Interdependence between myocardial deformation and perfusion in patients with T2DM and HFpEF: a feature-tracking and stress perfusion CMR study.

BACKGROUND: Patients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve. METHODS: This study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM-HFpEF (n = 74) and the T2DM-non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain. RESULTS: Patients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P < 0.05). Furthermore, LV longitudinal PSSR, LA reservoir, and LA conduit strain were notably impaired in patients with T2DM without HFpEF compared to controls (all P < 0.05), but LV torsion, LV radial PSSR, and LA booster strain compensated for these alterations (all P < 0.05). Multivariate linear regression analysis demonstrated that LA reservoir and LA booster strain were independently associated with global MPRI (ß = 0.259, P < 0.001; ß = - 0.326, P < 0.001, respectively). Further, the difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI. Global stress PI, LA booster, global rest PI, and global MPRI showed high accuracy in diagnosing HFpEF among patients with T2DM (areas under the curve [AUC]: 0.803, 0.790, 0.740, 0.740, respectively). CONCLUSIONS: Patients with T2DM and HFpEF exhibited significant LV systolic and diastolic deformation, decreased LA reservoir strain, severe impairment of myocardial perfusion, and elevated LA booster strain that is a compensatory response in HFpEF. Global MPRI was identified as an independent influencing factor on LA reservoir and LA booster strain. The difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI, suggesting a possible mechanistic link between microcirculation impairment and cardiac dysfunction in diabetes. Myocardial perfusion and LA strain may prove valuable for diagnosing and managing HFpEF in the future.

Co-exposure to lead and high-fat diet aggravates systemic inflammation in mice by altering gut microbiota and the LPS/TLR4 pathway.

This study reports the toxicity of Pb exposure on systemic inflammation in high-fat-diet (HFD) mice and the potential mechanisms. Results indicated that Pb exacerbated intestinal barrier damage and increased serum levels of lipopolysaccharide (LPS) and diamine oxidase in HFD mice. Elevated LPS activates the colonic and ileal LPS-TLR4 inflammatory signaling pathway and further induces hepatic and adipose inflammatory expression. The 16S rRNA gene sequencing results showed that Pb promoted the abundance of potentially harmful and LPS-producing bacteria such as Coriobacteriaceae_UCG-002, Alloprevotella, and Oscillibacter in the intestines of HFD mice, and their abundance was positively correlated with LPS levels. Additionally, Pb inhibited the abundance of the beneficial bacteria Akkermansia, resulting in lower levels of the metabolite short-chain fatty acids (SCFAs). Meanwhile, Pb inhibited adenosine 5'-monophosphate-activated protein kinase signaling-mediated lipid metabolism pathways, promoting hepatic lipid accumulation. The above results suggest that Pb exacerbates systemic inflammation and lipid disorders in HFD mice by altering the gut microbiota, intestinal barrier, and the mediation of metabolites LPS and SCFAs. Our study provides potential novel mechanisms of human health related to Pb-induced metabolic damage and offers new evidence for a comprehensive assessment of Pb risk.

Lead exposure exacerbates liver injury in high-fat diet-fed mice by disrupting the gut microbiota and related metabolites.

Lead (Pb) is a widespread toxic endocrine disruptor that could cause liver damage and gut microbiota dysbiosis. However, the causal relationship and underlying mechanisms between the gut microbiota and Pb-induced liver injury are unclear. In this study, we investigated the metabolic toxicity caused by Pb exposure in normal chow (Chow) and high-fat diet (HFD) mice and confirmed the causal relationship by fecal microbial transplantation (FMT) and antibiotic cocktail experiments. The results showed that Pb exposure exacerbated HFD-induced hepatic lipid deposition, fibrosis, and inflammation, but it had no significant effect on Chow mice. Pb increased serum lipopolysaccharide (LPS) levels and induced intestinal inflammation and barrier damage by activating TLR4/NFκB/MLCK in HFD mice. Furthermore, Pb exposure disrupted the gut microbiota, reduced short-chain fatty acid (SCFA) concentrations and the colonic SCFA receptors, G protein-coupled receptor (GPR) 41/43/109A, in HFD mice. Additionally, Pb significantly inhibited the hepatic GPR109A-mediated adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway, resulting in hepatic lipid accumulation. FMT from Pb-exposed HFD mice exacerbated liver damage, disturbed lipid metabolic pathways, impaired intestinal barriers, and altered the gut microbiota and metabolites in recipient mice. However, mice exposed to HFD + Pb and HFD mice had similar levels of these biomarkers in microbiota depleted by antibiotics. In conclusion, our study provides new insights into gut microbiota dysbiosis as a potential novel mechanism for human health related to liver function impairment caused by Pb exposure.

