Chitosan-Magnesium Oxide Nanoparticles Improve Salinity Tolerance in Rice (Oryza sativa L.).

High-salinity (HS) stress is a global element restricting agricultural productivity. Rice is a significant food crop, but soil salinity has a detrimental impact on its yield and product quality. Nanoparticles (NPs) have been found as a mitigation method against different abiotic stresses, even HS stress. In this study, chitosan-magnesium oxide NPs (CMgO NPs) were used as a new method for rice plants to alleviate salt stress (200 mM NaCl). The results showed that 100 mg/L CMgO NPs greatly ameliorated salt stress by enhancing the root length by 37.47%, dry biomass by 32.86%, plant height by 35.20%, and tetrapyrrole biosynthesis in hydroponically cultured rice seedlings. The application of 100 mg/L CMgO NPs greatly alleviated salt-generated oxidative stress with induced activities of antioxidative enzymes, catalase by 67.21%, peroxidase by 88.01%, and superoxide dismutase by 81.19%, and decreased contents of malondialdehyde by 47.36% and H2O2 by 39.07% in rice leaves. The investigation of ion content in rice leaves revealed that rice treated with 100 mg/L CMgO NPs maintained a noticeably higher K+ level by 91.41% and a lower Na+ level by 64.49% and consequently a higher ratio of K+/Na+ than the control under HS stress. Moreover, the CMgO NPs supplement greatly enhanced the contents of free amino acids under salt stress in rice leaves. Therefore, our findings propose that CMgO NPs supplementation could mitigate the salt stress in rice seedlings.

n-3 polyunsaturated fatty acids improve depression-like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression.

INTRODUCTION: n-3 polyunsaturated fatty acids (PUFAs) are believed to be implicated in the pathogenesis of many inflammation-related diseases, including depression. METHODS: The mouse model of depression was established through chronic unpredictable mild stress (CUMS), the mice were intervened with n-3 PUFAs, and then the expression of toll-like receptor 4 (TLR4) was stimulated with lipopolysaccharides (LPS). Tail suspension test (TST), forced swimming test (FST) and sucrose preference test were performed to monitor the depression behavior of mice. Microglia activation was detected by Iba1 immunofluorescence, and neuronal injury was detected by Nissl staining. Concentrations of tumor necrosis factor (TNF)-α, Interleukin (IL)-6 and IL-1ß in the hippocampus were assessed via enzyme linked immunosorbent assay (ELISA). Quantitative real time polymerase chain reaction was used to detect IL-6, IL-1ß and TNF-α messenger RNA levels. Western blot was utilized for detection of TLR4 protein expression. RESULTS: CUMS significantly reduced the sucrose preference in mice, while increased the immobility time in FST and TST. Moreover, CUMS significantly aggravated microglia activation and neuronal damage in mice and increased the levels of IL-6, IL-1ß and TNF-α in hippocampal tissues, however, intervention with n-3 PUFAs could improve the above effects. Further, the increased TLR4 induced by LPS partially reversed the inhibition of n-3 PUFAs on depression-like behaviors, microglial activation and inflammatory injury of hippocampal neurons. CONCLUSION: n-3 PUFAs may ameliorate depression-like behaviors via reducing hippocampal neuroinflammation in CUMS-induced mice by regulating TLR4 expression, suggesting that n-3 PUFAs may be an effective antidepressant, which provides evidence for future treatment of depression.

Mechanisms of Xiong-Pi-Fang in treating coronary heart disease associated with depression: A systematic pharmacology strategy and in vivo pharmacological validation.

BACKGROUND: Coronary heart disease (CHD) and depression are very common and often co-existing disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating CHD associated with depression. However, its mechanism of action is still unknown. PURPOSE: To employ a systematic pharmacology approach for identifying the action mechanisms of XPF in treating CHD associated with depression. METHODS: We used a systematic pharmacology approach to identify the potential active mechanisms of XPF in treating CHD with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. RESULTS: Network pharmacology predicted 42 key targets and 20 signaling pathways involved in XPF-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic-pituitary-adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing CHD within the depression model in rats. In addition, XPF intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, XPF exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression. CONCLUSIONS: Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of XPF against CHD with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for CHD therapy with depression.

