Therapeutic effects of atorvastatin on doxorubicin-induced hepatotoxicity in rats via antioxidative damage, anti-inflammatory, and anti-lipotoxicity.

Doxorubicin (DOX), is a high efficiency anthracycline antitumor drug. However, the clinical application of DOX is limited mainly by dose-related adverse drug reactions. Currently, the therapeutic effects of Atorvastatin (ATO) on DOX-induced hepatotoxicity were studied in vivo. The results indicated that DOX impaired hepatic function, as measured by an increased levels of liver weight index and serum concentrations of aspartate transaminase and alanine transaminase, as well as alteration of hepatic histology. In addition, DOX increased the serum levles of triglyceride (TG) and nonestesterified fatty acid. ATO prevented these changes. Mechanical analysis revealed that ATO restored the changes of malondialdehyde, reactive oxygen radical species, glutathione peroxidase and manganese superoxide dismutase. Additionally, ATO inhibited the increased expression levels of nuclear factor-kappa B and interleukin 1ß, hence suppressing inflammation. Meanwhile, ATO inhibited cell apoptosis by dramatically decreasing the Bax/Bcl-2 ratio. In addition, ATO mitigated the lipidtoxicity by inhibiting the adipolysis of TG and accelerating hepatic lipid metabolism. Taken together, the results suggest ATO has therapeutic effect on DOX-induced hepatotoxicity via inhibition of oxidative damage, inflammatory and apoptosis. In addition, ATO attenuates DOX-induced hyperlipidemia via modulation of lipid metabolism.

JTC-801 inhibits the proliferation and metastasis of ovarian cancer cell SKOV3 through inhibition of the PI3K - AKT signaling pathway.

Ovarian cancer (OC) is the commonest cause of gynaecological cancer-associated death because of the wide metastasis and frequent recidivation. JTC-801 is a new synthetic compound with the function of reversing pain and anxiety symptoms as a selective opioid receptor-like1 receptor (belonging to the G-protein-coupled receptor) antagonist. We investigated the role and possible mechanisms of JTC-801 in the cell growth and metastasis of OC. It was observed that JTC-801 inhibited the proliferation, invasion and migration of cancer in SKOV3 cells. The apoptosis rate of SKOV3 cells treated with JTC-801 was significantly increased (P<0.05), and the expression results of relevant apoptosis proteins (BCL2, BAX, Active Caspase-3) indicated the JTC-801 could induce the apoptosis of SKOV3. Further, the expression levels of phosphorylated AKT, phosphorylated mTOR, P70 and CyclinD1 in the PI3K/AKT signaling pathway were obviously reduced in the JTC-801 treated SKOV3 group. This suggests that JTC-801 exerts its anticancer effect through the PI3K/AKT signaling pathway. Our data also highlights the possibility of using JTC-801 as a novel therapeutic drug for OC treatment mean while it plays the analgesic effect.

Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma.

BACKGROUND/AIM: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. PATIENTS AND METHODS: One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. RESULTS: There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. CONCLUSION: The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia.

Nanoparticles based on phenylalanine ethyl ester-alginate conjugate as vitamin B2 delivery system.

Phenylalanine ethyl ester (PAE)-alginate (Alg) conjugate (PAE-Alg, PEA) was synthesized and formation of an amide bond between PAE and Alg was confirmed by Fourier transformed-infrared and (1)H nuclear magnetic resonance spectroscopy. The degree of PAE substitution was 3.5-4.7 (PAE group per hundred sugar residues of Alg) which was determined by elemental analysis. The critical aggregation concentration values determined for PEA conjugates PEA1, PEA2, and PEA3 were 0.20, 0.12, and 0.10 mg/ml, respectively. The particle size of PEA nanoparticles (PEA-NPs) decreased from 425 nm to 226 nm with the increasing degree of PAE substitution. Vitamin B2 (VB2), as a model nutrient, was encapsulated into the nanoparticles. The drug-loading content increased with increasing degree of PAE substitution. The maximum VB2 loading capacity and loading efficiency of PEA3 nanoparticles were 3.53 ± 0.03% and 91.48 ± 0.80%, respectively. The in vitro release behavior of VB2 from the PEA-NPs showed a biphasic release profile with an initial burst release of about 40-50% of VB2 in the first 10 h followed by a steady and continuous release phase for the following 50 h in PBS, pH 7.4. The human colorectal carcinoma cell line was used to investigate the cytotoxicity of PEA-NPs. Our results showed that various concentrations of nanoparticles did not cause significant cytotoxicity against cell lines at normal concentrations.

Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes.

BACKGROUND: Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. METHODS: After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH) and low-affinity current (IPL), α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. RESULTS: After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. CONCLUSIONS: These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane.

Prospective Blinded Comparison of Computed Tomographic Enterography and Small Bowel Endoscopy in Obscure Gastrointestinal Bleeding.

BACKGROUND/AIMS: This study investigated the value of computed tomographic enterography with new techniques, such as multi-planar reformation, curved planar reformation, and blood vessel reformation technique, in evaluation of obscure gastrointestinal bleeding by comparing computed tomographic enterography and small bowel endoscopy. METHODOLOGY: We retrospectively evaluated 30 patients with pathologically proven obscure gastrointestinal bleeding. Patients with acute gastrointestinal bleeding were excluded. All patients successfully underwent computed tomographic enterography and small bowel endoscopy at Yantai Yuhuangding Hospital. Results of both methods in the same patient were compared with pathologic biopsy results from clinical operations or endoscopy. RESULTS: Among the 30 patients retrospectively examined by computed tomographic enterography and small bowel endoscopy, the clinical diagnostic accuracy of the two methods was 70% (21/30) and 80% (24/30), respectively. Computed tomographic enterography and small bowel endoscopy showed no statistical difference in the diagnosis of obscure gastrointestinal bleeding (P = 0.37). CONCLUSIONS: Computed tomographic enterography can supplement or partly replace small bowel endoscopy in the diagnosis of obscure gastrointestinal bleeding. Computed tomographic enterography not only costs patients less and causes them less suffering, but is also technically easy to perform.

Crosstalk between dopamine receptors and the Na⁺/K⁺-ATPase (review).

Dopamine (DA) receptors, which belong to the G protein-coupled receptor family, are the target of ~50% of all modern medicinal drugs and constitute a large and diverse class of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. Na+/K+-ATPase (NKA) is ubiquitous and crucial for the maintenance of intracellular ion homeostasis and excitability. Furthermore, it plays a critical role in diverse effects, including clinical cardiotonic and cardioprotective effects, ischemic preconditioning in the brain, natriuresis, lung edema clearance and other processes. NKA regulation is of physiological and pharmacological importance and has species- and tissue-specific variations. The activation of DA receptors regulates NKA expression/activity and trafficking in various tissues and cells, for example in the kidney, lung, intestine, brain, non-pigmented ciliary epithelium and the vascular bed. DA receptor-mediated regulation of NKA mediates a diverse range of cellular responses and includes endocytosis/exocytosis, phosphorylation/dephosphorylation of the α subunit of NKA and multiple signaling pathways, including phosphatidylinositol (PI)-phospholipase C/protein kinase (PK) C, cAMP/PKA, PI3K, adaptor protein 2, tyrosine phosphatase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase. Furthermore, in brain and HEK293T cells, D1 and D2 receptors exist in a complex with NKA. Among D1 and D2 receptors and NKA, regulations are reciprocal, which leads to crosstalk between DA receptors and NKA. In the present study, the current understanding of signaling mechanisms responsible for the crosstalk between DA receptors and NKA, as well as with specific consequent functions, is reviewed.

[Effects of the diet ratio of polyunsaturated fatty acids ω-3/ω-6 on experimental colitis in mice].

