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Background: Stroke is a major contributor to disability and death worldwide. Studies have demonstrated that inflammasome/pyroptosis and its mediated inflammatory response are important factors aggravating brain injury after stroke. We aimed to investigate and map the knowledge structure and global trends on inflammasome/pyroptosis in stroke. Methods: All relevant documents were obtained from the Web of Science on 5 June 2023. Bibliometric visualization diagrams were created using VOSviewer and CiteSpace. Excel was used for statistical analysis and drawing graphs. Results: A total of 1106 publications were included, with more articles published each year, especially since 2014. China (740 papers), Zhejiang University (57 papers), Wang J (25 papers), and the Journal of Neuroinflammation (45 papers) were the most productive countries, institutions, authors, and journals, respectively. The United States was the country with highest centrality (0.56) and total link strength (171), and all of the top 10 institutions were in China. China and the U.S. cooperated closely. The centralities of the top 10 authors were all lower than 0.01; no leader has yet emerged in this field. "NLRP3 inflammasome" ranked first with 447 occurrences among 2136 keywords, of which 56 terms appeared more than 10 times when categorized into four clusters: cluster 1 (inflammation), cluster 2 (pyroptosis), cluster 3 (NLRP3 inflammasome), and cluster 4 (neuroinflammation). The studies focused on the mechanisms of inflammasome/pyroptosis in stroke were mainly limited to cell and animal experiments. Conclusion: Interest in inflammasome/pyroptosis in stroke is progressively increasing. The NLRP3 inflammasome is the most extensively studied and has been a research hotspot. The mechanisms of cell death in stroke are complex and future studies are needed to strengthen the clinical research on the relationship between pyroptosis-related processes and stroke, determine at which stage NLRP3 inflammasome activation, and clarify the detailed mechanism of NLRP3 in stroke. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo. Method: Polysaccharides (GSRBPs) were extracted from Ganoderma sinense – full-fat rice bran (GS-FRB) and Ganoderma sinense – defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice. Result: All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1. Conclusion: GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin–eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV. [ABSTRACT FROM AUTHOR]

Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell–transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is known to play a crucial role in diabetic osteopathy. However, key genes and molecular mechanisms remain largely unclear. This study aimed to identify a crucial ferroptosis-related differentially expressed gene (FR-DEG) in diabetic osteopathy and investigate its potential mechanism. Methods: We identified fibronectin type III domain-containing protein 5 (FNDC5)/irisin as an essential FR-DEG in diabetic osteopathy using the Ferroptosis Database (FerrDb) and GSE189112 dataset. Initially, a diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ), followed by intraperitoneal injection of irisin. MC3T3-E1 cells treated with high glucose (HG) were used as an in vitro model. FNDC5 overexpression plasmid was used to explore underlying mechanisms in vitro experiments. Femurs were collected for micro-CT scan, histomorphometry, and immunohistochemical analysis. Peripheral serum was collected for ELISA analysis. Cell viability was assessed using a CCK-8 kit. The levels of glutathione (GSH), malondialdehyde (MDA), iron, reactive oxygen species (ROS), and lipid ROS were detected by the corresponding kits. Mitochondria ultrastructure was observed through transmission electron microscopy (TEM). Finally, mRNA and protein expressions were examined by quantitative real‐time PCR (qRT‐PCR) and western blot analysis. Results: The expression of FNDC5 was found to be significantly decreased in both in vivo and in vitro models. Treatment with irisin significantly suppressed ferroptosis and improved bone loss. This was demonstrated by reduced lipid peroxidation and iron overload, increased antioxidant capability, as well as the inhibition of the ferroptosis pathway in bone tissues. Furthermore, in vitro studies demonstrated that FNDC5 overexpression significantly improved HG-induced ferroptosis and promoted osteogenesis. Mechanistic investigations revealed that FNDC5 overexpression mitigated ferroptosis in osteoblasts by inhibiting the eukaryotic initiation factor 2 alpha (eIF2α)/activated transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) pathway. Conclusions: Collectively, our study uncovered the important role of FNDC5/irisin in regulating ferroptosis of diabetic osteopathy, which might be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms. Methods: The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1β, TNFα and IL6 were measured by qRT‒PCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRT‒PCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo. Results: TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons. Conclusion: TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis. [ABSTRACT FROM AUTHOR]

A meta‐analysis was performed to assess the effects of different regenerative technologies and materials on wound healing after surgical endodontic therapy and provide a reference for surgical endodontic treatment. We searched for studies on the use of regenerative technologies and materials in surgical endodontic therapy via PubMed, MEDLINE, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data from the time of database creation to December 2022. Two researchers independently screened the literature, extracted information based on the inclusion and exclusion criteria, and evaluated the quality of the included studies. A meta‐analysis was performed using Review Manager 5.4. The results showed that the use of regenerative technologies and materials significantly reduced wound healing failures (risk ratio [RR]: 0.30, 95% confidence intervals [CI]: 0.22–0.40, p < 0.001). Moreover, autologous platelet concentrations (APCs) (RR: 0.28, 95% CI: 0.15–0.53, p < 0.001) and collagen membrane plus bovine‐derived hydroxyapatite (RR: 0.27, 95% CI. 0.12–0.61, p = 0.002) were more effective in improving wound healing failure rates than collagen membrane alone (RR: 0.51, 95% CI: 0.20–1.25, p = 0.140). Our findings showed that APCs, as well as collagen membrane plus bovine‐derived hydroxyapatite, significantly improved wound healing after surgical endodontic therapy. In contrast, collagen membrane alone did not significantly improve wound healing outcomes. However, currently available studies vary significantly in sample size and methodologies. Hence, high‐quality randomised controlled studies with large sample sizes are necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Targeted therapy for malignant esophageal squamous cell carcinoma (ESCC) remains a big challenge for our clinicians. In an effort to search for the vulnerability of ESCC, we applied a high-throughput drug-screening strategy and found that CuET, a copper chelation product of disulfiram, had a strong synergy effect with the JMJD3/UTX inhibitor GSK J4 in treating ESCC in vitro and in vivo. Interestingly, JMJD3/UTX's diagnostic and prognostic value, as well as the underlying mechanisms associated with endoplasmic reticulum stress were revealed. Targeting JMJD3 and UTX in combination with disulfiram has the potential to provide a new safe, effective, and available therapy for ESCC. The alcohol-averse drug disulfiram has been reported to have anti-tumor effects and is well suited for drug combinations. In order to identify potential drug combinations in esophageal squamous cell carcinoma (ESCC), we screened a bioactive compound library with the disulfiram copper chelation product CuET. The Jumonji domain-containing protein 3 (JMJD3) and the ubiquitously transcribed tetratricopeptide repeat protein X-linked (UTX) inhibitor GSK J4 were identified. To further understand the molecular mechanism underlying the efficient drug combination, we applied quantitative mass spectrometry to analyze the signaling pathway perturbation after drug treatment. The data revealed that the synergistic effect of GSK J4 and CuET was due to the interaction among JMJD3 and UTX, which may play important roles in maintaining endoplasmic reticulum (ER) homeostasis in tumor cells. Interestingly, our clinical data analysis showed that high expression of JMJD3 and UTX was associated with T stage and worse prognosis of ESCC patients, further supporting the importance of the above findings. In conclusion, our findings suggest that the combination of CuET and targeting JMJD3/UTX may be a safe, effective, and available treatment for ESCC. [ABSTRACT FROM AUTHOR]

Laboratory animal science (LAS) advances scientific understanding of the care and use of animals that play a key role in research supporting the development of biomedicine. LAS has developed quickly in China in recent decades, and this report provides an analysis of the current status of the countrys LAS policies and administration. National and provincial laws, regulations, guidelines, and standards apply to quality control and licensing, quarantine and infectious disease control, breeding and husbandry, transgenic animals, staff qualifications, animal welfare, and imports, exports, and transportation. Regulation and oversight of lab animal use are the responsibility of the national Ministry of Science and Technology, provincial departments of science and technology, and institutional animal care and use committees. We begin with an explanation of the rationale behind this paper and then offer a brief history of policy-related activities and achievements. We then present various policies, discuss their implementation, and hypothesize about future policy developments. With the improvement of policies under an integrated, multitiered administration, the use of high-quality lab animals in Chinese scientific research is increasing and many more papers describing animal experiments performed in China are being published in international journals.

