Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

Antimicrobial Step-Down Therapy versus Conventional Antimicrobial Therapy in the Treatment of Patients with Sepsis.

Objective: This study was to evaluate the efficacy of antimicrobial step-down therapy versus conventional antimicrobial therapy in the treatment of patients with sepsis. Methods: Between September 2020 and September 2021, 65 patients with sepsis treated in the intensive care unit (ICU) of our hospital were recruited and assigned at a ratio of 1 : 1 to receive either conventional antimicrobial therapy (sulbactam plus cefoperazone) (control group) or antimicrobial step-down therapy (imipenem/cilastatin) (observation group). The results of drug sensitivity tests and clinical effects were evaluated comprehensively after 3-5 d of treatment, downgraded, and upgraded, or maintenance treatment was administered for 10 d. Outcome measures included clinical and laboratory indices and treatment efficacy. Results: Antimicrobial step-down therapy resulted in a significantly higher efficacy and lower levels of white blood cell (WBC) count and C-reactive protein (CRP) versus conventional antimicrobial therapy (P < 0.05). The patients given antimicrobial step-down therapy showed a significantly shorter duration of antimicrobial drug administration, temperature recovery, time of respiratory support, and ICU stays versus conventional antimicrobial therapy (P < 0.05). Conclusion: Antimicrobial step-down therapy contributes to the mitigation of inflammatory responses in patients with sepsis and shortens the duration of antimicrobial drug use and ICU stay versus conventional antimicrobial therapy. The reliability of the conclusions can be further increased if multicenter and large sample clinical observations can be conducted, which is the direction of endeavor for future clinical studies.

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)-mediated DNA methyltransferase 1/B-cell lymphoma-2 (DNMT1/Bcl-2) axis in sepsis-induced myocardial injury. Mice and HL-1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed lncRNA in sepsis samples through microarray profiling, and the upregulated expression of lncRNA SNHG1 was confirmed in myocardial tissues of LPS-induced septic mice and HL-1 cells. Further experiments suggested that silencing of lncRNA SNHG1 reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. LncRNA SNHG1 inhibited Bcl-2 expression by recruiting DNMT1 to Bcl-2 promoter region to cause methylation. Inhibition of Bcl-2 promoter methylation reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. In vivo experiments substantiated that lncRNA SNHG1 silencing alleviated sepsis-induced myocardial injury in mice. Taken together, lncRNA SNHG1 promotes LPS-induced myocardial injury in septic mice by downregulating Bcl-2 through DNMT1-mediated Bcl-2 methylation.

CCCTC-binding factor-mediated microRNA-340-5p suppression aggravates myocardial injury in rats with severe acute pancreatitis through activation of the HMGB1/TLR4 axis.

BACKGROUND: Severe acute pancreatitis (SAP) is a life-threatening disorder associated with multisystem organ failure. This study aimed to investigate the function of high mobility group box 1 (HMGB1) in SAP-induced myocardial injury. METHODS: A rat model with SAP was induced. The pathological changes in rat pancreatic and cardiac tissues were examined by HE staining. Cardiomyocyte apoptosis in rat cardiac tissues, and the serum levels of myocardial injury markers and pro-inflammatory cytokines were examined. Rat primary cardiomyocytes were treated with H2O2 for in vitro experiments. The regulatory molecules of HMGB1 were predicted by bioinformatics analysis. Altered expression of HMGB1, microRNA (miR)-340-5p and CCCTC-binding factor (CTCF) was introduced in rats or cells to investigate their roles in myocardial injury. RESULTS: CTCF and HMGB1 were highly expressed but miR-340-5p was poorly expressed in cardiac tissues of rats with SAP. HMGB1 silencing reduced toll-like receptor 4 (TLR4) expression to promote proliferation and reduce apoptosis of H2O2-treated cardiomyocytes. miR-340-5p targeted HMGB1 mRNA, while CTCF suppressed miR-340-5p transcription. CTCF upregulation or miR-340-5p downregulation blocked the effects of HMGB1 silencing on cardiomyocytes. In vivo, CTCF silencing alleviated injury in rat pancreatic and cardiac tissues and reduced the expression of creatine kinase-MB (CK-MB), lactic dehydrogenase, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) in rat serum. But further overexpression of HMGB1 or inhibition of miR-340-5p aggravated the symptoms in rats. CONCLUSION: This study demonstrated that CTCF reduces transcription of miR-340-5p to promote HMGB1 expression, which activates TLR4 expression and promotes myocardial injury in rats with SAP.

miR-340-5p inhibits pancreatic acinar cell inflammation and apoptosis via targeted inhibition of HMGB1.