OBJECTIVE: To investigate the effect of changed ratio of polyunsaturated fatty acids (PUFA) on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Thirty-two male BALB/c mice were randomly divided into two groups: control group and PUFA group, PUFA group was continuously divided into 3 sub-groups: PUFA ω-3/ω-6 1:3 group, PUFA ω-3/ω-6 1:15 group and PUFA ω-3/ω-6 1:30 group. According to the difference in the sub-groups, PUFA group mice were fed with the corresponding modified diet. The control group was fed with the common diet, whose ratio of PUFA ω-3/ω-6 was 1:15. After eight weeks of different diets, experimental colitis in the three sub-groups of PUFA group was induced by DSS exposure. The mice were placed on three five-day cycles of 30 g/L DSS with ten days of recovery after each cycle, then were sacrificed after the final ten-day period. Overall symptomatic score and histopathological score were evaluated. And levels of mucosal prostaglandin E2 (PGE2) in the proximal and distal colon were measured respectively by enzyme immunoassay. RESULTS: The changed ratio of PUFA ω-3/ω-6 had no effect on the weight gain of the growing mice. Although there were no significant differences among the PUFA groups from the three separate aspects: weight gain, stool character and blood in the stool, there were significant differences among the three groups in overall symptomatic scores. A further comparison showed the overall symptomatic score of 1:3 group was significantly lower than that of the 1:30 group (P<0.05). There were significant differences among the PUFA groups in the histopathological score. The following comparison between the sub-groups showed the histopathological score of the 1:3 group was significantly lower than that of the 1:30 group (P<0.05). One mouse in the 1:30 group died of severe hemorrhage and one mouse also in this group had a huge dysplastic adenomatous polyp. The mucosal PGE2 which could reflect the level of intestinal inflammation showed that in the distal colon, the inflammations were obvious, and the levels of mucosal PGE2 of the distal colon in the 1:15 group [(153.0 ± 49.4) ng/g tissue] and the 1:30 group [(192.4 ± 94.0) ng/g tissue] were significantly higher than that of the control group [(43.2 ± 13.4) ng/g tissue, P<0.05], but there was no significant difference between the 1:3 group [(43.4 ± 8.2) ng/g tissue] and the control group. Although the mucosa damages were sparing in proximal colon, the level of mucosal PGE2 of the proximal colon in 1:30 group [(97.4 ± 64.8) ng/g tissue] markedly increased as compared with the control group [(21.6 ± 16.0) ng/g tissue, P<0.01], there were no differences among the 1:3 group [(36.6 ± 4.6) ng/g tissue], the 1:15 group [(18.8 ± 6.4) ng/g tissue] and the control group. CONCLUSION: The colonic inflammatory severity and the level of mucosal PGE2 in the experimental colitis mice were affected by the changed ratio of PUFA ω-3/ω-6 in the feed. Increased ratio of PUFA ω-3/ω-6 in the feed had a protective effect on the intestinal mucosa in the experimental colitis mice, otherwise had hazards. Before the inflammation happened, changed ratio of PUFA ω-3/ω-6 firstly altered the local inflammatory factors, such as PGE2, and then affected the inflammatory severity.

Gap junction -mediated cAMP movement between oocytes and somatic cells.

Cyclic AMP (cAMP) plays a critical role in oocyte meiotic maturation. However, the source of cAMP surge prior to maturation and the direction of gap junction-dependent cAMP movement are unclear. In this study, inhibition of gap junctional communication (GJC) using carbenoxolone (3.5 h) induced meiotic resumption in ~90% of follicle-enclosed oocytes (FEOs). The concentration of cAMP in a single oocyte was higher than that in a single cumulus cell, suggesting that the movement of cAMP proceeds from the oocyte to cumulus cells under passive diffusion. The mRNAs of adenylyl cyclases and the corresponding proteins were mainly detected in oocytes. Persistent or transient incubation with forskolin induced meiotic resumption in FEOs. The maturation induced by persistent forskolin treatment was inhibited by carbenoxolone. However, carbenoxolone had no effect on the maturation of FEOs transiently treated with forskolin or persistently treated with follicle-stimulating hormone. Oocyte maturation was inhibited by sequential treatment with carbenoxolone followed by forskolin. The carbenoxolone-induced maturation was accompanied by a cAMP surge, increased PDE3A and MAPK activation, and decreased levels of cGMP and cAMP-dependent PKA I activation.

Na⁺-K⁺-ATPase, a potent neuroprotective modulator against Alzheimer disease.

Alzheimer disease (AD) is a neurodegenerative disorder clinically characterized by progressive cognitive and memory dysfunction, which is the most common form of dementia. Although the pathogenesis of neuronal injury in AD is not clear, recent evidences suggest that Na⁺-K⁺-ATPase plays an important role in AD, and may be a potent neuroprotective modulator against AD. This review aims to provide readers with an in-depth understanding of Na⁺-K⁺-ATPase in AD through these modulations of some factors that are as follows, which leads to the change of learning and memory in the process of AD. 1. The deficiency in Na⁺, K⁺-ATPase α1, α2 and α3 isoform genes induced learning and memory deficits, and α isoform was evidently changed in AD, revealing that Na⁺, K⁺-ATPase α isoform genes may play an important role in AD. 2. Some factors, such as ß-amyloid, cholinergic and oxidative stress, can modulate learning and memory in AD through the mondulation of Na⁺-K⁺-ATPase activity. 3. Some substances, such as Zn, s-Ethyl cysteine, s-propyl cysteine, citicoline, rivastigmine, Vit E, memantine, tea polyphenol, curcumin, caffeine, Alpinia galanga (L.) fractions, and Bacopa monnieri could play a role in improving memory performance and exert protective effects against AD by increasing expression or activity of Na⁺, K⁺-ATPase.

