Th9/IL-9 may participate in the pathogenesis of multiple myeloma.

INTRODUCTION: This research is aimed to evaluate the correlation between Th9-associated cytokine levels in MM patients, clinical features, and therapy. METHODS: Peripheral blood samples were taken in 52 MM patients and 20 healthy volunteers matched by sex and age. The patients with MM were separated into two groups: the untreated group (27) and the remission group (25). An enzyme-linked immunosorbent assay (ELISA) was used to measure the IL-9 plasma levels. The levels of Th9-associated cytokines' mRNA expression (IL-9, PU.1, and IRF4) were measured in RT-qPCR. We also analyzed the correlations between the IL-9 plasma levels and the clinical parameters of newly diagnosed MM patients. RESULTS: The IL-9 plasma levels and the Th9-associated cytokines (IL-9, PU.1, and IRF4) mRNA levels in newly diagnosed MM patients were significantly elevated than those in healthy volunteers and significantly decreased after achieving remission. Moreover, PU.1 and IRF4 had a positive correlation with the IL-9 mRNA expression. Then, we found that the upregulation of IL-9 plasma levels correlates with the severity of anemia and decreased albumin Levels. CONCLUSION: The results demonstrate that Th9/IL-9 may be involved in the pathogenesis of MM and is correlated with worse patient conditions such as lower hemoglobin and serum albumin. More work is necessary to confirm whether they might serve as a useful therapeutic target and prognostic marker for MM.

Internode Length Is Correlated with GA3 Content and Is Crucial to the Harvesting Performance of Tea-Picking Machines.

High labor costs and labor shortages are limiting factors affecting the tea industry in Anhui Province. Thus, exploiting the full mechanization of shoot harvesting is an urgent task in the tea industry. Tea quality is greatly influenced by the integrity rate of tea leaves; therefore, it is important to choose tea cultivars suitable for machine picking. In this study, seven tea cultivars were used to investigate the relationship between internode length and blade angle with respect to newly formed tea shoots and machine harvesting in field experiments (Xuanchen City, Kuiling village) conducted throughout the year (in the autumn of 2021, in the early spring of 2022, and in the summer of 2022). Our results showed that the internode length (L2 or L4) had a significant and positive correlation with the integrity rate of tea buds and leaves in seven tea cultivars over three seasons. However, no significant correlation was found between the blade angle and the integrity rate of tea buds and leaves. In addition, a strong and positive correlation was found between the levels of GA1 (R2 > 0.7), GA3 (R2 > 0.85), and IAA (R2 > 0.6) regarding the internodes and internode lengths of the seven tea cultivars. Moreover, the relative expression levels of CsGA20ox, CsGA3ox1, and CsGA3ox2 in Echa1 (the longer internode) were significantly higher compared with those in Zhenong113 (the shorter internode). Overall, our results show that the internode length is an important factor for the machine harvesting of tea leaves and that the level of GA3 is strongly associated with internode length.

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

BACKGROUND: The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). METHODS: In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2 /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2 /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. RESULTS: The median follow-up was 14 months (range 2-36). The primary end point of overall response rate in the intent-to-treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). CONCLUSION: The 5-day 20-mg/m2 /day and 8-day 12-mg/m2 /day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators.

NMDA receptors play an important physiological role in regulating synaptic plasticity, learning and memory. GluN2A subunits are the most abundant functional subunits of NMDA receptors expressed in mature brain, and their dysfunction is related to various neurological diseases. According to subunit composition, GluN2A-containing NMDA receptors can be divided into two types: diheteromeric and triheteromeric receptors. In this review, the expression, functional and pharmacological properties of different kinds of GluN2A-containing NMDA receptors as well as selective GluN2A regulators were described to further understand this type of NMDA receptors.

Satisfaction as a Mediator and Its Interaction With Adherence to Labor Analgesia Protocols: A Cross-Sectional Survey of Chinese Medical Personnel.

Background: Although the Chinese promotion of labor analgesia began in 2018 to improve maternal health, high-quality medical care is difficult to provide to pregnant women when medical staff cannot implement standard labor analgesia procedures. This study aims to examine medical personnel's adherence to labor analgesia protocols and to explore the relationships among adherence, satisfaction, and other factors. Methods: The data were from a national cross-sectional dataset (N = 13,944) of the 2020 Chinese Labor Analgesia Pilot Evaluation Project. Mediating and moderating effects analyses were used to examine the role of satisfaction as a mediator between support measures and adherence. Results: There were differences in adherence between different types of medical personnel. Support measures and satisfaction had a positive association with adherence to labor analgesia protocols. Satisfaction had a significant mediating and moderating effect on the relationship between support measures and adherence to labor analgesia standards. Moderating effects of professional titles and attitudes were also observed. Conclusion: Primary health care policies worth considering include comprehensive incentives for medical institutions to improve the use of labor analgesia by medical personnel. It is also worth considering providing more training opportunities for the staff in anesthesiology departments.

