Distributed Cubature Information Filtering Method for State Estimation in Bearing-Only Sensor Network.

The problem of state estimation based on bearing-only sensors is increasingly important while existing research on distributed filtering solutions is rather limited. Therefore, this paper proposed the novel distributed cubature information filtering (DCIF) method for addressing the state estimation challenge in bearing-only sensor networks. Firstly, the system model of the bearing-only sensor network was constructed, and the observability of the system was analyzed. The sensor nodes are paired to measure relative angle information. Subsequently, the coordinated consistency theory is employed to achieve a unified state estimation of the maneuvering target. The DCIF method enhances the observability of the system, addressing the issues of large accuracy errors and divergence in traditional nonlinear filtering algorithms. Building upon the theoretical proof of consistency convergence in DCIF, four simulation experiments were conducted for comparison. These experiments validate the effectiveness and superiority of the DCIF method in bearing-only sensor networks.

Does antibiotic therapy for chronic endometritis improve clinical outcomes of patients with recurrent implantation failure in subsequent IVF cycles? A systematic review and meta-analysis.

PURPOSE: This study aims to assess whether antibiotic therapy for chronic endometritis (CE) could improve subsequent IVF outcomes in patients with recurrent implantation failure (RIF). METHODS: Studies that explore CE treatment in patients with RIF were retrieved from PubMed, EMBASE, Wanfang, and Google Scholar up to Jan 31, 2022. All retrieved studies were selected according to the inclusion and exclusion criteria. The main outcome measures include implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), and miscarriage rate (MR). Odds ratios (ORs) were analyzed for pregnancy outcomes with a 95% confidence interval (CI). RESULTS: Nine articles were enrolled in this study. Patients receiving oral antibiotic administration (OAA) did not show any advantage over patients without CE with regard to IR, OPR/LBR, and MR, but they showed a higher CPR. Patients with cured CE after OAA therapy had significantly higher CPR, IR, and OPR/LBR compared with patients without CE. Patients with persistent CE after OAA therapy had significantly lower IR, CPR, and OPR/LBR compared with patients without CE. Patients with cured CE had significantly higher IR, CPR, and OPR/LBR compared with persistent CE patients. CONCLUSIONS: Antibiotic treatment may improve the pregnancy outcomes of RIF patients in subsequent IVF cycles only if the condition of CE is confirmed cured in a control biopsy afterwards. Otherwise, no sufficient evidence has shown improvements in clinical outcomes in RIF patients with persistent CE.

microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway.

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.

Overexpression of long noncoding RNA SLC26A4-AS1 inhibits the epithelial-mesenchymal transition via the MAPK pathway in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.

Serum metabolite profiles are associated with the presence of advanced liver fibrosis in Chinese patients with chronic hepatitis B viral infection.

BACKGROUND: Accurate and noninvasive diagnosis and staging of liver fibrosis are essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients. METHODS: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively. RESULTS: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4, and AST/ALT ratio, with both greater sensitivity and specificity. CONCLUSIONS: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression in patients with chronic hepatitis B virus infection.

Identification of an Immune Score-Based Gene Panel with Prognostic Power for Oral Squamous Cell Carcinoma.

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.

Immunohistochemical basigin expression level in thyroid cancer tissues.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Hepatoprotective effect of Xiayuxue decoction ethyl acetate fraction against carbon tetrachloride-induced liver fibrosis in mice via inducing apoptosis and suppressing activation of hepatic stellate cells.

CONTEXT: Xiayuxue decoction (XYXD), a traditional Chinese medicine, is used for treating liver disease. However, the potential active constituents and mechanisms are still unclear. OBJECTIVE: To explore the main active fraction extracts, active ingredients and possible mechanisms of XYXD for anti-hepatic fibrosis. MATERIALS AND METHODS: Different fractions including ethyl acetate fraction (EF) were prepared from XYXD. These fractions, especially EF, were used to evaluate cell viability, proliferation, cell cycle, cytotoxicity and activation in hepatic stellate cells (HSCs). Liver fibrosis model was established by CCl4 in C57BL/6 mice, and allocated to CCl4 group, XYXD group and EF group with normal mice as control. Further, mitochondrial apoptosis-related proteins of HSCs, destruction and angiogenesis of liver sinusoidal endothelial cells (LSECs) and active ingredients of EF were evaluated. RESULTS: The inhibition of proliferation, increase of S or/and G2/M phase population and suppression of α-SMA and COL-1 expression were obeserved in EF treated-JS1 and -LX2. Liver fibrosis-related indicators were improved by EF similar to XYXD in vivo. EF induced the apoptosis of HSCs in CCl4-induced fibrosis, and inhibited the expression of HSCs apoptosis pathway-related proteins (JNK and p38-MAPKs), and LSECs destruction and angiogenesis. Multiple ingredients (emodin, rhein, aloe-emodin, prunasin) in EF have shown inhibited the activation of JS1. DISCUSSION AND CONCLUSION: EF was the main active fraction extracts of XYXD, and the underlying mechanisms might relate to induction of HSCs apoptosis. Emodin, rhein, aloe-emodin and prunasin were main active ingredients of EF, which provides a potential drug for the treatment of liver fibrosis.

