Ferrostatin-1 Blunts Right Ventricular Hypertrophy and Dysfunction in Pulmonary Arterial Hypertension by Suppressing the HMOX1/GSH Signaling.

Ferroptosis plays a critical role in pulmonary arterial hypertension (PAH)-induced right ventricular (RV) dysfunction, but key genes remain largely unclear. We here identified HMOX1 as an essential ferroptosis-related differentially expressed gene in PAH by bioinformatic analysis using FerrDb, GSE119754, and GSE3675 datasets, respectively. Notably, there were marked increases in HMOX1 and iron levels in RV of monocrotaline-induced PAH rats with reduced TAPSE levels. More importantly, treatment with ferrostatin-1 effectively attenuated RV hypertrophy, remodeling, myocardial fibrosis, and dysfunction in PAH rats. In cultured H9C2 cells and primary neonatal rat cardiomyocytes, pretreatment with ferrostatin-1 and knockdown HMOX1 by siRNA strikingly blunted hypoxia-induced promotion of lipid peroxidation, ferroptosis, and cardiomyocyte injury by potentiating glutathione (GSH) and nitric oxide signaling, respectively. In summary, ferrostatin-1 attenuates RV hypertrophy, fibrosis, and dysfunction in PAH by suppressing the HMOX1/GSH signaling. Targeting HMOX1 ferroptosis signaling functions as a potential therapeutic strategy for patients with PAH.

Protective mechanisms of neral as a plant-derived safener against fenoxaprop-p-ethyl injury in rice.

BACKGROUND: The use of herbicide safeners effectively minimises crop damage while maintaining the full efficacy of herbicides. The present study aimed to assess the potential protective effects of neral (NR) as a safener, in order to mitigate injury caused by fenoxaprop-p-ethyl (FE) on rice. RESULTS: The alleviating effect of NR was similar to that of the safener isoxadifen-ethyl (IE). The root elongation of rice was significantly promoted under the FE + NR and FE + IE treatments, as compared to the FE treatment. The transcriptome analysis further suggested that the effects of NR treatment on plant metabolic pathways differed from those of IE treatment. In total, 895 and 47 up-differentially expressed genes induced by NR (NR-inducible genes) and IE (IE-inducible genes) were identified. NR-inducible genes were mainly enriched in phytohormone synthesis and signalling response, including 'response to brassinosteroid', 'response to jasmonic acid', 'response to ethylene', 'brassinosteroid metabolic process', 'brassinosteroid biosynthesis' and 'plant hormone signal transduction'. In contrast, IE-inducible genes were predominantly enriched in glutathione metabolism. The activity of glutathione S-transferase was found to be increased after IE treatment, whereas no significant increase was observed following NR treatment. Moreover, several transcription factor genes, such as those encoding AP2/ERF-ERF and (basic helix-loop-helix) bHLH were found to be significantly induced by NR treatment. CONCLUSION: This is the first report of the utilisation of NR as an herbicide safener. The results of this study suggest the toxicity of FE to rice is mitigated by NR through a distinct mechanism compared to IE. © 2023 Society of Chemical Industry.

Difference of ventricular synchrony between LBBP, LBFP and LVSP: A speckle tracking echocardiographic study.

PURPOSE: Left bundle branch area pacing (LBBAP) has emerged as a physiological and stable form of pacing. We aim to compare the mechanical ventricular synchrony of LBBP, LBFP, and LVSP. METHODS: Proximal Left bundle branch pacing (LBBP), left bundle fascicular pacing (LBFP) and left ventricular septal pacing (LVSP) were identified in patients with bradycardia who successfully underwent LBBAP. Patients with left ventricular ejection fraction (LVEF) < 50% or QRS duration (QRSd) ≥ 120 ms were excluded. By using electrocardiograms, the left ventricular activation time (LVAT) and QRS duration (QRSd) were measured to examine electrophysiological synchrony. As indications of mechanical synchrony, global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and peak strain dispersion (PSD) were evaluated by using 2-dimensional speckle tracking echocardiography (2D-STE). RESULTS: In 56 patients, data were collected during LBBP (n = 18), LBFP (n = 16), and LVSP (n = 22). LVSP resulted in a longer LVAT (91.3 ± 14.9 ms) than LBBP (77.1 ± 10.8 ms, P < 0.05) and LBFP (72.1 ± 9.6 ms, P < 0.05), but all three groups had similar QRSd. There were no differences in GLS, GCS, GRS, or PSD between LBBP, LBFP, and LVSP. CONCLUSIONS: In patients with normal cardiac function and narrow QRS, though LBBAP with LBB capture resulted in better electrophysiological synchrony than without, the mechanical synchrony of the three groups was comparable.