A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.

Multiple myeloma (MM) is a distinguished hematologic malignancy, with existing studies elucidating its interaction with neutrophil extracellular traps (NETs), which may potentially facilitate tumor growth. However, systematic investigations into the role of NETs in MM remain limited. Utilizing the single-cell dataset GSE223060, we discerned active NET cell subgroups, namely neutrophils, monocytes, and macrophages. A transcriptional trajectory was subsequently constructed to comprehend the progression of MM. Following this, an analysis of cellular communication in MM was conducted with a particular emphasis on neutrophils, revealing an augmentation in interactions albeit with diminished strength, alongside abnormal communication links between neutrophils and NK cells within MM samples. Through the intersection of differentially expressed genes (DEGs) between NET active/inactive cells and MM versus healthy samples, a total of 316 genes were identified. This led to the development of a 13-gene risk model for prognostic prediction based on overall survival, utilizing transcriptomics dataset GSE136337. The high-risk group manifested altered immune infiltration and heightened sensitivity to chemotherapy. A constructed nomogram for predicting survival probabilities demonstrated encouraging AUCs for 1, 3, and 5-year survival predictions. Collectively, our findings unveil a novel NET-related prognostic signature for MM, thereby providing a potential avenue for therapeutic exploration.

Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high-fat diet-fed mice.

BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota. RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota. CONCLUSION: The findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. © 2023 Society of Chemical Industry.

Retrospective Study of the Application Value Analysis of Ultrasound-Guided Technology in Peripheral Deep Venous Catheterization of Neonates.

Objective: To investigate the application value analysis of ultrasound-guided technology in peripheral deep venous catheterization of neonates. Method: A total of 94 neonates who underwent peripheral deep venous catheterization treatment from March 2020 to August 2021 in our hospital were selected and divided into the study group and the control group according to the simple randomized method, and each group had 47 cases. The control group was performed peripheral deep venous catheterization through X-ray examination, while the study group was performed peripheral deep venous catheterization through ultrasound-guided technology. The catheter placement, catheter retention time and adjustment times, the incidence of complications (limb swelling, pain, fluid leakage, and phlebitis), and the intervention satisfaction of family members were counted. Results: The success rate of one-time catheterization in the study group was higher than that in the control group, the operation time was shorter than that in the control group, and the amount of bleeding was less than that in the control group. The indwelling time of catheter in the study group was longer than that in the control group, and the number of adjustments was less than that in the control group. The incidence of complications in the study group was lower than that in the control group. The intervention satisfaction of family members in the study group was higher than that in the control group. Conclusion: Peripheral deep venous catheterization in neonates through ultrasound-guided technology can reduce operation time and blood loss and ensure the success rate of one-time catheterization, resulting in a long indwelling time of catheter, low number of adjustments, and low incidence of complications, which has safety and high intervention satisfaction of family members.

Melatonin alleviates the heat stress-induced impairment of Sertoli cells by reprogramming glucose metabolism.

Sertoli cells (SCs) provide structural and nutritional support for developing germ cells. Normal glucose metabolism of SCs is necessary for spermatogenesis. Melatonin could alleviate the effects of heat stress on spermatogenesis. However, the influences of heat stress on glucose metabolism in SCs remain unclear, and the potential protective mechanisms of melatonin on SCs need more exploration. In this study, boar SCs were treated at 43°C for 30 min, and different concentrations of melatonin were added to protect SCs from heat stress-induced impairment. These results showed that heat stress-induced oxidative stress caused cell apoptosis, inhibited the pentose phosphate pathway, and decreased the ATP content. Furthermore, heat stress increased the expressions of glucose intake- and glycolytic-related enzymes, which enhanced the glycolysis activity to compensate for the energy deficit. Melatonin relieved heat stress-induced oxidative stress and apoptosis by activating the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 signaling pathway to increase the capacity of antioxidants. In addition, melatonin enhanced heat-shock protein 90 (HSP90) expression through melatonin receptor 1B (MTNR1B), thereby stabilizing hypoxia-inducible factor-1α (HIF-1α). Activation of the HIF-1α signaling pathway enhanced glycolysis, promoted the pentose phosphate pathway, and increased cell viability. Our results suggest that melatonin reprograms glucose metabolism in SCs through the MTNR1B-HSP90-HIF-1α axis and provides a theoretical basis for preventing heat stress injury.

