Antioxidant, Antimicrobial and Anti-Inflammatory Activities of Essential Oil Derived from the Wild Rhizome of Atractylodes macrocephala.

The present study investigated the chemical composition, antioxidant, antimicrobial, and anti-inflammatory activities of essential oil (EO) derived from the wild rhizomes of Atractylodes macrocephala Koidz. (AMA) growing in Qimen County (eastern China). GC/MS analysis identified fifteen compounds, representing 92.55 % of AMA EO. The major compounds were atractylone (39.22 %), ß-eudesmol (27.70 %), thymol (5.74 %), hinesol (5.50 %), and 11-isopropylidenetricyclo[4.3.1.1(2,5)]undec-3-en-10-one (4.71 %). Ferricyanide reducing, 1,1-diphenyl-2-picyrlhydrazyl (DPPH) and 3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) scavenging assays revealed that AMA EO exhibited strong antioxidant capacities. Additionally, AMA EO showed inhibitory effects on growth of Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, and Bacillus subtilis, with the minimum inhibitory concentrations (MIC) ranging from 0.5 to 2.0 mg/mL. Treatments with AMA EO also significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2 ) production in lipopolysaccharide-stimulated RAW264.7 cells, indicating anti-inflammatory activity of AMA EO. Furthermore, treatments with AMA EO decreased the transcriptional levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which might be the molecular mechanisms underlying its anti-inflammatory effects. Overall, these results provide a theoretical basis for further study and application of AMA EO in food and medicine products.

Intermedin1-53 Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress.

OBJECTIVE: Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress. APPROACH AND RESULTS: In angiotensin II-induced ApoE-/- mouse and CaCl2-induced C57BL/6J mouse model of AAA, IMD1-53 significantly reduced the incidence of AAA and maximal aortic diameter. Ultrasonography, hematoxylin, and eosin staining and Verhoeff-van Gieson staining showed that IMD1-53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl2. Mechanistically, IMD1-53 attenuated oxidative stress, inflammation, vascular smooth muscle cell apoptosis, and matrix metalloproteinase activation. IMD1-53 inhibited the activation of redox-sensitive signaling pathways, decreased the mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase subunits, and reduced the activity of nicotinamide adenine dinucleotide phosphate oxidase in AAA mice. Expression of Nox4 was upregulated in human AAA segments and in angiotensin II-treated mouse aortas and was markedly decreased by IMD1-53. In vitro, vascular smooth muscle cells with small-interfering RNA knockdown of IMD showed significantly increased angiotensin II-induced reactive oxygen species, and small-interfering RNA knockdown of Nox4 markedly inhibited the reactive oxygen species. IMD knockdown further increased the apoptosis of vascular smooth muscle cells and inflammation, which was reversed by Nox4 knockdown. Preincubation with IMD17-47 and protein kinase A inhibitor H89 inhibited the effect of IMD1-53, reducing Nox4 protein levels. CONCLUSIONS: IMD1-53 could have a protective effect on AAA by inhibiting oxidative stress.

Intermedin1-53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho.

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD1-53 treatment reduced vascular calcification. The expression of α-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD1-53-treated rats with CKD. In vitro, IMD1-53 increased α-Klotho protein level in calcified vascular smooth muscle cells. α-Klotho knockdown blocked the inhibitory effect of IMD1-53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD1-53 to upregulate α-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD1-53 may attenuate vascular calcification by upregulating α-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling.

Enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated Enterovirus A71 vaccine in Jiangsu, China, 2012-2013.

Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD.

Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice.

Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.

Endoplasmic reticulum stress-mediated apoptosis is activated in intestines of mice with Trichinella spiralis infection.

Gastrointestinal helminth infection, including Trichinella spiralis, initiates a series of intestinal structural, cellular and physiological changes. Intestinal invasion is an important stage of trichinellosis because it determines the development and subsequent course of the disease and its consequences. Apoptosis mediated by endoplasmic reticulum stress (ERS) plays a key role in infectious diseases, but the effect of T. spiralis infection on inducing apoptosis in the small intestine has been neglected. We investigated apoptosis and changes in ERS-associated apoptosis molecules in the intestine of mice with T. spiralis infection. TUNEL staining and detection of the apoptotic marker cleaved caspase 3 revealed that apoptosis occurred in the mouse intestine at days 3 and 7 post-infection. The ER chaperone 78-kDa glucose-regulated protein (GRP78) was upregulated at days 3 and 7 post-infection. The ERS-associated apoptosis molecules C/EBP homologous protein, cleaved caspase 12 and c-Jun NH2-terminal kinase were upregulated at days 3 and 7, days 3, 7 and 10 and days 7 and 10 post-infection, respectively. Thus, apoptosis occurred in the intestine of mice with T. spiralis infection, and the ERS-mediated apoptosis pathway was activated by infection with this small intestine dwelling nematode.

