Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Design and Synthesis of C4-Symmetric Axially Chiral ß-Aryl Porphyrins and Application for Supporting Ir(III)-Catalyzed Enantioselective C-H Alkylation.

A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.

Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy.

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.

METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients.

Background: N6-methyladenosine (m6A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6A's effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods: We analyzed the m6A enzymes and m6A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m6A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results: Methyltransferase-like 3 (METTL3), an m6A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m6A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion: The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients.

Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.

Inhibiting the MAPK pathway improves heart failure with preserved ejection fraction induced by salt-sensitive hypertension.

Heart failure (HF) preserved ejection fraction (HFpEF) accounts for almost 50% of HF, and hypertension is one of the pathogenies. The MAPK signaling pathway is closely linked to heart failure and hypertension; however, its function in HEpEF resulting from salt-sensitive hypertension is not well understood. In this work, a salt-sensitive hypertension-induced HEpEF model was established based on deoxycorticosterone acetate-salt (DOCA-salt) hypertension mice. The impact of the MAPK inhibitor (Doramapimod) on HEpEF induced by salt-sensitive hypertension was assessed through various measures, such as blood pressure, transthoracic echocardiography, running distance, and histological analysis, to determine its therapeutic effectiveness on cardiac function. In addition, the effects of high salt on myogenic cells were also evaluated in vitro using qRTPCR. The LV ejection fractions (LVEF) in DOCA-salt hypertension mice were over 50%, indicating that the salt-sensitive hypertension-induced HFpEF model was successful. RNA-seq revealed that the MAPK signaling pathway was upregulated in the HFpEF model compared with the normal mice, accompanied by hypertension, impaired running distance, restricted cardiac function, increased cross-sectional and fibrosis area, and upregulation of heart failure biomarkers, including GAL-3, LDHA and BNP. The application of Doramapimod could improve blood pressure, cardiomyocyte hypertrophy, and myocardial fibrosis, as well as decrease the aforementioned heart failure biomarkers. The qRTPCR results showed similar findings to these observations. Our findings suggest that the use of a MAPK inhibitor (Doramapimod) could be a potential treatment for salt-sensitive hypertension-induced HFpEF.

Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.

Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis.

AIM: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. METHODS: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. RESULTS: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. CONCLUSIONS: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.

Association of serum Asprosin concentrations with heart failure.

BACKGROUND: To analyze the association of serum Asprosin concentrations with heart failure (HF). METHODS: A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis. RESULTS: Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003-1.018; OR = 1.058, 95% CI:1.004-1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis. CONCLUSIONS: Serum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.

Internet use and depressive symptoms among Chinese older adults: Two sides of internet use.

Objective: To explore the relationship between internet use which includes time spent on the internet, internet skills, types of online activities, and depressive symptoms in older adults. Methods: We used 2020 China Family Panel Studies (CFPS) data with 3,171 older adults aged 60 years. Depression symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D), and internet use was measured by time spent on the internet, internet skills, and types of online activities. Multiple linear regression models were used to explore the relationship between internet use and depressive symptoms in older adults. Results: Longer time spent on the internet was associated with higher scores of depressive symptoms (ß = 0.14). Higher internet skills were associated with lower scores of depressive symptoms (ß = -0.42). Watching short-form videos (ß = 1.34) was associated with higher depressive symptom scores, and the use of the WeChat function (ß = -0.96) was associated with lower depressive symptom scores, while online games and online shopping were not significant. Conclusion: The effect of internet use on depressive symptoms in older adults is a double-edged sword. Controlling the time spent on the internet, improving internet skills, and guiding specific a type of online activities in older adults can improve depressive symptoms through rational use.

Lactobacillus plantarum-Derived Postbiotics Ameliorate Acute Alcohol-Induced Liver Injury by Protecting Cells from Oxidative Damage, Improving Lipid Metabolism, and Regulating Intestinal Microbiota.

Here, the aim was to evaluate the protective effect of Lactobacillus plantarum-derived postbiotics, i.e., LP-cs, on acute alcoholic liver injury (ALI). After preincubation with LP-cs, HL7702 human hepatocytes were treated with alcohol, and then the cell survival rate was measured. C57BL/6 male mice were presupplemented with or without LP-cs and LP-cs-loaded calcium alginate hydrogel (LP-cs-Gel) for 3 weeks and given 50% alcohol gavage to establish the mouse model of ALI, LP-cs presupplementation, and LP-cs-Gel presupplementation. The histomorphology of the liver and intestines; the levels of serum AST, ALT, lipid, and SOD activity; liver transcriptomics; and the metagenome of intestinal microbiota were detected in all mouse models. In vitro, LP-cs significantly increased the survival rate of alcohol-treated cells. In vivo, presupplementation with LP-cs and LP-cs-Gel restored the levels of serum AST, ALT, and SOD activity, as well as TC and TG, after acute alcohol intake. In the LP-cs-presupplemented mice, the genes involved in fatty acid metabolic processes were upregulated and the genes involved in steroid biosynthesis were downregulated significantly as compared with the ALI mice. LP-cs significantly increased the abundance of intestinal microbiota, especially Akkermansia muciniphila. In conclusion, LP-cs ameliorates ALI by protecting hepatocytes against oxidative damage, thereby, improving lipid metabolism and regulating the intestinal microbiota. The effect of LP-cs-Gel is similar to that of LP-cs.

