalamus and the preoptic area was localised by in situ hybridisation. OX1R was detected in arcuate nuclei (ARC), median eminence (ME), the lateral hypothalamic nuclei and preoptic area (POA) and it was scattered along the third ventricle from the paraventricular (PVN) to the ventromedial hypothalamic nuclei (VMH). OX2R was localised in the PVN, ARC, ME, ventral VMH and a small region of the ventral POA. Gene expression for OX1R and OX2R in central and peripheral tissues was analysed using quantitative real time RT-PCR. Both orexin receptor genes were expressed in the hypothalamus, POA, hippocampus, amygdala, olfactory bulb, pineal gland and recess and pituitary gland, whereas only OX1R mRNA was detected in the testis, kidney and adrenal gland. The expression of the genes for orexin receptors in this range of ovine tissues suggests roles for orexins in multiple physiological functions, with actions at both central and peripheral levels.

Animals↗

Predicting pregnancy-induced hypertension with dynamic hemodynamics.

AIM: To study dynamic changes in the hemodynamic parameters in pregnant women during different weeks of gestation and to comprehend changes to the cardiovascular system in normal pregnant women and in patients with pregnancy-induced hypertension (PIH), with the object of finding predictors of pregnancy-induced hypertension. METHODS: Radialis artery pulse waves of 132 pregnant women were examined from 10 weeks of gestation onward, and the subjects' hemodynamics were examined every 4 weeks. RESULTS: In the women with PIH hemodynamic changes occurred earlier than the onset of disease and even presented in early pregnancy; there might be another mode, and there were factors disturbing the blood pressure modulating mechanism. CONCLUSION: The prediction of PIH from the dynamic changes in hemodynamic parameters has significant implications for clinical practice.

Adult↗

Long-term care placement of dementia patients and caregiver health and well-being.

CONTEXT: Placing a relative with dementia into a long-term care facility is common among caregivers. Placement transition and factors that affect caregiver health and well-being after placement of the patient are not well described. OBJECTIVE: To assess the impact of placing a relative with dementia in a long-term care facility on caregivers' health and well-being. DESIGN, SETTING, AND PARTICIPANTS: Prospective study from 1996 to 2000 of the placement transition in a sample of 1222 caregiver-patient dyads recruited from 6 US sites. A total of 180 patients were placed in a long-term care facility during the 18-month follow-up period. Data collected before and after placement were analyzed to identify factors associated with placement, the nature of contact between caregivers and their institutionalized relatives after placement, and the relation of both of these factors to health outcomes among dementia caregivers. MAIN OUTCOME MEASURES: Caregiver depression (symptoms on the Center for Epidemiological Studies-Depression [CES-D] scale; range, 0-60) and anxiety (State Trait Inventory; range, 10-40) and use of prescription medications for depression and anxiety. RESULTS: Caregivers who institutionalized their relative reported depressive symptoms and anxiety to be as high as they were while in-home caregivers. Overall CES-D scores for depression did not change from before to after placement (median [IQR], 15.0 [8-24.5] and 15.0 [7.7-28]; P =.64). Overall anxiety scores on the State Trait Inventory also did not change significantly (median [IQR], 22.0 [19-27] before vs 21.1 [18-27] after; P =.21). These effects were most pronounced among caregivers who were married to the patient (P =.02 for depression), visited more frequently (P =.01 for depression and P<.001 for anxiety), and were less satisfied with the help they received from others (P =.003 for depression and P<.001 for anxiety). The use of antidepressants did not change significantly before (21.1%) to after (17.9%) placement (P =.16). The use of anxiolytics before to after placement increased from 14.6% to 19% (P =.02), and nearly half of caregivers (48.3%) were at risk for clinical depression following placement of their relative. CONCLUSIONS: The transition to institutional care is particularly difficult for spouses, almost half of whom visit the patient daily and continue to provide help with physical care during their visits. Clinical interventions that better prepare the caregiver for a placement transition and treat their depression and anxiety following placement may be of great benefit to these individuals.

Aged↗

Controlled protein assembly on a switchable surface.

The strategy presented in this work supplies a general method of controlling protein assembly on a switchable low-density SAM, which may open a new way to design functional biocomposite films for biosensors or protein chips.

Protein Engineering↗

Mass analyzed threshold ionization spectroscopy of 5-methylindole and 3-methylindole cations and the methyl substitution effect.

