NE Levels Research Articles

Hydrogen sulfide ameliorated preeclampsia via suppression of toll-like receptor 4-activated inflammation in the rostral ventrolateral medulla of rats

This study aims to determine whether toll-like receptor 4 (TLR4)-mediated inflammation in rostral ventrolateral medulla (RVLM) causes sympathetic overactivity leading to preeclampsia (PE) and if TLR4 inhibition with hydrogen sulfide (H2S) would reduce PE severity. Thirty patients with PE and 30 pregnant controls were involved. PE in rats was induced through deoxycorticosterone acetate and normal saline. NaHS (donor of H2S), lipopolysaccharide (LPS) (TLR4 agonist), and TAK-242 (TLR4 inhibitor) were injected in lateral cerebral ventricle to investigate their effect on microglia-mediated inflammation in RVLM, sympathetic activation, and PE symptoms. In patients with PE, plasma levels of NE, TNF-α, and interleukin-1β were high compared with those of controls, whereas levels of H2S were low. Rats with PE showed an increased amount of renal sympathetic nerve activity and plasma levels of NE, with decreased H2S levels in RVLM. Microglia-mediated inflammation was observed in the RVLM of PE rats. Central infusion of LPS in pregnant rats induced microglia-mediated inflammation, sympathetic nervous tension, and PE-like symptoms, whereas TAK-242 reduced PE symptoms. NaHS treatment lessened microglia-mediated inflammation in the RVLM, sympathetic tension, and symptoms of PE both in PE rats and LPS-treating pregnant rats.These results suggest that inflammation in the RVLM caused by microglial activation might contribute to the progression of PE via an overactive sympathetic system. H2S could reduce PE via inhibiting inflammation in the RVLM. These results might provide a new target for the treatment of PE.

Effect Observation of Electro-Acupuncture Anesthesia Combined with General Anesthesia in Elderly Patients Undergoing Gastrointestinal Tumor Resection.

ObjectiveTo investigate the anesthetic effect of electro-acupuncture (EA) anesthesia combined with general anesthesia in elderly patients undergoing gastrointestinal tumor resection, and to analyze the effects of EA anesthesia on inflammatory factors, stress state and T lymphocyte subsets in elderly patients.MethodsTotal of 118 elderly patients who underwent gastrointestinal tumor resection in our hospital from June 2018 to March 2021 were selected and divided into the control group (59 cases) and the observation group (59 cases) according to the random number method. General anesthesia was adopted in the control group and EA anesthesia combined with general anesthesia was adopted in the observation group. The anesthesia effect, stress state, levels of inflammatory factors, T-lymphocyte subsets and adverse reactions were compared.ResultsThe VAS score, agitation score and respiratory normalization time in the observation group were lower than those in the control group (p < 0.05). After surgery, the levels of serum Cor, ET, NE and DA in the observation group were lower than those in the control group (p < 0.05). At 24 h after surgery, the levels of serum TNF-α, IL-6 and IL-1β in the observation group were lower than those in the control group (p < 0.05). At 24 h after surgery, the levels of , , and in the two groups were lower than those before surgery, and the levels of , , and in the observation group were higher than those in the control group (p < 0.05). During the hospitalization, the total incidence rate of adverse reactions after anesthesia in the observation group was lower than that in the control group (p < 0.05).ConclusionEA anesthesia combined with general anesthesia has good anesthesia effect when used for gastrointestinal tumor resection in the elderly. It can stabilize the internal environment of patients, alleviate postoperative stress response and inflammatory response, and regulate the body immune function. Moreover, it has high safety and can significantly reduce the occurrence of postoperative adverse reactions.

Upregulated iRhom2 in the Hypothalamic Paraventricular Nucleus is Associated with TACE‐Mediated Shedding of Transforming Growth Factor‐α and Sympathetic Excitation in Heart Failure Rats