Objective: The purpose of this study is to reveal the mechanism of action of Yi Qi Tong Qiao Pill (YQTQP) in the treatment of allergic rhinitis (AR), as well as establish a paradigm for the researches on traditional Chinese medicine (TCM) from systematic perspective. Methods: Based on the data collected from TCM-related and disease-related databases, target profiles of compounds in YQTQP were calculated through network-based algorithms and holistic targets of TQTQP was constructed. Network target analysis was performed to explore the potential mechanisms of YQTQP in the treatment of AR and the mechanisms were classified into different modules according to their biological functions. Besides, animal and clinical experiments were conducted to validate our findings inferred from Network target analysis. Results: Network target analysis showed that YQTQP targeted 12 main pathways or biological processes related to AR, represented by those related to IL-4, IFN-γ, TNF-α and IL-13. These results could be classified into 3 biological modules, including regulation of immune and inflammation, epithelial barrier disorder and cell adhesion. Finally, a series of experiments composed of animal and clinical experiments, proved our findings and confirmed that YQTQP could improve related symptoms of AR, like permeability of nasal mucosa epithelium. Conclusion: A combination of Network target analysis and the experimental validation indicated that YQTQP was effective in the treatment of AR and might provide a new insight on revealing the mechanism of TCM against diseases. Trial registration Name of the registry: Chinese Clinical Trial Registry: Trial registration number: ChiCTR-TRC-13,003,137: Date of registration: Registered 29 March 2013 - Retrospectively registered: URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=6422. [ABSTRACT FROM AUTHOR]

Objective: This research employed a network meta-analysis (NMA) to examine the effectiveness of five traditional Chinese medicine (TCM) monomers for promoting motor function recovery in rats with blunt spinal cord injury (SCI). Methods: Wangfang, China National Knowledge Infrastructure, Web of Science, Embase, Chinese Scientific Journal Database, PubMed, and the Chinese Biomedical Literature Databases were searched for retrieving relevant articles published from their inception to December 2022. Two reviewers performed screening of search results, data extraction, and literature quality assessment independently. Results: For this meta-analysis, 59 publications were included. Based on the recovery of motor function at weeks 1, 2, 3, and 4 in NMA, almost all TCM groups had significantly increased positive effects than the negative control animals. In terms of cumulative probability, the tanshinone IIA (TIIA) group ranked first in restoring motor function in the first week after blunt SCI, and the resveratrol (RSV) group ranked first during the last 3 weeks. Conclusion: The NMA revealed that TCM monomers could effectively restore motor function in the rat model of blunt SCI. In rats with blunt SCI, TIIA may be the most effective TCM monomer during the first week, whereas RSV may be the most effective TCM monomer during the last 3 weeks in promoting motor function recovery. For better evidence reliability in preclinical investigations and safer extrapolation of those findings into clinical settings, further research standardizing the implementation and reporting of animal experiments is required. [ABSTRACT FROM AUTHOR]

Background and objectives: Depression is a common comorbidity of dementia and may be a risk factor for dementia. Accumulating evidence has suggested that the cholinergic system plays a central role in dementia and depression, and the loss of cholinergic neurons is associated with memory decline in aging and Alzheimer's patients. A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) is correlated with depression and dysfunction of cognition in mice. In this study, we examined the potential regenerative mechanisms of knockdown the RNA-binding protein polypyrimidine tract binding protein (PTB) in reversing depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons. Methods: We lesioned cholinergic neurons in mice induced by injection of 192 IgG-saporin into HDB; then, we injected either antisense oligonucleotides or adenoassociated virus-shRNA (GFAP promoter) into the injured area of HDB to deplete PTB followed by a broad range of methodologies including behavioral examinations, Western blot, RT-qPCR and immunofluorescence. Results: We found that the conversion of astrocytes to newborn neurons by using antisense oligonucleotides on PTB in vitro, and depletion of PTB using either antisense oligonucleotides or adeno-associated virus-shRNA into the injured area of HDB could specifically transform astrocytes into cholinergic neurons. Meanwhile, knockdown of PTB by both approaches could relieve the depression-like behaviors shown by sucrose preference, forced swimming or tail-suspension tests, and alleviate cognitive impairment such as fear conditioning and novel object recognition in mice with lesioned cholinergic neurons. Conclusion: These findings suggest that supplementing cholinergic neurons after PTB knockdown may be a promising therapeutic strategy to revert depressionlike behaviors and cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. Method: ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. Result: The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. Conclusion: Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration. [ABSTRACT FROM AUTHOR]

Background: In mouse, it was discovered that resveratrol (Res) enhanced osteoporosis (OP) by boosting osteogenesis. Besides, Res can also have an impact on MC3T3-E1 cells, which are crucial for the control of osteogenesis and thus increase osteogenesis. Although some articles have discovered that Res enhanced autophagy to promote the value-added differentiation of MC3T3, it is unclear exactly how this affects the process of osteogenesis in mouse. Therefore, we will show that Res encourages MC3T3-E1 proliferation and differentiation in mouse pre-osteoblasts and further investigate the autophagy-related mechanism for this impact. Methods: (1) MC3T3-E1 cells were separated into blank control group and various concentrations (0.01, 0.1, 1, 10, 100µmol/L) of group in order to determine the ideal Res concentration. In the Res group, Cell Counting Kit-8 (CCK-8) was used to measure the proliferation activity of pre-osteoblasts in mice in each group after resveratrol intervention. Alkaline Phosphatase (ALP) and alizarin red staining were used to gauge the degree of osteogenic differentiation, and RT-qPCR was used to measure the expression levels of Runx2 and OCN in the osteogenic differentiation ability of the cells. (2) In the experiment, four groups were set up: the control group, 3MA group, Res group, and Res + 3MA group. To examine cell mineralization, ALP and alizarin red staining were utilized. RT-qPCR and Western blot detection of cell autophagy activity levels and osteogenic differentiation capacity in each group following intervention. Results: (1) Resveratrol might increase the number of mice pre-osteoblast, with the impact being most pronounced at 10µmol/L (P < 0.05). The nodules developed substantially more often than in the blank control group, and Runx2 and OCN expressions significantly increased (P < 0.05). (2) In contrast to the Res group, after 3MA purine blocked autophagy, the Res + 3MA group's alkaline phosphatase staining and the development of mineralized nodules were reduced. Runx2, OCN, LC3II / LC3I expression decreased, p62 expression increased (P < 0.05). Conclusion: The present study partially or indirectly demonstrated that Res may, through increased autophagy, induce osteogenic differentiation of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis. Methods: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR‐1206 and circ_0043256 or Krüppel‐like factor 2 (KLF2) was verified by dual‐luciferase reporter assay. Results: Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR‐1206 and miR‐1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR‐1206. Rescue assay showed that miR‐1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR‐1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre‐clinically, lentivirus‐mediated circ_0043256 overexpression impeded lung cancer growth in nude mice. Conclusion: Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR‐1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Oncolytic viral therapy is a promising method for tumor treatment. Currently, several oncolytic viruses (OVs) have been used as tumor therapy at different phases of research and clinical trials. OVs not only directly lyse tumor cells due to viral replication but also initiate host antitumor immune responses. Previous studies have primarily focused on how OVs activate adaptive immune responses in immune cells. However, the role of innate immune responses in tumors induced by OVs remains unclear. Methods: To determine the innate immune responses induced by vesicular stomatitis virus (VSV), the mutant VSVΔM51 strain was used for the infection and quantitative polymerase chain reaction (qPCR) was employed to measure the transcriptional levels of antiviral genes. The knockdown efficiency of RIG‐I was examined by qPCR. Viral titers were measured by plaque assays. Tumor models were established by intradermally implanting RIG‐I‐knockdown and control LLC cells into the flank of wild type C57BL/6J mice. When the tumors reached approximately 50mm3, they were infected with VSVΔM51 via intratumoral injections to examine its therapeutic effect. Results: Infection with VSVΔM51 triggered remarkable innate immune responses in several tumor cell lines through the cytoplasmic RIG‐I sensing pathway. Moreover, we found that intratumoral injection of VSVΔM51 effectively reduced tumor growth in murine LCC lung cancer model. Importantly, VSVΔM51‐induced antitumor therapy was more effective in murine LLC tumor model established using Rig‐I‐knockdown cells compared with the tumor model established using control cells. Conclusion: RIG‐I‐mediated innate immune signaling in tumor cells plays a negative role in regulating antitumor therapy with VSVΔM51 virus. [ABSTRACT FROM AUTHOR]