[Impact of priming on seed germination and seedling growth of Oldenlandia diffusa under drought stress].

Current study was carried out to optimize the priming condition of Oldenlandia diffusa seeds, and improve germination rate and seed vigor of 0. diffusa seeds under drought conditions. Uniform design was used to optimize the concentration and priming time of three priming materials (PEG, KNO3, GA3). Different concentrations of polyethylene glycol (PEG) was used to simulate drought stress. The seedling was cultured in 1/4 Hoagland medium for 30 d. The results showed that seed priming treatment with 366 mg x kg(-1) GA3 for 1h resulted in significant increase in germination rate, germination index, vigor, root length, plant height and biomass of O. diffusa seeds under drought stress (15% PEG), while seed priming with 3.0% KNO3 for 1 h showed little effect on germination and growth of O. diffusa seeds under drought stress. Seed priming treatment with appropriate GA3 concentration and priming time could enhance seed germination and drought resistance of O. diffusa in seedling stage.

Systemic cytokine profiles and splenic toll-like receptor expression during Trichinella spiralis infection.

Parasitic helminth and their products can suppress or modulate the host immune response for long-term survival and continued infection. Commonly, helminth can induce conditional T helper cell type 2 (Th2) response, regulatory T cell and cytokines, and altered function of antigen presentation cells by modulating toll-like receptors (TLRs). The helminth Trichinella spiralis establishes chronic infection in skeletal muscles of a wide range of mammalian hosts. We infected mice with T. spiralis and investigated Th1/Th2/Th17 cytokine profiles in serum and expression of TLRs and related signal molecules in spleen at various times post-infection. The infection evoked a mixed Th1/Th2 and inhibited Th17 immune response, with initial predominance of a Th1 response in intestine stage and subsequent predominance of a Th2 response in muscle stage. Different stages of infection had different impacts on the expression of TLRs and related signaling molecules. In the adult stage of infection, TLR1 and TLR4 were upregulated and the MyD88-dependent signal pathway was activated. The muscle larvae inhibited TLR4 and TRIF-dependent signal pathway. Our results implied that T. spiralis infection may regulate Th1/Th2/Th17 cytokine production through TLRs.

[Cardiovascular effects and pathophysiological significance of adrenomedullin family peptides].

Adrenomedullin family includes adrenomedullin (ADM), intermedin (IMD) and different peptide fragments derived from prepro-ADM or prepro-IMD. Recent researches found the interaction between different prepro-peptides or different peptide fragments, which plays a crucial role in maintaining homeostasis of cardiovascular system as well as participates in the occurrence and development of cardiovascular disease. This review intends to introduce cardiovascular effects and pathophysiological significance of adrenomedullin family peptides from function level, receptor level and signaling pathway.

Association between motoric cognitive risk syndrome and future falls among Chinese community-dwelling elderly: A nationwide cohort study.

BACKGROUND: Motoric Cognitive Risk syndrome (MCR), known as the predementia stage, is characterized by both subjective cognitive complaint (SCC) and slow gait. This study aimed to investigate the causal relationship between MCR, its components, and falls. METHODS: Participants aged ≥ 60 years were selected from China Health and Retirement Longitudinal Study. SCC was determined by participants' responses to the question "How would you rate your memory at present?" with "poor" being the indicative answer. Slow gait was defined as one standard deviation or more below age- and gender-appropriate mean values of gait speed. MCR was identified when both SCC and slow gait were presented. Future falls were investigated by the question "have you fallen down during follow-up until wave 4 in 2018?" Logistic regression analysis was performed to test the longitudinal association of MCR, its components and future falls during the following 3 years. RESULTS: Of 3748 samples in this study, the prevalence of MCR, SCC, and slow gait was 5.92%, 33.06%, and 15.21%, respectively. MCR increased the risk of falls during the following 3 years by 66.7% compared to non-MCR after controlling for covariates. In the fully adjusted models, with the healthy group as reference, MCR (OR = 1.519, 95%CI = 1.086-2.126) and SCC (OR = 1.241, 95%CI = 1.018-1.513), but not slow gait, increased the risk of future falls. CONCLUSIONS: MCR independently predicts future falls risk in the following 3 years. Measuring MCR can be a pragmatic tool for early identification of falls risk.

