Search

How to reshape the cross-border agricultural supply chain is a common concern in the global agricultural field. Using the bibliometrics method, 761 studies in the literature were selected from the core database of WOS (Web of Science) to explore research hotspots and development trends in this field, clarify the historical context, and explore future trends. Using the knowledge map visualization software CiteSpace, an in-depth review and visualization analysis of hot topics in this field were conducted. The results showed that since 2017, research in this field has shown a strong development trend. The United States and the University of Wageningen are the field's most influential country and research institution, respectively. Sustainability is the journal with the highest number of publications in the field. Research hotspots included cross-border agricultural product safety, cross-border agricultural supply chain systematization, and technology integration, and gradually evolved towards the high-quality development of digital intelligence with informatization, digitization, and big data as the main focus. The sustainability of cross-border agricultural supply chains and the resilience of the global food supply system have become the main lines of research in this field. [ABSTRACT FROM AUTHOR]

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In addition to its use for heroin addiction pharmacotherapy in general, buprenorphine has advantages in treating maternal heroin abuse. To examine the gestational effects of buprenorphine on opioid receptor signaling, the [35S]-GTPγS in situ binding induced by the μ agonist [D-Ala2,MePhe4,Gly5-ol] enkephalin (DAMGO) or the nociceptin/orphanin FQ (N/OFQ) agonist was measured in mesolimbic structures of pup brains from pregnant rats administered with buprenorphine±naloxone, naloxone, or methadone by osmotic minipump. Drug- and gender-based changes in DAMGO- and N/OFQ-induced GTPγS binding were discovered in mesolimbic regions of dam, P2, and P7 brains. Buprenorphine and/or methadone gestational treatment attenuated DAMGO-induced GTPγS binding in some dam and male P2 mesolimbic regions. Methadone diminished DAMGO-induced GTPγS binding in almost all monitored brain regions of the dam but had few effects on their N/OFQ-induced GTPγS binding. Naloxone used in combination with buprenorphine blocked the inhibition by buprenorphine alone on DAMGO-induced GTPγS binding. In contrast to its inhibitory effects on DAMGO-induced GTPγS binding, buprenorphine stimulated N/OFQ-induced GTPγS binding in male P2 nucleus accumbens and lateral septum. Brain region-dependent gender differences in DAMGO-induced GTPγS binding were seen in P2 pups, and males showed greater sensitivity to buprenorphine and methadone than females. Our findings on μ opioid receptor (MOR) GTP-binding regulatory protein (G protein) coupling and its gender dependency are consistent with our earlier studies on μ receptor binding adaptation induced by buprenorphine in dams and neonatal rats after in utero treatment regimens, and they extend the gestational effects of this opiate to μ and N/OFQ receptor functionality. [Copyright &y& Elsevier]

Progesterone, which acts as a neurosteroid in nervous system, has been shown to have neuroprotective effects in different experiments in vitro and in vivo. Our previous study demonstrates that progesterone exerts neuroprotections in Alzheimer’s disease-like rats. Present study attempted to evaluate the protective effects of progesterone on Aβ-treated neurons and potential mechanisms involved in neuroprotection. Results showed that treatment with progesterone protected primary cultured rat cortical neurons against Aβ 25–35 -induced apoptosis. Furthermore, we observed that progesterone alleviated mitochondrial dysfunction by rescuing mitochondrial membrane potential under Aβ challenge. Moreover, progesterone could also attenuate Bax/Bcl-2 proteins ratio upregulation and inhibit the activation of caspase-3 in Aβ-treated neurons. These indicate that progesterone attenuates Aβ 25–35 -induced neuronal toxicity by inhibiting mitochondria-associated apoptotic pathway. Both classic progesterone receptors (classic PR) and progesterone receptor membrane component 1 (PGRMC1), a special progesterone membrane receptor, are broadly expressed throughout the brain. The protective effect of progesterone was partially abolished by PGRMC1 inhibitor AG205 rather than classic PR antagonist RU486 in this study. Additionally, progesterone protected neurons by inhibiting Aβ-induced activation of JNK, which was an upstream signaling component in Aβ-induced mitochondria-associated apoptotic pathway. But this process was independent of PGRMC1. Taken together, these results suggest that progesterone exerts a protective effect against Aβ 25–35 -induced insults at least in part by two complementary pathways: (1) progesterone receptor membrane component 1-dependent inhibition of mitochondrial apoptotic pathway, and (2) blocking Aβ-induced JNK activation. The present study provides new insights into the mechanism by which progesterone brings neuroprotection. This article is part of a Special Issue entitled ‘Steroids & Nervous System’. [ABSTRACT FROM AUTHOR]