Background: White adipose tissue can be classified based on its location as subcutaneous and visceral fat, and the latter accumulation is reported to be more detrimental to metabolism. Endoplasmic reticulum (ER) stress has been demonstrated to regulate lipogenesis. The peptide angiotensin(1–7) [Ang(1–7)], which can be produced from angiotensin II (AngII) by angiotensin-converting enzyme 2 (ACE2), plays its role through Mas receptor, also participates in the regulation of lipid metabolism in adipose tissue, however, whether ER stress is involved in the mechanism remains unclear. Therefore, we aimed to explore the role of Ang(1–7) pathway in regulating visceral adipose tissue expansion and ER stress. Methods: ACE2 knockout (KO), Mas KO and C57BL/6 J mice were fed with high fat diet. Db/db mice were treated with either normal saline, Ang(1–7) or Ang(1–7) combined with Mas receptor inhibitor A779 using mini osmotic pumps. Fat mass was weighted, fat distribution was evaluated by MRI, and lipid profile and adipokines in epididymal adipose tissue were measured by ELISA kits, and histology of epididymal adipose tissue was also analyzed in multiple animal models. Additionally, differentiated 3T3-L1 cells were pre-loaded with palmitic acid to induce ER stress, then treated with drugs as those administrated to db/db mice. ER stress and lipogenesis related proteins in mice adipose and differentiated 3T3L-1 cells were analyzed by Western blot. Results: ACE2 or Mas KO mice exhibited increased visceral adipose tissue, adipocyte size and protein expression of lipogenesis and ER stress related markers in epididymal adipose tissue compared to wild-type mice. Db/db mice treated with Ang(1–7) displayed decreased visceral fat mass, adipocyte size and protein expression of lipogenesis and ER stress markers in epididymal adipose tissue compared to those treated with normal saline, while A779 partly attenuated these effects. Additionally, Ang(1–7) improved ER stress and lipogenesis markers in differentiated 3T3-L1 cells pre-loaded with palmitic acid. Conclusions: Our findings indicated that Ang(1–7) attenuated visceral adipose tissue expansion and lipogenesis by suppression of ER stress via Mas receptor. The present study provides a potential perspective for Ang(1–7) for the therapeutics of obesity and related disorders. [ABSTRACT FROM AUTHOR]

Background: 'Taikong blue' lavender, a space-bred cultivar of Lavandula angustifolia, is one of the main lavender essential oil production crops in Xinjiang Province, China. Several cases of local usage indicated that 'Taikong blue' lavender essential oil (TLEO) had excellent anti-inflammatory and antioxidant properties for skin problems. However, to date, substantial data on these functions are lacking. In this study, we aimed to investigate the composition and bioactivities of TLEO and the potential underlying mechanisms through LPS-induced inflammatory models of HaCaT and RAW264.7 cells. Methods: The composition of TLEO was determined by GC‒MS. To study the anti-inflammatory and antioxidative properties of TLEO, we induced HaCaT and RAW264.7 cells by LPS. TLEO (0.001%-0.1%, v/v) was used to treat inflamed cells with dexamethasone (DEX, 10 μg/mL) as the standard drug. A variety of tests were carried out, including biochemical assays, ELISA, RT‒PCR, and western blotting. Docking of components was performed to predict potential ligands. Results: The GC‒MS analysis revealed that 53 compounds (> 0.01%) represented 99.76% of the TLEO, and the majority of them were esters. TLEO not only reduced the levels of oxidative stress indicators (NO, ROS, MDA, and iNOS at the mRNA and protein levels) but also protected the SOD and CAT activities. According to the RT‒PCR, ELISA, and Western blot results, TLEO decreased inflammation by inhibiting the expression of TNF-α, IL-1β, IL-6, and key proteins (IκBα, NF-кB p65, p50, JNK, and p38 MAPK) in MAPK-NF-кB signaling. Molecular docking results showed that all of the components (> 1% in TLEO) were potent candidate ligands for further research. Conclusion: The theoretical evidence for TLEO in this study supported its use in skin care as a functional ingredient for cosmetics and pharmaceutics. [ABSTRACT FROM AUTHOR]

Background: Accumulated evidence indicates that astragalus polysaccharide (APS) may have a beneficial impact on ulcerative colitis (UC) by suppressing inflammation and decreasing oxidative stress. Nevertheless, the credibility of the evidence for this practice is unclear. Therefore, we intended to conduct a systematic review and meta-analysis of animal studies to assess the antiinflammatory and antioxidant activity of APS when used in the treatment of UC. Methods: Electronic bibliographic databases including PubMed, EMBASE, Web of Science, Chinese Biomedical Literature (CBM), Wanfang Database, CQVIP Database and China National Knowledge Infrastructure (CNKI) were retrieved for relevant animal studies. The methodological quality of animal studies was evaluated based on the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE's RoB tool). A meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using STATA 12.0 software. This study was registered with PROSPERO, number CRD42021272595. Results: Twenty qualified publications involving 591 animals were included in this study. There was a significant association of APS with levels of disease activity index (DAI), colon macroscopic damage index (CMDI), colon histopathologic score (CHS), myeloperoxidase (MPO), tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA) compared with that in the control group. Sensitivity analysis that eliminated one study at each stage did not change these results. Egger's test and funnel plot showed that publication bias was existed. Conclusion: In this meta-analysis, APS treatment significantly mitigated colonic damage by reducing the levels of MPO, TNF-α, IL-6, IL-1β, and MDA and recovering the SOD activity. These results demonstrated a protective role of APS in the treatment of UC and showed that the anti-inflammatory and antioxidant activity were implicated in the underlying mechanisms. Hence, APS may represent a promising candidate for treating UC. However, due to potential publication bias, a cautious interpretation is needed. [ABSTRACT FROM AUTHOR]

Background. Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA-146a-mediated cellular autophagy. Methods. A collagen-induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC-Q/TOF-MS. Histological changes; miRNA-146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA-146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR-containing serum to observe the effects of miRNA-146a-mediated autophagy via the PI3K/AKT/mTOR pathway on CIA-affected rats. Results. Forty and thirty-one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA-146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA-146a-mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. Conclusion. WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA-146a-mediated PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background. An important feature of aging cells is the gradual loss of physiological integrity. As aging progresses, MSCs change preferring to differentiate toward adipocytes rather than osteoblasts. Oxidative stress accumulation is an important factor in age-related bone loss. Many experiments have demonstrated the good therapeutic effect of Ginsenoside (Rg1) on oxidative stress injury. In this study, we investigated the effect of Rg1 on the osteogenic-adipogenic differentiation balance of bone marrow mesenchymal stem cells (BMMSC). Objective. To analyze the potential application value of Rg1 in the treatment of senile osteoporosis. Methods. BMMSCs were isolated from healthy donors of different ages and identified based on isotype and by multi-differentiation induction. Rg1 was used to treat BMMSCs, The differentiation propensity was analyzed by induction of differentiation assay. Antioxidant capacity of BMMSCs as measured by oxidative stress product assay Related mechanism studies were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (qRT‐PCR), immunofluorescence, western blotting, and inhibitor treatment. Moreover, Observation of the effects of Rg1 on aging BMMSCs under in vivo conditions by treatment of aged mice with Rg1 injections. Results. Rg1 treatment rescued age‐induced switch of BMMSCs differentiation fate in vitro. In elderly people, Rg1 markedly increased osteogenic differentiation of BMMSCs by decreasing oxidative stress, while inhibiting adipogenic differentiation. However, this effect was abolished in BMMSCs by an Nrf2-inhibitor. Notably, aging mice showed a reduction in adipocyte distribution in the bone marrow and a decrease in oxidative stress products after a 3-month period of Rg1 treatment. Conclusion. We have uncovered a novel function for Rg1 that involves attenuating bone loss via Nrf2 antioxidant signaling, which in turn may potentially be utilized as a therapeutic agent for improving osteogenic differentiation in aging BMMSCs. [ABSTRACT FROM AUTHOR]