The H1-H2 domain of the α1 isoform of Na+-K+-ATPase is involved in ouabain toxicity in rat ventricular myocytes.

The composition of different isoforms of Na+-K+-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H1-H2 domain of α1 and α2 isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α1 or α2 isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca²âº](i)), attenuated mitochondrial Ca²âº overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 µM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca²âº](i) and the contractility induced by 1 µM but not that induced by 1 mM OUA. These results indicate that the H1-H2 domain of the NKA α1 isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease.

[Study on differentiation of human umbilical cord-derived mesenchymal stem cells into human sweat gland cells in vitro and the relative signal pathway].

OBJECTIVE: To study the differentiation potential of human umbilical cord-derived mesenchymal stem cells (UCMSC) into human sweat gland cells (hSGC) and the role of extracellular signal-regulated kinase (ERK) pathway. METHODS: UCMSC and hSGC were isolated and cultured in vitro. The former was identified with expression of CD14, CD29, CD34, CD44, CD45, CD105, cytokeratin 7 (CK7), CK19, and carcinoembryonic antigen (CEA), while the latter was identified with expression of CK19 and CEA. UCMSC with density of 5 x 10(4) cells per well placed in lower compartment of Transwell chamber were divided into control group (C, cultured with nutrient solution without any stimulation), thermal injury group (TI, treated with heat-shocked hSGC with density of 1 x 10(4) cells per well inoculated into the upper compartment of Transwell chamber for indirect co-culture), thermal injury + EGF group (TIE, treated with indirect co-culture as used in TI group, with addition of 50 ng/mL EGF), thermal injury + PD98059 group (TIP, treated with indirect co-culture as used in TI group, with addition of 10 nmol/mL ERK specific inhibitor PD98059) according to the random number table. One week after culture, the positive expression rates of CK7 and CK19 in UCMSC were detected by flow cytometry, the expression of CK19 and CEA in UCMSC were examined with immunohistochemical staining and the positive expression rate of CEA was calculated, and the expression level of phosphorylated ERK (pERK) was determined by Western blotting. Data were processed with one-way analysis of variance. RESULTS: (1) CD29, CD44, and CD105 were highly expressed in UCMSC, accompanied by low or negative expression of CD14, CD34, CD45, CK7, CK19, and CEA. The expression of CK19 and CEA were positive in hSGC. The two results showed that UCMSC and hSGC were pure. (2) Compared with those of C group [(2.2 +/- 1.5)%, (2.2 +/- 0.7)%, (3.3 +/- 0.7)%, 0.640 +/- 0.026], the expression levels of CK7, CK19, CEA, and pERK in UCSMC of TI group [(6.4 +/- 0.7)%, (5.7 +/- 0.3)%, (7.4 +/- 1.0)%, 0.790 +/- 0.049] and TIE group [(14.3 +/- 1.0)%, (12.6 +/- 1.1)%, (17.6 +/- 2.3)%, 1.200 +/- 0.032] were significantly increased (with F value respectively 78.49, 139.36, 87.13, and 191.74, P values all below 0.01), and those of TIE group were higher than those of TI group (with F value from 50.14 to 145.47, P values all below 0.01). There were no obvious difference in the 4 indexes between TIP group and C group (with F value from 0.00 to 0.13, P values all above 0.05). CONCLUSIONS: UCMSC co-cultured with heat-shocked hSGC can differentiate into hSGC, and ERK signal pathway participates in the process of differentiation of UCMSC into hSGC.

[Effect of proteasome inhibitor on migration ability and hepatocyte growth factor expression of bone marrow mesenchymal stem cells in multiple myeloma patients].