Tumor necrosis factor (TNF)‐α converting enzyme (TACE), also known as a disintegrin and metalloprotease (ADAM)17, is a key mediator of cell signaling by proteolytically cleaving extracellular domains of various cytokines and growth factors. TACE‐mediated shedding of transforming growth factor (TGF)‐α, has been shown to transactivate epidermal growth factor receptor (EGFR) to activate the mitogen‐activated protein kinase signaling pathway in the pathophysiological conditions. We previously reported that both TACE and TGF‐α are upregulated in the hypothalamic paraventricular nucleus (PVN, a critical cardiovascular and autonomic center) and contribute to the sympathetic excitation in heart failure (HF). However, the mechanisms by which TACE and TGF‐α are upregulated in the PVN in HF remain unclear. Recent evidence reveals that inactive Rhomboid proteins (iRhoms) including iRhom1 and iRhom2 are essential upstream regulators of TACE/ADAM17. The present study sought to determine the expression of iRhoms and its relationship with TACE‐mediated shedding of TGF‐α in the PVN in HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). The left ventricular function and infarction size were assessed by echocardiography. Four weeks later, these animals were euthanized to collect cerebrospinal fluid (CSF), PVN tissues and blood for molecular and biochemical measurements. All values are expressed as the mean ± SD. Real‐time PCR showed abundant mRNA expression of both iRhom1 and iRhom2 in the PVN and brain cortex in Sham or HF rats. Compared with Sham rats, HF rats had significantly (*P&lt;0.05) increased mRNA expression of iRhom2 (2.00 ± 0.57* vs 1.03 ± 0.28, HF vs Sham) but not iRhom1 (1.32 ± 0.41 vs 1.02 ± 0.21) in the PVN. Additionally, HF rats exhibited marked increases in mRNA expression of TACE (2.25 ± 1.15* vs 1.04 ± 0.36) in the PVN and the plasma level of norepinephrine (NE, a marker of sympathetic excitation, 12.39 ± 4.96* vs 5.82 ± 2.76 ng/mL), along with elevated levels of TGF‐α (23.54 ± 6.25* vs 10.08 ± 4.38 pg/mL) in CSF. The levels of epidermal growth factor (9.88 ± 3.59 vs 8.15 ± 4.24 pg/mL) in the CSF did not alter significantly in HF compared with Sham rats. Moreover, the linear regression analysis indicated that the mRNA expression of iRhom2 in the PVN was positively correlated with TACE level in the PVN (R2 = 0.62, P &lt;0.01), TGF‐α level in the CSF (R2 = 0.64, P &lt;0.01) and NE level in the plasma (R2 = 0.63, P &lt;0.01). These results suggest that the upregulated expression of iRhom2 in the PVN may promote ectodomain shedding of TGF‐α by enhancing TACE expression to drive sympathetic activation in HF. Brain iRhom2 is a potential target for therapeutic intervention in HF.

Crocin ameliorates depressive-like behaviors induced by chronic restraint stress via the NAMPT-NAD+-SIRT1 pathway in mice

AimTo investigate the effects of crocin on depression induced by chronic restraint stress (CRS) in mice. MethodsDepression model was established induced by CRS. All mice were divided into 4 groups randomly: normal group, model group, sertraline group and crocin group. From the 28th day after treatment, serials behaviors were conducted to evaluate the effects of crocin, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), open field test (OFT), novel objective recognition test (NORT), social interaction test (SIT), and dominance tube test (DTT). Contents of Nicotinamide phosphoribosyltransferase (NAMPT), BDNF, CREB, pCREB and SIRT1 in prefrontal cortex (PFC) were detected by WB. The levels of CORT, DA, 5-HT, NE and NAD+ in PFC were also detected by ELISA. ResultsThe results showed that crocin ameliorated the depressive-like behaviors, which manifested by increased sucrose consumption ratio and decreased immobility time in FST and TST. Crocin also increased the exploration time and exploration number in T2 phase in NORT, social preference index and social novelty index in SIT, reduced the defensive behavior in DTT. The results of WB showed crocin reversed the decreased contents of NAMPT, SIRT1, BDNF and pCREB/CREB in PFC induced by CRS. Additionally, crocin decreased the expression of cortisol (CORT) and increased the contents of DA, 5-HT, NAD+, but had no effects on NE between groups in PFC. ConclusionIn view of the findings, crocin ameliorates depression in mice, which may be associated with regulating NAMPT-NAD+-SIRT1 pathway.