Genetic diversity analysis of volunteer wheat based on SSR markers.

Volunteer wheat is a kind of wheat with weed characteristics, distributed widely in the main wheat-producing areas of China. It seriously damages the yield and quality of cultivated wheat. To study the genetic diversity and population structure within and between volunteer wheat and cultivated wheat (Triticum aestivum L.), 195 volunteer wheat seeds and 29 cultivated wheat seeds were analysed based on 16 pairs of highly-polymorphic microsatellite simple sequence repeats (SSR) primers and a microchip capillary electrophoresis (MCE) detection system. A total of 110 polymorphic alleles were detected by MCE with each pair of primers identifying 2-15 alleles with an average of 6.875 alleles. The polymorphic information content (PIC) ranged from 0.1089 to 0.7843, with an average of 0.5613. Genetic diversity arguments from 224 samples showed that the volunteer wheat was more varied than cultivated wheat. Based on the SSR information, the 224 samples were classified into seven groups, which corresponded to the volunteer wheats and cultivated wheats through principal coordinates analysis (PCA). We propose that the volunteer wheat and cultivated wheat have rather distant phylogenetic relationships. Hence, it is important for wheat breeding to study the genetic relationship between volunteer wheat and cultivated wheat.

Effects of 3-month dapagliflozin on left atrial function in treatment-naïve patients with type 2 diabetes mellitus: Assessment using 4-dimensional echocardiography.

BACKGROUND: The sodium-glucose transporter-2 (SGLT-2) inhibitor dapagliflozin can improve left ventricular (LV) performance in patients with type 2 diabetes mellitus (T2DM). However, the effects on left atrial (LA) function in treatment-naïve T2DM patients remain unclear. The aim of our study was 1) to investigate the effects of 3-month treatment with dapagliflozin on LA function in treatment-naïve patients with T2DM using 4-dimensional automated LA quantification (4D Auto LAQ) and 2) to explore linked covariation patterns of changes in clinical and LA echocardiographic variables. METHODS: 4D Auto LAQ was used to evaluate LA volumes, longitudinal and circumferential strains in treatment-naïve T2DM patients at baseline, at follow-up, and in healthy control (HC). Sparse canonical correlation analysis (sCCA) was performed to capture the linked covariation patterns between changes in clinical and LA echocardiographic variables within the treatment-naïve T2DM patient group. RESULTS: This study finally included 61 treatment-naïve patients with T2DM without cardiovascular disease and 39 healthy controls (HC). Treatment-naïve T2DM patients showed reduced LA reservoir and conduit function at baseline compared to HC, independent of age, sex, BMI, and blood pressure (LASr: 21.11 ± 5.39 vs. 27.08 ± 5.31 %, padjusted = 0.017; LAScd: -11.51 ± 4.48 vs. -16.74 ± 4.51 %, padjusted = 0.013). After 3-month treatment with dapagliflozin, T2DM patients had significant improvements in LA reservoir and conduit function independent of BMI and blood pressure changes (LASr: 21.11 ± 5.39 vs. 23.84 ± 5.74 %, padjusted < 0.001; LAScd: -11.51 ± 4.48 vs. -12.75 ± 4.70 %, padjusted < 0.001). The clinical and LA echocardiographic parameters showed significant covariation (r = 0.562, p = 0.039). In the clinical dataset, changes in heart rate, insulin, and BMI were most associated with the LA echocardiographic variate. In the LA echocardiographic dataset, changes in LAScd, LASr, and LASr_c were most associated with the clinical variate. CONCLUSION: Compared with HC, treatment-naïve patients with T2DM had lower LA function, and these patients benefited from dapagliflozin administration, particularly in LA function.