Aim of the Study. Late-onset Alzheimer's disease (LOAD) is recognized as a degeneration disorder in patients' central nervous system over 65 years old who will experience memory decline and cognitive impairment, causing great harm to the health of the elderly. To investigate the role of KL-FGF23-VD axis in LOAD and its molecular mechanism, we designed experiments from two dimensions of cells and animals. Materials and Methods. LOAD rats and Aβ microglia were constructed by using Aβ1-40 and IBO mixture. The effect of KL-FGF23-VD axis on LOAD was investigated by transfecting overexpressing and interfering with KL gene adenovirus, and IKK-16 was added to Aβ microglia to explore the effect of KL-FGF23-VD axis on regulation of IKK/NF-κB signaling pathway. Results. The results showed that, in KL-OE group, FGF23 was decreased in the hippocampus of LOAD rats compared with control and KL-si, and the trend was opposite in the KL-si group. The KL-FGF23-VD axis can alleviate inflammatory response, reduce the deposition of Aβ, and inhibit activation of the NF-κB pathway and neuron apoptosis in brain tissue of LOAD rats. In Aβ microglia, the expression of KL-FGF23-VD axis was consistent with animal experiments. The KL-FGF23-VD axis can inhibit the expression of Aβ microglia inflammatory factors and the activation of microglia and NF-κB pathway. Meanwhile, IKK expression was decreased in KL-OE group compared with KL-si and Control. In the IKK-16 addition group, the ability of KL-FGF23-VD axis to inhibit the activation of microglia and NF-κB pathway was enhanced. Conclusions. These findings suggest a potential role of the KL-FGF23-VD axis in AD treatment by regulating the IKK/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) is characterized by the presence of systemic clinical manifestations. Among them, pneumonia accounts for a significant cause of morbidity and mortality, highlighting an urgent need to explore possible susceptibility and potential mechanisms of pneumonia in MM. Recently, the gut–lung axis has emphasized the relevance of gut microbiota and pneumonia, indicating that the compromised function of gut microbiota may be susceptible to pneumonia. It has been previously shown that intestinal Klebsiella pneumonia enriches in MM patients and promotes MM progression in our previous work. In addition, host metabolism has been identified as a key regulator of MM. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. In this study, we explored the association between gut microbiota and MM with pneumonia. This is the first study to identify and elucidate the function of gut microbiota involved in MM with pneumonia. Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut–lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia. [ABSTRACT FROM AUTHOR]

Noncoding RNAs were discovered to control a variety of developmental mechanisms, including osteogenesis. According to emerging evidence, cryptochrome circadian-regulating (CRY) proteins have emerged as essential controllers of osteoblast differentiation. The linked processes, on the other hand, are still unknown. The specific process that underpins osteoblast differentiation and proliferation is yet unknown. This research gives a meta-analysis of CRY2's impact on mouse osteoblast differentiation via the control of the WNT/β–catenin signaling pathways. Western blot and quantitative real-time PCR were used to identify Cry2 expression levels, components in the osteoblast-associated signaling pathway, and osteoblast transcription markers. The osteogenic condition was measured utilizing alkaline phosphatase (ALP) and alizarin red (AR) staining, whereas cell growth rates were measured using CCK8 assays. An ectopic bone formation experiment was used to determine the osteogenic potential of osteoblasts. Cry2 stimulates the osteogenic development of mouse osteoblasts through canonical Wnt/β-catenin signaling, according to the findings. [ABSTRACT FROM AUTHOR]

The article reports that To understand why Procapra przewalskii does not show the same white myopathy as sheep in Se-deficient regions and to provide reference for feeding nutrition level of artificial population and selection of wild reintroduction areas in the later period, a Se-deficient model was established.

Objective. To observe the protective effect of gynostemma glycosides on retinal ganglion cells in rats with chronically high intraocular pressure. Materials and Methods. A total of 60 rats were randomly divided into group A (the blank group, 10 rats) and chronic high IOP model group (50 rats). The IOP model group (IOP above 22 mmHg) was then randomly divided into an additional 5 groups (10 rats per group): group B (negative control group) treated with normal saline; group C treated with gynostemma glycosides 25 mg/(kg-d); group D treated with gynostemma glycosides 50 mg/(kg-d); group E treated with gynostemma glycosides 100 mg/(kg-d); and group F (positive control group) treated with VitB1 and VitB12. The eyes of each rat were monitored from day 1 to 14 (D1–D14). On day 14, rats were euthanized, after which retinal tissue and optic nerve were examined using real-time PCR, western blot, HE staining, LFB staining, and TUNEL assay. Results. Groups A, C, D, E, and F had significantly lower expression of CD11b, GFAP, Brn3α, and more TUNEL cells than in group B (all P < 0.05). Moreover, the relative expression of STAT3 mRNA and JAK2 (mRNA and protein) in groups A, C, D, E, and F was significantly lower than in group B (P < 0.05), while in group E, the expression was lower than in group D (P < 0.05). Conclusion. Gynostemma glycosides protect retinal ganglion cells in rats with chronically high intraocular pressure possibly associated with the STAT3/JAK2 signaling pathway. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease, and the pathogenesis of PD is closely related to mitochondrial dysfunction. Previous studies have indicated that traditional Chinese medicine composition of Huangqin Decoction (HQD), including Scutellariae Radix, licorice, and Paeoniae Radix Alba, has therapeutic effects on PD, but whether HQD has a therapeutic effect on PD has not been reported. In this study, the protective effects of HQD on rotenone-induced PD rats were evaluated by behavioral assays (open field, rotating rod, suspension, gait, inclined plate, and grid) and immunohistochemistry. The mechanisms of HQD on attenuation of mitochondrial dysfunction were detected by biochemical assays and mitochondrial metabolomics. The results showed that HQD (20 g/kg) can protect rats with PD by improving motor coordination and muscle strength, increasing the number of tyrosine hydroxylase (TH)- positive neurons in rats with PD. Besides, HQD can improve mitochondrial dysfunction by increasing the content of adenosine triphosphate (ATP) and mitochondrial complex I. Mitochondrial metabolomics analysis revealed that the ketone body of acetoacetic acid (AcAc) in the rotenone group was significantly higher than that of the control group. Ketone bodies have been known to be used as an alternative energy source to provide energy to the brain when glucose was deficient. Further studies demonstrated that HQD could increase the expression of glucose transporter GLUT1, the content of tricarboxylic acid cycle rate-limiting enzyme citrate synthase (CS), and the level of hexokinase (HK) in rats with PD but could decrease the content of ketone bodies [AcAc and b-hydroxybutyric acid (b-HB)] and the expression of their transporters (MCT1). Our study revealed that the decrease of glucose metabolism in the rotenone group was parallel to the increase of substitute substrates (ketone bodies) and related transporters, and HQD could improve PD symptoms by activating the aerobic glycolysis pathway. [ABSTRACT FROM AUTHOR]

