Plasma levels of hydrogen sulfide and homocysteine correlate with the efficacy of antidepressant agents and serve as potential diagnostic and therapeutic markers.

OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.

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.

Role of AQP3 in the Vascular Leakage of Sepsis and the Protective Effect of Ss-31.

ABSTRACT: Aquaporins (AQPs) are a group of membrane proteins related to water permeability. Studies have shown that AQPs play a vital role in various diseases. Whether AQPs participate in regulating vascular permeability after sepsis and whether the subtype of AQPs is related are unknown. Ss-31, as a new antioxidant, had protective effects on a variety of diseases. However, whether Ss-31 has a protective effect on pulmonary vascular permeability in sepsis and whether its effect is related to AQPs are unclear. Using the cecum ligation perforation-induced septic rat and LPS-treated pulmonary vein endothelial cells, the role of AQPs in the regulation of the permeability of pulmonary vascular and its relationship to Ss-31 were studied. The results showed that the pulmonary vascular permeability significantly increased after sepsis, meanwhile the expressions of AQP3, 4, and 12 increased. Among those, the AQP3 was closely correlated with pulmonary vascular permeability. The inhibition of AQP3 antagonized the increase of the permeability of monolayer pulmonary vein endothelial cells. Further study showed that the expression of caveolin-1 (Cav-1) increased and occludin decreased after sepsis. The inhibition of AQP3 antagonized the decrease of Cav-1 and the increase of occludin in sepsis. Antioxidant Ss-31 decreased the expression of AQP3 and ROS levels. At the same time, Ss-31 improved pulmonary vascular permeability and prolonged survival of sepsis rats. In conclusion, AQP3 participates in the regulation of pulmonary vascular permeability after sepsis, and the antioxidant Ss-31 has a protective effect on pulmonary vascular permeability by downregulating the expression of AQP3 and inhibiting ROS production.

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.

Repetitive infusion of levosimendan in patients with chronic heart failure: a meta-analysis.

BACKGROUND: Repetitive or intermittent levosimendan infusion is gradually becoming more commonly considered for patients with advanced chronic heart failure. However, previous randomized controlled studies (RCTs) reported conflicting results on the effects of levosimendan when administered repetitively. The aim of this meta-analysis was to generate up-to-date evidence to assess the effect of levosimendan in this group of patients. MATERIAL AND METHODS: A literature review identified 8 qualified studies. A meta-analysis was performed to assess mortality and left ventricular ejection fraction (LVEF). RESULTS: Use of levosimendan contributed to significantly reduced mortality at the end of mid-term follow-up. The mortality rates in levosimendan and control group were 23 of 226 (10.2%) and 53 of 198 (26.8%), respectively (RR: 0.40, 95%CI: 0.26-0.63, P<0.0001). The trend of significantly decreased mortality was observed in levosimendan vs. placebo subgroup (RR: 0.28, 95%CI: 0.15-0.54, P=0.0001, I2=0%) but not in levosimendan vs. dobutamine, PGE1, or furosemide subgroup (p=0.19, p=0.64 and p=0.25, respectively). Levosimendan also contributed to significantly improved LVEF improvement at the end of follow-up (mean difference: 3.69%, 95CI: 0.92-6.45%, p=0.009). CONCLUSIONS: Intermittent or repetitive levosimendan infusion might be a promising strategy to reduce mortality and improve LVEF in patients with advanced chronic, but not necessarily acutely decompensated, heart failure to maintain disease stability.

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.

The association between peritoneal charge barrier dysfunction and protein lost during continuous ambulatory peritoneal dialysis.

BACKGROUND/AIMS: The main purpose of the present study was to determine the effect of peritoneal charge barrier dysfunction on hypoalbuminemia during CAPD. METHODS: We measured the association of dialysis dose, peritoneal equilibration test (PET) results (ratio of dialysate and plasma creatinine), and peritoneal charge barrier index (ratio of pancreatic and salivary α-amylase clearance) on protein loss in 33 patients on maintenance CAPD. All patients were from a single institution and were diagnosed with chronic nephritis (n = 18 cases), diabetic nephropathy (n = 8), hypertension (n = 5), and hepatitis B virus-associated glomerulonephritis (n = 2). RESULTS: The mean (± SD) dialysate protein loss was 4.04 g (± 1.97) per day. Protein loss was positively correlated with dialysis dose (r = 0.438, p = 0.01) but was not significantly correlated with PET results. The mean (± SD) peritoneal charge barrier index was 6.12 (± 21.20) and was inversely correlated with protein loss into the peritoneal dialysate (r = -0.532, p < 0.01). CONCLUSIONS: Taken together, our study of CAPD patients indicates that protein loss into the peritoneal dialysate increases with peritoneal dialysis dose and with disruption of the peritoneal charge barrier. © 2013 S. Karger AG, Basel.

High-level overproduction of Thermobifida enzyme in Streptomyces lividans using a novel expression vector.