Acute pancreatitis (AP) is a common gastrointestinal disease that affects 1 million individuals worldwide. Inflammation and apoptosis are considered to be important pathogenic mechanisms of AP, and high mobility group box 1 (HMGB1) has been shown to play a particularly important role in the etiology of this disease. MicroRNAs (miRs) are emerging as critical regulators of gene expression and, as such, they represent a promising area of therapeutic target identification and development for a variety of diseases, including AP. Using the online database query (microRNA.org), the current study identified a site in the 3' untranslated region of HMGB1 mRNA that was a viable target for miR-340-5p. The present study aimed to investigate the association between miR-340-5p and HMGB1 expression in pancreatic acinar cells following lipopolysaccharide (LPS) treatment by performing luciferase, western blotting and reverse transcription-quantitative PCR assays. The results suggest that miR-340-5p attenuates the induction of HMGB1 by LPS, thereby inhibiting inflammation and apoptosis via blunted activation of Toll-like receptor 4 and enhanced AKT signaling. Thus, the therapeutic application of miR-340-5p may be a useful strategy in AP via upregulation of HMGB1 and subsequent promotion of inflammation and apoptosis.

Interfering hsa_circ_0073748 alleviates caerulein-induced ductal cell injury in acute pancreatitis by inhibiting miR-132-3p/TRAF3/NF-κB pathway.

Circular RNA hsa_circ_0073748 (circ_0073748) is upregulated in patients with acute pancreatitis (AP), a clinically common sudden inflammatory response. MicroRNA (miR)-132-3p is a stress-induced factor with high conservation between species. Herein, expression and role of circ_0073748 and miR-132-3p in caerulein-induced pancreatitis were studied. Expression levels of circ_0073748, miR-132-3p, TNF receptor associated factor 3 (TRAF3), Bcl-2 and Bcl-2-associated X protein (Bax) were examined by reverse transcription-quantitative PCR and Western blotting. Cell proliferation was measured by MTS and EdU assays. Flow cytometry and assay kits detected apoptosis, inflammatory, and oxidative responses. Western blotting detected nuclear factor (NF)-κB signaling pathway. Circ_0073748 was upregulated and miR-132-3p was downregulated in AP patients' plasma and human pancreatic ductal HPDE6-C7 cells with caerulein induction. Interfering circ_0073748 and reinforcing miR-132-3p improved cell viability, EdU incorporation, and superoxide dismutase (SOD) activity of caerulein-treated HPDE6-C7 cells but suppressed malonaldehyde (MDA), IL-6 and TNF-α levels and apoptosis rate. Moreover, TRAF3 downregulation was allied with circ_0073748 silencing and miR-132-3p overexpression in caerulein-induced HPDE6-C7 cells. Mechanically, circ_0073748 was identified as a sponge for miR-132-3p to modulate TRAF3 expression, thus establishing a competitive endogenous RNA (ceRNA) regulation model. Notably, circ_0073748 blockage could suppress expressions of phosphorylated P65 (p-P65) and p-IκB in caerulein-induced HPDE6-C7 cells by promoting miR-132-3p and inhibiting TRAF3. Silencing circ_0073748 and upregulating miR-132-3p could alleviate caerulein-induced HPDE6-C7 injury and inactivate canonical NF-κB signal by inhibiting TRAF3. Circ_0073748/miR-132-3p/TRAF3 ceRNA pathway might be one underlying mechanism and therapeutic target of caerulein-induced AP.

MALAT1 shuttled by extracellular vesicles promotes M1 polarization of macrophages to induce acute pancreatitis via miR-181a-5p/HMGB1 axis.

