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Biomedical subjects

Hua Zhou

Publications and source records attributed to Hua Zhou.

64 records · Page 4Linked to original sources

PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure.

The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.

Animals↗

The induction of heat shock protein-72 attenuates cisplatin-induced acute renal failure in rats.

Induction of heat shock proteins (HSPs) is thought to play a protective role in ischaemic acute renal failure (ARF). However the role of HSPs in nephrotoxic ARF is not well explored. The aim of this study was to clarify the effects of the induction of HSP70s on cisplatin (CDDP) (6 mg/kg i.v.)-induced ARF in rats. Uranyl acetate (UA) or sodium arsenite (SA) were administered i.v. 14 days or 1 day respectively before CDDP injection to induce HSPs. Serum creatinine (SCr), tubular damage score and the numbers of apoptotic (TUNEL-positive) cells were examined 5 days after CDDP injection. The expression of HSP72, B-cell lymphoma gene product-2 (Bcl-2) and Bax were evaluated by Western blot analysis. We also investigated the effect of co-administration of chelerythrine chloride (Chel), which inhibits the induction of HSPs, with SA on the expression of HSP72 and nephrotoxicity. Pretreatment with UA or SA significantly induced renal HSP72 expression. Both UA and SA attenuated the CDDP-induced increase in SCr and tubular damage scores. Co-administration of Chel with SA abolished the SA-induced increment of HSP72 and the beneficial effects of SA. The protective effects of the induction of HSP72 were associated with an increased renal Bcl-2/Bax ratio and the reduction of TUNEL-positive cells in the outer stripe of outer medulla. Our findings suggest that HSP72 attenuates CDDP-induced nephrotoxicity. The protective effects of HSP72 are associated with an increased Bcl-2/Bax ratio and less apoptosis.

Acute Kidney Injury↗

Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment.

UNLABELLED: Bone response under combined mechanical and PTH stimuli is important in osteoporosis. A rat tail animal model with computer modeling was used to examine bone response to loading and PTH. PTH enhances and sustains increased bone formation rate, which directly correlates to mechanical microenvironment, suggesting beneficial effects of combined PTH treatment and exercise in preventing osteoporosis. INTRODUCTION: Using an in vivo rat tail vertebra model combined with a specimen-specific, high-resolution microcomputed tomography (microCT)-based finite element analysis (FEA) technique, trabecular bone response to combined dynamic compressive loading and parathyroid hormone (PTH) stimulation was characterized. MATERIALS AND METHODS: Two hundred twenty-four male Sprague-Dawley rats were randomly divided into seven treatment groups: (1) Control, (2) vehicle + 0N, (3) PTH + 0N, (4) vehicle + 50N, (5) PTH + 50N, (6) vehicle + 100N, and (7) PTH + 100N, with three treatment durations (1, 2, or 4 weeks). Rat PTH(1-34) was administered daily in the PTH-stimulated groups approximately 3 h before daily mechanical stimulation with 0, 50, or 100N dynamic compressive loading. microCT-based FEA was performed for each loaded vertebra after death. Bone histomorphometry was performed on trabecular bone with double fluorochrome labeling to assess bone formation. RESULTS: Daily mechanical loading or PTH administration significantly increased bone formation rate (BFR) compared with control or V + 0N with significant increases in both mineral apposition rate (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical loading, enhanced BFR mainly through a significant increase in MAR after the first week and through a significant increase in LS/BS after 2 and 4 weeks. Synergistic effects in BFR were present when PTH was combined with mechanical loading, especially after 2 and 4 weeks, where the increase in BFR was sustained. However, when either PTH or mechanical loading was the only stimulus, the bone formation response diminished to the level of Control animals after 4 weeks. Furthermore, significant correlations were observed between the bone formation indices and trabecular bone tissue mechanical microenvironments at 1 and 2 weeks, with PTH administration enhancing and sustaining these correlations into 4 weeks. CONCLUSIONS: The synergistic effects of combined PTH and mechanical stimulation on trabecular bone formation rate suggest a potential benefit for combined PTH administration and exercise in the treatment of osteoporosis.

Animals↗

[Effect of coriaria lactone on the ATP-sensitive potassium channels in pyrimidal neurons of rats].