Adaptability and Germination Characteristics of Volunteer Wheat in China's Main Wheat-Producing Areas.

Volunteer wheat commonly occurs and spreads rapidly in the main wheat-producing areas of China, seriously impacting cultivated wheat production. Limited information is currently available regarding the adaptability and germination traits of volunteer wheat. Therefore, this study's aim was to evaluate the effects of environmental conditions on the germination and emergence of volunteer wheat seeds through laboratory experiments. The results showed that the germination percentages and viability of volunteer wheat were significantly higher than those of cultivated wheat at a low temperature of 5 °C, and they were lower than those of cultivated wheat at high temperatures of above 30 °C. Compared to cultivated wheat, volunteer wheat was able to tolerate higher salinity and lower osmotic potential, especially long-dormancy volunteer wheat. The secondary germination ability of volunteer wheat was higher than that of cultivated wheat after water immersion. Furthermore, volunteer wheat could not emerge normally when the seeding depth was greater than 8 cm, and the emergence ability of the volunteer wheat was weaker than that of the cultivated wheats when the seeding depth was 4-8 cm, which indicates that the deep tillage of cultivated land could effectively prevent the spread of volunteer wheat. This study revealed differences in the germination characteristics of volunteer wheat and cultivated wheat under the influence of different environmental factors, which provides a basis for future studies concerning the control of volunteer wheat.

Transcriptomic analysis of maize uncovers putative genes involved in metabolic detoxification under four safeners treatment.

Isoxadifen-ethyl (IDF) and cyprosulfamide (CSA) can effectively protect maize from nicosulfuron (NIC) injury, while mefenpyr-diethyl (MPR) and fenchlorazole-ethyl (FCO) did not. Their chemical diversity and requirement to use them in combination with the corresponding herbicides suggest that their elicitation of gene expression are complex and whether it is associated with the safening activity remains elusive. In this study, our first objective was to determine whether or not the ability of four safeners to enhance the metabolic rate of nicosulfuron. It was found that nicosulfuron degradation in maize was accelerated by IDF and CSA, but not by FCO and MPR. Transcriptomic analysis showed that the number of genes induced by IDF and CSA were larger than that induced by FCO and MPR. Overall, 34 genes associated with detoxification were identified, including glutathione S-transferase (GST), cytochrome P450 (CYP450), UDP-glucosyltransferase (UGT), transporter and serine. Moreover, 14 detoxification genes were screened for further verification by real-time PCR in two maize inbred lines. Two maize inbred lines exhibited high expression levels of four genes (GST31, GST39, AGXT2 and ADH) after IDF treatment. GST6, GST19, MATE, SCPL18 and UF3GT were specifically up-regulated in telerant maize inbred line under IDF and IDF + NIC treatments. Seven genes, namely GST31, GST6, GST19, UF3GT, MATE, ADH and SCPL18, are induced by IDF and CSA to play a vital role in regulating the detoxification process of NIC. Accordingly, the GST activity in maize was accelerated by IDF and CSA, but not by FCO and MPR. This result is consistent with transcriptome and metabolic data.These results indicate that the mitigation of NIC damage is associated with enhanced herbicide metabolism. IDF and CSA were more effective in protecting maize from NIC injury due to their ability to enhance the detoxification of specific types of herbicides, compared to FCO and MPR. The chemical specificity of four safeners is attributed to the up-regulated genes related to the detoxification pathway.

The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients.

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.

Graphene dispersant-assisted in situ growth of Re-doped MoS2 nanosheets on carbon cloth and their performance for hydrogen evolution reaction.