This study was aimed to investigate the effect of proteasome inhibitor bortezomib on the migration ability and hepatocyte growth factor (HGF) expression of bone marrow mesenchymal stem cells (MSC) in multiple myeloma patients. Transwell assay was employed to measure the migration ability of bone marrow MSC in vitro before and after treatment with bortezomib. The HGF mRNA expression level was determined by real-time quantitative PCR. The results indicated that after treated with bortezomib of concentrations of 2.5 nmol/L for 48 hours, the migration activity of MSC decreased significantly as compared with control cohorts (p < 0.05). The HGF mRNA level in MSC after bortezomib treatment was significantly lower than that of control group (p < 0.05). It is concluded that bortezomib can inhibit the migration and down-regulate HGF mRNA expression of bone marrow MSC in multiple myeloma patients.

[Chemotaxis-related factors are expressed abnormally in bone marrow mesenchymal stem cells of multiple myeloma patients].

This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor (HGF), stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. The mRNA expression levels of HGF, SDF-1, MCP-1 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients were detected by real time quantitative RT-PCR and were compared with that in 9 controls. The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with controls (p < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with controls (p < 0.05). There was no significant difference in the mRNA expression levels of MCP-1 and IL-8 between MM and control cohorts (p > 0.05). It is concluded that BM-MSC from MM patients express HGF, SDF-1, MCP-1, IL-8, but these chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysregulated in MM patients, which may result from the interplay between MM cells and MSC.

Enhancement of Na/K pump activity by chronic intermittent hypobaric hypoxia protected against reperfusion injury.

Chronic intermittent hypobaric hypoxia (CIHH) has been shown to attenuate intracellular Na(+) accumulation and Ca(2+) overload during ischemia and reperfusion (I/R), both of which are closely related to the outcome of myocardial damage. Na/K pump plays an essential role in maintaining the equilibrium of intracellular Na(+) and Ca(2+) during I/R. It has been shown that enhancement of Na/K pump activity by ischemic preconditioning may be involved in the cardiac protection. Therefore, we tested whether Na/K pump was involved in the cardioprotection by CIHH. We found that Na/K pump current in cardiac myocytes of guinea pigs exposed to CIHH increased 1.45-fold. The K(1) and f(1), which reflect the portion of α(1)-isoform of Na/K pump, dramatically decreased or increased, respectively, in CIHH myocytes. Western blot analysis revealed that CIHH increased the protein expression of the α(1)-isoform by 76%, whereas the protein expression of the α(2)-isoform was not changed significantly. Na/K pump current was significantly suppressed in simulated I/R, and CIHH preserved the Na/K pump current. CIHH significantly improved the recovery of cell length and contraction during reperfusion. Furthermore, inhibition of Na/K pump by ouabain attenuated the protective effect afforded by CIHH. Collectively, these data suggest that the increase of Na/K pump activity following CIHH is due to the upregulating α(1)-isoform of Na/K pump, which may be one of the mechanisms of CIHH against I/R-induced injury.

Different Na+/K+-ATPase signal pathways was involved in the increase of [Ca2+]i induced by strophanthidin in normal and failing isolated guinea pig ventricular myocytes.

AIM: To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str). METHODS: A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 micromol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 micromol/L Str-only group by a video-based, motion-edge detection system. RESULTS: Str at 1, 10, and 25 micromol/L in NC and Str at 0.1, 1, 10, and 25 micromol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC. CONCLUSION: The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.

Poly[[diaqua(µ(2)-4,4'-dipyridyl sulfide-κN:N')(4,4'-dipyridyl sulfide-κN)(2-hydroxy-5-sulfonatobenzoato-κO)nickel(II)] dihydrate].

The asymmetric unit of the title helical coordination polymer, {[Ni(C(7)H(4)O(6)S)(C(10)H(8)N(2)S)(2)(H(2)O)(2)]·2H(2)O}(n), is comprised of an Ni(II) ion, one 5-sulfosalicylic acid dianion (HSSA), two 4,4'-dipyridylsulfide (4,4'-dps) ligands, and two coordinated and two uncoordinated water mol-ecules. The Ni(II) ion is coordinated by two water mol-ecules, one carboxyl-ate O atom of the HSSA dianion and three N atoms from three 4,4'-dps ligands in a distorted octa-hedral environment. Half of the 4,4'-dps ligands are µ(2)-bridging ligands which link adjacent Ni(II) centers, forming a one-dimensional helical structure along the b axis. This helical structure is further stabilized by O-H⋯O intra- and inter-molecular hydrogen bonds.