Natural products as the therapeutic strategies for addiction.

World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction.

Efficacy and safety of precision-guided transjugular extrahepatic portosystemic shunt (TEPS) in the management of cavernous transformation of the portal vein with portal hypertension: a case series.

BACKGROUND AND AIMS: Performing a Transjugular intrahepatic portal system shunt (TIPS) in patients with portal vein cavernous transformation (CTPV) poses significant challenges. As an alternative, transjugular extrahepatic portal vein shunt (TEPS) may offer a potential solution for these patients. Nonetheless, the effectiveness and safety of TEPS remain uncertain. This case series study aimed to evaluate the efficacy and safety of TEPS in treating patients with CTPV portal hypertension complications. METHODS: The study encompassed a cohort of 22 patients diagnosed with CTPV who underwent TEPS procedures. Of these, 13 patients manifested recurrent hemorrhagic episodes subsequent to conventional therapies, 8 patients grappled with recurrent or refractory ascites, and 1 patient experienced acute bleeding but refused endoscopic treatment. Comprehensive postoperative monitoring was conducted for all patients to rigorously evaluate both the technical and clinical efficacy of the intervention, as well as long-term outcomes. RESULTS: The overall procedural success rate among the 22 patients was 95.5% (21/22).During the TEPS procedure, nine patients were guided by percutaneous splenic access, three patients were guided by percutaneous hepatic access, five patients were guided by transmesenteric vein access from the abdomen, and two patients were guided by catheter marking from the hepatic artery. Additionally, guidance for three patients was facilitated by pre-existing TIPS stents. The postoperative portal pressure gradient following TEPS demonstrated a statistically significant decrease compared to preoperative values (24.95 ± 3.19 mmHg vs. 11.48 ± 1.74 mmHg, p < 0.01).Although three patients encountered perioperative complications, their conditions ameliorated following symptomatic treatment, and no procedure-related fatalities occurred. During a median follow-up period of 14 months, spanning a range of 5 to 39 months, we observed four fatalities. Specifically, one death was attributed to hepatocellular carcinoma, while the remaining three were ascribed to chronic liver failure. During the follow-up period, no instances of shunt dysfunction were observed. CONCLUSIONS: Precision-guided TEPS appears to be a safe and efficacious intervention for the management of CTPV.

CircRNA: a rising therapeutic strategy for lung injury induced by pulmonary toxicants.

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Skeletal muscle abnormalities, such as muscle mass depletion (sarcopenia) and fatty infiltration of the muscle (myosteatosis), are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt (TIPS). AIM: To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy (HE) and mortality after TIPS. METHODS: The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved. The transversal psoas muscle thickness (TPMT) and psoas muscle attenuation (PMA) measured from the unenhanced abdominal computed tomography (CT) at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis, respectively. The area under curve (AUC) was used to evaluate the discriminative power of TPMT, PMA, and relevant clinical parameters. Fur-thermore, log-rank test was performed to compare the incidence of overt HE and survival between the different groups, and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models. RESULTS: A total of 108 patients were collected. Among these patients, 45.4% of patients developed overt HE after TIPS treatment. Furthermore, 32.4% and 28.7% of these patients were identified to have myosteatosis and sarcopenia, respectively. Myosteatosis (51.0% vs 16.9%, P < 0.001) and sarcopenia (40.8 vs 18.6%, P = 0.011) were found to be more frequent in patients with overt HE, when compared to patients without overt HE. The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE (AUC = 0.713 and 0.778, respectively) was higher when compared to the neutrophil lymphocyte ratio (AUC = 0.636). The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis, followed by patients with myosteatosis or sarcopenia, while this was the lowest in patients without sarcopenia and myosteatosis. In addition, sarcopenia and myosteatosis were inde-pendently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients. CONCLUSION: CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

Predicting Outcome in Combination Treatment of TACE and Camrelizumab for Advanced Hepatocellular carcinoma: Tumor Hypervascularity and Reactive Cutaneous Capillary Endothelial Proliferation.