In this study, we constructed a novel Streptomyces-E.coli shuttle vector pZRJ362 combining the xylose isomerase promoter and amylase terminator. A gene encoding the endoglucanase Cel6A in Thermobifida fusca was amplified by PCR, cloned into Streptomyces lividans host strain using the novel expression vector and Pichia pastoris GS115 host strain using the vector pPICZα-C, respectively. Afterwards, the expression pattern and the maximum expression level were comparatively studied in both expression systems. The maximum enzyme activity of Cel6A-(His)6 secreted in S. lividans supernatant after 84-h of cultivation amounted to 5.56 U/mL, which was dramatically higher than that secreted in P. pastoris about 1.4 U/mL after 96-h of cultivation. The maximum expression level of Cel6A-(His)6 in S. lividans supernatant reached up to 173 mg/L after 84-h of cultivation. The endoglucanase activity staining SDS-PAGE showed that there were some minor proteins in S. lividans supernatant which may be the Cel6A derivant by proteolytic degradation, while there was no proteolytic product detected in supernatant of P. pastoris.

[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.

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

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.

[Correlations between chemokines CXCL12, CCL2, RANTES and early abortion].

OBJECTIVE: To explore the correlations between chemokines stromal cell-derived factor-1 (CXCL12), monocyte chemotactic protein-1 (CCL2), regulated upon activation normal T cell expressed and secreted (RANTES) and early abortion. METHODS: The villus and decidua tissues of recurrent spontaneous abortion group (n = 26), medical abortion group (n = 30) and normal early pregnancy women (control group, n = 30) were collected at our hospital from 2008 to 2009. And their expressions of CXCL12, CCL2, RANTES mRNA were determined by real-time fluorescence quantitative PCR (polymerase chain reaction). RESULTS: The CXCL12, CCL2 and RANTES mRNA gene expressions were detected in first-trimester placental villus and decidua tissues. And the gene expressions of CXCL12 mRNA in villus and decidua tissues in spontaneous abortion and medical abortion groups were significantly lower than that in the control group (P < 0.01). But the gene expressions of CCL2 and RANTES mRNA in villus and decidua tissues were significantly higher than that in the control group (P < 0.01). CONCLUSION: CXCL12, CCL2 and RANTES are co-expressed in human villus and decidua tissues. The lower CXCL12 mRNA expression and the higher expressions of CCL2 and RANTES mRNA play important roles in the pathogenesis of early abortion.

Interaction of genotype-ecological type-plant spacing configuration in sorghum [Sorghum bicolor (L.) Moench] in China.

Grain sorghum has been a significant contributor to global food security since the prehistoric period and may contribute even more to the security of both food and energy in the future. Globally, precise management techniques are crucial for increasing grain sorghum productivity. In China, with diverse ecological types, variety introduction occasionally occurs across ecological zones. However, few information is available on the effect of ecological type on genotype performance and how plant spacing configuration influences grain yield in various ecological zones. Hence, a series of two-year field experiments were conducted in 2020 and 2021 in four ecological zones of China, from the northeast to the southwest. The experiments included six widely adapted sorghum varieties under six plant spacing configurations (two row spacing modes: equidistant row spacing (60 cm) mode and wide (80 cm)-narrow (40 cm) row spacing mode; three in-row plant spacings: 10 cm, 15 cm, and 20 cm). Our results indicated that ecological type, variety, and plant spacing configuration had a significant effect on sorghum yield. Ecological type contributed the highest proportion to the yield variance (49.8%), followed by variety (8.3%), while plant spacing configuration contributed 1.8%. Sorghum growth duration was highly influenced by the ecological type, accounting for 87.2% of its total variance, whereas plant height was mainly affected by genotype, which contributed 81.6% of the total variance. All test varieties, developed in the south or north, can reach maturity within 94-108 d, just before fall sowing in central China. Generally, sorghum growth duration becomes longer when a variety is introduced from south to north. A late-maturing variety, developed in the spring sowing and late-maturing regions, possibly could not reach maturity in the early-maturing region. The row spacing modes had no significant affect on sorghum yield, but the equal-row spacing mode consistently caused higher yields with only one exception; this might imply that equal-row spacing mode was more advantageous for boosting sorghum yield potential. In contrast, decreasing in-row plant spacing showed significant positive linear associations with sorghum grain yield in most cases. In addition, these results demonstrated that sorghum is a widely adapted crop and enables success in variety introduction across ecological zones.

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.

[Warming-drying climate intensifies the restriction of moisture on radial growth of Pinus tabuli-formis plantation in semi-arid area of Northeast China]. / æš–å¹²åŒ–åŠ å‰§ä¸œåŒ—åŠå¹²æ—±åœ°åŒºæ²¹æ¾äººå·¥æž—å¾„å‘ç”Ÿé•¿çš„æ°´åˆ†é™åˆ¶.

