Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation.

Background: Uterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death. Methods: We wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein-protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select "hub genes". Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells. Results: We demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells. Conclusion: Our data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells.

Gonadotropin-releasing hormone (GnRH), which is synthesized and released by the hypothalamus, promotes the synthesis and secretion of follicle-stimulating hormone (FSH), thereby regulating the growth and reproduction of animals. GnRH analogues have been widely used in livestock production. MiRNAs, which are endogenous non-coding RNAs, have been found to play important roles in hormone regulation and other physiological processes in recent years. However, the roles of miRNAs in GnRH-mediated regulation of FSH secretion have rarely been studied. Herein, we treated bovine anterior adenohypophyseal cells with an exogenous GnRH analogue and found that miR-488 was differentially expressed. Through a combination of TargetScan prediction and dual luciferase reporter analysis, miR-488 was confirmed to be able to target the FSHB gene. Based on this finding, we verified the expression of Fshß and Lhß mRNA in the rat adenohypophysis before and after exogenous GnRH treatment in vivo and in vitro. Experiments on rat anterior adenohypophyseal cells showed that overexpression of miR-488 significantly inhibited Fshß expression and FSH synthesis, while knockdown of miR-488 had the opposite effects. Our results demonstrate that GnRH relies on miR-488 to regulate FSH synthesis, providing additional useful evidence for the significance of miRNAs in the regulation of animal reproduction.

Evaluation of Disease Activity of Systemic Lupus Erythematosus by D-dimer Combined with Red Blood Cell Distribution Width.

BACKGROUND: To investigate the value of D-dimer combined with red blood cell distribution width (RDW) in evaluating the disease activity of systemic lupus erythematosus (SLE). METHODS: A total of 105 SLE patients confirmed in our hospital from July 2018 to September 2020 were collected as the SLE group, and 60 healthy persons matched in age and gender during the same period were collected as the control group. According to the SLEDAI score, SLE patients were divided into SLE active group and SLE inactive group, and RDW and D-Dimer levels were detected. RESULTS: The level of RDW in the SLE active group [14.8 (13.4, 16.8)] was significantly higher than that in the SLE inactive group [13.4 (12.6, 14.37)] and control group [12.3 (12, 12.7)], with statistically significant differences (p < 0.05). The D-dimer level in the SLE active group was 1.36 (0.9, 2.25) mg/L, which was significantly higher than that in SLE inactive group [0.34 (0.22, 0.52)] mg/L and control group [0.15 (0.08, 0.19)] mg/L, with statistically significant differences (p < 0.05). Both RDW and D-dimer were positively correlated with the SLEDAI score (r = 0.393, p = 0.000), (r = 0.483, p = 0.000). The results of receiver operating characteristic curve showed that the area under the curve of RDW and D-Dimer alone was 0.875 and 0.954, respectively, while the area under the curve of RDW combined with D-Dimer was the largest, 0.984. CONCLUSIONS: The levels of RDW and D-dimer are closely related to the disease activity of SLE patients, and RDW combined with D-dimer is more valuable in assessing the disease activity of SLE patients.

Proteome analysis reveals a systematic response of cold-acclimated seedlings of an exotic mangrove plant Sonneratia apetala to chilling stress.