The vibrationally resolved mass analyzed threshold ionization spectra of jetcooled 5-methylindole (5MI) and 3-methylindole (3MI) have been recorded by ionizing via various vibronic levels of each species. The adiabatic ionization energies (IEs) of 5MI and 3MI are determined to be 61,696+/-5 and 60,679+/-5 cm(-1), which are less than that of indole by 895 and 1912 cm(-1), respectively. Comparing these data with those of 1-methylindole and indole suggests that the methyl substitution on the pyrrole part leads to a greater redshift in the IE than on the benzene part. These experimental findings are well supported by the theoretical calculations. Analysis on these new data shows that many active vibrations of the 5MI cation are related to the CH(3) torsion and in-plane ring bending vibrations. In contrast, the observed vibrational bands of the 3MI cation are very weak due to unfavorable Franck-Condon transition.

Journal Article↗

Visualization and analysis of white matter structural asymmetry in diffusion tensor MRI data.

This work presents a method that permits the characterization, quantification, and 3D visualization of white matter structural information contained within diffusion tensor MR imaging (DT-MRI) data. In this method, regions within the brain are defined as possessing linear, planar, or spherical diffusion. Visualization of this diffusion metric data is realized by generating streamtube and streamsurface models to represent regions of linear and planar diffusion. Quantification of differences in diffusion anisotropy between different regions of interest (ROIs) is then achieved by analyzing 2D barycentric histograms created from the complete distribution of diffusion metric values measured in each region. In four healthy volunteers, there was only a small degree of asymmetry (epsilon) in the number of linear, planar, or spherical diffusion voxels between the right and left hemispheres (epsilon approximately equal to +/- 2%). However, in a patient with a metastatic brain lesion there was marked asymmetry in both linear (epsilon approximately -10%) and planar (epsilon approximately equal to 5%) diffusion between comparable ipsilateral and contralateral regions, with a significant reduction in the number of linear diffusion voxels and an increase in the number of planar diffusion voxels in the tumor-bearing hemisphere. These results demonstrate the potential of this approach to characterize brain structure in both healthy and diseased subjects.

Adenocarcinoma↗

[Clinical efficacy and side effects of STI571 in treatment of patients with chronic myeloid leukemia].

BACKGROUND & OBJECTIVE: The aberrant regulation of the protein tyrosine kinase (PTK) activity of P210(BCR-ABL), which is the protein product of Bcr-Abl fusion gene leads to the pathogenesis of chronic myeloid leukemia (CML). Though STI571 can inhibit specifically the PTK activity of P210(Bcr-Abl) and greatly improve the clinic curative effect on CML in chronic phase, its effect on CML in accelerated phase and blast crisis is not clear. In this article, we attempted to analyze the clinic efficacy and side effect of STI571 treatment on CML patients in different phase. In addition, we analyzed the potential mechanism of STI571 resistance in accelerated/blast crisis CML with genetic methods. METHODS: A total of 22 cases of CML, 14 cases male and 8 female, 6 cases in chronic phase and 16 cases in accelerated/blast crisis phase, were treated with STI571. According to the efficacy standard, the hematological and cytogenetic response of 22 cases CML were analyzed, by determining the positive rate of Ph chromosome in bone marrow from the patients treated with STI571 for 3 months. Furthermore, the karyotype evolution of those patients showing STI571 resistance was analyzed. At the same time, the side effects and adverse events of STI571 treatment were evaluated. RESULTS: 6/6(100%) cases of CML patients in chronic phase acquired hematological CR and cytogenetic response. 4/16(25%) cases in accelerated phase or blast crisis acquired hematological CR and 8/16(50%) cases acquired cytogenetic response. 3 CML patients in blast crisis showed secondary STI571 resistance. The karyotype analysis shows 2 with 2 Ph chromosome and other additional abnormality. I/II grade non-hematological toxicity was observed in all the patients, including edema (77.3%), side effects of digestive system (36.4%) and myalgia (22.7%) et al. Severe hematological toxicities includes:(1)III/IV grade neutropenia (9 cases):1/6 cases of CML patients in chronic phase, 8/16 cases in accelerated phase or blast crisis; (2)III/IV grade thrombocytopenia (6 cases): 6/16 cases in accelerated phase or blast crisis. The percentage of III/IV grade neutropenia/thrombocytopenia in chronic phase and accelerated/blast crisis phase was compared and no significant statistical difference was observed. CONCLUSIONS: Hematological and cytogenetic responses of different degrees can be acquired in CML-CP and CML-AP/BC patients treated with STI571 and showing statistic difference. STI571 improves the clinic curative effect greatly on CML in chronic phase. CML patients in blast crisis have secondary STI571 resistance with novel 2 Ph chromosome and other additional abnormality, it furnishes the evidence of the gene changes. The slightness of non-hematological toxicity of STI571 in the treatment of chronic myeloid leukemia suggests this drug is relatively safe. Severe hematological toxicities, such as III/IV neutropenia and thrombocytopenia, are more common in accelerated/blast crisis than in chronic phase.