Aims: Progesterone receptor membrane component 1 (PGRMC1) has been reported to mediate the neuroprotective effect of progesterone, but the exact mechanism has not been elucidated. Therefore, the purpose of this study was to investigate the signalling pathway downstream of PGRMC1 in progesterone-induced neuroprotection. Recognition of the mechanism of progesterone opens novel perspectives for the treatment of diseases of the nervous system., Main Methods: The PGRMC1 protein level was knocked down in rat primary cortical neurons, and Aβ 25 - 35 was used to establish an Alzheimer's disease cell model. The neuroprotective effect of progesterone was assessed by Hoechst 33258 staining and a cell counting kit-8 (CCK-8) assay. Then, proteomic and bioinformatic methods were used to analyse the proteins altered in response to PGRMC1 silencing to identify target proteins and signalling pathways involved in PGRMC1-mediated progesterone-induced neuroprotection. These findings were further verified by using signalling pathway inhibitors and western blotting., Key Findings: The neuroprotective effect of progesterone was significantly attenuated with PGRMC1 silencing. The expression of many proteins in the Ras signalling pathway was significantly changed in response to PGRMC1 silencing. FTI-277 inhibited progesterone-induced neuroprotection. Progesterone increased the expression of total Ras and Grb2., Significance: These findings provide new perspectives for understanding the mechanism of and role of PGRMC1 in progesterone-induced neuroprotection. The Ras signalling pathway is the signalling pathway downstream of PGRMC1 in the mediation of progesterone-induced neuroprotection., Competing Interests: Declaration of competing interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020. Published by Elsevier Inc.)

Autophagy is an intracellular catabolic mechanism essential for recycling intracellular unfolding protein and eliminating toxic protein aggregates. Several studies have shown that deficient autophagy is implicated in the development of Alzheimer's disease (AD) progression. To date, rapidly emerging evidence suggests that neurosteroid progesterone (PG) may play an important role in ameliorating AD. However, the role of PG and its neuroprotective mechanism in regulating autophagy still require further investigation. Here, we investigated the protective effects of PG against Aβ-induced inflammatory responses in astrocytes and its underlying mechanism in mediating autophagy. Remarkably, Aβ induced astrocyte dysfunction in autophagic activation and up-regulated inflammatory secretion. However, the autophagy inducer rapamycin (RAPA) significantly suppressed Aβ-induced inflammation in astrocytes. In astrocytes, treatment with Aβ caused autophagy deficiency, whereas PG significantly increased autophagy activation. Finally, PG suppressed Aβ-induced neuroinflammatory production via enhancing autophagy together with regulating mTOR signaling. Taken together, these results show that autophagy is a vital mechanism against Aβ-induced neuroinflammatory responses in astrocytes and demonstrate the potential neuroprotective mechanism of PG in suppressing neuroinflammatory responses by enhancing autophagy. Therefore, uncovering the neuroprotective mechanism of PG may provide new insight into novel therapies for the amelioration of AD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of blood microenvironment of rats with hepatic fibrosis on differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes and its mechanisms., Methods: Eighteen male adult Sprague Dawley rats [weighing, (200±20) g] were used, liver fibrosis was induced in 12 rats by repeated intraperitoneal injections of thioacetamide. The serum was separated after successful model preparation, and the serum of 6 normal rats was collected. ELISA assay was used to detect the concentrations of epidermal growth factor (EGF), hepatocyte growth factor (HGF), oncostatin M (OSM), and basic fibroblastic growth factor (bFGF). Passage 3 HUCMSCs were divided into 3 groups: cells were cultured for 7 days in DMEM/F12 containing 10% fetal bovine serum and 5?mL/ L serum from rats with hepatic fibrosis (group A), in DMEM/F12 containing 10% fetal bovine serum and 5 mL/ L serum from normal rats (group B), and in DMEM/F12 containing 10% fetal bovine serum (group C). The morphological changes of the cells were observed. The expressions of α-fetoprotein (AFP) and cytokeratin 18 (CK18) were detected by immunofluorescence. The protein levels of albumin (ALB), tryptophan 2, 3-dioxygenase (TPH2), and CYP3A4 and MAPK/ERK signal pathway protein (P-ERK) were detected using Western blot. The content of blood urea nitrogen (BUN) was measured by diacetyl m onoxime method., Results: HE staining showed that the liver tissue of rats was in accordance with the change of fibrosis, indicating successful model preparation. In serum of normal rats and rats with hepatic fibrosis, the concentrations of EGF were (21.42±0.32) pg/mL and (17.57±0.31) pg/mL respectively, showing significant difference ( t =14.989, P =0.000); the concentrations of OSM were (129.96±0.65) pg/mL and (98.44±1.32) pg/mL respectively, showing significant difference ( t =37.172, P =0.000); the concentrations of HGF were below the detection limit and (1.03±0.12)?ng/ mL respectively; and the concentrations of bFGF were lower than the detection limit in both groups. No morphological changes of cells were observed in both groups at 7 days, and there was no significant difference between groups. At 7 days after culture, the cells in group A could express human hepatocyte biomarkers of AFP, CK18 and hepatocyte-specific-function proteins of ALB, TPH2, and CYP3 A4 while cells in groups B and C did not. Western blot showed that cells in each group could express P-ERK protein. The relative level of P-ERK protein in group A was significantly higher than that in groups B and C ( P &lt; 0.05), but no significant difference was found between groups B and C ( P &gt; 0.05). The BUN concentration of group A [(0.74±0.07)?mmol/ L] was significantly higher than that of groups B [(0.40±0.04)?mmol/ L] and C [(0.38±0.04) mmol/L] ( P &lt; 0.05), but no significant difference was shown between groups B and C ( P &gt; 0.05)., Conclusions: Under the condition of hepatic fibrosis, the level of HGF will increase while EGF and OSM will decrease. The formed blood microenvironment?will activate MAPK/ERK signal pathway in HUCMSCs, induce them differentiate into hepatocytes.