Acute pancreatitis (AP) is a serious condition carrying a mortality of 25-40%. Extracellular vesicles (EVs) have reported to exert potential functions in cell-to-cell communication in diseases such as pancreatitis. Thus, we aimed at investigating the mechanisms by which EV-encapsulated metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) might mediate the M1 polarization of macrophages in AP. Expression patterns of MALAT1, microRNA-181a-5p (miR-181a-5p) and high-mobility group box 1 protein (HMGB1) in serum of AP patients were determined. EVs were isolated from serum and pancreatic cells. The binding affinity among miR-181a-5p, MALAT1 and HMGB1 was identified. AP cells were co-cultured with EVs from caerulein-treated MPC-83 cells to determine the levels of M1/2 polarization markers and TLR4, NF-κB and IKBa. Finally, AP mouse models were established to study the effects of EV-encapsulated MALAT1 on the M1 polarization of macrophages in AP in vivo. MALAT1 was transferred into MPC-83 cells via EVs, which promoted M1 polarization of macrophages in AP. MALAT1 competitively bound to miR-181a-5p, which targeted HMGB1. Moreover, MALAT1 activated the TLR4 signalling pathway by regulating HMGB1. EV-encapsulated MALAT1 competitively bound to miR-181a-5p to upregulate the levels of IL-6 and TNF-α by regulating HMGB1 via activation of the TLR4 signalling pathway, thereby inducing M1 polarization of macrophages in AP. In vivo experimental results also confirmed that MALAT1 shuttled by EVs promoted M1 polarization of macrophages in AP via the miR-181a-5p/HMGB1/TLR4 axis. Overall, EV-loaded MALAT1 facilitated M1 polarization of macrophages in AP via miR-181a-5p/HMGB1/TLR4, highlighting a potential target for treating AP.

Curcumin protects against inflammation and lung injury in rats with acute pulmonary embolism with the involvement of microRNA-21/PTEN/NF-κB axis.

This study was intended to investigate the effect of Curcumin on acute pulmonary embolism (APE) via microRNA-21 (miR-21)/PTEN/NF-κB axis. APE model was induced on rats and administrated with Curcumin. Western blot analysis and RT-qPCR manifested the downregulation of Sp1, miR-21 and NF-κB, but the upregulation of PTEN in Curcumin-treated APE rats. Blood gas analysis, ELISA, and weighing of wet weight/dry weight (W/D) ratio indicated that Curcumin diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. Further mechanical analysis was conducted by dual-luciferase reporter assays and ChIP assay, which showed that Sp1 increased miR-21 expression by binding to the miR-21 promoter, and that PTEN was targeted by miR-21. The APE rats were injected with adenovirus to evaluate the effect of Sp1, miR-21, or PTEN on lung injury and inflammation. It was observed that downregulation of miR-21 or Sp1, or upregulation of PTEN diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. In summary, Curcumin decreased miR-21 expression by downregulating Sp1 to upregulate PTEN and to impair the NF-κB signaling pathway, thus suppressing lung injury and inflammation in APE rats.

Silencing of CREB Inhibits HDAC2/TLR4/NF-κB Cascade to Relieve Severe Acute Pancreatitis-Induced Myocardial Injury.

The purpose of the present study is to investigate the role of CREB in cardiomyocytes proliferation in regulation of HDAC2-dependent TLR4/NF-κB pathway in severe acute pancreatitis (SAP)-induced myocardial injury. The SAP rat model was developed by injecting sodium touracholate into SD rats and then infected with lentivirus vectors expressing sh-CREB in the presence/absence of LPS. The pathological alterations of rat pancreatic and cardiac tissues were observed by HE staining. TUNEL assay was used to study apoptosis of cardiomyocytes. Next, the loss- and gain-function assay was conducted in LPS-induced myocardial injury cardiomyocytes to define the roles of CREB, HDAC2, and TLR4 in cardiomyocyte proliferation, apoptosis, inflammation, and myocardial injury in vitro. ChIP assay was used to study the enrichment of CREB bound to HDAC2 promoter. RT-qPCR and Western blot analysis were used to detect the expressions of related mRNA and proteins in the NF-κB pathway, respectively. CREB was found to be overexpressed in both SAP tissues and cells. CREB directly bound to the promoter of HDAC2 and activated its expression. Overexpressed CREB or HDAC2 inhibited proliferation and promoted apoptosis of cardiomyocytes. Suppression of CREB inhibited the HDAC2/TLR4/NF-κB cascade to promote proliferation and inhibit apoptosis of cardiomyocytes. The in vitro results were validated in vivo experiments. Coherently, suppression of CREB can inhibit HDAC2/TLR4/NF-κB cascade to promote cardiomyocyte proliferation, thus ameliorating SAP-induced myocardial injury.

miR-29a-3p transferred by mesenchymal stem cells-derived extracellular vesicles protects against myocardial injury after severe acute pancreatitis.