Uniform distribution of electrochemically active transition metal compounds on carbon cloth can effective improve their hydrogen evolution reaction (HER) performance, however, harsh chemical treatment of carbon substrates is always unavoidable during this process. Herein, a hydrogen protonated polyamino perylene bisimide (HAPBI) was used as interface active agent for the in situ growth of rhenium (Re) doped MoS2 nanosheets on carbon cloth (Re-MoS2/CC). HAPBI contains a large conjugated core and multiple cationic groups and has been shown to be an effective graphene dispersant. It endowed the carbon cloth excellent hydrophilicity through simple noncovalent functionalization and, meanwhile, provided sufficient active sites to anchor MoO42- and ReO4- via electrostatic interaction. Uniform and stable Re-MoS2/CC composites were facilely obtained by immersing carbon cloth in HAPBI solution followed by hydrothermal treatment in the precursor solution. The doping of Re induced the formation of 1 T phase MoS2, which reached about 40% in the mixture with 2H phase MoS2. Electrochemical measurements showed an overpotential of 183 mV at a current density of 10 mA cm-2 in 0.5 mol L-1 H2SO4 when the molar ratio of Re to Mo is 1:100. This strategy can be further extended to construct other electrocatalysts that using graphene, carbon nanotubes, etc. as conductive additives.

Adenine derived reactive dispersant and the enhancement of graphene based composites.

HYPOTHESIS: Homogeneous dispersion of graphene is the precondition for constructing high performance graphene based composites. However, most of the current dispersants reported in literature still suffer excess usage to reach a desired graphene concentration. Residual of dispersant in composite may seriously affect its properties. Hence, it is expected to obtain effective dispersant with high reactivity to diminish its adverse impacts on graphene composites. EXPERIMENTS: A highly reactive graphene dispersant (DSiA) was synthesized by grafting silanol groups (Si-OH) onto adenine. Molecular structure and the performance of the dispersant were systematically characterized. Composites were fabricated by direct writing of the graphene dispersion on various substrates, and their features were evaluated by resistance, solvent erosion and tensile testing. FINDINGS: Graphene concentration can reach up to 6 mg mL-1 in the presents of DSiA at the weight ratio of 1:1 (DSiA: graphene). DSiA also exhibited good performance for stabilizing multi-walled carbon nanotubes (MWCNTs). Moreover, the dispersant is highly reactive. The graphene based composites showed good mechanical strength and excellent solvent resistance. Overall, the new dispersant provides an ideal choice to uniformly disperse graphene and suitable for fabricating high performance nanocarbon based composites.

Is the pacing site closer to the left ventricular septal endocardium in left bundle branch pacing or in left ventricular septal pacing?

PURPOSE: Distinguishing between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) is challenging. This study aimed to compare the echocardiographic distance from the pacing lead tip to the left ventricular (LV) septal endocardium between patients who underwent LBBP and those who underwent LVSP successfully. METHODS: Fifty-nine consecutive patients (age 71.9 ± 12.0 years, 35.6% male) with traditional indications for permanent cardiac pacing were included (LBBP group, n = 46; LVSP group, n = 13). Unipolar pacing from the final pacing sites generated narrow QRS complexes with a right bundle branch block pattern in all patients. After the procedure, a physician blinded to the group allocation performed echocardiographic measurements of the distance between the lead tip and the LV septal endocardium. RESULTS: The mean paced QRS duration was comparable between the LBBP group and the LVSP group (105.3 ± 15.6 ms vs. 109.2 ± 9.6 ms, P = 0.287). In the LBBP group, the interval from the left bundle branch potential to QRS onset was 28.7 ± 9.0 ms. During diastole, the mean distance between the lead tip and the LV septal endocardium was 0.6 ± 0.9 mm in the LBBP group and 3.0 ± 1.6 mm in the LVSP group (P < 0.001). During systole, the distance was 1.5 ± 1.4 mm in the LBBP group and 4.3 ± 2.6 mm in the LVSP group (P < 0.001). CONCLUSIONS: The landing zone of the lead tip was closer to the LV septal endocardium in the patients who underwent LBBP. There is a need for real-time intraprocedural monitoring of the distance between the lead tip and the LV septal endocardium when performing LBBP.