Adolescent↗

[The anti-tumor effects of dendritic cells co-cultured with cytokine induced killer cells after chemotherapy].

OBJECTIVE: To determine the changes in phenotype, proliferation activity and cytotoxicity of cytokine induced killer (CIK) cells after in vitro co-culturing with dendritic cells (DC), and then to investigate the auxiliary therapeutical effect of CIK cells after chemotherapy. METHODS: DC and CIK cells were generated by culturing prepheral blood mononuclear cells (PBMC) of healthy blood donors. Then the changes in the proliferation activity and phenotype of the cells were determined after DC and CIK cell co-culture. MTT assays were used to determine the cytotoxicity in vitro. The antitumor activity of DC and CIK cells were evaluated after chemotherapy in BALB/c nude mice bearing A549 lung cancer and BEL-7404 liver cancer respectively. RESULTS: DC and CIK cells promoted the antitumor effect of chemotherapy. Co-culture of DC with CIK cells produced a new cell population, whose cytotoxicity and proliferation activity were much higher than those of CIK cells. CONCLUSION: CIK cells co-cultured with DC are more potent than CIK cells alone in the anti-tumor effect.

Animals↗

[Promoter hypermethylation of DNA repair gene O6-methylguanine DNA methyltransferase in laryngeal squamous cell carcinoma].

OBJECTIVE: O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein. It plays a important role in the repair of DNA damage caused by the exposure to methylating agents. Hypermethylation of CpG islands in the promoter regions result in MGMT genes loss of transcription. This study explored the hypermethylation of CpG islands in the promoter regions of MGMT genes in laryngeal squamous cell carcinoma. METHODS: Methylation-specific PCR and semiquantify RT-PCR were used to study the promoter methylation of the MGMT gene and loss of transcription in laryngeal carcinoma tissues, tissues adjacent to the tumor and normal laryngeal tissues. RESULTS: Among the 46 laryngeal carcinoma, MGMT gene hypermethylation was present in 16 cases (34.8%). MGMT hypermethylation was not detected in all tissues adjacent to the tumors and 5 normal tissues. There is no statistical significant difference of promoter hypermethylation among the samples of different histological grade (chi2 = 3.130, P = 0.077) or samples from patients with different TNM stages (chi2 = 3.957, P = 0.138). No expression of MGMT mRNA was found in all hypermethylated laryngeal carcinoma tissues. Expression of MGMT mRNA was detected in all unmethylated laryngeal carcinoma tissues, tissues adjacent to the tumors and 5 normal tissues. Expression of MGMT mRNA in unmethylated laryngeal carcinoma tissues is higher than tissues adjacent to the tumors (t = 30.540, P < 0.01) and normal tissues (t = 31.882, P < 0.01). There is no statistical significant difference of MGMT mRNA expression between tissues adjacent to the tumors and normal tissues (t = 0.419, P = 0.677). CONCLUSION: MGMT gene promoter hypermethylation is associated with loss of its transcription.

Adult↗

[Proteome analysis of apoptotic K562 cells induced by harringtonine].

OBJECTIVE: To screen and identify apoptosis related proteins and explore the mechanism of harringtonine (HT)-induced K562 cells apoptosis. METHODS: Flow cytometry was used to distinguish K562 cells in the earlier stage of apoptosis from those in the later stage of apoptosis by annexin V and PI staining. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) coupled with computer image analysis was used to detect the changes in protein expression in the two stages of apoptosis. Proteins were identified by peptide mass fingerprint in combination with database searching. RESULTS: K562 cells treated with HT for 5 and 24 hours were in the early and later stages of apoptosis respectively. Statistical analysis showed 3 spots disappeared, 7 spots with decreased intensity and 10 spots with increased intensity in the 24 h HT induced apoptotic cells as compared with that in 5 h HT induced ones. Ten spots were selected on the basis of the intensity and the significant changes in abundance. Among them, 5 apoptosis related proteins were successfully identified by MALDI-TOF: keratin 9, BTF3, TrpRS, RS and prohibitin. CONCLUSIONS: Up-regulation of TrpRS, RS, prohibitin and down-regulation of BTF3 were involved in inhibition of transcription and protein synthesis in the apoptotic K562 cells induced by HT, whereas up-regulation of keratin 9 was related to apoptosis resistance.