Objective: To validate the robust predictive values of tumor vascularity and reactive cutaneous capillary endothelial proliferation (RCCEP) in combination treatment of transarterial chemoembolization (TACE) and camrelizumab for patients with advanced hepatocellular carcinoma (HCC) and then select the potential candidates who would survive best from such treatment. Methods: The clinical data of 113 patients with advanced HCC treated with TACE and camrelizumab from January 2019 to December 2021 were analyzed retrospectively. Mann Whitney U-test was used to evaluate the correlation between vascular distribution and RCCEP and tumor response; Kaplan Meier technique was used to evaluate time to progress (TTP) and overall survival (OS), and log rank test was used for comparison; multivariate Cox regression analysis was used to evaluate the related influencing factors. Results: The TTP and OS of TACE combined with carrelizumab in patients with advanced HCC were 7.1 and 14.3 months. Hypervascularity and development of RCCEP were good predictors of TTP (HR 2.561, P < 0.001; HR 1.486, P = 0.032) and OS (HR 2.854, P < 0.001; HR 1.634, P = 0.011). The median TTP and OS of patients with hypervascularity and RCCEP were 10.6 and 19.3 months, which were better than those with only hypervascularity (6.8 months, P = 0.016; 11.6 months, P = 0.003) and only RCCEP (6.2 months, P = 0.039; 13.5 months, P = 0.042), as well as those with neither (3.8 months, P < 0.001; 7.4 months, P < 0.001). Conclusion: Tumor hypervascularity and development of RCCEP were favorable predictive factors for the combination treatment of TACE and carrelizumab, with both of which the patients survived longest and might be the potential candidates.

A Case Report and Literature Review of Oligomeganephronia.

A 23-year-old woman was admitted to the hospital with proteinuria and mildly elevated creatinine, and a renal biopsy confirmed the diagnosis of oligomeganephronia (OMN). OMN is an extremely rare bilateral renal hypoplastic disease, and its diagnosis mainly relies on the pathological results obtained from renal biopsy. At present, there is no effective treatment for OMN. Here, we report a case with mild renal insufficiency and proteinuria as the main symptom and present a summary of the clinical characteristics of ON along with a review of the literature on OMN.

Novel roles of lipopolysaccharide and TLR4/NF-κB signaling pathway in inflammatory response to liver injury in Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. To date, the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown. AIM: To assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats. METHODS: A total of 180 rats were randomly assigned into nine groups, including four BCS model groups (1, 3, 6 and 12 wk), four sham-operated groups (1, 3, 6 and 12 wk), and a control group. Lipopolysaccharide (LPS) levels in each group were detected by the Tachypleus Amebocyte Lysate assay. The mRNA and protein levels of TLR4, NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-2 and interferon (IFN)-γ were quantified. In addition, 60 patients with BCS and 30 healthy controls were enrolled, and their blood samples were analyzed. RESULTS: Hepatic and plasma LPS levels were significantly increased in rats. The mRNA and protein expression levels of TLR4, NF-κB and inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in liver tissues were significantly higher in the BCS model groups compared with the other two groups. In addition, the model groups (1, 3, 6 and 12 wk after BCS induction) showed significant differences in the levels of LPS, TLR4, NF-κB, TNF-α, IL-2 and IFN-γ. Notably, there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4, NF-κB and inflammatory cytokines. Importantly, it was revealed that the levels of LPS, TLR4, NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients. CONCLUSION: LPS level is markedly elevated in BCS, in turn activating the TLR4/NF-κB signaling pathway, leading to induction of inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in response to BCS-induced liver injury.

Membranous Nephropathy Complicated with Disseminated Nocardia farcinica Infection: A Case Report and Literature Review.

Disseminated infection caused by Nocardia farcinica with primary nephrotic syndrome is exceedingly rare. A 66-year-old female visited the outpatient department due to fever and fatigue who had been diagnosed as membranous nephropathy and with a long-term prednisone and immunosuppressive therapy. After lung biopsy for many times, culture from space-occupying lesion of the right lung and species identification by mass spectrometry-based methods (MALDI-TOF) revealed Nocardia farcinica. By imaging examination, space-occupying lesions from the lungs, brain, abdominal cavity and kidney were found. After 2 weeks of meropenem intravenous and up to 6 months of trimethoprim-sulfamethoxazole (TMP-SMX) therapy, our patient has remained relapse-free at that time of writing. Disseminated infection caused by Nocardia farcinica is usually subacute with complex clinical manifestations. In addition, it can be easily confused with diseases such as tumor and mycobacterial infection, and lead to fatal consequences. Therefore, we hope that we can remind clinicians considering by discussing common features of disseminated Nocardia farcinica infection.

A role of peptidoglycan recognition protein in mediating insecticide detoxification in Glyphodes pyloalis.