Monocular Pedestrian 3D Localization for Social Distance Monitoring.

Social distancing protocols have been highly recommended by the World Health Organization (WHO) to curb the spread of COVID-19. However, one major challenge to enforcing social distancing in public areas is how to perceive people in three dimensions. This paper proposes an innovative pedestrian 3D localization method using monocular images combined with terrestrial point clouds. In the proposed approach, camera calibration is achieved based on the correspondences between 2D image points and 3D world points. The vertical coordinates of the ground plane where pedestrians stand are extracted from the point clouds. Then, using the assumption that the pedestrian is always perpendicular to the ground, the 3D coordinates of the pedestrian's feet and head are calculated iteratively using collinear equations. This allows the three-dimensional localization and height determination of pedestrians using monocular cameras, which are widely distributed in many major cities. The performance of the proposed method was evaluated using two different datasets. Experimental results show that the pedestrian localization error of the proposed approach was less than one meter within tens of meters and performed better than other localization techniques. The proposed approach uses simple and efficient calculations, obtains accurate location, and can be used to implement social distancing rules. Moreover, since the proposed approach also generates accurate height values, exclusionary schemes to social distancing protocols, particularly the parent-child exemption, can be introduced in the framework.

[Effects of dynamic nutrition support on energy metabolism, immune function and stress response after oral and maxillofacial tumor surgery].

PURPOSE: To observe the effect of dynamic nutrition support on postoperative energy metabolism, immune function and stress response in patients with oral and maxillofacial tumors. METHODS: Fifty-six patients with oral and maxillofacial tumor surgery were randomly divided into experimental group and control group (28 in each group). Patients in the experimental group received dynamic enteral and parenteral nutrition support according to the stress period after surgery, ω-3 fish oil fat milk injection and glutamine were added in the nutrition support program. Patients in the control group were given routine postoperative enteral and parenteral camp support. Energy metabolism, immune function and stress indexes were detected 1 day before surgery, 2 days after surgery and 7 days after surgery, respectively. SPSS 19.0 software package was used to analyze the data. RESULTS: Energy metabolism indexes in the experimental group were higher than the control group on day 2 after PA surgery and day 7 after ALB and PA surgery, while energy metabolism indexes in the experimental group were lower than the control group on day 2 and day 7 after FPG and TG surgery with significant difference(P<0.05). The levels of IgA, IgG, IgM, CD3+, CD4+ and CD4+/CD8+ in the experimental group were higher than those in the control group 7 days after surgery, with significant differences (P<0.05). The levels of CRP, TNF- and IL-6 in the experimental group were lower than those in the control group 7 days after surgery, and the difference was significant(P<0.05). There was no significant difference in postoperative complications between the two groups. CONCLUSIONS: Dynamic nutrition support can improve postoperative energy metabolism of patients with oral and maxillofacial tumors, improve immune function, and alleviate stress response.

Ssc-novel-miR-106-5p reduces lipopolysaccharide-induced inflammatory response in porcine endometrial epithelial cells by inhibiting the expression of the target gene mitogen-activated protein kinase kinase kinase 14 (MAP3K14).

As an important gram-negative bacterial outer membrane component, lipopolysaccharide (LPS) plays an important role in bacterial-induced endometritis in sows. However, how LPS induces endometritis is unclear. We stimulated sow endometrial epithelial cells (EECs) with LPS and detected cell viability and tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) secretion. LPS affected EEC viability and TNF-α and IL-1 secretion in a dose-dependent manner. LPS induced differential expression in 10 of 393 miRNAs in the EECs (downregulated, nine; upregulated, one). MicroRNA (miRNA) high-throughput sequencing of the LPS-induced EECs plus bioinformatics analysis and the dual-luciferase reporter system revealed a novel miRNA target gene: mitogen-activated protein kinase kinase kinase 14 (MAP3K14). Ssc-novel-miR-106-5p mimic, inhibitor and the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation inhibitor Bay11-7085 were used to detect EEC nuclear factor-κB phosphorylation levels (p-NF-κB) and TNF-α and IL-1 secretion. MiR-106-5p mimic downregulated MAP3K14 mRNA and protein expression levels, inhibited p-NF-κB levels and decreased IL-1 and TNF-α secretion, whereas miR-106-5p inhibitor had the opposite effect. Bay11-7085 inhibited p-NF-κB expression and TNF-α and IL-1 secretion. These results suggest that LPS downregulates ssc-novel-miR-106-5p expression in sow EECs to increase MAP3K14 expression, which increases p-NF-κB to promote IL-1 and TNF-α secretion.