Interferons, as the first line of defense against the viral infection, play an important role in innate immune responses. Type III interferon (IFN-λ) was a newly identified member of IFN family, which plays IFN-like antiviral activity. Towards a better understanding of the type III interferon system in birds, type III interferon lambda receptor (IFNLR1) was first identified in the Chinese goose. In this paper, we had cloned 1952 bp for goose IFNLR1 (goIFNLR1), including an ORF of 1539 bp, encoding a 512-amino acid protein with a 20 aa predict signal peptide at its N terminal and a 23 aa transmembrane region. The predicted amino acid sequence of goIFNLR1 has 90%, 73%, and 34% identity with duck IFNLR1 (predicted sequence), chicken IFNLR1, and human IFNLR1, respectively. And the age-related tissue distribution of goIFNLR1 was identified by Real Time quantitative PCR (RT-qPCR), we found that the goIFNLR1 has a mainly expression in epithelium-rich tissues similar to other species’, such as small intestinal, lung, liver, and stomach. Moreover, a relatively high expression of goIFNLR1 was also observed in the secondary immune tissues (harderian gland and cecal tonsil). The identification and tissue distribution of goIFNLR1 will facilitate further study of the role of IFN-λ in goose antiviral defense. [ABSTRACT FROM AUTHOR]

In this paper, a novel small-molecular apoptotic PET imaging probe, 18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result, 18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy. [ABSTRACT FROM AUTHOR]

11Beta-hydroxysteroid dehydrogenase (11β-HSD) enzymes control the glucocorticoid (GC) signaling, which is essential in regulating homeostasis. Our previous study revealed that Eclipta prostrata (EP) affected the activity and expression of 11β-HSD enzymes which might improve the efficacy and reduce the adverse drug effects of glucocorticoid in patients undergoing combinational therapy. However, it is still unclear which composition of EP plays a major role and how it works. In this paper, we chose Luteolin which is one of the main ingredients of EP and evaluated its effect and metabolism in combination with prednisone. The effects of different concentrations of Luteolin extract on prednisone/prednisolone metabolism indicated the enzyme activity of 11β-HSD, so the production rate (pmol/min per mg protein) of metabolites was used to indicate enzyme activity. Furthermore, we explored the influence of Luteolin on gene and protein expressions of 11β-HSD I/II in rat liver and kidney tissue. Our results showed that oral administration of Luteolin significantly increased the gene and protein expressions of hepatic 11β-HSD I and renal 11β-HSD II, which may improve the efficacy and reduce the adverse drug effect of glucocorticoid in clinical application. A potential clinical value of Luteolin would also be indicated in combination therapy with prednisone for the treatment of nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Background: Investigation on protective effects of Panax notoginseng against obesity and its related mechanisms is incomplete. Present study aimed to investigate the potential anti-obesity effect of the total saponins (PNS) and ethanolic extract of P. notoginseng (PNE). Methods: Six-week-old male C57BL/6J mice received 45% kcal fat diet for 12 weeks to induce obesity. Oral administration of PNS and PNE at 20 mg/kg/day was applied for the last 4 weeks in the obese mice. Lipid profile was determined by ELISA. Histological examination was performed in liver and fat tissues. Protein levels were measured by Western blot. Results: PNS and PNE did not cause weight loss. PNE but not PNS decreased the mass of epididymal and retroperitoneal white adipose tissue, accompanied by a reduction in adipocyte hypertrophy. PNS and PNE improved lipid profile by reducing the concentrations of triglyceride, total cholesterol and low-density lipoprotein cholesterol in plasma or liver samples. PNS and PNE also relieved fatty liver in obese mice. PNS and PNE inhibited expression and phosphorylation of endoplasmic reticulum (ER) stress-responsive proteins in hypertrophic adipose tissue. Conclusions: PNS and PNE can regulate ER stress-mediated apoptosis and inflammation to alleviate obesity. [ABSTRACT FROM AUTHOR]

Objective. Microglial BV-2 cells are activated in the brain following insomnia. Naringin (NAR) is a polymethoxylated flavonoid that is also commonly found in citrus fruits and is known for its antioxidant potential. However, the effect of NAR on microglial cells has rarely been studied in the brain of an organism after insomnia. This study aimed to investigate the effects and potential mechanisms of action of NAR on microglial cell activation and inflammation. Methods. BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066. With the exception of the control group, all groups were stimulated with LPS (1 μg/mL) for 6 h. CCK8 was used to quantify cell viability and a scratch test was performed to detect cell migration. The expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), nterleukin 10 (IL-10), and insulin like growth factor (1IGF-1) were measured by ELISA. Western blotting was performed to determine the levels of p-STAT3 and p-JAK. The Focalcheck™ Thin-Ring Fluorescent Microspheres kit was used to detect cell phagocytosis. Immunofluorescence was used to observe the expression of iNOS and arginase1 in BV-2 cells. Results. Compared with the control group, cell migration, cell viability, and the expression of IL-1β, IL-6, TNF-α, and iNOS were significantly increased in the model group, whereas the expression levels of IL-10, IGF-1, and arginase 1, as well as cell phagocytosis were reduced. With the increase in NAR concentration, cell migration, cell viability, the expression levels of IL-1β, IL-6, TNF-α, and iNOS decreased, while the expression of IL-10, IGF-1, and arginase 1 increased. Compared with the control group, p-STAT3, and p-JAK expression in the model group were significantly increased (P<0.05). Compared with the model group, the expression of p-STAT3 and p-JAK in the NAR, NAR + WP1066, and WP1066 groups was significantly decreased (P < 0.05). Conclusion. NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: Black-boned sheep is a precious genetic resource with black quality traits cultivated by the Pumi people in Tongdian Town, Lanping County, Nujiang Lisu Autonomous Prefecture, Northwest Yunnan, China. It has been included in the "National Breed List of Livestock and Poultry Genetic Resources." The local communities have a deep understanding of black-boned sheep. The traditional knowledge of black-boned sheep is essential to their conservation and sustainable development. In spite of this, there was no information on traditional knowledge associated with black-boned sheep so far. The aim of this study wasaimed to document traditional knowledge and culture, to elucidate information about forage plants, and to investigate the conservation strategy of black-boned sheep. Method: Four field surveys were conducted from July 2019 to May 2021. A total of seven villages and the Pumi Culture Museum in Lanping County are being investigated. A semi-structured interview method was used to interview 67 key informants. During the investigation, we also participated in the grazing activities of black-boned sheep, observed the appearance characteristics and the herd structure of the black-boned sheep, and demonstrated traditional knowledge regarding black-boned sheep, including grazing methods, forage plants, and related customs and habits. Results: We assumed that a majority of people in the current study sites were able to could distinguish black-boned sheep from their relatives by their black bones, blue-green gums, and blue-purple anus. The local people manage their black-boned sheep based on the number of sheep by sex, age, and role in a flock in the different breeding environments. Different grazing strategies have been adopted in different seasons. Through ethnobotanical investigations, 91 species of forage plants in 30 families were identified, including herbaceous, shrubs, lianas, and trees. Among all the plant species consumed by the black-boned sheep, Rosaceae species make up the greatest number, with 16, followed by Asteraceae, with 9, and 8 species of Fabaceae and Poaceae. Considering the abundance of forage plants and the preference for black-boned sheep, Prinsepia utilis and the plants of Rubus, Berberis, and Yushania occupy dominant positions. Plants used for foraging are divided into two categories: wild and cultivated. Due to the lack of forage plants in fall and winter, the local people mainly cultivate crops to feed their black-boned sheep. In addition, the black-boned sheep is an influential cultural species in the local community and plays a prominent role in the cultural identity of the Pumi people. Conclusion: Sheep play an essential role in the inheritance of the spiritual culture and material culture of the Pumi ethnic group. The formation of the black-boned sheep is inseparable from the worship of sheep by the Pumi people. With a long-term grazing process, the locals have developed a variety of traditional knowledge related to black-boned sheep. This is the experience that locals have accumulated when managing forests and grasslands. Therefore, both the government and individuals should learn from the local people when it comes to protecting black-boned sheep. No one knows black-boned sheep better than them. The foremost evidence of this is the rich traditional knowledge of breeding black-boned sheep presented by key informants. [ABSTRACT FROM AUTHOR]