Low temperature in winter was the most crucial abiotic stress that limits the mangrove afforestation northward. Previous study demonstrated that Sonneratia apetala initially transplanted to high latitude area exhibited a stronger plasticity of cold tolerance. To clarify the underlying mechanism, the physiological and proteomic responses to chilling stress were investigated in S. apetala leaves. Our results found that cold-acclimated seedlings had lower relative electrolyte leakage and MDA content than non-acclimated seedlings. On the contrary, higher chlorophyll content and photosynthetic capacity were observed in cold-acclimated seedlings. With proteomic analyses, the differentially accumulated proteins (DAPs) involved in ROS scavenging, photosynthesis and energy metabolism, carbohydrate metabolism, cofactor biosynthesis, and protein folding were suggested to play important roles in enhancing the cold tolerance of S. apetala. However, the down-regulation DAPs were suggested as a tradeoff between plant growth and chilling response. By the protein-protein interaction analyses, translation elongation factor G, chlorophyll A-B binding protein and ascorbate peroxidase 1 were suggested as the important regulators in cold-acclimated S. apetala seedlings under chilling stress. Based on the above results, a schematic diagram describing the mechanism of cold tolerance of exotic mangrove species S. apetala that was achieved by cold acclimation was presented in this study. SIGNIFICANCE: The major environmental factor limits the mangrove afforestation northward is the low temperature in winter. Previous study reported that Sonneratia apetala grew in high latitude exhibited a higher cold tolerance than that in low latitude, which was suggested as a result of cold acclimation. To further understand "how cold acclimation enhance the cold tolerance in S. apetala", the response of S. apetala subjected to chilling stress with or without cold acclimation was investigated in this study at the physiological and proteomic aspects. Our physiological results showed that S. apetala seedlings treated with cold acclimation exhibited a higher tolerance under chilling stress than that without cold acclimation. By using the comparative proteomic approaches and bioinformatic analyses, various biological processes were suggested to play an important role in enhancing the cold tolerance of S. apetala under chilling stress, such as ROS scavenging, photosynthesis and energy metabolism, carbohydrate metabolism, cofactor biosynthesis, and protein folding. Among these differentially accumulated proteins, translation elongation factor G (eEF-G), chlorophyll A-B binding protein (CAB) and ascorbate peroxidase 1 (APX1) were identified as the hub proteins function in coordinated regulating ROS scavenging, photosynthesis and protein biosynthesis in chloroplast and subsequently enhanced the cold tolerance of S. apetala under chilling stress. Our results provided a further understanding of cold acclimation in improving the cold tolerance in exotic mangrove species S. apetala.

Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p.

miRNAs are a family of short, noncoding RNAs that are involved in many processes in melanoma cells. MITF acts as a master regulator of melanocyte function, development and survival by modulating various genes. Hydroxyurea (HU) is used to treat melanoma, and miRNA expression is altered after HU treatment in B16 melanoma cells. In this study, we screened for miRNAs that were upregulated after HU treatment and that targeted the MITF gene. We found that miR-7013-3p exhibited increased expression after HU treatment and could bind to MITF. miR-7013-3p inhibited melanin production, proliferation, and migration and promoted apoptosis in B16 melanoma cells. The results may provide more information on the roles of miR-7013-3p in B16 melanoma cells.

circAkap17b acts as a miR-7 family molecular sponge to regulate FSH secretion in rat pituitary cells.

The pituitary gland functions as a prominent regulator of diverse physiologic processes by secreting multiple hormones. Circular RNAs (circRNAs) are an emerging novel type of endogenous noncoding RNA that have recently been recognized as powerful regulators participating in various biological processes. However, the physiological roles and molecular mechanisms of circRNAs in pituitary remain largely unclear. Herein, we concentrated on expounding the biological function and molecular mechanism of circRNA in rat pituitary. In this study, we identified a novel circRNA in pituitary tissue, circAkap17b, which was pituitary- and stage-specific. Then, we designed circAkap17b siRNA and constructed an overexpression plasmid to evaluate the effect of loss- and gain-of-circAkap17b function on FSH secretion. Interestingly, silencing circAkakp17b significantly inhibited FSH expression and secretion, while overexpression of circAkap17b enhanced FSH expression and secretion. Furthermore, dual luciferase reporter and RNA immunoprecipitation (RIP) assays confirmed that circAkap17b could serve as miR-7 sponge to regulate target genes. Additionally, miR-7b suppressed FSH expression and secretion by directly targeting Fshb through the dual luciferase reporter and RT-qPCR analysis. Additionally, rescue experiments showed that circAkap17b could regulate FSH secretion in pituitary cells through a circAkap17b-miR-7-Fshb axis. Collectively, we demonstrated that circAkap17b could act as a molecular sponge of miR-7 to upregulate expression of the target gene Fshb and facilitate FSH secretion. These findings provide evidence for a novel regulatory role of circRNAs in pituitary.

First report of Xanthomonas albilineans causing leaf scald on two chewing cane clones in Zhejiang province, China.