Apoptosis↗

[Two-dimensional polyacrylamide gel electrophoresis analysis of apoptosis in K562 cells induced by harringtonine].

BACKGROUND & OBJECTIVE: Harringtonine (HT),an anti-tumor drug,has been widely used to treat acute or chronic myeloid leukemia,and obtained satisfactory effects. Studies showed that the anti-tumor activity of HT is related with the apoptosis-inducing effect,but the molecular mechanisms remain unclear. This study was to analyze the protein maps contributed to the apoptosis in K562 cells induced by HT,and to screen the apoptosis-associated proteins. METHODS: Flow cytometry was used to distinguish K562 cells of early apoptosis stage from those of late apoptosis stage through Annexin V and PI staining. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to separate and compare the HT-induced apoptotic K562 cells and control K562 cells. RESULTS: When K562 cells were treated with 10 microg/ml HT for 5,a nd 24 hours,percentages of early apoptotic cells (Annexin V+/PI-) were 28.3%, and 18.1%(P< 0.01), while percentages of late apoptotic cells (Annexin V+/PI+) were 9.1%,and 20.2% (P< 0.01), respectively. Statistical analysis showed (1300+/-50) protein spots were resolved with a match rate of (88.3+/-2.0)% in control K562 cells. Ten protein spots in late apoptotic cells displayed changes in expression after induction of HT for 24 hours (P< 0.01), of which 8 showed higher expression, 1 decreased,and 1 only expressed in control k562 cells. CONCLUSION: These proteins may be apoptosis-associated proteins of K562 cells induced by HT.

Antineoplastic Agents, Phytogenic↗

[Mutation of mitochondrial DNA 4977 bp deletion in laryngeal squamous cell cancer].

BACKGROUND & OBJECTIVE: The 4977 bp deletion of mitochondrial DNA is a molecular marker of cell ageing, and some solid tumors. This study was to detect deletion of mitochondrial DNA 4977 bp in laryngeal squamous cell cancer, and explore its correlation with differentiation of laryngeal cancer tissues. METHODS: Thirty-five specimens were collected from patients with pathologically diagnosed laryngeal squamous cell cancer. The total DNA was amplified to identify the 4977 bp deletion of mitochondrial DNA by polymerase chain reaction (PCR), and PCR products were verified by direct sequencing. RESULTS: The 4977 bp deletion detected in 20 of 35 cancer tissues (57.14%), including 5 of 7 with well differentiation, 15 of 24 with moderate differentiation, and 0 of 4 with poor differentiation. Mutation incidence of cancer tissues with well or moderate differentiation were significantly higher than that of cancer tissues with poor differentiation, but there was no significant difference between cancer tissues with well and moderate differentiation. CONCLUSION: The 4977 bp deletion of mitochondrial DNA was detected in laryngeal squamous cell cancer tissues, it might be relates to differentiation of cancer tissues.

Adult↗

[Hypermethylation of the death-associated protein kinase promoter in laryngeal squamous cell cancer].

OBJECTIVE: To explore the relationship between hypermethylation of the promoter of death-associated protein kinase (DAPK) gene and laryngeal squamous cell cancer. METHODS: Promoter hypermethylation and mRNA expression of DAPK gene were detected by methylation-specific PCR, RT-PCR and gene sequencing. RESULTS: Among the 58 patients with laryngeal squamous cell cancer, hypermethylation of DAPK promoter was detected in 39 cases (67.2%). There was no significant difference in hypermethylation in relation to pathological grade and clinical staging, but a highly significant difference was observed between patients with and without lymph node metastasis (N0 and N1) (P < 0.001). DAPK promoter hypermethylation was detected in tumor adjacent tissues in 6 of the 58 cases. DAPK mRNA was not expressed in all laryngeal squamous cell cancers having hypermethylation of DAPK promoter, whereas it was expressed in normal laryngeal mucosa, laryngeal squamous cell cancers without hypermethylation and tumor adjacent tissues. CONCLUSION: Hypermethylation of DAPK promoter is associated with loss of its transcription in laryngeal squamous cell carcinoma. The high frequency hypermethylation of DAPK promoter illustrates its potential clinical application as tumor marker for diagnosis and prognosis.

Adult↗

End-of-life care and the effects of bereavement on family caregivers of persons with dementia.