[Effects of CO2 concentration and soil water content on short-term water-use efficiency at whole-plant level]. / CO2浓度和土壤含水量对植物个体尺度短期水分利用效率的影响.

Uncovering the variations of short-term water-use efficiency (WUEp) at whole-plant level in response to CO2 concentration (Ca) and soil water content (SWC) can improve the understanding of plant survival strategies under climate change. In this study, Platycladus orientalis saplings were cultured in simulated climate chambers.There were totally 15 treatments, including Ca of 400 (C400), 600 (C600) and 800 (C800) µmol·mol-1 and SWC of 35%-45% field water holding capacity (FC), 50%-60%FC, 60%-70%FC, 70%-80%FC and 95%-100%FC. The WUEp was measured by mini-lysimeters, weighting method, and static assimilation chamber. The results showed that both daytime (0.12-1.87 mol·h-1) and nighttime transpiration rates (0.01-0.16 mol·h-1) at whole-plant level reached the maximum at C400×70%-80%FC, while the whole-plant daytime net photosynthetic rate (2.12-22.10 mmol·h-1) reached the maximum at C800×70%-80%FC. In contrast, nighttime respiration rate (0.84-4.41 mmol·h-1) increased with increasing SWC, but decreased with increasing of Ca, reaching the maximum at C400×95%-100%FC. For WUEp (5.37-24.35 mmol·mol-1), it reached the maximum at C800×50%-60%FC, indicating that plants could use less water and fixed more carbon by adjusting adaptation strategies under high Ca and drought conditions. In addition, leaf instantaneous water-use efficiency was a good predictor of WUEP when the canopy structure was similar.

Effect of home-based exercise programs with e-devices on falls among community-dwelling older adults: a meta-analysis.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

A Prospective Study of Using Chaihu Shugan Powder Combined with Zu San Li Acupoint Stimulation to Improve the Prognosis of Liver Stagnation and Qi Stagnation Syndrome in Acute Pancreatitis.

Background: This study aimed to explore the clinical efficacy of Chaihu Shugan powder combined with Zu San Li acupoint stimulation on the acute pancreatitis of liver and qi stagnation syndromes, the protection of intestinal barrier function, the prevention of severe tendency, and safety evaluation. Method: Data were collected from October 2019-June 2021 at Xinhua Hospital, which is affiliated with Shanghai Jiao Tong University School of Medicine, Emergency Department. Eighty patients with acute pancreatitis were randomly divided into a control treatment group (40 people) and a combined traditional Chinese medicine (TCM) treatment group (40 people). Detailed records of hospitalised patients were obtained, including the general situation of patients' clinical diagnosis and clinical examination before and after treatment. The changes in inflammatory and immune indexes before and after treatment were recorded. Result: Compared with the standard treatment group, the relief time of abdominal pain in the TCM treatment group was significantly shortened with statistically significant differences. Compared with the standard treatment group, the levels of WBC, ALT, CA, hemodiastase, lipase, TG, and other factors in the TCM treatment group decreased, whereas the levels of DB, SCR, cholesterol, K+, and other factors increased. The differences were statistically significant (P < 0.05). Conclusion: Chaihu Shugan powder combined with Zu San Li acupoint stimulation can reduce the clinical manifestations of liver and qi stagnation syndromes of acute pancreatitis, protect the intestinal barrier function, prevent the tendency of severe illness and improve the prognosis.

Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study.

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury. We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral (right only) cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots, five times a week. Bilateral resting motor evoked potential amplitude was increased, central motor conduction time on the side receiving cortical stimulation was significantly decreased, and lower extremity motor score, Berg balance score, spinal cord independence measure-III score, and 10 m-walking speed were all increased after treatment. Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment. These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

Intermedin1-53 Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis.

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigated cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography, and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) were found in Ang II-treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3, and anti-fibrotic response. In conclusion, IMD alleviated cardiac fibrosis by inhibiting NLRP3 inflammasome activation through suppressing IRE1α via the cAMP/PKA pathway.