In recent years, outbreaks of leaf scald have been reported in two chewing cane clones "Guangdong Huangpi" and "Taoshang Guozhe" in Zhejiang province, China. From May to July 2019, we collected 11 and 13 leaf or stalk samples from symptomatic "Guangdong Huangpi" from four farms in Wenling and "Taoshang Guozhe" clones from three farms in Ruian, Zhejiang province, respectively. Leaves in young plants exhibited white pencil-line streaks (Supplement Fig. 1A & 1D) as well as partial or complete chlorosis of the leaf blade (Supplement Fig. 1B & 1E). Internal symptoms included an orange-red discoloration of the vascular bundles at the basal nodes of the stalk and discoloration extension into the internodes (Supplement Fig. 1C & 1F). Leaf and stalk tissues were used for bacterial isolation and purification on XAS medium, which is selective for Xanthomonas albilineans (Davis et al. 1994), using the streak plate method to obtain 24 isolates (Lin et al. 2018). Circular, convex, smooth, shiny and yellow colonies were isolated from all the samples. The pathogenicity of two isolates, XaCN30 from "Guangdong Huangpi" and XaCN43 from "Taoshang Guozhe", was confirmed with Koch's postulates according to the protocol reported by Lin et al. (2018). The incidences of diseased plants (56% and 63%) were observed in individual host clones at 28 d post-inoculation with isolates XaCN30 and XaCN43, respectively. Furthermore, all isolates were confirmed as X. albilineans via molecular methods. PCR amplification was conducted for all 24 isolates using the primer pairs XgyrB1F/XgyrB1R2 (Ntambo et al. 2019) and XAF1/XAR1 (Wang et al. 1999), which targeting the gyrB (encoding the b subunit of the DNA gyrase) and abc (encoding an ABC transporter) genes, and generating 904 bp and 608 bp amplicons, respectively. The PCR fragments were cloned into the pMD19-T vector (TaKaRa, Dalian, China). For each isolate, three single colonies of transformed Escherichia coli DH5α carrying targeted fragment were sequenced. These sequences were deposited into the GenBank with accession no. MT776053-MT776059 and MT776061-MT776077 for gyrB gene and MT776098-MT776104 and MT776106-MT776122 for abc gene. Based on the two concatenated DNA sequences of our 24 isolates, compared with 27 previously reported X. albilineans isolates obtained from the GenBank database, pairwise sequence identity analysis revealed that all 24 isolates from Zhejiang province had 99.4-100% identity with each other, 99.6-100% identity with 14 published domestic isolates, and 98.3-100% identity with 13 foreign isolates. Furthermore, phylogenetic analysis with MEGA 7.0 (Kumar et al. 2016) showed that the isolates from Zhejiang province clustered into two distinct groups (Supplement Fig. 2). One group consisted of 25 Chinese isolates (including all 11 isolates from Wenling) along with four isolates from the French West Indies (GPE PC73, GPE PC17, GPE PC86, and MTQ032), and one isolate from the USA (XaFL07-1), which were assigned to pulsed-field gel electrophoresis (PFGE) group B (Davis et al. 1997; Pieretti et al. 2012). A putative group was also proposed, which included all 13 isolates from Ruian, indicating that isolates from Ruian are distinct from the isolates isolated from other Chinese sugarcane-planting areas, including Wenling. We conclude that leaf scald disease in local clones of chewing cane are caused by X. albilineans in Zhejiang province in China, which will be helpful for leaf scald management in chewing cane, a cash crop.

Transfusion rates and disease spectrum in neonates treated with blood transfusion in China.