Role of Integrin ß1 in the progression and chemo-resistance of esophageal squamous cell carcinoma.

Objective: Integrins have been shown to play an important role in the tumorigenesis of many cancers. In this work, we aimed to explore the expression and clinical value of Integrin α5ß1 in esophageal squamous cell carcinoma (ESCC), and the effect of integrin ß1 on the development and chemo-resistance of ESCC cells. Methods: The expression profiling of integrins was analyzed in the mRNA expression dataset of ESCC. The expression of Integrin α5ß1 in 278 cases of ESCC tissues and 62 cases of paracancerous tissues was detected by immunohistochemistry (IHC). The association between the expression of Integrin α5ß1 and the survival of ESCC patients was analyzed by Kaplan-Meier analysis. The effect of Integrin ß1 on the proliferation, migration, and invasion of ESCC cells was examined by MTS, Transwell migration, and Transwell invasion assay. The effect of Integrin ß1 and L1 cell adhesion molecule (L1CAM) on cisplatin resistance was detected by MTS and the signal pathways involved were analyzed by Western blotting. Results: Integrin ß1 and Integrin α5 were significantly up-regulated in ESCC. High expression of Integrin ß1 was also related to worse overall survival of ESCC patients and patients with low levels of both Integrin ß1 and Integrin α5 showed the shortest survival. Results of IHC revealed that Integrin α5ß1 was up-regulated in ESCC and its high expression was associated with poor prognosis and could serve as an independent prognostic factor. siRNA-mediated Integrin ß1 silencing or antibody blocking restrained the proliferation, migration, and invasion of ESCC cells. Simultaneous knockdown of Integrin ß1 and L1CAM reduced the cisplatin resistance of ESCC cells. Further studies showed that knockdown of Integrin ß1 and L1CAM suppressed the activity of Akt signaling with or without cisplatin treatment. Moreover, dual high expression of Integrin ß1 and L1CAM was related to worse overall survival of ESCC patients treated with preoperative chemotherapy. Conclusion: Integrin α5ß1 was up-regulated in ESCC and could be used as a new prognostic indicator for ESCC patients. In addition, Integrin ß1 was involved in the proliferation, invasion, and chemo-resistance of ESCC cells.

Melatonin Alleviates Age-Associated Endothelial Injury of Atherosclerosis via Regulating Telomere Function.

BACKGROUND: Atherosclerosis is an aging-related disease, partly attributed to telomerase dysfunction. This study aims to investigate whether telomere dysfunction-related vascular aging is involved in the protection mechanism of melatonin (MLT) in atherosclerosis. METHODS: Young and aged ApoE-/- mice were used to establish atherosclerotic mice model. H&E staining and immunofluorescence assay were performed to detect endothelial cell injury and apoptosis. Inflammatory cytokines and oxidative stress-related factors were determined using corresponding commercial assay kits. Telomerase activity was detected by TRAP assay, and SA-ß-gal staining was conducted to evaluate cellular senescence. HUVECs were treated with H2O2 for 1 h to induce senescence. Western blot was performed to measure protein expression. RESULTS: An obvious vascular endothelial injury, reflected by excessive production of inflammatory cytokines, elevated ROS, MDA and SOD levels, and more apoptotic endothelial cells, was found in atherosclerotic mice, especially in aged mice, which were then greatly suppressed by MLT. In addition, telomere dysfunction and senescence occurred in atherosclerosis, especially in aged mice, while MLT significantly alleviated the conditions. CYP1A1, one of the targeted genes of MLT, was verified to be upregulated in atherosclerotic mice but downregulated by MLT. Furthermore, H2O2 induced a senescence model in HUVECs, which was accompanied with a remarkably increased cell viability loss and apoptosis rate, and a downregulated telomerase activity of HUVECs, and this phenomenon was strengthened by RHPS4, an inhibitor of telomerase activity. However, MLT could partly abolish these changes in H2O2- and RHPS4-treated HUVECs, demonstrating that MLT alleviated vascular endothelial injury by regulating senescence and telomerase activity. CONCLUSIONS: Collectively, this study provided evidence for the protective role of MLT in atherosclerosis through regulating telomere dysfunction-related vascular aging.

Mapping Maternal Health in the New Media Environment: A Scientometric Analysis.