OBJECTIVE: To acquire knowledge about the effect of Coriaria lactone (CL) on ATP-sensitive potassium channels (KATP) in cultured pyrimidal neurons of rats and the role of KATP in epileptogenesis. METHODS: Experiments were conducted by the use of cell culture technique and single channel patch clamp technique. RESULTS: The reversion potential of neuron KATP was nearly 0 mV under the condition of the same high K+ level in both bath solution and pole solution. The channel could be blocked by TEA, and the channel current could be induced by 30 mumol/L DNP but inhibited by 0.5 mol/L ATP. The conductance of KATP channel current was 78.23 +/- 12.04 pS, and this KATP channel could be remarkably activated by CL and specifically blocked by Glibenclamide. CONCLUSION: The activation of neuron KATP may play a role of decreasing the action potential and thus protecting the neurons from the seizure induced by CL.

Adenosine Triphosphate↗

[Enhancement effect of IL-2 on the proliferation of cultured mammary carcinoma cell line Bcap-37].

AIM: To investigate the effects of IL-2 on the proliferation of human mammary carcinoma cell line Bcap-37 and explore its possible mechanism. METHODS: Enhancement effect of IL-2 on proliferation of cultured Bcap-37 cells, the IL-2 expression on the cells, the expressions of IL-2Ralpha, beta, gamma mRNAs in the cells, the effect of IL-2 on DNA content at various periods of cell cycle and on Ca(2+) concentration in the cells were detected or observed by MTT colorimetry, immunohistochemical staining, RT-PCR, flow cytometry and laser scanning confocal microscope, respectively. RESULTS: IL-2 of 1x10(5) to 1x10(6) U/L significantly stimulated the proliferation of cultured Bcap-37 cells. IL-2 was secreted and IL-2Ralpha, beta and gamma were expressed by cultured Bcap-37 cells. IL-2(1x10(5) U/L) increased ratio of Bcap-37 cells in G(2) and S phases and decreased the Ca(2+) release from Bcap-37 cells. CONCLUSION: IL-2 significantly enhance the proliferation of mammary carcinoma cell line Bcap-37. The enhancement effect of IL-2 on Bcap-37 cell proliferation is possibly related to the expression of IL-2R and decreased Ca(2+) concentration in the cells.

Cell Cycle↗

Anabolic action of parathyroid hormone is skeletal site specific at the tissue and cellular levels in mice.

The cellular and molecular events triggering the anabolic response of the skeleton to exogenous parathyroid hormone (PTH) are not well understood. Despite the numerous bone mass studies in rats, few data are available for mice. Therefore, we treated 10-week-old female intact C57BL/6J mice with human PTH(1-34) delivered subcutaneously at a dose of 40 microg/kg per day 5 days a week for 3 weeks and 7 weeks. Bone mineral density (BMD) of total bone, femur, tibia, and lumbar vertebrae was measured weekly by PIXImus. Bone turnover was examined by histomorphometry, and gene expression of bone formation and resorption markers and osteoclastogenesis regulators in the excised femur and tibia was assessed by reverse-transcription polymerase chain reaction (RT-PCR) at 3 weeks and 7 weeks. The PTH-stimulated increase in BMD was more prominent in the tibia and femur than in the lumbar vertebrae, with an anabolic effect detected within 1-2 weeks and BMD continuing to increase. The appearance of a detectable PTH-stimulated increase in BMD was slower in the lumbar vertebrae where the increase was only significant after 7 weeks of treatment. Histomorphometric analysis of the proximal tibia at both 3 weeks and 7 weeks indicated significant time-dependent increases in trabecular area, trabecular number, trabecular and cortical widths, and osteoblast and osteoid perimeters. In the lumbar vertebrae, these stimulatory effects of PTH on trabecular area, trabecular number, and cortical width were smaller and not detected until 7 weeks. PTH-stimulated increases in bone turnover were evident by increased gene expression of osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), and receptor of activator nuclear factor kappaB (NF-kappaB) ligand (RANKL) in the tibia and femur. No significant difference in gene expression was observed between the two long bone sites. In conclusion, PTH exerts an anabolic action at the tissue and cellular levels in intact mice and the magnitude and temporal pattern of this anabolic action, as assessed by densitometry and histomorphometry, are skeletal site specific.