[Nondestructive imaging of elements distribution in biomedical samples by X-ray fluorescence computed tomography].

X-ray fluorescence computed tomography is a stimulated emission tomography that allows nondestructive reconstruction of the elements distribution in the sample, which is important for biomedical investigations. Owing to the high flux density and easy energy tunability of highly collimated synchrotron X-rays, it is possible to apply X-ray fluorescence CT to biomedical samples. Reported in the present paper, an X-ray fluorescence CT system was established at Shanghai Synchrotron Radiation Facility for the investigations of trace elements distribution inside biomedical samples. By optimizing the experiment setup, the spatial resolution was improved and the data acquisition process was obviously speeded up. The maximum-likelihood expectation-maximization algorithm was introduced for the image reconstruction, which remarkably improved the imaging accuracy of element distributions. The developed system was verified by the test sample and medical sample respectively. The results showed that the distribution of interested elements could be imaged correctly, and the spatial resolution of 150 m was achieved. In conclusion, the developed system could be applied to the research on large-size biomedical samples, concerning imaging accuracy, spatial resolution and data collection time.

Study on the medication rule of traditional Chinese medicine in the treatment of acute pancreatitis based on machine learning technology.

BACKGROUND: To analyze the rule of traditional Chinese medicine in the treatment of acute pancreatitis (AP). METHODS: Using machine learning technology and artificial intelligence, we collected 516 traditional Chinese medicine compounds for treating AP in the recent past 20 years, and analyzed the application of Chinese medicine in the field of AP. The data set was established by the ingredients of each prescription and its corresponding effectiveness. 90% of the data was divided into the training set, and the remaining 10% of the data was used as the test set. We employed random forest method to build a model to predict the efficacy of the prescriptions in the treatment of AP. The R-squared score and mean absolute error was used to evaluate the model's performance. RESULTS: The most frequently used drugs were rhubarb, Radix Bupleuri, Fructus Aurantii Immaturus, and Mirabilite. Rhubarb and Rhizoma Corydalis had the greatest curative effect. The random forest model that fit all data showed that its R-squared score reached 0.8021. And the results predicted on the test set showed that the R-squared score reached 0.7318. CONCLUSIONS: Soothing the liver, promoting qi, clearing heat, removing obstructions of organs, activating blood, and resolving stagnation are the treatment methods for AP.

Prospects for intelligent rehabilitation techniques to treat motor dysfunction.

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

The role of gut microbiota in the pathogenesis and treatment of acute pancreatitis: a narrative review.

To investigate the role played by gut microbiota in the development and treatment of acute pancreatitis. Gut microbiota is the largest micro-ecosystem in the human body, and is related to various system diseases. Acute pancreatitis is one of the common acute critical diseases in clinical practice, and there are various causative factors for the occurrence of this disease, such as alcohol, infection, obstruction and intestinal microecological factors. The dysbiosis of gut microbiota may play an important role in the pathogenesis of acute pancreatitis and affect prognoses, including gut microbiota structure disorder and bacterial translocation. It can also affect host metabolism and increase the production of toxic metabolites and affect the treatment of acute pancreatitis. Probiotics are live microorganisms that can give health benefits to the host when applied in sufficient quantities, which can effectively stimulate the growth and reproduction of the normal flora of the body, inhibit the overgrowth of pathogenic bacteria, and have a protective effect on the intestinal barrier function. A search of electronic databases (PubMed, EMBASE, Cochrane) has been realized to summarize the information. The paper briefly describes the concept of gut microbiota and acute pancreatitis, examines the role of gut microbiota in the development and treatment of acute pancreatitis, concludes the investigations of the therapeutic effect of probiotics for dysbiosis of gut microbiota in acute pancreatitis in order to provide a valid reference for the development of subsequent clinical strategies.

Intermedin1-53 attenuates atherosclerotic plaque vulnerability by inhibiting CHOP-mediated apoptosis and inflammasome in macrophages.

Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE-/-) mice. Six-week IMD1-53 infusion significantly reduced atherosclerotic lesion size. Of note, IMD1-53 lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD1-53 administration prevented ERS activation in aortic lesions of ApoE-/- mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE-/- mice. IMD1-53 decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD1-53 infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.