[Effects of intrathecal administration of AM22-52 on mechanical allodynia and CCL2 expression in DRG in bone cancer rats].

The pain peptide adrenomedullin (AM) plays a pivotal role in pathological pain. The present study was designed to investigate the effect of blockade of AM receptor on bone cancer pain (BCP) and its mechanism. BCP was developed by inoculation of Walker 256 mammary gland carcinoma cells in the tibia medullary cavity of Sprague Dawley rats. The selective AM receptor antagonist AM22-52 was administered intrathecally on 15 d after the inoculation. Quantitative real-time PCR was used to detect mRNA level of CC chemokine ligand 2 (CCL2) in dorsal root ganglion (DRG). Double immunofluorescence staining was used to analyze the localizations of CCL2 and AM in DRG of normal rats. The results showed that, from 6 to15 d after the inoculation, the animals showed significant reduction in the mechanical pain threshold in the ipsilateral hindpaw, companied by the decline in bone density of tibia bone. The expression of CCL2 mRNA in DRG of BCP rats was increased by 3 folds (P < 0.001 vs saline group). Intrathecal administration of AM22-52 abolished bone cancer-induced mechanical allodynia and increase of CCL2 mRNA level (P < 0.001). In normal rats, CCL2 was co-localized with AM in DRG neurons. These results suggest that AM may play a role in the pathogenesis of BCP. The increased AM bioactivity up-regulates CCL2 expression in DRG, which may contribute to the induction of pain hypersensitivity in bone cancer.

Probing interaction of a fluorescent ligand with HIV TAR RNA.

Trans-activator of Transcription (Tat) antagonists could block the interaction between Tat protein and its target, trans-activation responsive region (TAR) RNA, to inhibit Tat function and prevent human immunodeficiency virus type 1 (HIV-1) replication. For the first time, a small fluorescence ligand, ICR 191, was found to interact with TAR RNA at the Tat binding site and compete with Tat. It was also observed that the fluorescence of ICR 191 could be quenched when binding to TAR RNA and recovered when discharged via competition with Tat peptide or a well-known Tat inhibitor, neomycin B. The binding parameters of ICR 191 to TAR RNA were determined through theoretical calculations. Mass spectrometry, circular dichroism and molecular docking were used to further confirm the interaction of ICR 191 with TAR RNA. Inspired by these discoveries, a primary fluorescence model for the discovery of Tat antagonists was built using ICR 191 as a fluorescence indicator and the feasibility of this model was evaluated. This ligand-RNA interaction could provide a new strategy for research aimed at discovering Tat antagonists.

MnO2 nanosheet-assisted ligand-DNA interaction-based fluorescence polarization biosensor for the detection of Ag+ ions.

Silver (Ag+) ions are highly toxic to aquatic organisms and accumulate in the human body via the food chain. Therefore, the development of sensitive and selective quantitative analytical methods for detecting trace amounts of these ions is necessary. In the present study, a MnO2 nanosheet-assisted, ligand-DNA interaction and fluorescence polarization-based method was developed, for the first time, for sensitive detection of Ag+. The addition of Ag+ to the preformed proflavine-DNA complex induced the release of proflavine, which elicited weak changes in fluorescence polarization. The subsequent addition of MnO2 nanosheets magnified the observed changes, making this a feasible method for the detection of Ag+. The calibration graphs indicated good linearity over the concentration ranges of 30-240nM for Ag+, with a detection limit (S/N=3) of 9.1nM. This method additionally exhibits high selectivity. The mechanism underlying the changes in fluorescence polarization caused by the addition of Ag+ in the presence of MnO2 nanosheets was further explored in this study. These findings demonstrate that the present MnO2 nanosheet-assisted fluorescence polarization biosensor may represent a promising tool for the detection of Ag+ ions. The results for practical detecting Ag+ proved that this biosensor can be applied to environmental water sample analysis.