Geraniol prevents Helicobacterium pylori-induced human gastric cancer signalling by enhancing peroxiredoxin-1 expression in GES-1 cells.

Helicobacter pylori (H. pylori), a gram-negative bacterial microbiological carcinogen, has been identified as the leading jeopardy feature for developing human gastric cancer (GC). As a result, inhibiting H. pylori growth has been identified as an effective and critical technique for preventing GC development. In this study, geraniol inhibits H. pylori-induced gastric carcinogen signalling in human gastric epithelial cells (GES-1). Geraniol prevents cytotoxicity, ROS and apoptosis in H. pylori-induced GES-1 cells. Furthermore, geraniol protects against H. -induced antioxidant depletion caused by malondialdehyde, damage of reactive DNA and nuclear fragmentation. Geraniol significantly reduced the expression of phosphorylated mitogen activated protein kinases (MAPKs) proteins such as p38 MAPK, extracellular signal-regulated kinase-1 (ERK1), c-Jun N-terminal kinase (c-JNK), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in GES-1 infected with H. pylori. Furthermore, geraniol increased the antioxidant protein peroxiredoxin-1 (Prdx-1) in H. pylori-infected cells. Geraniol thus protects H. pylori-concomitant infection, and its resistance may be a possible method in preventing gastric cancer caused by H. pylori.

Correlation of patients' demographics and clinical symptoms with temporomandibular disorders.

OBJECTIVE: To investigate the correlation between basic characteristics and clinical features of patients with temporomandibular disorders (TMD). METHODS: The R language statistical tool was used to analyze the clinical information of 500 TMD patients, i.e., age, sex, joint noises, mouth opening pattern, and pain symptoms, as well as the results of the mandibular push-back test. A pairwise correlation analysis of each clinical feature was carried out. RESULTS: The highest incidence of TMD was observed in the age group of 20 to 30 years (240/500). Around 2/3 of the patients showed pain symptoms. Abnormal mouth opening patterns, joint noises, and temporomandibular joint synovitis (TMJS) were observed in 48.4, 65.4, and 34% of patients, respectively. CONCLUSION: Joint click and the corrected deviation of the mouth opening pattern are signs of early-stage TMD, whereas limited mouth opening and TMJS are indicators of progressive stage and complicated TMD.

Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive-Like Disorders by Promoting ATP Production.

Major depressive disorder (MDD) is a leading cause of disability worldwide. A comprehensive understanding of the molecular mechanisms of this disorder is critical for the therapy of MDD. In this study, it is observed that deubiquitinase Mysm1 is induced in the brain tissues from patients with major depression and from mice with depressive behaviors. The genetic silencing of astrocytic Mysm1 induced an antidepressant-like effect and alleviated the osteoporosis of depressive mice. Furthermore, it is found that Mysm1 knockdown led to increased ATP production and the activation of p53 and AMP-activated protein kinase (AMPK). Pifithrin α (PFT α) and Compound C, antagonists of p53 and AMPK, respectively, repressed ATP production and reversed the antidepressant effect of Mysm1 knockdown. Moreover, the pharmacological inhibition of astrocytic Mysm1 by aspirin relieved depressive-like behaviors in mice. The study reveals, for the first time, the important function of Mysm1 in the brain, highlighting astrocytic Mysm1 as a potential risk factor for depression and as a valuable target for drug discovery to treat depression.

Role of 5-HT2A Receptor in Modulating Glutamatergic Activity in the Ventrolateral Orbital Cortex: Implication in Trigeminal Neuralgia.

5-HT2A receptors (5-HT2ARs) are widely expressed in the central nervous system, including in the ventrolateral orbital cortex (VLO). The VLO is an important cortical component for pain processing. Brain 5-HT2ARs are implicated in both pro- and anti- nociceptive functions. However, the roles of 5-HT2ARs in the VLO in trigeminal neuralgia and neuronal synaptic function remain to be understood. We used chronic constriction injury of infraorbital nerve (IoN-CCI) model and shRNA mediated gene knockdown in mice to investigate the role of 5-HT2ARs in the VLO in trigeminal neuralgia. We found that knockdown of 5-HT2ARs in the VLO aggravated spontaneous pain and mechanical allodynia in mice after IoN-CCI. At the synaptic level, decreasing 5-HT2AR expression by shRNA or inhibition of 5-HT2AR activity by its antagonist ketanserin decreased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of the neurons in the VLO, whereas 5-HT2AR partial agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) enhanced sEPSCs of the neurons in the VLO. In summary, 5-HT2ARs in the VLO modulate the trigeminal pain by regulating neuronal glutamatergic activity.