Acid Phosphatase↗

[The role of hyperhomocysteinemia on atherosclerosis in patients with chronic renal failure].

OBJECTIVE: To determine whether atherosclerosis may be accelerated by hyperhomocysteinemia in patients with chronic renal failure (CRF). METHODS: One hundred and ninety-seven CRF patients and 53 healthy volunteers were included in this study. Plasma total homocysteine (tHcy) levels were measured by using fluorescence polarization immunoassay. Intima-media thickness (IMT) and prevalence atherosclerotic plaques of the extracranial common carotid artery were determined by high-resolution B-mode ultrasonography. The changes in brachial artery diameter during reactive hyperemia (D(h)) and after administration of sublingual nitroglycerin (D(n)) were analyzed during ultrasonic examination. RESULTS: The prevalence of hyperhomocysteinemia was 84.4% in the CRF patients. The mean level of tHcy (23.56 +/- 11.91) micro mol/L was significantly higher in the CRF patients than that in the healthy controls (7.97 +/- 2.65) micro mol/L (P < 0.01). The prevalence of atherosclerotic plaques and the mean IMT value of carotid artery were significantly increased in CRF patients compared with that in age-matched controls. Furthermore, arterial dilating function sush as D(h) and D(n) was significantly decreased in CRF patients [(D(h)) (4.05 +/- 3.81)% and (D(n)) (4.94 +/- 4.28)%] compared with that in controls [(D(h)) (8.81 +/- 6.15)% and (D(n)) (11.72 +/- 7.64)%] (P < 0.01). The levels of plasma tHcy were coherent with intensity of atherosclerosis in the CRF patients. Multiple stepwise regression analysis showed that in CRF patients, independent risk factors associated with value of IMT were level of tHcy, age, and duration of dialysis (RR = 0.484, P < 0.001), while those associated with D(h) arterial dilatation were plasma tHcy level, age, duration of dialysis and total cholesterol (RR = 0.263, P < 0.001) and those associated with D(n) were age and tHcy level (RR = 0.211, P < 0.001). CONCLUSION: The results indicate that atherosclerosis and dysfunction of arterial vasodilation in CRF patients are associated with increase of plasma tHcy. Hyperhomocysteinemia may be an independent risk factor for atherosclerosis seen in CRF patients.

Adult↗

[Detect maternal serum fetal DNA for prenatal diagnosis].

OBJECTIVE: To detect maternal serum fetal DNA for prenatal diagnosis of fetal sex. METHODS: Five to ten ml maternal serum was obtained from 24 pregnant women with 16 male fetuses and 8 female fetuses (including 4 carriers with X-linked diseases). The fetal sex was detected by analyzing the karyotype from amniotic fluid and villus. Serum DNA was extracted, nested polymerase chain reaction was employed the male fetal DNA. RESULTS: The sensitivity of the first polymerase chain reaction was 62.5%. The sensitivity of the first and the second reaction was 100%. There was no false positive. Fetal sex of 4 X-linked disease carriers was diagnosed. The determinate rate was 100%. CONCLUSION: Using fetal DNA from maternal serum and nested polymerase chain reaction was a quick, simple and accurate method for prenatal diagnosis of the fetal sex.

Adult↗

Quantification of Aconitum alkaloids in aconite roots by a modified RP-HPLC method.

The three Aconitum alkaloids, aconitine (1), mesaconitine (2) and hypaconitine (3), are pharmacologically active but also highly toxic. A standardised method is needed for assessing the levels of these alkaloids in aconite roots in order to ensure the safe use of these plant materials as medicinal herbs. By optimising extraction, separation and measurement conditions, a reliable, reproducible and accurate method for the quantitative determination of all three Aconitum alkaloids in unprocessed and processed aconite roots has been developed. This method should be appropriate for use in the quality control of Aconitum products. The three Aconitum alkaloids were separated by a modified HPLC method employing a C18 column gradient eluted with acetonitrile and ammonium bicarbonate buffer. Quantification of Aconitum alkaloids, detected at 240 nm, in different batches of samples showed that the content of 1, 2 and 3 varied significantly. In general, the alkaloid content of unprocessed roots was higher than that of processed roots. These variations were considered to be the result of differences in species, processing methods and places of origin of the samples.

Aconitine↗