Left atrial strain for predicting recurrence in patients with non-valvular atrial fibrillation after catheter ablation: a single-center two-dimensional speckle tracking retrospective study.

BACKGROUND: Although catheter ablation (CA) is an effective treatment for non-valvular atrial fibrillation (AF), a good many of patients still have a recurrence following post-operation. Prediction of AF recurrence by evaluating left atrial (LA) phase function with speckle tracking echocardiography (STE) may be helpful for risk stratification and clinical management for AF patients. Therefore, the current study aimed to assess the prognostic value of LA strains in non-valvular AF patients after CA. METHODS: A total of 95 non-valvular AF patients (70.5% paroxysmal AF, 56.8% males, mean age 63.2 ± 9.7 years) were included in this retrospective study between October 2019 and August 2020. Transthoracic echocardiography was performed in all the subjects and STE was used to analyze the LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) during different phases before CA. Patients were followed up with until January 2022. The endpoint was AF recurrence. RESULTS: Over a median follow-up period of 26.0 months (interquartile range, 24.7-26.7 months), 26 patients experienced recurrence and 69 stayed in sinus rhythm. Compared with no-recurrence group, maximum volume of LA (LAVmax), minimum volume of LA (LAVmin) and LA volume index (LAVI) were increased in the recurrence group, while LAEF, LASr and LASct were worsened (P < 0.05). Multivariable logistic regression analysis revealed that LASct was an independent predictor of AF recurrence (odds ratio, 0.89; 95% confidence interval (CI), 0.82-0.97; P = 0.007) and receiver operating characteristic (ROC) curve analysis showed an area under the curve of LASct<8% was 0.70 (95% CI, 0.59-0.79; P = 0.0008). CONCLUSIONS: LASct was of independent predictive value of AF recurrence. LA function assessed by STE may contribute to the risk stratification for AF patients and selection of suitable patients for CA.

The mechanism of exogenous gibberellin A3 protecting sorghum shoots from S-metolachlor Phytotoxicity.

BACKGROUND: S-metolachlor (MET) was used to prevent weed infestation in sorghum fields, but inappropriate application could result in phytotoxicity on sorghum. Exogenous gibberellin A3 (GA3 ) has been applied for alleviating the phytotoxicity of MET. However, its detoxification mechanism is still not well known. RESULTS: Leaf deformity of sorghum caused by 200 mg/L MET was alleviated by treating sorghum shoots with 800 mg/L GA3 , and the injury recovery rate of growth index was over 73%. More importantly, GA3 could not accelerate the metabolic rate of MET in sorghum. The result of phytohormone metabolomics showed that endogenous GA3 content in sorghum decreased by 78.10% with MET treatment, while abscisic acid (ABA) content increased by 120.2%, resulting in 10.3-fold increase of ABA/GA3 ratio. Content of ABA and GA3 increased by 11.9- and 21.1-fold with MET and GA3 treatment, respectively, leading to ABA/GA3 ratio restoration. Moreover, MET inhibited the expression of genes encoding key enzymes related to GA synthesis including CPS1, KO2, KAO, GA20ox1D and ABA8ox gene related to ABA metabolism. The transcription levels of GA metabolism-related genes CYP714D1 and GA2ox were up-regulated by 11.2- and 7.2-fold, while ABA synthesis-related genes NCED and ZEP were up-regulated by 8.0- and 3.0-fold, respectively, with MET and GA3 treatment. CONCLUSION: In this study, exogenous GA3 protecting sorghum shoots from MET phytotoxicity was due to supplement the MET-induced GA3 deficiency by absorbing exogenous GA3 , and restore homeostasis of ABA and GA3 by promoting ABA synthesis, which provides novel insights for mechanism of GA3 alleviating MET phytotoxicity. © 2022 Society of Chemical Industry.

Comparison of fibrosing mediastinitis patients with vs. without markedly increased systolic pulmonary arterial pressure: a single-center retrospective study.