Cryopreservation of human ovarian tissue using the silver closed vitrification system.

PURPOSE: The aim of this study is to evaluate the feasibility of using a hand-made silver container for the cryopreservation of human ovarian cortex. METHODS: Human ovarian cortex tissues were vitrified using an open vitrification system (OVS) of needle immersed vitrification (NIV) and two closed vitrification systems (CVS) of a plastic vial (plastic CVS) and a silver container (silver CVS). Outcomes of vitrification were evaluated morphologically and histologically by in vitro culture and xenotransplantation. The apoptosis of primordial follicles was assessed by TUNEL staining. The production of E2 and P4 was examined by a chemiluminescent immunoassay. Blood vessels were visualized with CD31 staining. RESULTS: Compared with the fresh ovarian cortex tissue, ovarian cortex tissues that were vitrified using the three different carriers and then warmed showed significantly reduced percentages of normal primordial follicles, viability of primordial follicles, E2 and P4 levels during in vitro culture and decreased amounts of blood vessels. However, much better outcomes were obtained with NIV and silver CVS than with plastic CVS, based on the better morphology and viability of primordial follicles, higher E2 and P4 production during an in vitro culture, and greater numbers of blood vessels after xenografting. Importantly, the outcomes of ovarian cortex cryopreservation with silver CVS were similar and comparable to those with NIV. CONCLUSIONS: The hand-made silver container as a CVS is a promising carrier for the cryopreservation of the human ovarian cortex.

The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis.

PURPOSE: The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion polymorphism was implicated in recurrent implantation failure (RIF), but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk. METHODS: A comprehensive search for relevant articles was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for HLA-G 14-bp polymorphism and RIF were calculated. RESULTS: A total of five studies were included. In studies conducted in RIF patients and controls who had at least one spontaneous pregnancy, meta-analysis revealed no statistically significant association between the HLA-G 14-bp polymorphism and RIF in allele contrast and all genetic models in the overall population, but significant association was found in the population of Caucasian origin under allele contrast (OR = 1.73, 95% CI, 1.20, 2.50) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 3.09, 95% CI, 1.43, 6.65). In studies conducted in RIF patients and controls who had successful pregnancy following IVF-ET, the meta-analysis showed that there was statistically significant association between the HLA-G 14 bp polymorphism and RIF in allele contrast (OR = 1.74, 95% CI, 1.13, 2.67) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 10.20, 95% CI, 2.47, 42.14) and dominant model (OR = 4.34, 95% CI, 1.72, 10.92). No publication bias was found in the present studies. CONCLUSIONS: This meta-analysis suggested that the HLA-G 14-bp insertion allele may increase the risk of RIF in Caucasians. Further studies with large sample size of different ethnic populations are necessary.

The cytochrome P4501A1 gene polymorphisms and endometriosis: a meta-analysis.

PURPOSE: Cytochrome P450 1A1 (CYP1A1) polymorphisms were implicated in endometriosis risk, but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of CYP1A1 polymorphisms on endometriosis risk. METHODS: PubMed, Embase, and CNKI databases were searched to identify the eligible studies focusing on the associations between CYP1A1 MspI and Ile462Val polymorphisms and susceptibility to endometriosis. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for CYP1A1 polymorphisms and endometriosis were calculated. RESULTS: Pooled analysis of 12 studies involved a total of 1555 cases and 2868 controls showed that in all genetic models, no significant association between CYP1A1 MspI polymorphism and endometriosis risk was observed in the overall, Asians and Caucasians population, respectively. Interestingly, increased endometriosis risk was associated with carrying the C allele of CYP1A1 combined with GSTM1 null genotypes. For CYP1A1 Ile462Val polymorphism, eight studies were available (878 cases and 1991 controls). In the overall analysis, CYP1A1 Ile462Val polymorphism had a statistically significant association with increased endometriosis risk in allele contrast and all genetic models except the model of Val/Ile vs. Ile/Ile. In the subgroup analysis by ethnicity, significant elevated endometriosis risk was associated with CYP1A1 Ile462Val polymorphism in Asians but not in Caucasians under all genetic models. No publication bias was found in the present studies. CONCLUSIONS: This meta-analysis suggested that CYP1A1 Ile462Val polymorphism was associated with an increased risk of endometriosis, particularly in Asians. CYP1A1 MspI polymorphism may not be associated with endometriosis risk, but GSTM1 and CYP1A1 MspI polymorphism may have a joint effect on endometriosis risk.