Simple Summary: We show that CLU, especially cytoplasmic precursor CLU, is downregulated in lung cancer and correlates with poor survival. The silencing of CLU promotes lung cancer cell migration and invasion, while the overexpression of CLU potently inhibits these phenomena. Interestingly, secretory CLU proteins are slightly decreased in lung cancer tissue and fail to exert similar anti-metastatic effects like cytoplasmic precursor CLU, demonstrating that cytoplasmic precursor CLU is the primary functional isoform of CLU, which exerts the anti-metastatic effects of lung cancer. Mechanistically, cytoplasmic precursor CLU binds ROCK1 to decrease phosphorylation of ERK1/2 by inhibiting the kinase activity of ROCK1, leading to an anti-metastatic effect in lung cancer cells. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer. Clusterin (CLU) is a heterodimeric glycoprotein that has been detected in diverse human tissues and implicated in many cellular processes. Accumulating evidence indicates that the expression of secreted CLU correlates with the progression of cancers. However, the molecular mechanisms underlying its tumor-suppressive roles are incompletely uncovered. In this study, we demonstrate that precursor CLU is widely downregulated in lung cancer tissue, in which secretory CLU proteins are slightly decreased. Impressively, overexpressing CLU potently inhibits the migration, invasion and metastasis of lung cancer cells, whereas silencing CLU promotes this behavior; however, it appears that secretory CLU fails to exert similar anti-metastatic effects. Interestingly, the cytoplasmic precursor CLU binds ROCK1 to abrogate the interaction between ROCK1 and ERK and impair ERK activity, leading to the suppression of lung cancer invasiveness. Meanwhile, the expression of CLU was remarkably diminished in lung cancer bone metastasis loci when compared with subcutaneous tumors in the mouse model and hardly detected in the bone metastasis loci of lung cancer patients when compared with the primary. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer. [ABSTRACT FROM AUTHOR]

Excessive inflammation is responsible for arteriovenous fistula (AVF) failure, which determines the therapeutic effect of chronic renal failure (CRF). Macrophage polarization is of great significance in the inflammatory response. Hirudin (Hiru) has been reported to possess a definite anti-inflammatory effect. This study is to uncover the impacts of Hiru on classically (M1)/alternatively (M2) macrophage polarization in the CRF rat model and rat vascular smooth muscle cells (VSMCs). After the CRF rat model was administrated with different concentrations of Hiru, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were tested. H&E staining was to detect vascular injury, and IHC assay was to analyze inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) expressions in vascular tissues. Levels of inflammatory factors were examined by ELISA. Besides, western blot was to estimate the levels of marker proteins related to macrophage, proliferation, and apoptosis. CCK-8 was to measure cell viability. We discovered that Hiru alleviated renal function injury and vascular injury, exacerbated VSMC hyperplasia, and stimulated the differentiation and activation of M1 macrophage towards M2 macrophage in vivo. Moreover, after treatment with lipopolysaccharide (LPS)/IFN-gamma (IFN-γ), the increased M1/M2 ratio and enhanced levels of inflammatory factors were observed. Furthermore, Hiru boosted the proliferation and ameliorated the inflammatory response and apoptosis of rat VSMCs during the process of coincubation of M1-conditioned medium (CM). Collectively, Hiru played a protective role against vascular injury in CRF directly or through its influence on M1 macrophage polarization and inflammation. [ABSTRACT FROM AUTHOR]

Background: Tanshinone I (Tan-I), an ingredient of Salvia miltiorrhiza, displays protective effects in several disease models. We aim to study the effect of Tan-I on renal fibrosis and explore its underlining mechanism. Methods: Rat renal fibroblasts (NRK-49F) were used as an in vitro model to study the effect of Tan-I. Mouse renal fibrosis model was induced by unilateral ureteral obstruction (UUO) or peritoneally injection of aristolochic acid I (AAI). Results: We found that Tan-I dose-dependently inhibited the expression of pro-fibrotic markers in rat renal fibroblasts. Masson staining and Western blotting analysis showed that Tan-I treatment attenuated renal fibrosis in UUO or AAI induced fibrotic kidneys. RNA sequencing analysis identified inhibin beta-A (INHBA), a ligand of TGF-β superfamily, as a downstream target of Tan-I in fibrotic kidneys, which were further verified by qPCR. Western blotting analysis showed that INHBA is up-regulated in UUO or AAI induced fibrotic kidneys and Tan-I reduced the expression of INHBA in fibrotic kidneys. Inhibition of INHBA by Tan-I was further confirmed in rat fibroblasts. Moreover, knockdown of INHBA reduced the expression of pro-fibrotic markers and abolished the ani-fibrotic effect of Tan-I in rat renal fibroblasts. Conclusions: We conclude that Tan-I attenuates fibrosis in fibrotic kidneys through inhibition of INHBA. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of fermented mushroom of Cordyceps sinensis (CS), rich in selenium (Se- CS), on uterine cervical cancer in mice. The methylcholanthrene- (MCA-) induced tumor model was used in this paper. After the mice were administered Se-CS, the animals showed 40% tumor incidence (P < 0.05). Se-CS also enhanced the immune functions. Se-CS treatment showed significant (P < 0.05-0.01) restoration in the level of glutathione content, lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+/K+-ATPase activity, and glutathione S transferase activity. This finding suggested that the concomitant use of Se and CS could be a potential therapeutic approach to improve the efficacy of therapy for uterine cervical cancer. [ABSTRACT FROM AUTHOR]

Identifying Helicobacter pylori (H. pylori, Hp) infection in animals before and after artificial infection influences the subsequent experiment. We established effective and noninvasive detection methods, including the gastric fluid nested polymerase chain reaction (PCR) method and the 13C-urea breath test, which can detect Hp before modeling Hp infection in Mongolian gerbils. We designed a gas collection equipment for gerbils. Hp nested PCR was also performed on gastric fluid, gastric mucosa, duodenal contents, and faeces of gerbils challenged with Hp. Conventional Hp detection methods, including rapid urease assay and immunohistochemistry, were compared. Moreover, we assessed the natural infection of Hp in 135 gerbils that had never been exposed to Hp artificially from the major laboratory gerbil groups in China. In 10 Hp infected gerbils, the positive detection results were 100%, 100%, 90%, and 10% in gastric fluid, gastric mucosa, duodenal contents, and faeces with nested PCR, respectively. A rapid urease test performed on gastric mucosa showed that all animals were infected with Hp. Immunohistochemical detection and bacteria culture of gastric mucosa samples that were positive by the nested PCR method also confirmed the presence of Hp. 9% (3/35) and 6% (2/31) natural infection rates were found in conventional gerbil groups from the Capital Medical University and Zhejiang Laboratory Animal Center. In conclusion, we established two noninvasive Hp detection methods that can be performed before modelingHp infection, including the gastric fluid nested PCR method and the 13C-urea breath test. [ABSTRACT FROM AUTHOR]