Postoperative Adjuvant Transarterial Chemoembolization Plus Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma: a Multicentre Retrospective Study.

Purpose: This study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection. Patients and Methods: Patients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan-Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0. Results: The 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408-0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥5 cm, tumour number <3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P<0.05). Some patients (33.33%) experienced grade ≥3 AEs in the TACE plus TKI group. Conclusion: TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

Mechanisms of Lian-Gui-Ning-Xin-Tang in the treatment of arrhythmia: Integrated pharmacology and in vivo pharmacological assessment.

BACKGROUND: Lian-Gui-Ning-Xin-Tang (LGNXT), a classical traditional Chinese medicine (TCM) formula, has been widely used in clinical practice and has shown satisfactory efficacy in the treatment of arrhythmias. However, its mechanism of action in the treatment of arrhythmias is still unknown. Moreover, the complex chemical composition and therapeutic targets of LGNXT pose a challenge in pharmacological research. PURPOSE: To analyze the active compounds and action mechanisms of LGNXT for the treatment of arrhythmias. METHODS: Here, we used an integrated pharmacology approach to identify the potential active compounds and mechanisms of action of LGNXT in treating arrhythmias. Potential active compounds in LGNXT were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and the potential related targets of these compounds were predicted using an integrated in silico approach. The obtained targets were mapped onto relevant databases to identify their corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. RESULTS: Eighty-three components were identified in herbal materials and in animal plasma using UPLC-Q-TOF/MS and were considered the potential active components of LGNXT. Thirty key targets and 57 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified as possible targets and pathways involved in LGNXT-mediated treatment using network pharmacology, with the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/Ca2+ system pathway being the most significantly affected. This finding was validated using an adrenaline (Adr)-induced rat model of arrhythmias. Pretreatment with LGNXT delayed the occurrence, shortened the duration, and reduced the severity of arrhythmias. LGNXT exerted antiarrhythmic effects by inhibiting cAMP, PKA, CACNA1C, and RyR2. CONCLUSIONS: The findings of this study revealed that preventing intracellular Ca2+ overload and maintaining intracellular Ca2+ homeostasis may be the primary mechanisms of LGNXT in alleviating arrhythmias. Thus, we suggest that the ß-adrenergic receptor (AR)/cAMP/PKA/Ca2+ system signaling hub may constitute a promising molecular target for the development of novel antiarrhythmic therapeutic interventions. Additionally, we believe that the approach of investigation of the biological effects of a multi-herbal formula by the combination of metabolomics and network pharmacology, as used in this study, could serve as a systematic model for TCM research.

The Effects of Ischemic Preconditioning Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis.

OBJECTIVE: Ischemic preconditioning (IPC) has gradually been promoted in clinical practice to lower the risk of cardiovascular surgery and postoperative complications. We investigated the role of IPC on vascular endothelial function and the relationship between IPC, flow-mediated dilation (FMD), and brachial artery diameter (BAD). METHODS: Systematic searches were conducted in PubMed, Medline, Cochrane Library, Embase, and Scopus databases from their inception to March 20, 2020. This research included randomized controlled trials (RCTs) with adults, and the values of FMD and BAD were considered as the primary outcomes. Ten studies comprising 292 participants were included in the meta-analysis. RESULTS: Regarding FMD, we observed beneficial effects of IPC on endothelial function (standardized mean difference (SMD): 1.82; 95% confidence interval (CI): 0.64, 3.01; p < 0.001; I 2 = 89.9%). However, the available evidence did not indicate that IPC affected BAD (SMD: 0.08; 95% CI: -0.03, 0.18; p > 0.05; I 2 = 76.5%). CONCLUSIONS: Our meta-analysis indicated a significant effect of IPC on the endothelial function of the blood vessels, affecting FMD but not BAD.

Green Tea Polyphenols Promote Functional Recovery from Peripheral Nerve Injury in Rats.