Effects of mir-195 Targeted Regulation of JAK2 on Proliferation, Invasion, and Apoptosis of Gastric Cancer Cells.

Background: Overexpression of miR-195 can make gastric cancer cells stay in G1/G2 phase. miR-195 has been shown to inhibit gastric cancer cell replication and accelerate cell death by targeting JAK2. However, the relationship between miR-195, JAK2, and gastric cancer is not clear. Objective: To observe the effect of mir-195 regulated by JAK2 on the growth, invasion, and death of gastric cancer cells. Methods: MGC803 and NCI gastric N87 cells were introduced into the negative control sequences of miR-195 and RNA, respectively. To detect the expression of miR-195 in cells, to detect the effect of miR-195 on mitosis and proliferation of tumor cells, to analyze the effect of miR-195 on cell invasion and metastasis, and to detect the regulation of miR-195 on JAK2 expression. Results: The level of miR-195 in miR-195-MIMICS group was significantly higher than that in miR-NC group. The cell survival rate of miR-195 mimic group was lower than that of miR-NC group (P < 0.05). Compared with miR-NC group, the number of cells in G1 phase increased, the cells in G2 phase and S phase decreased, and the proportion of cells in G2 and S phase decreased in miR-195 mimic group. The scratch distance of miR-195 simulator group was larger than that of control group. The number of invasive cells in the miR-195 mimic group was significantly lower than that in the control group. The expression of JAK2 protein in miR-195 mimic group was lower than that in miR-NC group. There was a significant negative correlation between the expression level of miR-195 and JAK2 (rhabdomile 0.326 and record 0.00). There are continuous interaction fragments between JAK2 and miR-195. The luciferase activity of miR-195 mimic and wild type JAK2 sequence expression vector was significantly lower than that of wild type JAK2 sequence expression vector. Conclusion: miR-195 may inhibit the occurrence, metastasis, and invasion of gastric tumor by downregulating the expression of JAK2. miR-195/JAK2 may be a new molecular target for the treatment of gastrointestinal tumors.

Temporomandibular joint synovial chondromatosis: An analysis of 7 cases and literature review.

OBJECTIVE: To investigate the diagnosis and treatment procedure of synovial chondromatosis (SC) of the temporomandibular joint (TMJ). METHODS: Clinical features, imaging features, surgical methods, and prognosis of 7 patients with SC of the TMJ were analyzed. We also reviewed and analyzed surgery-relevant literature included in the Pubmed database in the past decade using the search terms "synovial chondromatosis" and "temporomandibular joint", and found 181 cases. RESULTS: There was no specific difference in the symptoms of SC in the TMJ in different Milgram's stages in our cases and the cases mentioned in the literature. The main symptoms of SC in the TMJ were pain (100%, 7/7; 64.64%, 117/181), limited mouth opening (57.14%, 4/7; 53.59%, 97/181), swelling (14.29%, 1/7; 28.18%, 51/181), crepitus (28.57%, 2/7; 19.34%, 35/181), and clicking (14.29%, 1/7; 9.94%, 18/181) in our cases and cases from literature separately. The imaging features of SC were occupying lesions (including loose bodies or masses) (71.42%, 5/7; 37.57%, 68/181), bone change in condyle or glenoid fossa (1/7, 14.29%; 34.81%, 63/181), effusion (42.86%, 3/7; 20.99%, 38/181), joint space changes (42.86%, 3/7; 11.05%, 20/181) in our cases and cases from literature separately. The surgical procedures seem to depend mainly on the involved structures and the extension of the lesion rather than the Milgram's stage. CONCLUSIONS: The clinical features of SC in the TMJ are nonspecific and easy to be misdiagnosed. MRI is helpful in the diagnosis of SC in the TMJ. The surgical procedures mainly depend on the involved structures and the extension of the lesion.

Ectoderm-derived frontal bone mesenchymal stem cells promote traumatic brain injury recovery by alleviating neuroinflammation and glutamate excitotoxicity partially via FGF1.

BACKGROUND: Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. METHODS: A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs. RESULTS: Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2ß. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. CONCLUSIONS: Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.

Computed Tomography Images of Spontaneous Portosystemic Shunt in Liver Cirrhosis.

Spontaneous portosystemic shunt (SPSS) refers to collateral vessels that communicate between the portal vein system and systemic circulation. SPSS mainly includes esophageal varices, gastric varices, left gastric vein, recanalized paraumbilical vein, abdominal wall varices, and spontaneous splenorenal shunt. SPSS contributes to the development of hepatic encephalopathy caused by portal vein inflow bypassing and carries a higher risk of death in liver cirrhosis. Abdominal contrast-enhanced computed tomography is a major imaging approach to establish a diagnosis of SPSS and evaluate its location and feature. This review primarily describes the main contrast-enhanced CT features of SPSS in liver cirrhosis.

Practice guidance for the use of terlipressin for liver cirrhosis-related complications.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.