PHR1 involved in the regulation of low phosphate-induced leaf senescence by modulating phosphorus homeostasis in Arabidopsis.

Phosphorus (P) is a crucial macronutrient for plant growth, development, and reproduction. The effects of low P (LP) stress on leaf senescence and the role of PHR1 in LP-induced leaf senescence are still unknown. Here, we report that PHR1 plays a crucial role in LP-induced leaf senescence, showing delayed leaf senescence in phr1 mutant and accelerated leaf senescence in 35S:PHR1 transgenic Arabidopsis under LP stress. The transcriptional profiles indicate that 763 differentially expressed SAGs (DE-SAGs) were upregulated and 134 DE-SAGs were downregulated by LP stress. Of the 405 DE-SAGs regulated by PHR1, 27 DE-SAGs were involved in P metabolism and transport. PHR1 could bind to the promoters of six DE-SAGs (RNS1, PAP17, SAG113, NPC5, PLDζ2, and Pht1;5), and modulate them in LP-induced senescing leaves. The analysis of RNA content, phospholipase activity, acid phosphatase activity, total P and phosphate content also revealed that PHR1 promotes P liberation from senescing leaves and transport to young tissues under LP stress. Our results indicated that PHR1 is one of the crucial modulators for P recycling and redistribution under LP stress, and the drastic decline of P level is at least one of the causes of early senescence in P-deficient leaves.

Prognostic Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Acute Ischemic Stroke Patients After Thrombolysis.

Context: The neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte ratio (PLR) is an inflammation marker of acute ischemic stroke, but the predictive value of NLR and PLR before and after thrombolysis for short-term prognosis in acute ischemic stroke patients after thrombolysis remains largely obscure. This study attempts to clarify the predictive value of NLR and PLR before and after thrombolysis for short-term prognosis in acute ischemic stroke patients after thrombolysis. Design: A retrospective study was carried out in the Affiliated Hospital of Hangzhou Normal University involving 120 patients visiting the neurology department of our hospital from May 2019 to October 2022 and meeting the selection criteria. The participants were assigned to the good prognosis group and the poor prognosis group based on the modified Rankin scale score. Laboratory data collected include NLR and PLR at admission as well as NLR and PLR collected from venous blood within 24 h after thrombolysis. Results: Age, hyperlipidemia, atrial fibrillation, rheumatic heart disease, and National Institutes of Health Stroke Scale (NIHSS) scores after thrombolysis depicted statistical significance between both groups (P < .05). Hyperlipidemia, atrial fibrillation, and NIHSS scores before thrombolysis were independent risk elements for adverse prognosis (P < .05). NLR and PLR before and after thrombolysis in the poor prognosis group depicted an elevation relative to that in the good prognosis group (P < .05). The area under the curve of NLR or PLR predicting adverse prognosis after thrombolysis depicted an elevation relative to that before thrombolysis (P < .05). Conclusion: The predictive value of NLR and PLR post-thrombolysis for short-term prognosis in acute ischemic stroke patients depicts an elevation relative to pre-thrombolysis; our study provides effective predictive indicators for short-term prognosis in acute ischemic stroke patients.

Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3ß/ß-catenin and TGF-ß1/Smad2/3 signaling pathways.

BACKGROUND: Pirfenidone (PFD) is effective for pulmonary fibrosis (PF), but its action mechanism has not been fully explained. This study explored the signaling pathways involved in anti-fibrosis role of PFD, thus laying a foundation for clinical application. METHODS: Pulmonary fibrosis mice models were constructed by bleomycin (BLM), and TGF-ß1 was used to treat human fetal lung fibroblasts (HLFs). Then, PFD was added into treated mice and cells alone or in combination with ß-catenin vector. The pathological changes, inflammatory factors levels, and Collagen I levels in mice lung tissues were assessed, as well as the activity of HLFs was measured. Levels of indices related to extracellular matrix, epithelial-mesenchymal transition (EMT), Wnt/GSK-3ß/ß-catenin and TGF-ß1/Smad2/3 signaling pathways were determined in tissues or cells. RESULTS: After treatment with BLM, the inflammatory reaction and extracellular matrix deposition in mice lung tissues were serious, which were alleviated by PFD and aggravated by the addition of ß-catenin. In HLFs, PFD reduced the activity of HLFs induced by TGF-ß1, inhibited levels of vimentin and N-cadherin and promoted levels of E-cadherin, whereas ß-catenin produced the opposite effects to PFD. In both tissues and cells, Wnt/GSK-3ß/ß-catenin and TGF-ß1/Smad2/3 signaling pathways were activated, which could be suppressed by PFD. CONCLUSIONS: PFD alleviated pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3ß/ß-catenin and TGF-ß1/Smad2/3 signaling pathways, which might further improve the action mechanism of anti-fibrosis effect of PFD.