This study aimed to investigate blood transfusion rates and spectrum of diseases in hospitalized neonates treated with blood transfusion in China to provide supporting data for future studies on neonatal blood transfusion.Data on hospitalized neonates were obtained from more than 100 experts from the Department of Neonatology of 55 hospitals in China between January 1, 2012 and December 31, 2016, using a standardized survey. A statistical analysis was conducted to evaluate the data collected, including the blood transfusion rates, blood component transfused, spectrum of diseases, and spectrum of major diseases.Between 2012 and 2016, 541,128 neonates were hospitalized in the 55 hospitals surveyed. There were 70,433 neonates who received blood transfusion, with an average transfusion rate of 13.02%. The rates of red blood cell transfusion, platelet transfusion, and plasma transfusion were 9.44%, 0.66%, and 4.77%, respectively. The neonatal blood transfusion rate was 17.99% in Northeast China, 9.74% in Northwest China, and between 10.60% and 16.22% in other regions. The neonatal blood transfusion rate was 12.3% in general hospitals and 13.8% in women and children's hospitals. The top 10 diseases identified in hospitalized neonates treated by blood transfusion were, in rank order, as follows:prematurity,pneumonia, hyperbilirubinemia, bacterial sepsis, respiratory distress syndrome, anemia, hemolytic disease, asphyxia, hemorrhage, and necrotizing enterocolitis.The neonatal blood transfusion rate in China is 13.03%.The rank order in the disease spectrum of the hospitalized neonates and that in hospitalized neonates treated with blood transfusion are different.

Effects of minimally invasive approaches on chronic subdural hematoma by novel YL-1 puncture needle and burr-hole methods.

The objective of this study is to investigate effects of minimally invasive approaches on outcome of chronic subdural hematoma (CSDH) by novel YL-1 puncture needle and burr-hole methods. A retrospective analysis was performed in 158 hospitalized CSDH patients from January, 2013 to December, 2017 in Kunshan Hospital of Traditional Chinese Medicine. Patients' gender, age, history of trauma, volume of hematoma, hematoma location, application of urokinase, surgical approach, the operation time, hospitalized time, and CT scans 3 months after discharge were recorded. Prognostic indicators including symptom relief and post-hospital neuro-imaging findings were extracted to evaluate surgical efficacy. Statistical methods were conducted to evaluate surgical efficacy. Both YL-1 puncture needle and burr-hole surgeries had a satisfying follow-up (93.67%). There was non-significant group difference in follow-up results (p > 0.05). While YL-1 needle group needs less operation time ((p < 0.001) and hospitalized time (p < 0.001), gender (p = 0.144), age (p = 0.394), history of head trauma (p = 0.445), volume of hematoma (p = 0.068), hematoma location (p = 0.281), and application of urokinase (p = 0.545) were shown non-significantly associated with these two minimally invasive approaches. Volume of hematoma was significantly associated with follow-up outcomes (p = 0.016). Novel YL-1 puncture needle and classic burr-hole craniotomy are both proved to be safe and effective minimally invasive surgeries, which can provide an early intervention and minimally invasive strategy for neurosurgeons.

COL1A1 affects apoptosis by regulating oxidative stress and autophagy in bovine cumulus cells.

The collagen type I alpha 1 chain (COL1A1), as a major component of extracellular matrix, plays a potential role in the growth and development of bovine follicles. However, its specific role in bovine cumulus cells remains unclear. In this study, we examined apoptosis, the cell cycle and reactive oxygen species after inhibition of COL1A1 expression by siRNA in bovine cumulus cells. Cell proliferation was measured by CCK-8, and mitochondrial membrane potential was detected by fluorescence intensities of JC-1 staining. Moreover, cell autophagy was detected by immunofluorescence, and cell migration was detected by a cell scratch assay. Lactic acid and cholesterol concentration were measured to evaluate the glucose utilization and cholesterol synthesis activity in cumulus cell by optical density detection method. RT-qPCR and Western blot analysis were used to measure changes in key gene expression. The results showed that cumulus cells were found to have an abnormal cell cycle, and the numbers of cells in S phase were significantly reduced, accompanied by decreases in cholesterol synthesis, and cell proliferation ability and an increase in apoptosis rate with siRNA-COL1A1 treatment. These findings were likely due to inhibition of COL1A1 resulting in high levels of ROS in the cells, a decrease in mitochondrial membrane potential, an increase in intracellular autophagy, activation of the apoptotic pathway, and a decrease in lactic acid conversion ability. COL1A1 plays an important role in regulating the physiological and biological functions of bovine cumulus cells.

Differentially expressed lncRNA-m433s1 regulates FSH secretion by functioning as a miRNA sponge in male rat anterior pituitary cells†.