Study Question: How does ectopic endometrial stromal cell (Ecto-ESC)-derived extracellular vesicular Legumain pseudogene 1 (EV-LGMNP1), a newly identified pseudogene of Legumain (LGMN), contribute to M2-phenotype macrophage polarization, and does it predict recurrence in patients with ovarian endometriosis (EMs)?Summary Answer: EV-LGMNP1, which is abundant in Ecto-ESCs and serum from ovarian EMs, can direct macrophages towards an M2 phenotype by upregulating LGMN expression and is a promising biomarker for predicting ovarian EMs recurrence.What Is Known Already: Extracellular vesicles (EVs) can mediate cell-to-cell crosstalk to promote disease progression via cargo molecule transport. Recently, LGMNP1, a newly identified pseudogene of LGMN, has been reported to promote cancer progression by upregulating LGMN. LGMN is a well-studied protein that can induce M2-like polarization.Study Design, Size, Duration: An in vitro study was conducted with Ecto-ESCs isolated from ectopic endometrial samples, collected from two patients with ovarian EMs (diagnosed by laparoscopy and histological analysis). A clinical retrospective cohort study of 52 ovarian EMs patients and 21 controls with available preoperative serum samples was carried out (2013-2017). The follow-up period ended either at the time of recurrence or on 31 December 2018.Participants/materials, Setting, Methods: Ecto-ESC-derived EVs (EV/Ecto-ESCs) were characterized by nanoparticle tracking analysis, transmission electron microscopy and western blotting. EV internalization by THP-1 cells, which are the most widely used primary human macrophages model, was detected by fluorescence labelling. After EV treatment, THP-1 cell polarization was detected by quantitative real-time PCR (qRT-PCR) and western blot analyses of CD86 (M1-related marker) and CD206 (M2-related marker). LGMNP1 mRNA expression level in EVs from both primary ectopic endometrioc stromal cells and serum was examined using qRT-PCR. Additionally, the expression of LGMN, the downstream target gene of LGMNP1, in THP-1 cells was evaluated using qRT-PCR and western blotting. Kaplan-Meier and multivariate Cox regression analyses were applied to evaluate the independent predictive factors of EMs recurrence-free survival. A novel nomogram model based on serum EV-LGMNP1 was then formulated to predict EMs recurrence.Main Results and the Role Of Chance: In vitro assays demonstrated that EV/Ecto-ESCs drove macrophages towards an M2-like phenotype. Moreover, LGMNP1 contributed to EV/Ecto-ESC-induced M2 macrophage polarization by upregulating LGMN mRNA expression levels. Clinically, serum EV-LGMNP1 was more highly expressed in recurrent EMs patients than in controls and EMs patients without recurrence. Survival analysis and our novel nomogram reconfirmed that serum EV-LGMNP1 was a novel promising and meaningful non-invasive biomarker for predicting EMs recurrence.Large Scale Data: N/A.Limitations, Reasons For Caution: In vitro experiments were only performed on samples from two patients with ovarian endometriosis, and a larger sample size is needed. ESCs isolated from the eutopic endometrium of EMs and non-EMs patients should be studied in the future. Additionally, in vitro experiments should be performed using endometrial epithelium cells and further in vivo experiments, such as using mice endometriotic models to investigate whether EV/Ecto could induce M2 macrophage polarization, should be conducted. Moreover, multicentre, large-sample data are needed to validate our predictive nomogram model.Wider Implications Of the Findings: Our study provides novel insights into the mechanism of M2 polarization involved in ovarian EMs progression mediated by an 'EV-shuttled pseudogene LGMNP1' mode. In addition, serum EV-LGMNP1 may serve as a novel non-invasive biomarker for predicting recurrence, providing a new therapeutic target for ovarian EMs.Study Funding/competing Interest(s): This project was supported by funding from the National Natural Science Foundation of China (81971361), the Natural Science Foundation of Shanghai Science and Technology (19ZR1406900), the Shanghai 'Rising Stars of Medical Talent' Youth Development Program (AB83030002019004), the Clinical Research Plan of SHDC (SHDC2020CR4087), the Shanghai Municipal Health Commission (202040498), the Research and Innovation Project of the Shanghai Municipal Education Commission (2019-01-07-00-07-E00050) and the Clinical Research Plan of SHDC (SHDC2020CR1045B). There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

Background: Gastrodin (GAS), is a kind of phenolic compound extracted from the traditional Chinese herbal medicine Gastrodia elata Blume (GEB). This study was aimed at probing into the protective effect of GAS on peripheral nerve injury (PNI) and the underlying mechanism. Methods: A rat model with PNI was established, followed by intraperitoneal injection of GAS (20 mg/kg/day). Sciatic nerve function index (SFI) was used to analyze the function of sciatic nerve. The amplitude and latency of compound muscle action potential (CMAP) were examined by electrophysiology. Schwann cells (SCs) were isolated from fetal rats and treated with GAS 200 μg/mL, and H2O2-induced model of oxidative stress injury was established. EdU and Transwell assays were adopted to detect the viability and migration of SCs. Dual-luciferase reporter gene assays were applied to verify the binding site between miR-497 and brain-derived neurotrophic factor (BDNF) 3'UTR. MiR-497 expression was probed by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF, neurofilament-200 (NF-200) and myelin basic protein (MBP) expression levels were detected by Western blotting. Malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, glutathione content (GSH) and catalase (CAT) activity in SCs were also measured. Results: GAS treatment could significantly increase the SFI and amplitude of CMAP, shorten the refractory period, and ameliorate muscle atrophy of the rats with PNI. GAS treatment could markedly restrain miR-497 expression and increase the expression levels of BDNF, NF-200 and MBP in SCs. BDNF was confirmed as the target of miR-497 and BDNF overexpression could reverse the impacts of miR-497 overexpression on the proliferation, migration, and oxidative stress response of SCs. Conclusions: GAS promotes the recovery of PNI via modulating miR-497 / BDNF axis and inhibiting oxidative stress. [ABSTRACT FROM AUTHOR]

Objective. Nicorandil has been widely used for the treatment of angina pectoris and myocardial infarction. The purpose of this study was to investigate whether nicorandil plays a protective role in exhaustive exercise (EE)-induced myocardial injury. Methods. Here, we applied the rat EE model and treated them with exercise preconditioning (EP, reported to protect the heart) or different doses of nicorandil gavage, respectively, to explore whether there are protective effects of single EP or nicorandil or a combination of both and the potential mechanism. Forty-nine male Sprague Dawley rats were randomly divided into control, EE, EP + EE, nicorandil (with low, middle, and high dose) + EE, and EP + nicorandil (middle dose) + EE. Blood samples and myocardial tissues were collected to analyze the myocardial injury-related index. Results. EE induced myocardial structural damage and altered the myocardial injury markers, which were partially reversed by pretreatment of nicorandil. In addition, oxidative stress and inflammation lead to the accumulation of reactive oxygen species (ROS) products and further damage to the myocardium, while pretreatment of nicorandil reduces the oxidative stress response and inflammation. Moreover, nicorandil suppressed the myocardial apoptosis induced by EE, as indicated by a decrease of Bax and caspase-3 expression and an increase of Bcl-2 expression. Finally, the pathway in which nicorandil plays a role may be involved in the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Pretreatment of nicorandil increased the protein level of myocardial eNOS and NO production. Conclusion. Our result demonstrated that nicorandil has protective effects in EE-induced myocardial injury with dose-dependent effects. A combination of nicorandil and EP can further improve the protective effects. Taken together, nicorandil can be potentially used as an intervention method in EE-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Background: Patrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction. Method: P. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out. Results: The content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities. Conclusion: Patrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

The meridian-collateral theory is the theoretical basis of acupuncture-moxibustion therapy. Professor Bonghan Kim, a professor of the Pyongyang Medical University of the Democratic People's Republic of Korea, claimed that he found the anatomical structure of meridian-collaterals, named Bonghan corpuscles (BHCs) and Bonghan ducts (BHDs) system orprimo vascular system (PVS), in 1962. From 1963 to 1965, researchers from our institute conducted a series of comparative anatomical experiments, trying to reproduce the so-called BHC- and BHD-like structures in different strains of animals. In the present paper, the authors introduced their research findings about BHC- and BHD-like structures in the young rabbit's umbilicus including its external appearance, ectoplasm and endoplasm, and about strip-like and node-like objects in the blood vessels and loymph vessels near the larger abdominal and cervical blood vessels and chromaffin tissue in the back wall of the rabbits abdominal cavity and between the bilateral kidneys. In spite of existence of the BHC- and BHD-like structures in the rabbit, there has been no proved evidence for their association with the meridian-collateral system described in acupuncture medicine. In the present historical review, the authors also make a discussion about the significance of those findings. [ABSTRACT FROM AUTHOR]

Corydalis saxícola Bunting, also named Yanhuanglian in China, is widely used in folk prescriptions to treat hepatitis, hepato- cirrhosis and hepatic cancer. Its active components consists mainly of alkaloids, which have poor solubility in water. The previous study showed that the absolute bioavailabilities (BA) of the alkaloids were only about 10% after oral administration to rats, compared to intravenous administration. In this paper, the solid dispersion (SD) method was used to improve the BAs of dehydro- cavidine (YHL-1), coptisine (YHL-2), and dehydroapocavidine (YHL-3), the main alkaloids of the extract of Corydalis saxícola Bunting, by improving their solubility. The results showed that using PEG 4000 as a carrier at an amount equivalent to 7 folds of the extract could significantly improve the solubility of the compounds in water, pH 1.2 HC1 and pH 7.2 PBS. DSC and X-ray detection indicated that the drug might be in a dissolved or amorphous state in SD, which was different from that in the physical mixture. The formulation was further studied in terms of BA enhancement by cumulative urinary excretion after oral administration to rats. A new method using high performance liquid chromatography (HPLC) coupled to a diode-array detector (DAD) was established. The results showed that the relative BAs (RE BAs) of YHL-1, YHL-2 and YHL-3 were all significantly improved by about 1 fold after oral administration of SD solution, compared to the extract suspension (p < 0.05). [ABSTRACT FROM AUTHOR]