BACKGROUND: Although family caregiving has been intensively studied in the past decade, little attention has been paid to the impact of end-of-life care on caregivers who are family members of persons with dementia or to the caregivers' responses to the death of the patient. METHODS: Using standardized assessment instruments and structured questions, we assessed the type and intensity of care provided by 217 family caregivers to persons with dementia during the year before the patient's death and assessed the caregivers' responses to the death. RESULTS: Half the caregivers reported spending at least 46 hours per week assisting patients with activities of daily living and instrumental activities of daily living. More than half the caregivers reported that they felt they were "on duty" 24 hours a day, that the patient had frequent pain, and that they had had to end or reduce employment owing to the demands of caregiving. Caregivers exhibited high levels of depressive symptoms while providing care to the relative with dementia, but they showed remarkable resilience after the death. Within three months of the death, caregivers had clinically significant declines in the level of depressive symptoms, and within one year the levels of symptoms were substantially lower than levels reported while they were acting as caregivers. Seventy-two percent of caregivers reported that the death was a relief to them, and more than 90 percent reported belief that it was a relief to the patient. CONCLUSIONS: End-of-life care for patients with dementia was extremely demanding of family caregivers. Intervention and support services were needed most before the patient's death. When death was preceded by a protracted and stressful period of caregiving, caregivers reported considerable relief at the death itself.

Activities of Daily Living↗

Effect of multicomponent interventions on caregiver burden and depression: the REACH multisite initiative at 6-month follow-up.

Meta-analysis was used to examine pooled parameter estimates of 9 active compared with 6 control conditions of the Resources for Enhancing Alzheimer's Caregiver Health (REACH) project at 6 months on caregiver burden and depressive symptoms. Associations of caregiver characteristics and outcomes were examined. For burden, active interventions were superior to control conditions (p = .022). Also, active interventions were superior to control conditions for women versus men and for caregivers with lower education versus those with higher education. For depressive symptoms, a statistically significant association of group assignment was found for Miami's family therapy and computer technology intervention (p = .034). Also, active interventions were superior to control conditions for Hispanics, nonspouses, and caregivers with lower education. Results suggest interventions should be multicomponent and tailored.

Aged↗

Using a new taxonomy to combine the uncombinable: integrating results across diverse interventions.

Researchers have examined numerous psychosocial and behavioral interventions intended to alleviate distress among family caregivers of persons with dementia. Many of these interventions are complex, combining numerous treatment components. Although some multicomponent interventions have been successful in reducing caregiver distress, the impact of specific elements of these interventions on outcomes is not known. The article presents results of an analytic approach that allows researchers to describe the individual elements of multicomponent interventions and to examine the relationships between those components and outcomes. This approach is successfully applied to interventions being evaluated in the Resources for Enhancing Alzheimer's Caregiver Health (REACH) program. The results indicate that actively targeting caregiver behavior is effective in achieving positive outcomes with respect to caregiver depression.

Aged↗

[Detection of core-binding factor in acute leukemia with interphase fluorescence in situ hybridization].

OBJECTIVE: To detect the chromosomal abnormalities involving the core-binding factor (CBF) in acute leukemia at initial diagnosis with interphase in situ hybridization (I-FISH) technique, and monitor the minimal residual disease (MRD) after treatment with I-FISH. This study also aim to compare the sensitivity of I-FISH at initial diagnosis with that of conventional G-banding analysis. METHODS: Based on the diagnosis of bone marrow morphology, 15 acute leukemia patients were examined with conventional G-banding and I-FISH techniques. Seven of these patients were monitored for MRD with I-FISH after treatment. RESULTS: On the basis of the false-positive rate acquired from normal subjects, the normal cutoff values of the 3 probes including AML1/ETO translocation probe, MYH11 breakpoint region probe and ETV6/AML1 translocation probe were 4.13%, 1.95% and 2.12% respectively. With conventional G-banding analysis, 40% (6/15) patients were found with chromosomal abnormality involving CBF, including 5 of the 8 M2 patients with t (8;21) and 1 of the 2 M4EO patients with inv (16). No B-ALL cases were identified with t (12;21). With I-FISH, however, 80% (12/15) of the cases were found with genetic abnormality involving CBF, including all the 8 M2 cases with AML1/ETO fusion gene, both of the M4EO cases with CBFbeta/MYH11 and 2 of the 5 B-ALL cases with ETV6/AML1. In the 7 cases monitored for MRD level with I-FISH, 2 M2 cases and 1 B-ALL case were with positive results. CONCLUSIONS: I-FISH is more sensitive than conventional G-binding analysis in detecting the chromosomal abnormalities involving CBF in acute leukemia. At the time of initial diagnosis, combination of the two techniques may lead to more comprehensive and accurate results.

Adolescent↗