Long noncoding RNAs (lncRNAs) are important regulators that have multiple functions in a variety of biological processes. However, the contributions of lncRNAs to follicle-stimulating hormone (FSH) secretion remain largely unknown. In this study, we first identified a novel lncRNA, lncRNA-m433s1, as an intergenic lncRNA located in the cytoplasm. We next used MS2-RIP assays to demonstrate that lncRNA-m433s1 interacted with miR-433. Furthermore, we detected the levels of lncRNA-m433s1, miR-433, and Fshß expression, FSH concentrations, and apoptosis upon overexpression and knockdown of lncRNA-m433s1, revealing that lncRNA-m433s1 upregulated Fshß expression. Globally, lncRNA-m433s1 reduced the inhibitory effect of miR-433 on Fshß and further regulated FSH secretion as a competing endogenous RNA (ceRNA) by sponging miR-433. This ceRNA model will provide novel insight into the regulatory mechanisms of lncRNAs associated with rat reproduction.

Good hemostatic effect of platelets stored at 4°C in an in vitro model of massive blood loss and thrombocytopenia.

This study compared the corrective effects of storage of platelets at 4°C and at 22°C in an in vitro model of massive blood loss and thrombocytopenia to provide an experimental basis for the storage of platelets for clinical applications.In vitro model of massive blood loss and thrombocytopenia were constructed by the in vitro hemodilution method and cell washing method. Using storage of platelets at 4°C (1, 3, 5, 7, 10, 14 days) and at 22°C (1, 3, 5 days) to correct the coagulation condition of the different models, by thromboelastography and by routine blood indices.①Platelets stored at 4°C (1, 3, 5,7, 10, 14 days) and at 22°C (1, 3, 5 days) to correct the in vitro model of massive blood loss. Platelet count results improved from 17 to 27 × 10/L to greater than 120 × 10/L for 4°C storage, and 20 to 27 × 10/L to greater than 120 × 10/L for 22°C storage. Thromboelastography maximum amplitude (TEG-MA) results improved from 8.8 to 15.4 mm to greater than 43 mm for 4°C storage, and 12.2 to 14.4 mm to greater than 44.8 mm for 22°C storage. Thromboelastography reaction time values decreased from 9.9-24.9 minutes to 3.8-5.5 minutes for 4°C storage, and 9.9-22.7 minutes to 4.3-4.5 minutes for 22°C storage. ②Platelets stored at 4°C (1, 3, 5,7, 10, 14 days) and at 22°C (1, 3, 5 days) to correct the in vitro model of thrombocytopenia. Platelet count results improved from 12 to 34 × 10/L to greater than 99 × 10/L for 4°C storage, and 12 to 34 × 10/L to greater than 120 × 10/L for 22°C storage. TEG-MA results improved from 21.4 to 32.1 mm to greater than 49.1 mm for 4°C storage, and 21.4 to 31.6 mm to greater than 50.5 mm for 22°C storage.Platelets stored at 4°C and 22°C have the same correcting effect for 1, 3, and 5 days. Platelets stored at 4°C for 7 to 14 days have similarly hemostatic effect on the in vitro model of massive blood loss and thrombocytopenia.

Control of cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing.

The aim of this study was to assess the control of blood glucose, blood pressure (BP), serum low-density lipoprotein cholesterol (LDL-c), and other cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing. We performed a cross-sectional, multi-center survey of 4056 patients with type II diabetes aged ≥40 years. In total, 22.6% were current smokers, 10.8% often drank alcohol, 29.0% were obese, and 67.4% participated in adequate levels of physical activity. About 70% of patients reported comorbid hypertension or dyslipidemia. Of these, 70.8% were being treated for diabetes and 79.3% for hypertension; 20.5% were receiving statins and 28.5% aspirin. The proportions of patients achieving their therapeutic target were 52.6% for fasting plasma glucose, 58.2% for BP, and 33.0% for LDL-c. Only 11.1% achieved all three goals. Among 1960 (48.3%) patients with a record of hemoglobin A1C, 27.8% achieved the hemoglobin A1C target (<6.5%). These data suggest that blood glucose and BP were more likely to be well controlled than LDL-c, the likelihood of control of multiple risk factors is low, and that the statin and aspirin use should be intensified in patients with a substantial risk of cardiovascular disease.