Glyphodes pyloalis Walker has become one of the most significant mulberry pests, and it has caused serious economic losses in major mulberry growing regions in China. Peptidoglycan recognition proteins (PGRPs) are responsible for initiating and regulating immune signalling pathways in insects. However, their roles responding to chemical pesticides is still less known. This study aimed to investigate the possible detoxication function of GpPGRP-S2 and GpPGRP-S3 in G. pyloalis in response to chlorfenapyr and phoxim. The chlorfenapyr and phoxim treatment significantly induced the expression level of GpPGRP-S3 at 48 h. In addition, the expression levels of GpPGRP-S2 and GpPGRP-S3 in the chlorfenapyr/phoxim treatment group were significantly higher in midgut than those in the control group at 48 h. The results of the survival experiment showed that silencing either GpPGRP-S2 or GpPGRP-S3 would not influence the survival rate of G. pyloalis which treated with phoxim, however, silencing GpPGRP-S2 or GpPGRP-S3 would cause G. pyloalis to be more easily killed by chlorfenapyr. The expression of carboxylesterase GpCXE1 was significantly induced by chlorfenapyr/phoxim treatment, while it was suppressed once silenced GpPGRP-S2 followed with chlorfenapyr treatment or silenced GpPGRP-S3 followed with phoxim treatment. These results might suggest that under the chlorfenapyr/phoxim treatment condition, the connection between GpPGRPs and detoxification genes in insect was induced to maintain physiological homeostasis; and these results may further enrich the mechanisms of insects challenged by insecticides.

mSphere of Influence: Surface Sensing in Biofilm Formation.

Kara B. De Leόn works in the field of microbial ecology, environmental biofilms, and microbial genetics. In this mSphere of Influence article, she reflects on how the paper "Multigenerational memory and adaptive adhesion in early bacterial biofilm communities" by C. K. Lee et al. (C. K. Lee, J. de Anda, A. E. Baker, R. R. Bennett, et al., Proc Natl Acad Sci U S A 115:4471-4476, 2018, https://dx.doi.org/10.1073/pnas.1720071115) made an impact on her by changing the way she thinks about initial cell attachment to a surface in an environment.

Characterization and Functional Analysis of trehalase Related to Chitin Metabolism in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae).

Glyphodes pyloalis Walker (G. pyloalis) is a serious pest on mulberry. Due to the increasing pesticide resistance, the development of new and effective environmental methods to control G. pyloalis is needed. Trehalase is an essential enzyme in trehalose hydrolysis and energy supply, and it has been considered a promising target for insect pest control. However, the specific function of trehalase in G. pyloalis has not been reported. In this study, two trehalase genes (GpTre1 and GpTre2) were identified from our previous transcriptome database. The functions of the trehalase in chitin metabolism were studied by injecting larvae with dsRNAs and trehalase inhibitor, Validamycin A. The open reading frames (ORFs) of GpTre1 and GpTre2 were 1,704 bp and 1,869 bp, which encoded 567 and 622 amino acid residues, respectively. Both of GpTre1 and GpTre2 were mainly expressed in the head and midgut. The highest expression levels of them were in 5th instar during different development stages. Moreover, knockdown both of GpTre1 and GpTre2 by the dsRNAs led to significantly decreased expression of chitin metabolism pathway-related genes, including GpCHSA, GpCDA1, GpCDA2, GpCHT3a, GpCHT7, GpCHSB, GpCHT-h, GpCHT3b, GpPAGM, and GpUAP, and abnormal phenotypes. Furthermore, the trehalase inhibitor, Validamycin A, treatment increased the expressions of GpTre1 and GpTre2, increased content of trehalose, and decreased the levels of glycogen and glucose. Additionally, the inhibitor caused a significantly increased cumulative mortality of G. pyloalis larvae on the 2nd (16%) to 6th (41.3%) day, and decreased the rate of cumulative pupation (72.3%) compared with the control group (95.6%). After the activities of trehalase were suppressed, the expressions of 6 integument chitin metabolism-related genes decreased significantly at 24 h and increased at 48 h. The expressions of GpCHSB and GpCHT-h, involved in chitin metabolism pathway of peritrophic membrane in the midgut, increased at 24 h and 48 h, and there were no changes to GpCHT3b and GpPAGM. These results reveal that GpTre1 and GpTre2 play an essential role in the growth of G. pyloalis by affecting chitin metabolism, and this provides useful information for insect pest control in the future.

OFF-transient alpha RGCs mediate looming triggered innate defensive response.