BACKGROUND: The new media provides a convenient platform to access, use and exchange health information. And as a special group of health care, maternal health care is still of international concern due to their high mortality rate. Scientific research is a good way to provide advice on how to improve maternal health through stringent reasoning and accurate data. However, the dramatic increase of publications, the diversity of themes, and the dispersion of researchers may reduce the quality of information and increase the difficulty of selection. Thus, this study aims to analyze the research progress on maternal health under the global new media environment, exploring the current research hotspots and frontiers. METHODS: A scientometric analysis was carried out by CiteSpace5.7.R1. In total, 2270 articles have been further analyzed to explore top countries and institutions, potential articles, research frontiers, and hotspots. RESULTS: The publications ascended markedly, from 29 in 2008 to 472 publications by 2020. But there is still a lot of room to grow, and the growth rate does not conform to the Price's Law. Research centers concentrated in Latin America, such as the University of Toronto and the University of California. The work of Larsson M, Lagan BM and Tiedje L had high potential influence. Most of the research subjects were maternal and newborn babies, and the research frontiers were distributed in health education and psychological problems. Maternal mental health, nutrition, weight, production technology, and equipment were seemingly hotspots. CONCLUSION: The new media has almost brought a new era for maternal health, mainly characterized by psychological qualities, healthy and reasonable physical conditions and advanced technology.

Therapeutic time windows of compounds against NMDA receptors signaling pathways for ischemic stroke.

Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti-stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor-related compounds from showing efficacy in all clinical trials for ischemic stroke. In this perspective, the determination of therapeutic time windows of these kinds of compounds is useful in ensuring a therapeutic effect and accelerating clinical application. This mini-review discussed the therapeutic time windows of compounds against NMDA receptors signaling pathways, described related influence factors and the status of clinical studies. The purpose of this review is to look for compounds with wide therapeutic time windows and better clinical application prospect.

Promotion of rs3746804 (p. L267P) polymorphism to intracellular SLC52A3a trafficking and riboflavin transportation in esophageal cancer cells.

Riboflavin is an essential micronutrient for normal cellular growth and function. Lack of dietary riboflavin is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). Previous studies have identified that the human riboflavin transporter SLC52A3a isoform (encoded by SLC52A3) plays a prominent role in esophageal cancer cell riboflavin transportation. Furthermore, SLC52A3 gene single nucleotide polymorphisms rs3746804 (T>C, L267P) and rs3746803 (C >T, T278M) are associated with ESCC risk. However, whether SLC52A3a (p.L267P) and (p.T278M) act in riboflavin transportation in esophageal cancer cell remains inconclusive. Here, we constructed the full-length SLC52A3a protein fused to green fluorescent protein (GFP-SLC52A3a-WT and mutants L267P, T278M, and L267P/T278M). It was confirmed by immunofluorescence-based confocal microscopy that SLC52A3a-WT, L267P, T278M, and L267P/T278M expressed in cell membrane, as well as in a variety of intracellular punctate structures. The live cell confocal imaging showed that SLC52A3a-L267P and L267P/T278M increased the intracellular trafficking of SLC52A3a in ESCC cells. Fluorescence recovery after photobleaching of GFP-tagged SLC52A3a meant that intracellular trafficking of SLC52A3a-L267P and L267P/T278M was rapid dynamics process, leading to its stronger ability to transport riboflavin. Taken together, the above results indicated that the rs3746804 (p.L267P) polymorphism promoted intracellular trafficking of SLC52A3a and riboflavin transportation in ESCC cells.

Correlation of A-Kinase Interacting Protein 1 With Clinical Features, Treatment Response, and Survival Profiles in Patients With Multiple Myeloma.

OBJECTIVE: The present study aimed to detect A-kinase interacting protein 1 expression and further explore the association of A-kinase interacting protein 1 with clinical features and prognosis in patients with multiple myeloma. METHODS: Totally, 152 de novo symptomatic patients with multiple myeloma and 30 healthy donors were enrolled. Bone marrow mononuclear cells derived plasma cells were collected from patients with multiple myeloma before initial treatment and from healthy donors on the enrollment, respectively, and then A-kinase interacting protein 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction. Treatment response (complete response and overall response rate) was assessed, and survival profiles (progression-free survival and overall survival) were calculated in patients with multiple myeloma. RESULTS: A-kinase interacting protein 1 protein/messenger RNA expressions were elevated in patients with multiple myeloma compared to healthy donors, and A-kinase interacting protein 1 (area under the curve: 0.809, 95% confidence interval: 0.726-0.891)/messenger RNA (area under the curve: 0.839, 95% confidence interval: 0.764-0.914) presented good value in differentiating patients with multiple myeloma from healthy donors. In patients with multiple myeloma, A-kinase interacting protein 1 /messenger RNA expressions negatively correlated with albumin while positively correlated with Beta-2-microglobulin, lactate dehydrogenase, International Staging System stage, and t (4;14). Meanwhile, there were 39 (25.7%) complete response patients, 113 (74.3%) noncomplete response patients, 112 (73.7%) overall response rate patients, and 40 (26.3%) nonoverall response rate patients. Complete response and overall response rates were decreased in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. Additionally, progression-free survival and overall survival were reduced in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. CONCLUSION: A-kinase interacting protein 1 exhibits the potency as a biomarker for multiple myeloma progression and prognosis, which implies the clinical application of A-kinase interacting protein 1 in multiple myeloma management.