Adipose tissue-derived stem cell therapy for erectile dysfunction in rats: a systematic review and meta-analysis.

OBJECTIVE: We aimed to systematically assess the effect of adipose tissue-derived stem cell (ADSC) therapy and its influential factors on the treatment of erectile dysfunction (ED) in rats. METHODS: Two authors independently searched for published studies through PubMed and EMBASE from study inception until August 31, 2016. A meta-analysis was used to combine the effect estimate from the published studies. A subgroup analysis was performed to identify the effect of some influential factors. The pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model analysis. RESULTS: Twenty studies with a total of 248 rats were included in this meta-analysis. The pooled analysis showed that ADSC therapy significantly increased the ratio of intracavernous pressure and mean arterial pressure (ICP/MAP; SMD 3.46, 95% CI 2.85-4.06; P < 0.001) compared to control therapy. The levels of neuronal nitric oxide synthase (nNOS; SMD 6.37, 95% CI 4.35-8.39; P < 0.001), the cavernous smooth muscle content (CSMC; SMD 3.65, 95% CI 2.65-4.65; P < 0.001), the ratio of cavernous smooth muscle and collagen (CSM/collagen; SMD 4.16, 95% CI 2.59-5.72; P < 0.001), and the cyclic guanosine monophosphate (cGMP; SMD 7.12, 95% CI 2.76-11.48; P = 0.001) were higher following ADSC therapy than following control therapy. Subgroup analysis showed that ADSCs modified by growth or neurotrophic factors significantly recovered erectile function (P < 0.001) compared with ADSC therapy. CONCLUSION: The adequate data indicated that ADSC therapy recovered erectile function and regenerated cavernous structures in ED rats, and ADSCs modified by some growth and neurotrophic factors accelerated the recovery of erectile function and cavernous structures in ED rats.

Hydrogen Sulfide-Mediated Polyamines and Sugar Changes Are Involved in Hydrogen Sulfide-Induced Drought Tolerance in Spinacia oleracea Seedlings.

Hydrogen sulfide (H2S) is a newly appreciated participant in physiological and biochemical regulation in plants. However, whether H2S is involved in the regulation of plant responses to drought stress remains unclear. Here, the role of H2S in the regulation of drought stress response in Spinacia oleracea seedlings is reported. First, drought stress dramatically decreased the relative water content (RWC) of leaves, photosynthesis, and the efficiency of PSII. Moreover, drought caused the accumulation of ROS and increased the MDA content. However, the application of NaHS counteracted the drought-induced changes in these parameters. Second, NaHS application increased the water and osmotic potential of leaves. Additionally, osmoprotectants such as proline and glycinebetaine (GB) content were altered by NaHS application under drought conditions, suggesting that osmoprotectant contributes to H2S-induced drought resistance. Third, the levels of soluble sugars and polyamines (PAs) were increased differentially by NaHS application in S. oleracea seedlings. Moreover, several genes related to PA and soluble sugar biosynthesis, as well as betaine aldehyde dehydrogenase (SoBADH), choline monooxygenase (SoCMO), and aquaporin (SoPIP1;2), were up-regulated by H2S under drought stress. These results suggest that H2S contributes to drought tolerance in S. oleracea through its effect on the biosynthesis of PAs and soluble sugars. Additionally, GB and trehalose also play key roles in enhancing S. oleracea drought resistance.

Hirschsprung disease is associated with an L286P mutation in the fifth transmembrane domain of the endothelin-B receptor in the N-ethyl-N-nitrosourea-induced mutant line.