Determining the Paleostress Regime during the Mineralization Period in the Dayingezhuang Orogenic Gold Deposit, Jiaodong Peninsula, Eastern China: Insights from 3D Numerical Modeling

The Dayingezhuang orogenic gold deposit, located in the northwestern Jiaodong Peninsula, is hosted by the Zhaoping detachment fault, but the paleostress regime during the mineralization period remains poorly understood. In this study, a series of numerical modeling experiments with variable stress conditions were carried out using FLAC3D software to determine the orientation of paleostress and the fluid migration processes during the ore-forming period. The results show that the simple compression or tension stress model led to fluid downward or upward flow along the fault, respectively, accompanying the expansion deformation near the hanging wall or footwall of the Zhaoping fault, which is inconsistent with the known NE oblique mineralization distribution at Dayingezhuang. The reverse and strike-slip model shows that the shear stress was distributed in the gentle dip sites of the fault, and the expansion space occurred in the geometric depression sites of the fault, which is also inconsistent with the known mineralization distribution. The normal and strike-slip model shows that shear stress was distributed in the sites where the fault geometry transforms from steep to gentle. In addition, the expansion deformation zones appeared at sites with dip angles of 35~60° in the footwall and extended along with the NE-trending distribution from shallow to deep levels. The numerical results are quite consistent with the known mineralization, suggesting that the fault movement during the mineralization stage is a combination of the local strike-slip and the NW–SE extension in the Dayingezhuang deposit. Under this stress regime (σ1 NE–SW, σ2 vertical, σ3 NW–SE), the NE dilation zones associated with fault deformation served as channels for the ore-forming fluid migration. Based on the numerical modeling results, the deeper NE levels of the No. 2 orebody in the Dayingezhuang deposit have good prospecting potential. Thus, our study not only highlights that gold mineralization at Dayingezhuang is essentially controlled by the detachment fault geometry associated with certain stress directions but also demonstrates that numerical modeling is a robust tool for identifying potential mineralization.

Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Combined with Hyperbaric Oxygen (HBO) on Awakening of Coma Patients with Traumatic Brain Injury.

Coma caused by craniocerebral injury is a common condition of neurosurgical acute injury. There is no specific method to promote awakening in a clinic. Early comprehensive treatment may be helpful to patients. The common methods are hyperbaric oxygen (HBO) and low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the application effect and mechanism of rTMS combined with HBO on coma patients with traumatic brain injury need to be further studied. The brain stem auditory evoked potential (BAEP) is examined by the Kennedy coma recovery scale (CRS-R), the recovery of brain function and the state of consciousness are evaluated, and the therapeutic effect is evaluated by the Glasgow Coma Scale (GCS). Cerebrospinal fluid NE level, MCA blood flow velocity, and left brainstem and right brainstem auditory evoked potential are used to evaluate brain rehabilitation. RTMS combined with HBO could shorten the wake-up time, improve the wake-up rate, improve the GCS score and CRS-R score, shorten the brain wave latency time of the left and right brainstem, increase the NE level of cerebrospinal fluid, and decrease the blood flow velocity of MCA. RTMS combines with HBO can improve the nerve excitability of brain cells, reduce the disturbance of consciousness, promote the functional recovery of brain injury, and has a certain role in promoting the awakening of patients with traumatic brain injury coma.

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo.

PurposeInflammation and accompanying pain is a common global health problem that seriously affects human quality of life worldwide. Here, we aimed to investigate the anti-nociceptive and anti-inflammatory activities of the ethyl acetate extract of B. chinensis (EAEBc) along with the underlying mechanisms of action.MethodsThe in vitro anti-inflammatory activity of EAEBc was explored using an LPS-induced RAW264.7 cell inflammatory model. Nitric oxide (NO) production, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were evaluated. In vivo anti-nociceptive and anti-inflammatory activities of EAEBc were assessed with the aid of classical experimental mouse models. In addition, LPS-induced biomarker contents (TNF-α, IL-1β, IL-6, NO, iNOS, and PGE2) and formalin-induced serum inflammatory factors (NO, PGE2, 5-HT, β-EP, substance P, and NE) were determined in mice.ResultsIn vitro, EAEBc significantly reduced LPS-induced NO generation and suppressed the production of TNF-α, IL-1β, and IL-6 in RAW264.7 cells in a concentration-dependent manner. In vivo, EAEBc downregulated serum TNF-α, IL-1β, IL-6, NO, iNOS, and PGE2 contents in mice with LPS-induced inflammation in a dose-dependent manner. EAEBc displayed anti-inflammatory activity in carrageenan-induced paw edema and xylene ear edema tests. Intragastric administration of EAEBc at test doses of 100 and 200 mg/kg led to inhibition of nociception and capillary permeability induced by acetic acid to varying degrees. Similarly, EAEBc exerted analgesic effects in the formalin and hot plate tests. In particular, the administration of EAEBc reversed the changes in the levels of inflammatory indicators NO, PGE2, 5-HT, β-EP, substance P, and NE in a mouse model of formalin-induced pain.ConclusionOur findings provide considerable evidence to support the extensive application of B. chinensis in traditional medicine and demonstrate the utility of this plant species as an effective candidate for prevention or treatment of various pain and inflammation-related conditions.