Ginsenoside Rg3 alleviates the migration, invasion, and angiogenesis of lung cancer cells by inhibiting the expressions of cyclooxygenase-2 and vascular endothelial growth factor.

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 µg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.

Indacaterol/glycopyrronium affects lung function and cardiovascular events in patients with chronic obstructive pulmonary diseases: A meta-analysis.

BACKGROUND: Bronchodilators are the cornerstone for treating patients with chronic obstructive pulmonary diseases (COPD), although some studies have shown that dual bronchodilators may exacerbate incidence of adverse cardiovascular events. Here, we evaluated the cardiopulmonary safety of indacaterol/glycopyrronium (IND/GLY) using a meta-analysis. METHODS: We searched PubMed, OVID, Cochrane Library and Web of Science databases, using "indacaterol/glycopyrronium", "indacaterol/glycopyrrolate", "IND/GLY", "QVA149", "chronic obstructive pulmonary diseases", "COPD", "chronic obstructive airway disease", "chronic obstructive lung disease" as key words. Acute exacerbation of COPD and FEV1 as indicators of pulmonary function and occurrence of hypertension, atrial fibrillation, myocardial infarction and heart failure as indicators of cardiovascular safety. RESULTS: A total of 23 articles, comprising 21,238 participants, were included in the analysis. FEV1 values were significantly different compared to IND/GLY and single bronchodilator therapy (LABA or LAMA), with the MD 0.11 L (95%CI: 0.10-0.13, P<0.01). Hypertension was more frequent in the IND/GLY, than the single bronchodilator therapy group, although this difference was insignificant (IND/GLY vs LABA, RR=1.88, P = 0.09; IND/GLY vs LAMA, RR=1.42, P = 0.08; IND/GLY vs LABA+ICS, RR=1.85, P = 0.23). In addition, IND/GLY did not significantly increase the risk of myocardial infarction (IND/GLY vs LAMA or double therapy, total RR: 1.49, 95%CI: 0.72-3.08, P = 0.28), atrial fibrillation (IND/GLY vs LAMA, RR: 1.62, 95%CI: 0.64-4.10, P = 0.31) and heart failure (IND/GLY vs LAMA, RR: 0.40, 95%CI: 0.07-2.33, P = 0.31) in COPD patients. CONCLUSIONS: IND/GLY significantly reduced incidence of acute COPD exacerbations, and slowed down the decline of FEV1. Adequate safety measures are needed to control incidence of adverse cardiovascular events.

SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells.

Background and aim: A potent and selective vascular endothelial growth factor receptor (VEGFR) inhibitor SU5416, has been developed for the treatment of solid human tumors. The binding of VEGF to VEGFR plays a crucial role in the pathophysiology of respiratory disorders. However, the impact of SU5416 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Thus, this study aimed to illuminate the biofunction of SU5416 in the mouse model of ALI. Methods: Wild-type (WT) and toll-like receptor 4 (TLR4)-deficient (TLR4-/-) C57BL/6 mice were used to establish LPS-induced ALI model. The primary pulmonary microvascular endothelial cell (PMVEC) was extracted for detection of endothelial barrier function. Results: LPS significantly increased the number of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid (BALF). In addition, LPS increased alveolar epithelial cells injury, inflammation infiltration and vascular permeability of PMVEC in WT and TLR4-/- mice. Western blotting experiment indicated VEGF/VEGFR and TLR4/NF-κB pathways were involved in the progression of LPS-stimulated ALI. Consistent with previous research, dexamethasone treatment appeared to be an effective therapeutic for mice with ALI. Moreover, treatment with SU5416 dramatically attenuated LPS-induced immune responses in mice lung tissues via inhibiting VEGF/VEGFR and TLR4/NF-κB pathways. Finally, SU5416 also decreased vascular permeability of PMVEC in vitro. Conclusion: SU5416 ameliorated alveolar epithelial cells injury and histopathological changes in mice lung via inhibiting VEGF/VEGFR and TLR4/NF-κB signaling pathways. We also confirmed that SU5416 could restrain vascular permeability in PMVEC through improving the integrity of endothelial cell. These findings suggested that SU5416 may serve as a potential agent for the treatment of patients with ALI.