Hirschsprung disease (HSCR), or colonic aganglionosis, is a congenital disorder characterized by the absence of intramural ganglia along variable lengths of the colon, resulting in intestinal obstruction. It is the most common cause of congenital intestinal obstruction, with an incidence of 1 in 5,000 live births. N-ethyl-N-nitrosourea (ENU)-induced mutagenesis is a powerful tool for the study of gene function and the generation of human disease models. In the current study, a novel mutant mouse with aganglionic megacolon and coat color spotting was generated by ENU-induced mutagenesis. Histological and acetylcholinesterase (AChE) whole-mount staining analysis showed a lack of ganglion cells in the colon in mutant mice. The mutation was mapped to chromosome 14 between markers rs30928624 and D14Mit205 (Chr 14 positions 103723921 bp and 105054651 bp). The Ednrb (Chr 14 position 103814625-103844173 bp) was identified as a potential candidate gene in this location. Mutation analysis revealed a T>C missense mutation at nucleotide 857 of the cDNA encoding endothelin receptor B (EDNRB) in which a proline was substituted for the highly conserved Lys-286 residue (L286P) in the fifth transmembrane (TM V) domain of this G protein-coupled receptor. The mutant mouse was named Ednrb(m1yzcm) (Ednrb; mutation 1, Yangzhou University Comparative Medicine Center). The results of the present study implicate the structural importance of the TM V domain in Ednrb function, and the Ednrb(m1yzcm) mouse represents a valuable model for the study of HSCR in humans.

The reduced state of the plastoquinone pool is required for chloroplast-mediated stomatal closure in response to calcium stimulation.

Besides their participation in photosynthesis, leaf chloroplasts function in plant responses to stimuli, yet how they direct stimulus-induced stomatal movement remains elusive. Here, we showed that over-reduction of the plastoquinone (PQ) pool by dibromothymoquinone (DBMIB) was closely associated with stomatal closure in plants which required chloroplastic H2O2 generation in the mesophyll. External application of H2 O2 reduced the PQ pool, whereas the cell-permeable reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) reversed the DBMIB-induced over-reduction of the PQ pool and stomatal closure. Mesophyll chloroplasts are key players of extracellular Ca(2+) (Ca(2+)o)-induced stomatal closure, but when treated with either 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) or NAC they failed to facilitate Ca(2+)o-induced stomatal closure due to the inhibition of chloroplastic H2 O2 synthesis in mesophyll. Similarly, the Arabidopsis electron transfer chain-related mutants npq4-1, stn7 and cas-1 exhibited diverse responses to Ca(2+)o or DBMIB. Transcriptome analysis also demonstrated that the PQ pool signaling pathway shared common responsive genes with the H2 O2 signaling pathway. These results implicated a mechanism for chloroplast-mediated stomatal closure involving the generation of mesophyll chloroplastic H2O2 based on the reduced state of the PQ pool, which is calcium-sensing receptor (CAS) and LHCII phosphorylation dependent.

Leukemia Risk After Cardiac Fluoroscopic Interventions Stratified by Procedure Number, Exposure Latent Time, and Sex: A Nationwide Population-Based Case-Control Study.

A number of cardiac fluoroscopic interventions have increased rapidly worldwide over the past decade. Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation have become increasingly popular, and these advancements have allowed patients to receive repetitive treatments for restenosis. However, these advancements also significantly increase radiation exposure that may lead to higher cumulative doses of radiation. In the present study, a nationwide population-based case-controlled study was used to explore the risk of leukemia after cardiac angiographic fluoroscopic intervention.A total of 5026 patients with leukemia and 100,520 control patients matched for age and sex (1:20) by a propensity score method without any cancer history were enrolled using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan between 2008 and 2010. All subjects were retrospectively surveyed (from year 2000) to determine receipt of cardiac fluoroscopic interventions. Data were analyzed using conditional logistic regression models, and estimated crude and adjusted odds ratios (95% confidence interval).After adjusting for age, gender, and comorbidities, PTCA was found to be associated with an increased risk of leukemia with an adjusted OR of 1.566 (95% CI, 1.282-1.912), whereas coronary angiography alone without PTCA and cardiac electrophysiologic study were not. Our results also showed that an increased frequency of PTCA and coronary angiography was associated with a higher risk of leukemia (adjusted OR: 1.326 to 1.530 [all P < 0.05]). Gender subgroup analyses demonstrated that men were associated with a higher risk of leukemia compared with women.These results provide additional data in the quantification of the long-term health effects of radiation exposure derived from the cardiac fluoroscopic diagnostic and therapeutic intervention. PTCA alone or PTCA with coronary angiography was associated with an elevated risk of leukemia. Continued follow-up of existing cohorts will be valuable to help assess lifetime risks of cancer.