Animals respond to visual threats, such as a looming object, with innate defensive behaviors. Here, we report that a specific type of retinal ganglion cell (RGC), the OFF-transient alpha RGC, is critical for the detection of looming objects. We identified Kcnip2 as its molecular marker. The activity of the Kcnip2-expressing RGCs encodes the size of the looming object. Ablation or suppression of these RGCs abolished or severely impaired the escape and freezing behaviors of mice in response to a looming object, while activation of their somas in the retina, or their axon terminals in the superior colliculus, triggered immediate escape behavior. Our results link the activity of a single type of RGC to visually triggered innate defensive behaviors and underscore that ethologically significant visual information is encoded by a labeled line strategy as early as in the retina.

Endophytic bacteria promote the quality of Lyophyllum decastes by improving non-volatile taste components of mycelia.

Endophytic bacteria are always related to the host different traits, including the secondary metabolites production. However, the effect and mechanism of endophytic bacteria in the mushrooms fruit body on mycelia are still not clear. In this study, we investigated the effect of endophytic bacterial metabolites on the quality of Lyophyllum decastes mycelia. Soluble sugars, starch, protein, free amino acids, 5'-Nucleotides, EUC, and organic acids contents of mycelia were analyzed. We found that endophytic bacterial metabolites significantly increased the contents of soluble sugars, starch, protein, free amino acids, organic acids, and EUC. The present study thus suggests that endophytic bacteria could promote the quality of Lyophyllum decastes by improving non-volatile taste components of mycelia.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PURPOSE: Transcatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC. METHODS: The clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups. RESULTS: One month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05). CONCLUSION: Compared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid-related hepatic sinusoidal obstruction syndrome.

BACKGROUND: Treatments for hepatic sinusoidal obstruction syndrome (HSOS) are limited. AIM: To evaluate transjugular intrahepatic portosystemic shunting (TIPS) as a treatment for pyrrolidine alkaloid-related HSOS (PA-HSOS). METHODS: This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China (June 2015 to January 2019). Baseline clinical characteristics and follow-up data were extracted from the medical records. All patients included in this study experienced failure of initial therapy. Patients were divided into the TIPS and conservative treatment groups according to the therapy they received. Liver function, maximal ascites depth, imaging characteristics, pathology findings, and survival were compared between groups. RESULTS: The TIPS group included 37 patients (28 males), and the conservative treatment group included 17 patients (11 males). Baseline characteristics were similar between groups. There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up (3-48 mo). The 3-, 6-, 12- and 24-mo survival rates were 94.6%, 94.6%, 94.6% and 94.6%, respectively, in the TIPS group and 70.6%, 57.8%, 57.8% and 57.8%, respectively, in the conservative treatment group. Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group (P = 0.001). Compared with the pre-treatment value, maximal ascites depth was significantly lower at 1 wk, 2 wk, 1 mo, and 3 mo for the TIPS group (all P < 0.05) but not in the conservative treatment group. Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS. Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement. CONCLUSION: TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.

Identifications, Characteristics, and Expression Patterns of Small Heat Shock Protein Genes in a Major Mulberry Pest, Glyphodes pyloalis (Lepidoptera: Pyralidae).

Six candidate sHSP genes were identified from the Glyphodes pyloalis transcriptome. All sHSP genes included full-length open reading frames and shared high similarity with the sequences of other lepidopteran species. These sHSP genes encoded 175-191 amino acid residues, and the predicted proteins had a molecular weight from 19.5 to 21.8 kDa. All GpsHSPs were expressed at lower levels at larval stages. All GpsHSPs were expressed at higher levels at diapaused, prepupal, or pupal stages, suggesting that sHSPs may be involved in metamorphosis in G. pyloalis. In addition to the developmental stage, extreme temperatures can induce variations in the expression of sHSPs genes. All GpsHSPs were significantly upregulated in larvae following exposure to heat shock, except GpHSP21.4 which downregulated at 4 h following exposure to the cold shock treatment. Furthermore, Starvation influenced the expression patterns of GpsHSPs as a function of the duration of food deprivation. Four GpsHSPs increased their expression with time of starvation until reaching to the peak level at 6 d of starvation. Finally, parasitism by the endoparasitoid Aulacocentrum confusum He et van Achterberg (Hymenoptera: Braconidae)-induced fluctuations in the expression of all GpsHSPs, and the expression varied with time after parasitization. Our results from this study strongly suggest functional differentiation within the sHSPs subfamily in G. pyloalis. The present study would provide further insight into the roles of sHSPs in G. pyloalis and novel avenues for promoting integrated management of this pest.