INTRODUCTION: Fibrosing mediastinitis (FM) complicated with pulmonary hypertension (PH) has been considered as an important cause of morbidity and mortality. This study was designed to observe the possible effects of abnormal hemodynamics on patients by conducting a between-group comparison according to the presence of markedly increased systolic pulmonary arterial pressure (SPAP), so as to provide more information for clinical management. MATERIALS AND METHODS: Fifty-one patients with clinically diagnosed FM were divided in two groups (SPAP < 50 mmHg group; SPAP ≥ 50 mmHg group) and retrospectively included in the study. Data mainly including demographic factors, echocardiographic data, results of right heart catheter and computed tomography (CT) examination were retrieved from the medical database. Echocardiographic parameters pre- and post- balloon pulmonary angioplasty (BPA) treatment were also collected in 8 patients. RESULTS: Significant changes in cardiac structure, hemodynamics and cardiac function were detected in patients complicated with markedly increased SPAP. Patients in the SPAP ≥ 50 mmHg group had increased right heart diameter, right heart ratio and velocity of tricuspid regurgitation (VTR) (p < 0.05). Deteriorated right heart function was also observed. There was no significant difference in CT findings between the two groups, except that more patients in the SPAP ≥ 50 mmHg group had pleural effusion (p < 0.05). After primary BPA in 8 patients, improvement in the right atrium proportion was observed. CONCLUSIONS: Changes due to significantly increased SPAP in patients with FM include adverse structure and function of the right heart, but differences in CT findings were not significant. Echocardiography has advantages as a noninvasive tool for the evaluation of cardiac structure, function and hemodynamics in patients with FM.

Transcriptome analysis and the identification of genes involved in the metabolic pathways of fenoxaprop-P-ethyl in rice treated with isoxadifen-ethyl hydrolysate.

Fenoxaprop-P-ethyl (FE) is a highly effective weed control agent for rice fields, but it causes phytotoxicity in crops. A whole-plant bioassay has revealed that isoxadifen-ethyl hydrolysate (IH) can significantly improve the tolerance of rice to FE, but the molecular mechanisms underlying this phenomenon are still unclear. In this study, we performed RNA-Seq analysis using rice seedlings treated with FE and IH to determine the IH-regulated candidate genes involved in metabolic resistance to FE. We also analyzed spatiotemporal expression using quantitative reverse transcription polymerase chain reaction to reveal the expression patterns of these genes under different treatments. The results showed that genes encoding metabolic enzymes, such as cytochrome P450 monooxygenases, glutathione-s-transferases, UDP-glycosyltransferase, carboxylesterase, and ATP-binding cassette transporter, were influenced by the application of IH. Most of these genes were upregulated, and their products were involved in various stages of FE metabolism. Tolerance to FE was primarily mediated by CarE15, CYP86A1, GSTU6, GST4, UGT13248, UGT79, and ABCC4, all of which played a vital role in regulating the detoxification process of FE. Our findings elucidated the protective mechanisms of IH, which can help alleviate the phytotoxic effects of FE and expand its potential for application in agriculture.

MicroRNA-122-5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3.

Hypertensive renal injury is accompanied by tubular interstitial fibrosis leading to increased risk for renal failure. This study aimed to explore the influences of miR-122-5p in hypertension-mediated renal fibrosis and damage. 14-week-old male SHR and WKY rats were randomly assigned to treat with rAAV-miR-122-5p or rAAV-GFP for 8 weeks. There were marked increases in miR-122-5p and Kim-1 levels and decreases in FOXO3 and SIRT6 levels in hypertensive rats. Transfection with rAAV-miR-122-5p triggered exacerbation of renal fibrosis, apoptosis and inflammatory injury in SHR, associated with downregulated levels of FOXO3, SIRT6, ATG5 and BNIP3 as well as upregulated expression of Kim-1, NOX4, CTGF, and TGF-ß1. In cultured primary mouse renal tubular interstitial fibroblasts, exposure to angiotensin II resulted in obvious downregulation of FOXO3, SIRT6, ATG5, BNIP3 and nitric oxide levels as well as augmented cellular migration, oxidative stress, and inflammation, which were exacerbated by miR-122-5p mimic while rescued by miR-122-5p inhibitor and rhFOXO3, respectively. Notably, knockdown of FOXO3 strikingly blunted cellular protective effects of miR-122-5p inhibitor. In summary, miR-122-5p augments renal fibrosis, inflammatory and oxidant injury in hypertensive rats by suppressing the expression of FOXO3. Pharmacological inhibition of miR-122-5p has potential therapeutic significance for hypertensive renal injury and fibrosis-related kidney diseases.