AIMS: Acute pancreatitis (AP) is an inflammatory disease of the pancreas that may affect local tissues or remote organ systems, while severe acute pancreatitis (SAP) is a life-threatening disorder associated with multiple organ failure. In this investigation, we set about to determine whether microRNA-29a-3p (miR-29a-3p) carried by mesenchymal stem cell (MSCs)-derived extracellular vesicles (EVs) affects the myocardial injury during SAP. MAIN METHODS: EVs were isolated from MSCs of rat bone marrow by differential centrifugation. An SAP rat model was developed and treated with MSCs-EVs and/or alteration of miR-29a-3p and HMGB1 expression, followed by assessment of the rats' cardiac function and inflammation. Next, cardiomyocytes H9C2 were co-cultured with MSC-EVs and internalization of EVs was evaluated, followed by evaluation of whether EVs could transmit miR-29a-3p cargos into H9C2 cells and affect their biological functions. KEY FINDINGS: EVs derived from MSCs were observed to protect against SAP-induced myocardial injury. In SAP-induced rats, miR-29a-3p was under-expressed in myocardial tissues. In addition, we also confirmed that miR-29a-3p could be transferred into the H9C2 cardiomyocytes by MSC-derived EVs, which downregulated the expression of inflammatory markers and improve cardiac function to attenuate myocardial injury. Furthermore, miR-29a-3p inhibited the expression of HMGB1 to downregulate TLR4 expression and further inactivate the Akt signaling pathway. SIGNIFICANCE: These findings support the cardioprotective action of miR-29a-3p transmitted by MSCs-derived EVs in SAP-induced myocardial injury via downregulation of the HMGB1/TLR4/Akt axis, highlighting a promising target for the EV-based therapy for SAP.

Direct Synthesis and Enhanced Rectification of Alloy-to-Alloy 2D Type-II MoS2(1- x ) Se2 x /SnS2(1- y ) Se2 y Heterostructures.

The interfacial tunable band alignment of heterostructures is coveted in device design and optimization of device performance. As an intentional approach, alloying allows band engineering and continuous band-edge tunability for low-dimensional semiconductors. Thus, combining the tunability of alloying with the band structure of a heterostructure is highly desirable for the improvement of device characteristics. In this work, the single-step growth of alloy-to-alloy (MoS2(1- x ) Se2 x /SnS2(1- y ) Se2 y ) 2D vertical heterostructures is demonstrated. Electron diffraction reveals the well-aligned heteroepitaxial relationship for the heterostructure, and a near-atomically sharp and defect-free boundary along the interface is observed. The nearly intrinsic van der Waals (vdW) interface enables measurement of the intrinsic behaviors of the heterostructures. The optimized type-II band alignment for the MoS2(1- x ) Se2 x /SnS2(1- y ) Se2 y heterostructure, along with the large band offset and effective charge transfer, is confirmed through quenched PL spectroscopy combined with density functional theory calculations. Devices based on completely stacked heterostructures show one or two orders enhanced electron mobility and rectification ratio than those of the constituent materials. The realization of device-quality alloy-to-alloy heterostructures provides a new material platform for precisely tuning band alignment and optimizing device applications.

HDAC1 promotes artery injury through activation of VAV3 by binding to miR-182-5p in atherosclerotic mice model.