Exploration of a Brain-Liver-Communication-Related Mechanism Involved in the Experimental Perimenopausal Depression Rat Model using Chaihu-Shugan-San.

Existing research suggests the involvement of a brain-liver-communication-related mechanism in the occurrence of depression. In this study, we selected Chaihu-Shugan-San (CSS), a traditional Chinese herbal medicine that can simultaneously affect liver and depression, as a probe to investigate the involvement of the brain-liver-communication-related mechanism in perimenopausal depression. A total of 50 experimental perimenopausal depression rat models were established by ovariectomy surgery (PMS) followed by chronic unpredictable mild stress (CUMS) processes. Animals underwent CSS treatment or treatments with CSS + Ly294002, an inhibitor of the PI3K/Akt signalling pathway. We observed the behavioural performances of depression and anxiety, serum concentrations of biochemical indices, serum estrogen two levels, hippocampal 5-HT and NE levels and the morphological changes in liver tissues. The protein and mRNA expressions of PI3K and Akt were also evaluated. CSS treatment significantly ameliorated the behavioural performance, partial biochemical indices and the morphological changes in the liver tissues of PMS + CUMS rats. Ly294002 partially inhibited the CSS effects. The expressions of PI3K and Akt were significantly downregulated by PMS + CUMS processes but upregulated by CSS treatment, which could be significantly suppressed by Ly294002. A brain-liver-communication-related mechanism may be involved in perimenopausal depression, where the PI3K/Akt signalling pathway plays a vital role.

Tetrandrine Ameliorates Rheumatoid Arthritis in Mice by Alleviating Neutrophil Activities.

Rheumatoid arthritis (RA) is a common autoimmune disease worldwide. Neutrophils play critical roles in the onset and development of RA and are the promising target for RA treatment. Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the traditional Chinese herbal Stephania tetrandra S. Moore. Tetrandrine is effective in alleviating RA by inhibiting macrophage inflammatory response, fibroblast overproliferation, and pannus formation. However, whether tetrandrine regulates the activities of neutrophils in RA is largely unknown. In this study, we adopted adjuvant-induced arthritis (AA) murine model to explore the effect of tetrandrine on RA and neutrophils. Twenty-eight mice were divided into four groups. The control group was injected with PBS in the limbs and treated with PBS by intraperitoneal injection (i.p.) from Day 10 to Day 37. The arthritis murine model was induced by injecting FCA into the ankle joints of hind limbs. The AA group, the AA + TET group, and the AA + DEX group mice were treated with PBS, tetrandrine (6 mg/kg), or dexamethasone (1 mg/kg) i.p. daily, respectively. Arthritic scores were evaluated, and the joint diameter was measured every three days. A cytometric bead assay was performed to measure the concentrations of IFN-γ, TNF-α, and IL-6 in the serum. H&E staining and Safranin O-fast staining were adopted to monitor the tissue changes in the joint. Immunohistochemistry assays were applied to detect the MPO, NE, CitH3, and PAD4 expression levels. To assess the effect of tetrandrine on neutrophil activities in vitro, CCK8 tests were applied to determine cell viability. The qPCR and ELISA were performed to determine IL-1β and IL-6 expression levels. Immunofluorescence assays were performed to measure the formation of NETs. The results indicated that tetrandrine significantly alleviated the symptoms of RA in terms of the ankle diameter (from 4.629 ± 2.729 to 3.957 ± 0.257; P < 0.01) and ankle score (from 4.000 ± 0.000 to 3.286 ± 0.756; P < 0.05). Tetrandrine treatment significantly increased the cartilage areas and decreased serum IL-6 significantly (from 5.954 ± 2.127 to 2.882 ± 2.013; P < 0.01). The immunohistochemistry assays also showed decreased expression levels of NE, MPO, PAD4, and CitH3 induced by tetrandrine in comparison with the AA group (P < 0.01). The qPCR assays and ELISAs showed that tetrandrine had an anti-inflammatory effect in vitro by significantly inhibiting IL-6 (P < 0.01). The immunofluorescence assays showed that NET formation induced by PMA could be reduced by tetrandrine (P < 0.01). In conclusion, tetrandrine has good efficacy in treating RA by regulating neutrophil-involved inflammation and NET formation.

Aerobic Exercise Improves Pulmonary Fibrosis by Improving Insulin Resistance and Inflammation in Obese Mice.