Numerous studies have suggested that ketamine administration can induce neuroapoptosis in primary cultured cortical neurons. Neurosteroids modulate neuronal function and serve important roles in the central nervous system, however the role of neurosteroids in neuroapoptosis induced by ketamine remains to be elucidated. The present study aimed to explore whether neurosteroidogenesis was a pivotal mechanism for neuroprotection against ketamine-induced neuroapoptosis, and whether it may be selectively regulated under ketamine-induced neuroapoptosis conditions in primary cultured cortical neurons. To study this hypothesis, the effect of ketamine exposure on neurosteroidogenesis in primary cultured cortical neurons was investigated. Cholesterol, a substrate involved in the synthesis of neurosteroids, was added to the culture medium, and neurosteroids were quantified using high-performance liquid chromatography-tandem mass spectrometry analysis. The data demonstrated that cholesterol blocked ketamine-induced neuroapoptosis by promoting the synthesis of various neurosteroids, and the pathway of neurosteroid testosterone conversion into estradiol was inhibited by ketamine exposure. These data suggest that endogenous neurosteroids biosynthesis is critical for neuroprotection against ketamine-induced neuroapoptosis and inhibiting the biosynthesis of neuroprotective-neurosteroid estradiol is of notable importance for ketamine-induced neuroapoptosis.

Objective: To investigate the differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes induced by rat fibrotic liver tissue extracts., Methods: Liver fibrosis was induced in the Sprague Dawley rats (weighting, 180-220 g) by repeated intraperitoneal injections of 3% thioacetamide-saline at a dose of 200 mg/kg twice a week for 4 weeks; fibrotic liver tissues were used to prepare liver homogenate supernatants. The HUCMSCs at passage 3 were cultured in DMEM/F12 with 10% fetal bovine serum (FBS) (control group) and in DMEM/F12 with 10% FBS and 50 g/L liver homogenate supernatants (experimental group) for 7 days. The morphological changes of the cells were recorded; the protein levels of cytokeratin 18 (CK18), alpha fetoprotein (AFP), and CYP3A4 were measured using Western blot. The glycogen storing ability of the cells was detected by periodic acid-schiff (PAS) staining. Furthermore, the synthesis of albumin (ALB) and blood urea nitrogen (BUN) was measured., Results: In experimental group, after 1 day of induction, the stem cells of fusiform shape began to lose sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with round and irregular shape at 7 days. Positive expressions of AFP, CK18, and CYP3A4 were observed in the experimental group, but negative expression in the control group. The concentrations of BUN and ALB were (0.43 ± 0.07) mmol/L and (8.08 ± 0.41) µg/mL in the control group and were (2.52 ± 0.20) mmol/L and (41.48 ± 4.11) µg/mL in the experimental group, showing significant differences (t=24.160, P = 0.000; t = 19.810, P = 0.000). PAS staining results showed navy blue nucleus and lavender cytoplasm in the control group, but dark purple cell body and visible nucleus in the experimental group., Conclusion: HUCMSCs could differentiate into hepatocyte-like cells induced by rat fibrotic liver tissue extracts, which have hepatocyte biomarkers (AFP, CK18, and CYP3A4) and hepatocyte-specific functions of glycogen storage, urea production and ALB secretion, so they could partially replace the function of hepatocytes, that may be one of the therapeutic mechanisms of stem cell transplantation.