Atherosclerosis (AS) is one of the significant chronic inflammatory pathology considering public health impact. Up-regulation of HDAC1 has been proved to be related with endothelial dysfunction which is correlated intimately with AS. Our research aims to investigate how histone deacetylase 1 (HDAC1)/miR-182-5p/vav guanine nucleotide exchange factor 3 (VAV3)/AKT axis participates in AS in terms of molecular mechanism. We detected miR-181-5p in human umbilical vein endothelial cells after treatment with aorta and ox-LDL in AS model mice. Dual luciferase reporter assay was employed to verify interaction of miR-182-5p and VAV3. ChIP was performed to determine the relationship between HDAC1 and promoter of miR-182-5p. Protein levels of HADC1, VAV3, AKT, p-AKT, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein 1 (MCP-1) were detected by western blot analysis. CCK8 and flow cytometry were used to detect cell viability and apoptosis, respectively. After different treatments, the ability of cells to form monoclonal cells was detected, and AS was evaluated by detecting arterial injury and inflammation-related factors. Overexpression of HDAC1 could inhibit HUVECs proliferation and promote AS in mouse model. It was verified by dual luciferase assay that miR-182-5p could bind to VAV3 3'UTR mRNA. Meanwhile, HDAC1 repressed miR-182-5p expression through binding to miR-182-5p promoter and then inhibit VAV3 expression further. In summary, HDAC1 promoted AS through AKT pathway, which was improved by VAV3 activation mediated by miR-182-5p. Our results demonstrated that HDAC1 repressed miR-182-5p and activating AKT pathway via improving VAV3 to promote AS progression.

Glaucocalyxin A Protects H9c2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of Akt/Nrf2/HO-1 Pathway.

Myocardial infarction (MI) is one of the most serious cardiovascular diseases associated with myocardial ischemia/reperfusion (I/R) injury. Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid that has been found to ameliorate myocardial I/R injury in mice. However, the mechanism has not been fully investigated. In the present study, we aimed to investigate the effect of GLA on rat cardiomyocytes H9c2 cells exposed to hypoxia/reoxygenation (H/R). The results showed that GLA treatment improved cell viability of H/R-stimulated H9c2 cells. Administration with GLA suppressed the H/R-stimulated reactive oxygen species (ROS) production in H9c2 cells. GLA also elevated the activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase in H/R-stimulated H9c2 cells. Moreover, GLA prevented H/R-stimulated cell apoptosis in H9c2 cells, as evidenced by increased bcl-2 expression, decreased bax expression, as well as reduced caspase-3 activity. Furthermore, GLA enhanced the activation of protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in H9c2 cells exposed to H/R. Additionally, treatment with LY294002 reserved the protective effects of GLA on H/R-stimulated oxidative injury in H9c2 cells. In conclusion, these findings suggested that GLA protected H9c2 cells from H/R-stimulated oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. Thus, GLA might be a promising therapeutic agent for the prevention and treatment of myocardial I/R.

Effects of sepsis on hippocampal volume and memory function.

BACKGROUND: This study aimed to determine the effects of sepsis on brain integrity, memory, and executive function. METHODS: Twenty sepsis patients who were not diagnosed with sepsis-associated encephalopathy (SAE) but had abnormal electroencephalograms (EEGs) were included. The control group included twenty healthy persons. A neuropsychological test of memory and executive function and a brain magnetic resonance imaging scan were performed. The volumes of cortex and subcortex were measured using the FreeSurfer software. Acute Physiology and Chronic Health Evaluation II (APACHE II) score was used to determine the disease severity. RESULTS: In the sepsis group, the levels of immediate free recall, immediate cued recall, and delayed cued recall in the California Verbal Learning Test-II (CVLT-II) were significantly lower; the explicit memory (recollection process) in the process dissociation procedure test was lower; and the volumes of the left and right hippocampi were significantly lower compared with the control group. The volume of the presubiculum in the hippocampus of sepsis patients showed statistically significant decrease. In the sepsis group, the volumes of the left and right hippocampi were negatively correlated with the APACHE II score and positively with immediate free recall, immediate cued recall, and delayed cued recall in the CVLT-II; moreover, the hippocampal volume was significantly correlated with recollection but not with familiarity. CONCLUSIONS: Patients with abnormal EEGs during hospitalization but with no SAE still have reduced hippocampal volume and memory deficits. This finding indicates that sepsis leads to damage to specific parts of the hippocampus.

JANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells.