BackgroundPrevious studies have demonstrated that obesity is associated with pulmonary fibrosis. We attempted to identify whether regular aerobic exercise (AE) can protect against high-fat diet (HFD)-associated pulmonary fibrosis.MethodsForty-eight C57BL/6 mice were randomly assigned to four groups: chow group (Ch), chow plus exercise group (CE), obesity group (Ob), and obesity plus exercise group (OE). The mice were fed either an HFD or a chow diet for 16 weeks, and low-intensity aerobic exercise (AE) was performed in the last 8 weeks. We measured the degree of pulmonary fibrosis; pulmonary inflammation; oxidative stress parameters; insulin resistance-related indicators; the number of inflammatory cells in bronchoalveolar lavage fluid (BALF); the mRNA expression levels of IL-10, IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, NE, and sirt-1; and the BALF levels of CXCL-1, IL-17, TGF-β, IL-10, IL-1β, and TNF-α in lung tissue.ResultsAE in obese mice protected against obesity-associated pulmonary fibrosis, chronic inflammation, pro-oxidative/antioxidative imbalance, and insulin resistance. AE ameliorated the HFD-induced inflammatory response and neutrophil infiltration in the lung. AE downregulated BALF levels of CXCL-1, IL-1β, TNF-α IL-17, and TGF-β but upregulated BALF levels of IL-10. AE decreased IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, and NE mRNA expression levels but upregulated IL-10 and sirt-1 mRNA expression levels in the lung.ConclusionsAE protects against HFD-induced pulmonary fibrosis by improving obesity-associated insulin resistance, chronic low-grade inflammation, and pro-oxidative/antioxidative imbalance. AE improved HFD-induced pulmonary fibrosis by suppressing IL-17, TGF-β, NE, and MMP-9 expression and activating IL-10 and sirt-1 expression.

Clinical Study of Heart Failure with Left Ventricular Ejection Fraction Regimen Treated with Entresto.

Heart failure is a group of syndromes caused by various cardiac structural or functional disorders leading to impaired ventricular filling and (or) ejection capacity. Because of decreased ventricular systolic function and impaired ejection function, the amount of cardiac output cannot meet the body's metabolic needs; organ and tissue blood perfusion is insufficient; at the same time, pulmonary circulation and (or) systemic circulation congestion; the clinical manifestations are mainly dyspnea and weakness but restricted physical activity and edema. Treatment of the disease should include preventing and delaying the onset of wails, relieving symptoms of clinical wails, improving its long-term prognosis, and reducing mortality. The aim of the study is to observe the efficacy and safety of Entresto in the treatment of left ventricular ejection fraction heart failure (HFpEF). Seventy-eight patients with HFpEF treated in our hospital from October 2017 to April 2018 were randomized into a treatment group (Entresto 50 mg + basic treatment, n = 39) and a control group (basic treatment, n = 39). The course of treatment was ten weeks. The levels of brain natriuretic peptide (BNP) and echocardiographic indicators (LVMI, LVEF, LVEDD, LVESD, E/E′ Ratio, E/A ratio, DT), 6-minute walking test (6MWD), and Minnesota Quality of Life Scale (MLHFQ) were analyzed before and after treatment. LVMI, LVEF, LVEDD, LVESD, E/E′ ratio, E/A ratio, DT, and BNP were all significantly improved in the Entresto group after treatment. In the control group, except for LVEDD, LVESD, the E/A ratio, and BNP, other indicators were significantly improved after treatment (P < 0.05). Posttreatment, both groups had significantly improved 6MWD and MLHFQ scores (P < 0.05). Differences in these parameters between the two groups were statistically significant (P < 0.05). After treatment, the levels of NE, AngII, ALD, and MMP-9 in the two groups were decreased (P < 0.05), with the lower lever in the treatment group (P < 0.05). The effective rate was 76.92% in the control group and 94.87% in the Entresto group, and this rate difference was statistically significant (P < 0.05). The number of patients re-hospitalized due to cardiovascular events was 2 (the Entresto group) vs. 7 (the control group) cases; worsening of heart failure was observed in 1 patient (the Entresto group) vs. 6 (the control group), and the difference between the two groups was statistically significant (P < 0.05). However, the incidence of adverse reactions between the two groups was not statistically significant. Entresto can significantly improve left ventricular diastolic function in heart failure patients with preserved left ventricular ejection fraction and improve quality of life. This treatment is safe and effective and worthy of clinical application. This trail is registered with ChiCTR2000031486. This trial was approved by the Chinese Clinical Trial Registry (clinical trial number: ChiCTR2000031486). The registration number of this study is 2022-R008.