bFGF and VEGF improve the quality of vitrified-thawed human ovarian tissues after xenotransplantation to SCID mice.

PURPOSE: The aim of this research is to study whether basic fibroblast growth factor (bFGF) alone or in combination with vascular endothelial growth factor (VEGF) could improve the quality of vitrified-thawed human ovarian tissue xenotransplanted to severe combined immune deficiency (SCID) mice. METHODS: After collection and cryopreservation, thawed human ovarian tissue were cultured in vitro for 2 days and then xenografted to severe combined immune deficiency (SCID) mice for 7 days. The in vitro culture medium was separated into six groups, including (A) the blank control group, (B) the human recombinant bFGF (150 ng/ml) group, (C) the bFGF (150 ng/ml)+human recombinant VEGF (25 ng/ml) group, (D) bFGF (150 ng/ml)+VEGF (50 ng/ml) group, (E) bFGF (150 ng/ml)+ VEGF (75 ng/ml) group and (F) bFGF (150 ng/ml) + VEGF (100 ng/ml) group. In addition, eight pieces of thawed ovarian tissue were transplanted without in vitro culture, which serve as the fresh control group. The effect of transplantation was assessed by histological analysis, immunohistochemical staining for CD34, Ki-67, and AC-3 expression, and microvessel density (MVD). RESULTS: There was no significant difference between the fresh and blank control group. Compared to the blank control group, the number of follicles, MVD, and rate of Ki-67-positive cells increased significantly in groups B, C, D, E, and F, while apoptosis decreased significantly. Compared to the bFGF treatment group, no significant difference appeared in group C, D, E, and F. CONCLUSIONS: The administration of bFGF alone or in combination with VEGF improved the quality of postgraft human ovarian tissue, though VEGF, regardless of different concentrations, did not influence effect of bFGF.

Corrigendum: Review of novel functions and implications of circular RNAs in hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2023.1093063.].

Mitochondrial genome study of Camellia oleifera revealed the tandem conserved gene cluster of nad5-nads in evolution.

Camellia oleifera is a kind of high-quality oil supply species. Its seeds contain rich unsaturated fatty acids and antioxidant active ingredients, which is a kind of high-quality edible oil. In this study, we used bioinformatics methods to decipher a hexaploid Camellia oil tree's mitochondrial (mt) genome based on second-generation sequencing data. A 709,596 bp circular map of C. oleifera mt genome was found for the first time. And 74 genes were annotated in the whole genome. Mt genomes of C. oleifera and three Theaceae species had regions with high similarity, including gene composition and gene sequence. At the same time, five conserved gene pairs were found in 20 species. In all of the mt genomes, most of nad genes existed in tandem pairs. In addition, the species classification result, which, according to the gene differences in tandem with nad5 genes, was consistent with the phylogenetic tree. These initial results provide a valuable basis for the further researches of Camellia oleifera and a reference for the systematic evolution of plant mt genomes.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

In vitro culture thawed human ovarian tissue: NIV versus slow freezing method.

The aim of this study was to determine if the needle immersed vitrification method (NIV) can improve the growth potential of thawed ovarian tissue in vitro culture. Human ovarian cortical tissues were cryopreserved using NIV and slow freezing method. After 14 days of culture, the preservation outcomes of NIV and slow freezing groups were analyzed histologically using light microscope and apoptosis was assessed by TUNEL assay. The result showed that the percentage of morphologically abnormal primordial follicles was lower in NIV group than in slow freezing group (P < 0.05). The incidence of TUNEL-positive primordial follicles was lower in NIV group than in slow freezing group (P < 0.05). The study showed that cryopreservation of human ovarian tissue with NIV was effective in improving the growth potential of frozen-thawed ovarian tissue in vitro culture.