Plantation ecosystems are more vulnerable than natural ones to global climate change. Using the dendrochronology method, we established tree-ring width chronologies of Pinus tabuliformis distributed in the semi-arid region of Northeast China. We examined its growth dynamics, analyzed the relationship between radical growth and climate factors, and explored the effects of global warming on the growth and distribution of P. tabuliformis. The results showed that tree-ring width chronologies of P. tabuliformis were negatively correlated with mean temperature of growing season (May-July), and positively correlated with precipitation and Palmer drought severity index (PDSI) in the early growing season (April) and in the growing season (May-July). Water availability was the main limiting factor for the radial growth of P. tabuliformis. Along the increasing precipitation gradient from southwest to northeast, tree growth became more sensitive to annual mean temperature, and the correlation with annual precipitation shifted from positive to negative, indicating that tree growth in the relative arid area (southwest of the study area) was more severely restricted by water availability. Drought stress caused by climate warming resulted in growth declines at some sites in the southwest area. With the continuous warming-drying climate, the distribution boundary of P. tabuliformis in the study area would shrink locally, with the suitable growth boundary moving northward.

[Effects of moisture and heat coupling on xylem growth of Pinus tabuliformis in Shenyang, China]. / 水热耦合对沈阳地区油松木质部生长的影响.

Based on the micro-core technology, we can accurately examine the tree cambium phenology and the radial growth at the cellular scale, and reveal the relationship between tree growth and climate. Pinus tabuliformis is one of the constructive species in forests of northern China. We investigated the growth pattern of P. tabuliformis in Shenyang and the changes in cambium and xylem cells throughout the growing season (April to November) in 2020. Results showed that the dividing activity in cambium started in early April and ended at the end of September. Xylem began to grow from the appearance of enlargement cells (mid April) to the end of the disappearance of lignified cells (late October), with a growth trajectory of 'S' shape curve. Approximately 53 xylem cells per row in radical direction were produced in 2020. The maximum growth rate (0.55 ind/row/day) occurred at the end of May, while the change of earlywood and latewood cells occurred at the end of July. When the minimum temperature above 0 ℃ in Shenyang, the cambium began to divide. The minimum critical temperature that affected the beginning and ending of xylem growth was 2-3 ℃. Precipitation promoted the growth in the growing season. The high temperature and insufficient water supply at the end of July were the main factors driving the differentiation of xylem cells to form earlywood and latewood.

[Tree species identification of wooden funeral utensil from Qing Dynasty's tombs and its potential of ecological and environmental indicator in Shenyang, Northeast China]. / æ²ˆé˜³æ¸ å¢“æœ¨è´¨è‘¬å ·çš„æ ‘ç§é‰´å®šåŠç”Ÿæ€çŽ¯å¢ƒçš„æŒ‡ç¤ºæ½œåŠ›.

The wood used for funeral utensil in ancient tomb is a kind of valuable materials and important for understanding vegetation, climate and society conditions in the history. Here, we identified the tree species and dated the time of wooden utensils for funeral excavated from tombs in Shuijia Village, Shenyang, using wood anatomy methods and dendrochronological techniques. The results showed that 7 out of the 16 wood samples were identified as Pinus tabuliformis from Pinaceae, 8 were Larix sp. from Pinaceae and most likely Larix olgensis, and the rest one was Acer sp. from Aceraceae. Currently, these tree species are still widely distributed in Liaoning Province, indicating that forest structure (tree species composition) is relatively stable and that the climate at that time was quite similar to that at present. The timbers used for wooden utensils of funeral for civilian tombs had regional biogeographic characteristics and reflected regional social productivity development level in Mukden (now Shenyang) in Qing Dynasty: most of them were native tree species with low cost and high availability; the main timber trees were conifer species, and a few of them were broadleaved trees. These timbers were likely from the forest in Shenyang or mountainous areas in Eastern Liaoning, with Hunhe River waterway being an important transport way for timbers to Shenyang. Some P. tabuliformis and Larix sp. timbers could be cross-dated well, and the growth period of the trees was determined to be 1680s-1770s (early to mid-Qing Dynasty). The variations of tree-ring width of these timbers had good consistency and high climate sensitivity, reflecting the consistency of regional climate and environment. These timbers have the potential to indicate the climate condition of the early to mid-Qing Dynasty.

[Altitudinal differentiation in the radial growth of Betula platyphylla and its response to climate in cold temperate forest: A case of Oakley Mountain, Northeast China].

Climate change has profound impacts on the structure and function of forest ecosystem. Under the background of climate warming, the growth patterns and climate responses of different species in different environments determine the development and stability of ecosystems. Using the method of tree chronology with ring width data of Betula platyphylla in Oakley Mountain of Daxing'an Mountains, we examined the relationship between the growth climate response of the pioneer B. platyphylla in larch forest and temperature rise and altitudinal changes. The results showed that climate warming resulted in the differentiation on B. platyphylla in different altitude. The radial growth of B. platyphylla increased significantly at the low altitude area (1050 m), while there were little changes at the relatively high altitude area (1250 m). Before the time of rapid warming (1980), the radial growth of B. platyphylla on two altitude areas were significantly stressed by low temperature in winter (October to February). During the period of rapid warming (1981-2010), low temperature stress in winter did not affect tree growth, with the growing season (May to July) temperature becoming the main limiting factors to the radial growth of B. platyphylla at the relatively high altitude areas. The growth of B. platyphylla increased in the low altitude stands with favorable water and heat conditions. The distribution of B. platyphylla may generally spread to high altitude sites in the study area under climate warming.

The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review.

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.