[Treatment of intertrochanteric fractures over age of 80 years old patients with proximal femur intramedullary nail].

OBJECTIVE: To explore the clinical effects of proximal femur intramedullary nail (PFNA) in treating intertrochanteric fracture in elderly patients. METHODS: From January,2008 to December,2010,the data of 86 elderly patients (aged, 80 to 93 years) with intertrochanteric fracture who underwent internal fixation were retrospectively analyzed. Of them, 54 patients (22 males and 32 females) were treated with close reduction and PFNA internal fixation(PFNA group),and 32 patients (12 males and 20 females) were treated with open reduction and nail-plate internal fixation (control group). Operation time, volume of blood loss, postoperative complications, time of hospitalization and bone union, hip function were compared between two groups. RESULTS: All patients were followed up more than 2 years. Operation time, volume of blood loss, postoperative complications,time of hospitalization in PFNA group were less than that of control group (P<0.01). There was no significant difference in time of bone union between two groups (P>0.05). According to Harris score to evaluate the function of hip joint, PFNA group was better than that of control group (P<0.01). CONCLUSION: Treatment of elderly patients with intertrochanteric fractures with PFNA internal fixations can obtain satisfactory results, the method is better than that of traditional method.

[Risk early warning and multimodal prevention of postoperative venous thromboembolism for hip fractures].

OBJECTIVE: To study the efficacy and safety of multimodal prevention of postoperative venous thromboembolism for hip fractures. METHODS: From March 2009 to July 2011, preoperatively, patients were assigned to two groups on the basis of an assessment of their risk factors. One hundred and twelve patients were considered to be low risk, involving 47 males and 65 females,with an average age of (72.40 +/- 13.29) years ranging from 42 to 88,and were managed with aspirin (100 mg once daily for 14 days) as well as intermittent gasing compression devices. Twenty-six patients were considered to be high risk, involving 12 males and 14 females with an average age of (78.50 +/- 12.76) years ranging from 65 to 84,and were managed with low-molecular-weight heparin (0.4 ml,subcutaneous injection once daily for 14 days) and intermittent gasing compression. All patients were underwent Doppler ultrasonography within 24 hours before hospital discharge. All patients were followed-up for 3 months postoperatively. The incidence of deep venous thrombosis of lower limb, pulmonary embolism, gastrointestinal hemorrhage were recorded. RESULTS: Overall, there were no fatal pulmonary embolism, 1 case of symptomatic pulmonary emboli in low risk group, and none were detected in the high-risk group. Deep venous thrombosis was detected in association with 6 (6.25%) of the 112 procedures in the low-risk group and 2 (7.69%) of the 26 operations in the high-risk group. Paitents were selected in opened reduction and internal fixation, the quantity of bleeding, decrease of hemoglobin, hematoma rate, and gastrointestinal hemorrhage rate of low risk group were (538.10 +/- 390.20) ml, (30 +/- 19) g/L, 0, and 1 (1.03%) respectively; those of the high-risk group were (585.95 +/- 403.96) mL, (32 +/- 20) g/L,1 (4.76%), (4.76%), there were no significant different between the two groups, all P > 0.05. CONCLUSION: There were no statistic significances between the aspirin as well as intermittent gasing compression devices and the low-molecular-weight heparin and intermittent gasing compression in preventing venous thromboembolism (VTE) in postoperative postoperative venous thromboembolism for hip fractures. However, there are potential advantages to reduce complications of bleeding and cardiovascular disease. Multimodal prevention of postoperative venous thromboembolism can protect postoperative patients with hip fractures.