Review of novel functions and implications of circular RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies, with high incidence and mortality. As the majority of HCC patients are diagnosed at an advanced stage and die of recurrence and metastasis, its pathology and new biomarkers are needed. Circular RNAs (circRNAs) are a large subclass of long non-coding RNAs (lncRNAs) with covalently closed loop structures and abundant, conserved, stable, tissue-specific expression in mammalian cells. CircRNAs exert multiple functions in HCC initiation, growth and progression, serving as promising biomarkers for diagnosis, prognosis and therapeutic targets for this disease. This review briefly describes the biogenesis and biological functions of circRNAs and elucidates the roles of circRNAs in the development and progression of HCC, especially regarding epithelial-mesenchymal transition (EMT), drug resistance and interactions with epigenetic modifications. In addition, this review highlights the implications of circRNAs as potential biomarkers and therapeutic targets for HCC. We hope to provide novel insight into the roles of circRNAs in HCC.

Corrigendum: Programmed cell death and lipid metabolism of macrophages in NAFLD.

[This corrects the article DOI: 10.3389/fimmu.2023.1118449.].

Programmed cell death and lipid metabolism of macrophages in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has now become the leading chronic liver disease worldwide with lifestyle changes. This may lead to NAFLD becoming the leading cause of end-stage liver disease in the future. To date, there are still no effective therapeutic drugs for NAFLD. An in-depth exploration of the pathogenesis of NAFLD can help to provide a basis for new therapeutic agents or strategies. As the most important immune cells of the liver, macrophages play an important role in the occurrence and development of liver inflammation and are expected to become effective targets for NAFLD treatment. Programmed cell death (PCD) of macrophages plays a regulatory role in phenotypic transformation, and there is also a certain connection between different types of PCD. However, how PCD regulates macrophage polarization has still not been systematically elucidated. Based on the role of lipid metabolic reprogramming in macrophage polarization, PCD may alter the phenotype by regulating lipid metabolism. We reviewed the effects of macrophages on inflammation in NAFLD and changes in their lipid metabolism, as well as the relationship between different types of PCD and lipid metabolism in macrophages. Furthermore, interactions between different types of PCD and potential therapeutic agents targeting of macrophages PCD are also explored.

PDGF-BB is involved in HIF-1α/CXCR4/CXCR7 axis promoting capillarization of hepatic sinusoidal endothelial cells.

Background: The activation of HIF-1α/CXCR4 pathway in liver sinusoidal endothelial cells (LSECs) could downregulate CXCR7, leading to the capillarization of LSECs to promote hepatic fibrosis. However, the mechanism between CXCR4 and CXCR7 is still undefined. The aim is to investigate the role of PDGF-BB in the dedifferentiation of LSECs and hepatic stellate cells (HSCs) activation. Methods: The activation of HIF-1α/CXCR4 pathway in two kinds of liver fibrosis models were observed. The effects of HIF-1α, CXCR4, PDGF-BB on the dedifferentiation of LSECs were investigated by using the inhibitors of HIF-1α, CXCR4 or PDGFR-ß separately or transfecting with a CXCR4 knockdown lentiviral vector. In addition, the relationship between LSECs and HSCs was demonstrated by co-culture of LSECs and HSCs using the transwell chamber. Results: CXCR4 upregulation and CXCR7 downregulation were accompanied by LSECs capillarization and HSCs activation both in CCl4-induced and BDL-induced fibrotic liver. In vitro, downregulation of HIF-1α significantly descreased CXCR4 and CD31 expression, and enhanced the expressions of CXCR7, CD44 and LYVE1. Downregulation of CXCR4 in LSECs significantly downregulated PDGF-BB, PDGFR-ß and CD31, and enhanced CXCR7, CD44 and LYVE1 expression, while the expression of HIF-1α did not change significantly. STI571, a PDGF receptor inhibitor, could significantly downregulate PDGFR-ß and increase the expression of CXCR7 to inhibit the dedifferentiation of LSECs. In addition, alleviateion the dedifferentiation of LSECs could decrease the expression of PDGFR-ß of HSCs, then inhibiting the activation of HSCs. Conclusions: This study revealed that HIF-1α/CXCR4/PDGF-BB/CXCR7 axis promoted the dedifferentiation of LSECs, consequently triggering HSCs activation and liver fibrosis.