BACKGROUND Peripheral nerve injury (PNI) is a common and progressive disorder with sensory and motor deficits in the peripheral nervous system (PNS). Treatment is difficult, with unfavorable prognosis. Green tea polyphenols (GTPs) exert neuroprotective effects on regeneration of the central nervous system (CNS). However, the effects of GTPs on functional recovery of the PNS have not been fully characterized. Consequently, the present study investigated the effects of GTPs on nerve regeneration of rats with PNI. MATERIAL AND METHODS The model of PNI was established in rats by sciatic nerve injury (SNI). Adult male Wistar rats with SNI were randomly divided into a vehicle group and a GTPs group. The compound muscle action potential (CMAP) of rat sciatic nerves (SN) was measured using the CM6240 physiological signal acquisition and processing system. The wet weight of the triceps muscle was determined using an analytical balance. The number of myelinated nerve fibers was counted under an optical microscope. Ultrastructure of the regenerated nerves in SN was observed by transmission electron microscopy. The mRNA and protein expression of nerve growth factor (NGF), growth-associated protein-43 (GAP-43), neurofilament 200 (NF200), and myelin-associated glycoprotein (MAG) in SN stumps were measured by real-time quantification PCR (RT-qPCR) and Western blot, respectively. RESULTS In rats with SNI, GTPs relieved the adhesion between nerve anastomosis and surrounding tissues, and significantly increased nerve conduction velocity, wet weight of the triceps muscle, and development and axonal regeneration of myelinated nerve fibers. Moreover, GTPs promoted the mRNA and protein expressions of NGF, GAP-43, NF200, and MAG in SN stumps. CONCLUSIONS GTPs promotes nerve regeneration in rats with SNI.

[Determination of amino acid contents in cottonseeds using near infrared reflectance spectroscopy].

A total of 445 samples with great variability in amino acid contents were harvested for different seasons in different regions for developing calibration equations of amino acid content in cottonseeds. The spectral data of cotton kernel powder was processed using the first derivative mathematical treatment combined with SNV and de-trend, as well as modified partial least squares (MPLS) regression method. The chemometric models for 17 amino acids present in cottonseed were developed, and 12 of them were excellent for the determination of related amino acids, namely asparagic acid, threonine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, phenylalanine, lysine, histidine, and arginine, with RPDc of 3.735-7.132 and determination coefficient (r2) of 0.910-0.979 in external validation. For those 12 amino acids, their values predicted by NIRS are comparable to those obtained by the chemical method with good accuracy. The RPDc of serine, methionine, tyrosine and proline were 2.205 -2.814, and their determination coefficient (r2) were 0.800-0.830 in external validation. For those 4 amino acids, the values from NIRS are not so accurate as chemical analysis, but could be used in sample screening in cotton breeding program. While the equation for cystine was useless as its RPDc was only 1.358, which was not suitable for estimating its content in cottonseeds.

Effect of Lidan Granule on bile lithogenesis in patients with choledocholithiasis combined with cholecystolithiasis.

OBJECTIVE: To observe the effect of Lidan Granule (, LDG) on bile lithogenic tendency and biliary 33.5 kd vesicular protein (VP) and to explore its mechanism. METHODS: Sixty patients with choledocholithiasis combined with cholecystolithiasis were randomly assigned to the LDG treated group, the sodium cholate treated group for positive control, and the untreated control group, 20 patients in each group. The 4 bile lithogenic trend indexes, including lithogenic index (LI), unconjugated bilirubin percent (UCB%), unconjugated bilirubin saturation index (BSI) and Z-value, were determined before and after treatment. The content of VP in bile was determined as well. RESULTS: Before treatment, the LI, UCB%, BSI and Z-value in the LDG treated group were 1.298+/- 0.265, 34.72+/-2.96, 0.353+/-0.093 and 0.556+/-0.499, respectively, which was decreased after the 2-week treatment to 0.926+/-0.208, 8.93+/-1.19, 0.154+/-0.056 and 0.257+/-0.211, respectively (all P<0.05). Meantime, the content of VP was also lowered from 0.050+/-0.005 g/L to 0.032+/-0.005 g/L. However, no significant change in any of the above-mentioned indexes was found in the other two groups. CONCLUSION: LDG could effectively suppress bile lithogenic trend and reduce 33.5 kd VP in bile.