IMPACT STATEMENT: Accumulating evidence suggests that vascular remodeling due to immoderate proliferation and migration of SMCs is a common process occurring in APE. In this work, we tried to find a breakthrough in the pathological mechanism to alleviate the prognosis of APE by improving SMCs proliferation and explored the effect of JANEX-1 on PDGF-induced proliferation-related molecules in PVSMCs and assessed the therapeutic potential of JAK3 for vascular remodeling in APE mice. We demonstrated that JANEX-1, blocking JAK3 expression or activity, reduced JAK3/STAT3 signaling pathway, VEGF expression and FAK activation, and PDGF-induced proliferation of PVSMCs. Moreover, JANEX-1 inhibited the thrombus-induced intimal hyperplasia and the expression of VEGF and FAK activation in neointimal SMCs of APE mice. The data are helpful to elucidate the pharmacological mechanism and potential therapeutic effect of JANEX-1 in APE.

miR­106b­5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells.

Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR­106b­5p on APE was demonstrated in platelet­derived growth factor (PDGF)­induced PASMCs in vitro and in an APE­mouse model in vivo. The results showed that miR­106b­5p expression was downregulated in PDGF­induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR­106b­5p agomiR, and increased following treatment with miR­106b­5p antagomiR. miR­106b­5p targeted the 3' untranslated region of NOR­1 mRNA and reduced NOR1 expression. NOR1 overexpression reversed the effects of miR­106­5p on PDGF­induced PASMCs. The functional roles of miR­106b­5p in PDGF­induced PASMCs and an APE mouse­model, and the underlying molecular mechanisms were evaluated. AgomiR­106b­5p improved APE­induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR­106­5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF­induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.

Symmetry-Reduction Enhanced Polarization-Sensitive Photodetection in Core-Shell SbI3 /Sb2 O3 van der Waals Heterostructure.

Structural symmetry is a simple way to quantify the anisotropic properties of materials toward unique device applications including anisotropic transportation and polarization-sensitive photodetection. The enhancement of anisotropy can be achieved by artificial symmetry-reduction design. A core-shell SbI3 /Sb2 O3 nanowire, a heterostructure bonded by van der Waals forces, is introduced as an example of enhancing the performance of polarization-sensitive photodetectors via symmetry reduction. The structural, vibrational, and optical anisotropies of such core-shell nanostructures are systematically investigated. It is found that the anisotropic absorbance of a core-shell nanowire is obviously higher than that of two single compounds from both theoretical and experimental investigations. Anisotropic photocurrents of the polarization-sensitive photodetectors based on these core-shell SbI3 /Sb2 O3 van der Waals nanowires are measured ranging from ultraviolet (UV) to visible light (360-532 nm). Compared with other van der Waals 1D materials, low anisotropy ratio (Imax /Imin ) is measured based on SbI3 but a device based on this core-shell nanowire possesses a relatively high anisotropy ratio of ≈3.14 under 450 nm polarized light. This work shows that the low-symmetrical core-shell van der Waals heterostructure has large potential to be applied in wide range polarization-sensitive photodetectors.

MicroRNA-301b promotes the proliferation and invasion of glioma cells through enhancing activation of Wnt/ß-catenin signaling via targeting Glypican-5.

Accumulating evidence has suggested that Glypican-5 (GPC5) is a tumor suppressor gene in many types of cancers. However, whether GPC5 is involved in glioma remains unknown. This study was designed to explore the expression, biological function and regulatory mechanism of GPC5 in glioma. Our results demonstrated that GPC5 expression was significantly decreased in multiple glioma cell lines. Gain-of-function experiments showed that the ectopic expression of GPC5 markedly inhibited the proliferation, invasion and Wnt/ß-catenin signaling of glioma cell lines. GPC5 was identified as a target gene of microRNA-301b (miR-301b). Further data showed that miR-301b expression was significantly up-regulated in glioma tissues and cell lines. In addition, miR-301b expression was inversely correlated with GPC5 expression in clinical glioma tissues. The overexpression of miR-301b promoted the proliferation, invasion and Wnt/ß-catenin signaling of glioma cell lines, whereas the inhibition of miR-301b showed the opposite effect. However, the silencing of GPC5 significantly reversed the antitumor effect of miR-301b inhibition. Overall, our results revealed a tumor suppressive role of GPC5 in glioma and suggested that GPC5 expression was regulated by miR-301b. Our study indicates that the inhibition of miR-301b represses the proliferation and invasion of glioma cells by up-regulating GPC5 expression.