The potent radioprotective agents: Novel nitronyl nitroxide radical spin-labeled resveratrol derivatives.

It is commonly known that radiotherapy is still a key modality for treatment of cancer. Though this effect is desirable during radiotherapy, it leads to radiotoxicity on normal healthy cells. In the present research, we designed, synthesized and analyzed a series of nitronyl nitroxide radical (NITR) spin-labeled resveratrol (RES) derivatives. The cytotoxicity of the newly synthesized substances was tested on Jurkat T cells. The derivatives were studied as reactive oxygen species (ROS) scavenger to protect ionizing radiation of Jurkat T cells upon 6 Gy X-irradiation. The experimental results revealed that compound 2 and 3 could significantly alleviate the damage of Jurkat T cells, as evidenced by decreasing ROS production and restoring the cell apoptosis. Further mechanism investigations indicated that the radioprotective effects of the novel derivatives were largely associated with modulating the expression of apoptotic proteins including cIAP-1, cIAP-2, cytochrome c, caspase-3 and caspase-9. Based on the experimental result, we disclosed that the novel NITR spin-labeled RES derivatives exhibit the potential to be used as the novel radioprotective candidates to ameliorate the injury induced by ionizing radiation.

Insight into the practical models for prediciting the essential role of the cytochrome P450-mediated biotransformation in emodin-associated hepatotoxicity.

Emodin is widely present in Chinese herbs with broad application prospects, however, the conflicting reports of its hepatotoxicity have created a concern. It was therefore aimed to develop practical models to elucidate the outcome of CYP450 biotransformation on emodin. HepG2 and rat liver microsomes (RLM) coculture system was first utilized for prediction. It was found that emodin (35 µM)-mediated cytotoxicity was alleviated only when the cofactor of CYP450 NADPH (1 mM) was present. Similarly, both the pan-CYP450 inhibitor 1-aminobenzotriazole (ABT) (2 mM) and the heat-inactivated liver microsomes completely abolished the protective effect of RLM (0.75 mg/mL). Consistently, ABT significantly increased the toxicity of emodin in primary rat liver cells. Along similar lines, only the monohydroxylation metabolite M3 that accounted for neglectable amount of the whole metabolites showed similar toxicity to emodin, both M1 and M2 exhibited far less toxcity than emodin in THLE-2 cells. In vivo study further supported that ABT (50 mg/kg, s.c.) aggravated the hepatotoxicity of emodin (80 mg/kg, i.p.) on mice, as emodin treatment only mediated slight increase of liver index and histological score likely due to the metabolic detoxication of emodin, whereas ABT co-administration resulted in severe liver injury as reflected by the dramatic increase of the liver index value, serum ALT and AST levels, and histopathological score. Moreover, it was explored that ROS generation together with the electrophilicity of emodin contributed to its hepatotoxicity. These findings not only provided a clear evidence of the metabolic detoxification of emodin, but also shed a light on the hepatotoxic mechanisms of emodin, which would lay a solid foundation for the rational application of emodin in the future.

Efficacy of peripheral arterial access for peripheral blood stem cells collection.