Stewartiacids A-N, C-23 carboxylated triterpenoids from Chinese Stewartia and their inhibitory effects against ATP-citrate lyase and NF-κB.

Fourteen previously undescribed naturally occurring C-23 carboxylated triterpenoids, stewartiacids A-N (1-14), were isolated and characterized from the twigs and leaves of the ornamental and medicinal plant Stewartia sinensis (Chinese Stewartia), a 'vulnerable' species endemic to China. The new structures were elucidated on the basis of spectroscopic data, single crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. Stewartiacids A (1) and B (2) are isoursenol derivatives. Stewartiacid C (3) is a 12-oxo-γ-amyrin analogue. Both isoursenol and γ-amyrin derivatives are quite rare in nature. Stewartiacids D (4) and E (5) are 13,27-cycloursane-type compounds. Stewartiacids K (11) and L (12) are ursane-type triterpene and phenylpropanol adducts built through a 1,4-dioxane ring, which are also seldom reported in the literature. The rest are common C-23 carboxylated ursane-type (6-10) and oleanane-type (13, 14) pentacyclic triterpenoids. Stewartiacids G (7), K (11), and L (12) showed moderate inhibitory effects against ATP-citrate lyase (ACL), with IC50 values of 12.5, 2.8, and 10.6 µM, respectively. Stewartiacid K (11) also exhibited moderate inhibition (IC50: 16.8 µM) of NF-κB.

FLT3/FLT3L-mediated CD103+ dendritic cells alleviates hepatic ischemia-reperfusion injury in mice via activation of treg cells.

BACKGROUND: This study was conducted to investigate the protective effect of Fms-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L)-dependent CD103+ dendritic cells (DCs) on hepatic ischemia-reperfusion injury (IRI). METHODS: A mouse model of hepatic IRI and cellular model following hypoxia-reperfusion (H/R) treatment were established. Peripheral blood and liver tissues were obtained and analyzed by flow cytometer in terms of percentage of CD103+DCs and regulatory T (Treg) cells. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined to assess liver function. Moreover, pro-inflammatory cytokines levels including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The histological morphology of liver tissues was examined with hematoxylin and eosin (HE) staining. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay. Treg-associated cytokines transforming growth factor (TGF)-ß and IL-10 expressions were measured using quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CD103+ DCs were significantly decreased in peripheral blood and liver tissues of mouse model of hepatic IRI. In vivo experiments indicated that CD103+ DCs infusion ameliorated IRI-induced liver damage and Treg inhibition. Further investigations demonstrated that FLT3/FLT3L-dependent CD103+ DCs suppressed hepatocyte apoptosis via activation of Treg cells in vitro. CONCLUSION: FLT3/FLT3L-induced CD103+ DCs alleviated hepatic IRI through activating Treg cells.

Identification of differentially expressed genes in hip cartilage with femoral head necrosis, based on genome­wide expression profiles.

Necrosis of the femoral head (NFH), a severe orthopedic disease in adults, involves the collapse of the femoral head. The pathophysiological mechanisms underlying NFH are yet to be fully investigated. The aim of the present study was to identify potentially important genes and signaling pathways involved in NFH and investigate their molecular mechanisms. Gene expression profiles of patients with NFH and healthy controls were compared using the Gene Expression Omnibus (GEO) database repository of the National Center of Biotechnology Information. GSE74089 from the GEO database included 4 patients with NFH and 4 healthy individuals. A total of 1,191 differentially expressed genes (DEGs) were identified between the patients with NFH and controls, including 743 upregulated and 448 downregulated DEGs. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that upregulated DEGs were mainly involved in the phosphoinositide 3­kinase/protein kinase B signaling pathway, focal adhesion and extracellular matrix­receptor interactions. Additionally, protein­protein interaction (PPI) analysis identified the most central DEGs as vascular endothelial growth factor A, Jun proto­oncogene, cyclin D1, fibroblast growth factor 2, HECT domain and ankyrin repeat­containing E3 ubiquitin protein ligase 1, protein kinase Cα, bone morphogenetic protein 2 and prostaglandin­endoperoxide synthase 2. PPI analysis also identified guanine nucleotide­binding protein, γ13 as the most commonly downregulated gene based on different centrality. The results of the present study may provide novel insight into the genes and associated pathways involved in NFH, and aid the identification of novel therapeutic targets and biomarkers in the treatment of NFH.