Heat shock protein family B member 1 facilitates ezrin activation to control cell migration in esophageal squamous cell carcinoma.

Ezrin plays an important role in the development and progression of human esophageal squamous cell carcinoma (ESCC), providing a link between the cortical actin cytoskeleton and the plasma membrane to govern membrane structure and protrusions. However, the mechanism by which ezrin is activated still remains unknown in ESCC. Here, we identify a novel interaction between ezrin and heat shock protein family B (small) member 1 (HSPB1) in ESCC cells by mass spectroscopy and co-immunoprecipitation. HSPB1 only interacts with inactive ezrin and binds to the α-helical coiled coil region of ezrin. Knockdown of HSPB1 resulted to the decline of phosphorylation at ezrin Thr567, markedly suppressing the ability of ezrin to bind to the actin cytoskeleton and migration of ESCC cells. Furthermore, neither the constitutively active phosphomimetic ezrin T567D, nor inactivated ezrin T567A could restore cell migration following HSPB1 knockdown. Low HSPB1 expression was associated with favorable overall survival of ESCC patients. Taken together, HSPB1, as an important partner, participates in the activation of ezrin and merits further evaluation as a novel therapeutic target against human ESCC.

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins.

Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.

The differences between GluN2A and GluN2B signaling in the brain.

The N-methyl-d-aspartate (NMDA) receptor, a typical ionotropic glutamate receptor, is a crucial protein for maintaining brain function. GluN2A and GluN2B are the main types of NMDA receptor subunit in the adult forebrain. Studies have demonstrated that they play different roles in a number of pathophysiological processes. Although the underlying mechanism for this has not been clarified, the most fundamental reason may be the differences between the signaling pathways associated with GluN2A and GluN2B. With the aim of elucidating the reasons behind the diverse roles of these two subunits, we described the signaling differences between GluN2A and GluN2B from the aspects of C-terminus-associated molecules, effects on typical downstream signaling proteins, and metabotropic signaling. Because there are several factors interfering with the determination of subunit-specific signaling, there is still a long way to go toward clarifying the signaling differences between these two subunits. Developing better pharmacology tools, such as highly selective antagonists for triheteromeric GluN2A- and GluN2B-containing NMDA receptors, and establishing new molecular biological methods, for example, engineering photoswitchable NMDA receptors, may be useful for clarifying the signaling differences between GluN2A and GluN2B.

The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells.

EZR, a member of the ezrin-radixin-moesin (ERM) family, is involved in multiple aspects of cell migration and cancer. SMYD3, a histone H3-lysine 4 (H3-K4)-specific methyltransferase, regulates EZR gene transcription, but the molecular mechanisms of epigenetic regulation remain ill-defined. Here, we show that antisense lncRNA EZR-AS1 was positively correlated with EZR expression in both human esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Both in vivo and in vitro studies revealed that EZR-AS1 promoted cell migration through up-regulation of EZR expression. Mechanistically, antisense lncRNA EZR-AS1 formed a complex with RNA polymerase II to activate the transcription of EZR. Moreover, EZR-AS1 could recruit SMYD3 to a binding site, present in a GC-rich region downstream of the EZR promoter, causing the binding of SMYD3 and local enrichment of H3K4me3. Finally, the interaction of EZR-AS1 with SMYD3 further enhanced EZR transcription and expression. Our findings suggest that antisense lncRNA EZR-AS1, as a member of an RNA polymerase complex and through enhanced SMYD3-dependent H3K4 methylation, plays an important role in enhancing transcription of the EZR gene to promote the mobility and invasiveness of human cancer cells.

Ezrin Ser66 phosphorylation regulates invasion and metastasis of esophageal squamous cell carcinoma cells by mediating filopodia formation.