Objective: To observe the in vivo migration of human umbilical cord mesenchymal stem cells (hUCMSCs) labeled with the PKH26 red fluorescent dye after transplantation into rats with liver cirrhosis., Methods: Frozen hUCMSCs were resuscitated and labeled with PKH26. Labeling efficiency and fluorescent maintenance time of the PKH26-1abeled cells were measured. Morphology of the labeled and unlabeled (control) cells was observed by microscopy. The cell growth curve was determined using the MTT method. The PKH26-1abeled hUCMSCs were transplanted via tail vein injection into healthy (control) rats and rats with liver cirrhosis. Migration of the PKH26-1abeled hUCMSCs observed 48 h later in frozen liver sections under a fluorescence microscope., Results: The labeling ratio of PKH26 to hUCMSCs was 100%. Growth of the labeled cells was good. The cell morphology was not significantly different between the labeled and unlabeled cells; all cells were long and spindle-like. Cell proliferation was not impacted significantly by labeling.Fluorescence was maintained for at least 20 days, as detected by in vitro analysis. After transplantation into the rats, the PKH26-1abeled hUCMSCs were mainly distributed in the area surrounding the portal vein, the blood vessels, and the false lobule of the cirrhotic liver; a small amount ofhUCMSCs were present in the spleen and lung., Conclusion: PKH26 is an ideal fluorescent dye to label hUCMSCs. The PKH26 labeling technique can be used to study the migration of hUCMSCs in cirrhotic liver.

A simplified method has been established using liquid chromatography-negative atomspheric pressure ionization mass spectrometry (LC-MS) to simultaneously determine two conjugated neurosteroids from rat brain regions. Neurosteroids were separately isolated in a two-step procedure using chloroform/2-butanol (50: 50, v/v) where the first step was to extract sulfated steroids, then steroid fractions were purified by solid phase extraction (SPE), and finally the sulfated steroid was solvolyzed. Estrogen sulfate was chosen as internal standard. All steroids were derivatized with 2-nitro-4-trifluoromethylphenylhydrazine (2NFPH) and analyzed by LC-MS using selected-ion monitoring. LC-MS was performed on an Agilent 1100 liquid chromatograph-mass spectrometer with atmospheric pressure chemical ionization (APCI) interface, and the hydrazones of oxosteroids was analyzed in a negative-ion mode. A Zorbax SB C18 column was used with a flow rate of 1 mL/min at 40 degrees C. The mobile phase consisted of acetonitrile and distilled water. The concentrations of PREGS and DHEAS in male rat brain regions were (4.14 +/- 1.33 ) ng/g and (2.26 +/- 0.76) ng/g (pituitary gland), (1.98 +/- 1.13) ng/g and (1.80 +/- 0.93) ng/g (hypothalamus), (1.08 +/- 0.48 ) ng/g and (0.81 +/- 0.23) ng/g (frontal cortex), (0.72 +/- 0.19) ng/g and (0.77 +/- 0.12) ng/g (hippocampus), (1.70 +/- 0.45) ng/g and (1.44 +/- 0.71 ) ng/g (amygdale), (0.92 +/- 0.27) ng/g and (0.85 +/- 0.44) ng/g (striatum), (3.62 +/- 1.77) ng/g and (3.17 +/- 2.11) ng/g (nucleus accumbens), respectively. Good linearity and accuracy were observed for each steroid. The procedure was suitable for measuring concentrations of the sulfated steroids in rat brain regions simultaneously.

A simplified method has been established to simultaneously characterize different neurosteroids in rat brain by gas chromatography/mass spectrometry (GC-MS). Neurosteroids were isolated separately in a two-step procedure using ethyl acetate in the first step to extract the unconjugated steroids and chloroform/2-butanol(50/50,v/v) in the second step to extract sulfated steroids. All steroid fractions were further purified by solid phase extraction (SPE) and the sulfated steroids were solvolyzed. All steroids were derivatized with heptafluorobutyric acid anhydride and analyzed by GC-MS (electrospray ionization) using selected ion monitoring. In male rat brain, the concentrations of pregnenolone (PREG), progesterone (PROG), allo-pregnanolone (AP) and dihydroepiandrosterone (DHEA) were (8.53 +/- 1.11) ng/g, (7.01 +/- 2.60 )ng/g, (1.17 +/- 0.19 )ng/g, and (0.92 +/- 0.20) ng/g, respectively. The concentrations of pregnenolone sulfate (PREGS) and dihydroepiandrosterone sulfate (DHEAS) were (5.94 +/- 2.03) ng/g and (1.93 +/- 0.92) ng/g, respectively. Good linearity and accuracy were observed for each steroid. The procedure was suitable for measuring the concentrations of endogenous neurosteroids, simultaneously including the sulfates in rat brain.