The Mechanisms of SAA/TLR4 Inducing Angiogenesis in Rheumatoid Arthritis through NETs Formation

Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.

Microglial activation induced by LPS mediates excitation of neurons in the hypothalamic paraventricular nucleus projecting to the rostral ventrolateral medulla

Microglia are known to be activated in the hypothalamic para-ventricular nucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticity of presympathetic PVN neurons associated with the modulation of sympathetic outflow remains poorly investigated. In this study, we analyzed the direct link between microglial activation and spontaneous firing rate along with the underlying synaptic mechanisms in PVN neurons projecting to the rostral ventrolateral medulla (RVLM). Systemic injection of LPS induced microglial activation in the PVN, increased the frequency of spontaneous firing activity of PVN-RVLM neurons, reduced GABAergic inputs into these neurons, and increased plasma NE levels and heart rate. Systemic minocycline injection blocked all the observed LPS-induced effects. Our results indicate that LPS increases the firing rate and decreases GABAergic transmission in PVN-RVLM neurons associated with sympathetic outflow and the alteration is largely attributed to the activation of microglia. Our findings provide some insights into the role of microglial activation in regulating the activity of PVN-RVLM neurons associated with modulation of sympathetic outflow in cardiovascular diseases.

Development and Application of the Intelligent Seed Processing Technology and Equipment

Seed processing is an important link in the seed industry chain. Crop seed industry is a national strategic and basic core of industry. Drying, cleaning, selecting, grading, coating, packaging and storage of crop seeds are the main measures to realize the precision sowing of crops and the increase of grain yield and income. Continuously improving the intelligence and fi ne level of seed processing equipment is of great signifi cance to ensure the production and supply of excellent seeds and the stability of agricultural production. This paper describes the development status of modern seed processing equipment technology in China, introduces the establishment of seed processing equipment engineering technology research center, taking maize, rice, wheat and cotton seed processing technology and machinery as an example, describes the key technologies and technological process of the breakthrough in the major crop seed processing, analyzes the existing problems of seed processing equipment in China at this stage as well as the development trend in the future, provides a reference for government decision makers in resolving the problem of mechanical damage in the process of seed processing and further improving the intellectualization level of seed processing, promotes the common progress of the global seed processing equipment technology.

Efficacy and Safety of Different Dosages of Decitabine in the Treatment of High-Risk Patients with Myelodysplastic Syndrome

To investigate the efficacy of high-risk myelodysplastic syndrome (MDS) patients treated by different doses of decitabine (DAC) and its safety. Thirty patients with high-risk MDS were all treated by demethylation drug DAC. According to the doses of DAC, 30 patients were divided into 10-day regimen [6 mg/(m2·d)×10 d, 15 patients] group and 5-day regimen [15 mg/(m2·d)×5 d, 15 patients] group. The efficacy and adverse events of the patients in the two groups were observed. The patients were followed up to May 2020, in the 10-day regimen group, 10 cases achieved complete remission (CR), 3 cases achieved partial remission (PR), and 2 cases were progressive disease (PD). Four cases died, including 1 case for heart failure, 2 cases for respiratory failure and 1 case for serious infection. In the 5-day regimen group, 11 cases achieved CR, 1 case achieved PR, 3 cases were PD. Five cases died, including 2 cases for heart failure and 3 for serious infection. The CR rate and ORR of the patients in the two groups were 66.67% vs 73.33%, 86.67% vs 80.00%, respectively, which showed no significant differences, and the efficacy also showed no significant difference. After treatment, the levels of WBC, NE, Hb and PLT of the patients in 10-day regimen group were higher than those in 5-day regimen. In the 10-day regimen group, there were 11 cases of pneumonia, 2 cases of bacteremia, 1 case of skin infection and 1 case of urinary tract infection. While in the 5-day regimen group, 13 cases of pneumonia, 5 cases bacteremia, 1 case of skin infection and 3 cases of urinary tract infection. There were 2 cases with mild gastrointestinal response in the 10-day regimen group, and 7 cases with obvious nausea and anorexia in the 5-day regimen group. The symptoms were relieved after the treatment of acid suppression, stomach protection and antiemetic. The liver, kidney and heart function were monitored. One case liver function damage and 2 cases cardiac insufficiency were observed in the 10-day regimen group. Seven cases regimen cardiac insufficiency and 4 cases regimen liver function damage were observed in the 5-day regimen group. 10-day regimen and 5-day regimen are equally effective, but 10-day regimen is less myelosuppressive and more safer, which can be applied in clinical.