BACKGROUND: Ezrin, links the plasma membrane to the actin cytoskeleton, and plays an important role in the development and progression of human esophageal squamous cell carcinoma (ESCC). However, the roles of ezrin S66 phosphorylation in tumorigenesis of ESCC remain unclear. METHODS: Distribution of ezrin in membrane and cytosol fractions was examined by analysis of detergent-soluble/-insoluble fractions and cytosol/membrane fractionation. Both immunofluorescence and live imaging were used to explore the role of ezrin S66 phosphorylation in the behavior of ezrin and actin in cell filopodia. Cell proliferation, migration and invasion of ESCC cells were investigated by proliferation and migration assays, respectively. Tumorigenesis, local invasion and metastasis were assessed in a nude mouse model of regional lymph node metastasis. RESULTS: Ezrin S66 phosphorylation enhanced the recruitment of ezrin to the membrane in ESCC cells. Additionally, non-phosphorylatable ezrin (S66A) significantly prevented filopodia formation, as well as caused a reduction in the number, length and lifetime of filopodia. Moreover, functional experiments revealed that expression of non-phosphorylatable ezrin (S66A) markedly suppressed migration and invasion but not proliferation of ESCC cells in vitro, and attenuated local invasion and regional lymph node metastasis, but not primary tumor growth of ESCC cells in vivo. CONCLUSION: Ezrin S66 phosphorylation enhances filopodia formation, contributing to the regulation of invasion and metastasis of esophageal squamous cell carcinoma cells.

Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi­1 cells through upregulation of TRAIL death receptor expression, activation of caspase-8 and inhibition of cFLIP.

Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor­α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi­1 cells were primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the growth of Kasumi­1 cells and induce apoptosis in vitro and in vivo. Plumbagin enhanced TRAIL-induced apoptosis of Kasumi­1 cells in association with mitochondria damage, caspase activation, upregulation of death receptors (DRs) and decreased cFLIP expression. The effects of plumbagin on the expression of DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species (ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the production of ROS. In vivo, there was no obvious toxic pathologic change in the heart, liver and kidney tissues in any of the groups. Comparing with the control mice, a significantly increased number of apoptotic cells were observed in the combined treated mice by flow cytometry. Plumbagin also increased the expression of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest that both plumbagin and rsTRAIL could be used as a single agent or synergistical agents to induce apoptosis of leukemic Kasumi­1 cells in vitro and in vivo.

Seasonal dynamics of total flavonoid contents and antioxidant activity of Dryopteris erythrosora.

The seasonal dynamics of the total flavonoid contents in various parts of Dryopteris erythrosora, a traditional Chinese medicinal fern, and their antioxidant activity were investigated. The total flavonoids content in various parts of D. erythrosora showed an obvious seasonal dynamic change. The total flavonoid contents in stems (from 4.3% to 12.5%) were much higher than that in leaves with an average content of 2.01%. In spring, the total flavonoid contents in stems were relatively low, but increased rapidly from summer to winter. However, the seasonal dynamics of total flavonoid contents in leaves showed different model. The total flavonoid contents in the stems showed a negative correlation with that in the leaves from January to July. The correlation coefficient of about -0.7 was obtained. The antioxidant activity of the extracts also altered in proportion to the change of total flavonoid contents. In general, the extracts from stems always showed highest antioxidant potentials and it was suggested that the stems can be used as crude medicine.

Hydrogen sulfide reduces regional myocardial ischemia injury through protection of mitochondrial function.

Hydrogen sulfide (H2S) is a signaling gasotransmitter, involved in various physiological and pathological processes. H2S-donating drugs have been tested to conjugate the beneficial effects of H2S with other pharmaceutical properties. It has been shown that the endogenous cystathionine-γ-lyase (CSE)/H2S pathway participates in myocardial ischemia injury in isolated hearts in rats. The present study aimed to investigate the cytoprotective action of H2S against acute myocardial ischemia injury in rats. Isolated rat hearts were perfused and subjected to ischemic conditions for 4 h. The hearts were assigned to five groups: Sham, model, infarct plus low-dose (5 µmol/l) NaHS, infarct plus middle-dose (10 µmol/l) NaHS and infarct plus high-dose (20 µmol/l) NaHS. The administration of NaHS enhanced the activity of CSE, increased the content of H2S and reduced infarct volumes following myocardial ischemia injury. Furthermore, the administration of NaHS attenuated the injury to organelles (including the mitochondria, nucleus and myofilaments) by reducing lactate dehydrogenase activity, decreasing the level of mitochondrial malondialdehyde and increasing the activities of superoxide dismutase and glutathione peroxidase in the ischemic myocardial mitochondria. These protective effects of H2S against myocardial ischemia injury appeared to be mediated by its antioxidant activities and the preservation of mitochondrial function.

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.