Purpose. To study the therapeutic effect of Quyu (QY) Shengxin (SX) decoction (QYSXD) in mice with dextran sulfate sodium- (DSS-) induced ulcerative colitis and to investigate the effects of QYSXD on the regulation of the receptor-interacting protein kinase 1 (RIP1)/receptor-interacting protein kinase 3 (RIP3)/nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) signaling pathway. Method. Thirty-six mice were randomly divided into the following 6 groups: the experimental group (QYSX group), the model group (DSS group), the positive control group (5-aminosalicylic acid (5-ASA) group), the control group, the first component group (QY group), and the second component group (SX group). Each group included 6 mice. Ulcerative colitis (UC) was induced in the mice by providing 3.5% DSS in drinking water. The mice were weighed every day to evaluate the disease activity index (DAI). After 7 days, the mice were sacrificed, and colonic tissues were obtained for colon length measurement. The morphological changes in the colon and the pathological scores of the mice in each group were observed by hematoxylin-eosin (HE) staining. The messenger ribonucleic acid (mRNA) and protein expression levels of RIP1, RIP3, dynamin-related protein 1 (Drp1), NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), interleukin (IL)-1β, and IL-18 in the colon tissues of the mice in each group were detected and compared by real-time quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The levels of RIP1, RIP3, NLRP3, IL-1β, and IL-8 in the colonic mucosa were detected by ELISA. Western blotting was used to compare the protein expression of Drp1, caspase-1, mitochondrial fission protein 1 (FIS1), and mitophagy-associated protein light chain 3a/b (LC3a/b) among groups. The levels of reactive oxygen species (ROS) in the colonic mucosal cells were compared by immunofluorescence. Results. Compared with those in the DSS group, the mice with DSS-induced colitis in the QYSX group exhibited clearly higher body weights (P < 0.05) and DAI scores (P < 0.05). The colon lengths of the mice in the QYSX group were longer than those in the DSS group (P < 0.05), and the pathological score of the QYSX group was lower than that of the DSS group (P < 0.05). The RIP1, RIP3, Drp1, IL-1β, IL-18, and caspase-1 mRNA levels in the QYSX, 5-ASA, SX, and QY groups were significantly lower than those in the DSS group (P < 0.05), but there were no differences between the QYSX group and the 5-ASA group. The levels of RIP1, RIP3, NLRP3, IL-1β, and IL-18 in the QYSX group were lower than those in the DSS group (P < 0.01). The levels of Drp1, caspase-1, FIS1, and LC3a/b in the QYSX group and the 5-ASA group were lower than those in the DSS group (P < 0.05). The levels of ROS in the colonic mucosal cells in the QYSX, 5-ASA, and QY groups were lower than those in the DSS group (P < 0.05). Conclusion. QYSXD has certain therapeutic effects on DSS-induced colitis in mice and may be as effective as 5-ASA. QY and SX decoctions also have certain effects on colitis; however, these decoctions are not as beneficial as QYSXD. QYSXD may ameliorate colitis by inhibiting the expression of RIP1/RIP3/NLRP3 pathway-related proteins and reversing mitochondrial dysfunction to control inflammation. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is an important inflammatory phenotype in bowel disease (IBD), which is caused by multiple potential factors, including fungal dysbiosis. Candida albicans (C. albicans) was confirmed to be an important factor promoting the occurrence and development of UC. Sanhuang decoction (SHD) has been used for UC therapy in China for thousand of years, although its core active constituents and pharmacological mechanism remain undefined. Methods: In this work, a murine model of UC with C. albicans colonization was established with dextran sodium sulfate (DSS) and C. albicans intragastric administration. The major bioactive constituents and potential mechanism of SHD against UC with fungal dysbiosis were comprehensively examined by combining systems pharmacology and in vivo transcriptomics. Results: SHD attenuated C. albicans burden, reduced DAI, increased mucosal integrity and relived systemic inflammation in UC mice. Systems pharmacology analysis identified 9 core bioactive ingredients and 45 hub targets of SHD against UC. Transcriptomics analysis confirmed 370 differentially expressed genes (DEGs) after SHD treatment, which were mainly enriched in inflammatory and immune response related signaling pathways. Toll-like receptor and PI3K-Akt signaling pathway were screened out as the candidate targets involved in the action of SHD on fungal dysbiosis-associated UC, which were consistent with the findings in systems pharmacology. The expression of TLR4, IL-1β, NF-κB, PI3K and Akt proteins were stimulated by C. albicans, and partially reversed by SHD in UC mice. Conclusion: These findings suggested SHD could be a candidate for the treatment of fungal dysbiosis-associated UC via TLR4-NF-κB and PI3K-Akt signaling pathways. [ABSTRACT FROM AUTHOR]

Study Question: Is it possible to establish a new in-vitro activation (IVA) protocol for infertility treatment?Summary Answer: A new IVA procedure is an efficient and easily performed approach for infertility treatment of patients with diminished ovarian reserve (DOR).What Is Known Already: IVA of primordial follicles with or without stimulators has been developed to treat patients with primary ovarian insufficiency (POI) successfully. However, the efficiency of the procedure is still very low. There is a requirement to optimize the protocol with increased efficiency for clinical application.Study Design, Size, Duration: Newborn mouse ovaries were used to establish a new 1-h IVA protocol with the mechanistic target of rapamycin (mTOR) stimulator phosphatidic acid (PA, 200 µM) and the phosphatidylinositol-3-kinase (PI3K) stimulator 740Y-P (250 µg/ml); a prospective observational cohort study in POI patients was performed on 15 POI patients and 3 poor ovarian response (POR) patients in three different centers of reproductive medicine in China.Participants/materials, Setting, Methods: One-third of ovarian cortex was removed and processed into bigger strips (1 × 1 cm2, 1-2 mm thickness). Strips were then sutured back after treatment. The new approach only requires one laparoscopic surgery.Main Results and the Role Of Chance: Follicular activation and development increased in cultured mouse and human ovarian tissues after 1 h of stimulator treatment. Compared with tiny ovarian cortex pieces (1 × 1 mm2), large ovarian strips (1 × 1 cm2) showed the lowest apoptotic signals after incubation. We applied the orthotropic transplantation procedure with large strips in the clinic, and 9 of 15 POI patients showed at least one-wave follicular growth during the monitoring period. One patient was reported with one healthy delivery after natural conception and another patient with a healthy singleton delivery after IVF. All the contacted patients (n = 13) responded with no side effects on their health 2-4 years after IVA procedure.Limitations, Reasons For Caution: Further clinical trials with a large number of well-defined patients are required to compare different IVA protocols. A long-term follow-up system should be set up to monitor patient's health in the future cohort study.Wider Implications Of the Findings: By using stimulators, the findings in the study provide a more efficient IVA protocol for the treatment of patients with DOR. It requires only one laparoscopic surgery and thus minimizes patients' discomfort and costs. This strategy could be useful for patients diagnosed with POI and desire pregnancy as soon as possible after the operation.Study Funding/competing Interest(s): This work was supported by the National Key Research and Development Program of China (2018YFC1003703 and 2018YFC1004203); the National Natural Science Foundation of China (81871221); Co-construction of Provincial Department (201601006). The authors have no conflict of interest to disclose.Trial Registration Number: ChiCTR2000030872. [ABSTRACT FROM AUTHOR]

Background: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. Methods: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. Results: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. Conclusions: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis. [ABSTRACT FROM AUTHOR]