Renal sympathetic denervation can significantly reduce blood pressure and improve arterial stiffness in hypertensive beagles

To investigate the effect of renal sympathetic denervation (RDN) on blood pressure and arterial stiffness in hypertensive beagles and explore the underlying mechanism. Sixteen beagles were randomly divided into RDN group (n=8, fed with a high-salt high-fat diet to establish models of hypertension and treated with RDN), sham-operated group (n=4, fed with a high-salt high-fat diet to induce hypertension but only examined with renal arteriography) and control group (n=4, fed with formula dog food). The changes in blood pressure, arterial stiffness, endothelial function, and sympathetic activity were compared among the 3 groups and correlation analysis was performed. All the animal models of hypertension were established successfully in the beagles. At 3 months after the RDN, the changes in systolic blood pressure (SBP) differed significantly among the 3 groups (P=0.006), and the reduction in SBP was significantly greater in RDN group than in the other two groups (P < 0.05). The variations of diastolic blood pressure (DBP) also differed significantly among the 3 groups (P=0.016), and DBP reduction was more obvious in RDN group than in the control group (P=0.007), but similar to that in the sham-operated group (P=0.052). The changes of resistance index (RI) after the procedure were significantly different among the 3 groups (P=0.043), and the RDN group showed a greater reduction of RI than the control group (P=0.032) and sham group (P=0.043). Serum levels of eNOS, NO and Ang Ⅱ did not differ significantly among the groups either before or after RDN (P>0.05), but serum NE level was significantly higher in RDN group than in the control groupafter successful modeling (P=0.014), but similar to that in the sham group (P=0.560). Compared with the sham operation, RDN in the hypertensive beagles resulted in a significantly greater decrease of serum NE level (P=0.032) to almost the control level (P= 0.080). The changes of RI following RDN were significantly correlated with the changes of SBP, DBP and serum levels of NO and NE (P < 0.05). RDN can significantly reduce blood pressure and improve arterial stiffness in hypertensive beagles possibly by reducing sympathetic activity and blood pressure and promoting NO synthesis.

Quantifying the impact of changes in effective population size and expression level on the rate of coding sequence evolution

Molecular sequences are shaped by selection, where the strength of selection relative to drift is determined by effective population size (Ne). Populations with high Ne are expected to undergo stronger purifying selection, and consequently to show a lower substitution rate for selected mutations relative to the substitution rate for neutral mutations (ω). However, computational models based on biophysics of protein stability have suggested that ω can also be independent of Ne. Together, the response of ω to changes in Ne depends on the specific mapping from sequence to fitness. Importantly, an increase in protein expression level has been found empirically to result in decrease of ω, an observation predicted by theoretical models assuming selection for protein stability. Here, we derive a theoretical approximation for the response of ω to changes in Ne and expression level, under an explicit genotype-phenotype-fitness map. The method is generally valid for additive traits and log-concave fitness functions. We applied these results to protein undergoing selection for their conformational stability and corroborate out findings with simulations under more complex models. We predict a weak response of ω to changes in either Ne or expression level, which are interchangeable. Based on empirical data, we propose that fitness based on the conformational stability may not be a sufficient mechanism to explain the empirically observed variation in ω across species. Other aspects of protein biophysics might be explored, such as protein–protein interactions, which can lead to a stronger response of ω to changes in Ne.

Inference of local invasion pathways in two invasive crayfish species displaying contrasting genetic patterns