BACKGROUND: Transplantation of peripheral blood stem cells (PBSCs) mobilized by cytokines is increasingly applied to treat patients with hematologic diseases, such as lymphoma, multiple myeloma, leukemia, etc. Successful hematopoietic stem cell transplantation (HSCT) increasingly depends on the collection of hematopoietic stem cells (HSCs) from peripheral blood. Peripheral vein (PV) is the most common type of blood access. When the blood vessels are not well filled and the blood flow is insufficient, the machine will appear repeated low pressure alarm or pipeline coagulation, which seriously affects the collection efficiency. A peripheral artery (PA) is utilized for drawing blood, while a peripheral vein is used for blood return, that is a way to perform apheresis. The advantages of PA are that it ensures adequate extracorporeal circulation blood flow, stable blood flow rate, simple operation, and relatively low price. However, there are very few studies on the efficacy of peripheral arterial access for HSCs collection. Therefore, this retrospective study was conducted to assess the effectiveness of PA and PV access for PBSCs collection. METHODS: We performed a retrospective analysis of 150 apheresis procedures on 26 patients and 95 healthy donors collected by PV or PA access from March 1, 2020 to March 1, 2021. We compared the CD34+ cell count, collection efficiency (CE), duration of processing a single blood volume, number of low-pressure alarms, average blood flow rate and number of punctures between the two groups. Also, we analyzed adverse events. RESULTS: There was no significant difference in the quality of apheresis blood components between the PA group and the PV group. The CD34+ cells collected was 274.16 ± 216.31 × 106 in the PV group and 246.63 ± 127.94 × 106 in the PA group. The CE in the PA group was 49.50 ± 9.88%, higher than 42.39 ± 14.62% in the PV group. The duration of processing a single blood volume was 90.67 ± 15.35 min in the PV group and 79.68 ± 10.28 min in the PA group. The number of low-pressure alarms in the PA group was 0.38 ± 0.98, <2.42 ± 1.76 in the PV group, and the average blood flow rate in the PA group was 59.27 ± 2.18, higher than 54.21 ± 3.41 in the PV group. The difference was statistically significant (P < .05). The Number of punctures was 1.35 ± 0.75 in the PA group and 1.41 ± 1.01 in the PV group. There was no statistically significant difference. CONCLUSION: Peripheral artery is a safe, reliable, economical, convenient, and fast vascular access, which opens a new way to the establishment of vascular access for PBSCs collection.

Risk assessment in interstitial lung disease: the incremental prognostic value of cardiopulmonary ultrasound.

BACKGROUND: The mortality risk of chronic interstitial lung disease (ILD) is currently assessed using the ILD-GAP score. The present study evaluates whether the addition of cardiopulmonary ultrasound parameters to the ILD-GAP score can further improve the predictive value of ILD-GAP. METHODS: Medical records from 91 patients with ILD hospitalized from June 2015 to March 2016 were retrospectively examined. The Lung ultrasound (LUS) score, right ventricular (RV) function, and mechanics were obtained from the cardiopulmonary ultrasound. The ILD-GAP score was calculated from demographic characteristics and pulmonary function parameters. Patients were followed up with until May 2020. The primary endpoint was all-cause death. RESULTS: After exclusions, 74 patients with ILD were included in the analysis. During the follow-up period, 36 patients with ILD survived (ILDs), and 38 patients died (ILDd). Compared to ILDs, the ILDd cases exhibited a higher number of B-lines, LUS score, and RV end-diastolic base dimension (RVD), but lower RV function. In multivariate analysis, the ILD-GAP score (hazard ratio, 2.88; 95% CI 1.38-5.99, P = 0.005), LUS score (hazard ratio 1.13; 95% CI 1.04-1.24, P = 0.006), and RVD (hazard ratio 1.09, 95% CI 1.03-1.16, P = 0.004) were significantly related to the risk of death. Adding the LUS score and RVD to the ILD-GAP score significantly improved the predictive value compared to the ILD-GAP score alone (C statistics 0.90 vs 0.76, P = 0.018). CONCLUSION: We investigated the utility of a new prognostic model for ILD that includes both cardiopulmonary ultrasound parameters (LUS score and RVD) and the ILD-GAP score. This model better reflects the severity of pulmonary fibrosis and cardiac involvement, and has incremental predictive value over the ILD-GAP score alone.