Abstract The efficient management of invasive alien species (IAS) requires the identification of their introduction pathways. Genetic assessments have proven useful to inform invasion pathways at large (national to worldwide) scales, but studies at local scales are still rare, despite their importance for guiding management. In this study, genetic analyses were used to identify local invasion pathways of two invasive crayfish species (the spiny‐cheek crayfish Faxonius limosus and the red swamp crayfish Procambarus clarkii) in a dense network of artificial lakes. We first characterized the spatial patterns of genetic variability, effective population sizes (Ne) and among‐lakes recent migration events for each species using neutral microsatellite markers. We then identified the environmental factors affecting genetic variability and inferred the potential local invasion pathways. Results revealed different patterns of genetic variability between the two species: F. limosus displayed very low levels of genetic diversity, Ne and spatial structuring compared to P. clarkii, which displayed high genetic diversity, Ne and spatial genetic structuring. We also demonstrated context‐dependent effects of different environmental factors (fishery management, spatial distribution and lake size) on genetic variability indices. We did not identify local invasion pathways for F. limosus due to limited genetic variability, likely caused by a strong founder effect and potential parthenogenetic reproduction. Contrastingly, multiple invasion pathways (release, contaminant, unaided/corridor spread and stowaway) were identified for P. clarkii. Synthesis and applications. Although limited in some particular cases (e.g. for species having experienced strong shaping events and/or displaying asexual reproductive modes), neutral genetic variation assessments can provide important insights for inferring local invasion pathways in complex landscapes for invasive alien species displaying short generation times and complex invasion histories.

Sodium Danshensu promotes the healing of stage 2 pressure injury wounds in ischemia/reperfusion injury rat models: possible regulation of apoptosis and inflammatory response.

To investigate the protective effect and possible mechanism of sodium Danshensu (SDSS) against pressure injury caused by ischemia/reperfusion (I/R) injury. Sprague-Dawley rats were randomly divided into five groups of eight rats each: control group, model group, 10 mg/kg SDSS-treated group, 20 mg/kg SDSS-treated group, and 40 mg/kg SDSS-treated group. We used two round ferrite magnetic plates of 15 mm diameter and 3 mm thickness to establish stage 2 pressure injury model rats. Each rat was subjected to five cycles of ischemia and reperfusion to induce pressure injury. One cycle consisted of 2 h of ischemia and 0.5 h of reperfusion, which meant that each cycle included 2 h of pressure and 0.5 h of pressure relief. The outline of the wound was delineated by butter paper and marker pen, and histopathological changes were observed by hematoxylin and eosin staining. In addition, the number of apoptotic cells and the activity of caspase-3 were assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling and caspase-3 assay kits, respectively. The expression of apoptosis-regulatory proteins and inflammatory mediators was investigated by enzyme-linked immunosorbent assay. Results showed that treatment with SDSS for 7 d after establishing the pressure injury model remarkably improved the healing rate of the wound. SDSS also inhibited the levels of tumor ne- crosis factor-α, myeloperoxidase, and intercellular cell adhesion molecule-1; decreased the number of apoptotic cells; increased the ratio of B-cell lymphoma-2 (Bcl-2) / Bcl-2-associated X (Bax); and regulated the expression and activity of caspase-3. Our results suggest that SDSS exhibits a treatment efficacy for pressure injury caused by I/R injury possibly by inhibiting apoptosis and inflammatory response.

Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway.

Safflower extract (SE) improves depression in mice by inhibiting the TLR4-NLRP3 inflammatory signaling pathway. Chronic unpredictable mild stress (CUMS) was used to establish a mouse model of depression. A total of 60 adult male ICR mice were randomly divided into 6 groups: control group, depression group (CUMS only), SE (10 mg/kg) + depression group (CUMS+SE, 10 mg/kg), SE (30 mg/kg) + depression group (CUMS+SE, 30 mg/kg), Cli-095 + depression group (CUMS+Cli-95), and fluoxetine hydrochloride (FLU) + depression group (CUMS+FLU). We assessed the depressive behaviors of these mice using the sucrose preference test (SPT), the open field test (OFT), the forced swim test (FST), and the tail suspension test (TST). We measured the expression levels of SOD, MDA, GSH-Px, 5-HT, NE, TNF-α, IL-1β, and IL-6 using ELISA kits. Western blot was used to determine the relative expression levels of TLR4, p38, NF-κB, NLRP3, and caspase-1. SE significantly improved the results of the SPT, OFT, FST, and TST. SE also increased the expression levels of 5-HT and NE in the prefrontal cortex while decreased the expression levels of TNF-α, IL-1β, and IL-6 compared with CUMS. SE (10 or 30 mg/kg) or FLU (10 mg/kg) significantly inhibited the expression of TLR4 and p-p38 induced by CUMS. SE significantly inhibited the expression of p-NF-κB in the prefrontal cortex and hippocampus induced by CUMS. The decrease of NLRP3 and caspase-1 were obviously reversed after administration of SE (10 or 30 mg/kg) or FLU (10 mg/kg). The results showed that SE has potential antidepressant effects in CUMS mice, and its underlying mechanism may be related to its effects on inflammation and the TLR4-NF-κB-NLRP3 signaling pathway in the brain.