A ratiometric fluorescence RRE RNA-targeted assay for a new fluorescence ligand.

The Rev protein regulates HIV-1 gene expression. Small ligands that bind to the Rev response element (RRE) RNA would inhibit Rev function and suppress HIV-1 replication. A novel ratiometric fluorescence assay was applied in the present study to monitor ligand-RNA interactions by using red-emitting CdTe quantum dots (QDs) coated with silica as a reference. A small fluorescence ligand, ICR 191, was found to interact with RRE at the Rev binding site and compete with the Rev peptide. After adding red-emitting QDs to the interaction system, it was observed that ICR 191 did not fluoresce upon the addition of RRE, and fluorescence recovered when ICR 191 was displaced by a Rev model peptide, whereas the fluorescence of QDs remained constant. Furthermore, variations in the fluorescence ratios between ICR 191 and QDs were exploited to characterize the interactions of Rev with two known antagonists, neomycin B and tobramycin, by using RRE RNA with ICR 191 as a fluorescence indicator. Together, our results demonstrated that ratiometric fluorescence-based nanotechnology applications can be used for ligand-RNA interaction assays. This ICR 191-RRE RNA interaction assay can potentially be developed to build a screening model for assessing antagonists of the Rev binding element in RRE.

Selective detection of 2,4,6-trinitrophenol based on a fluorescent nanoscale bis(8-hydroxyquinoline) metal complex.

The reliable and accurate detection of explosives such as 2,4,6-trinitrophenol (TNP) and 2,4,6-trinitrotoluene (TNT) is in high demand for homeland security and public safety. Although extremely high sensitivity towards TNT has been demonstrated, detection of TNP remains a challenge. In this work, a fluorescent nanoscale complex composed of bis(8-hydroxyquinoline) and Al(3+) ions has been prepared, characterized and applied in detection of TNP. This complex exhibits the ability to sense the nitro explosive TNP via a fluorescence quenching mechanism with high selectivity. A simple paper test system for the rapid monitoring of TNP was also investigated. The results show that Bhq-Al is a quite ideal sensing material for trace-level detection of TNP.

A sensitive aptasensor for colorimetric detection of adenosine triphosphate based on the protective effect of ATP-aptamer complexes on unmodified gold nanoparticles.

Adenosine triphosphate (ATP) is the most direct source of energy in organisms. This study is the first to demonstrate that ATP-aptamer complexes provide greater protection for unmodified gold nanoparticles (AuNPs) against salt-induced aggregation than either aptamer or ATP alone. This protective effect was confirmed using transmission electron microscopy, dynamic light scattering, Zeta potential measurement, and fluorescence polarization techniques. Utilizing controlled particle aggregation/dispersion as a gauge, a sensitive and selective aptasensor for colorimetric detection of ATP was developed using ATP-binding aptamers as the identification element and unmodified AuNPs as the probe. This aptasensor exhibited a good linear relationship between the absorbance and the logarithm concentration of ATP within a 50-1000 nM range. ATP analogs such as guanosine triphosphate, uridine triphosphate and cytidine triphosphate resulted in little or no interference in the determination of ATP.

Cloning and expression analysis of interferon regulatory factor 7 in the Pacific cod, Gadus macrocephalus.

Interferon regulatory factor 7 (IRF7) plays an important role in regulating the response of type I interferon (IFN) to viral infection. To understand the mechanisms underlying immune reactions in the Pacific cod, Gadus macrocephalus, the gene encoding G. macrocephalus IRF7 was cloned and characterized. The cDNA of G. macrocephalus IRF7 was also cloned and sequenced. A cDNA sequence of 2032 bp was assembled using polymerase chain reaction (PCR) products. It contains an open reading frame of 1323 bp in length, which encoded a 440-amino acid polypeptide that comprised a DNA-binding domain (DBD), an IRF association domain (IAD), and a serine-rich domain (SRD). In the DBD, the tryptophan cluster consisted of only four tryptophans, which is a unique characteristic in fish IRF7. The mRNA of IRF7 was detected in various tissues, including in the spleen, thymus, kidney, intestine, and gills, using relative quantification PCR (R-qPCR). Dynamic expression of IRF7 was observed in larvae throughout post-hatching (ph) development, with the highest level detected at day of ph (dph) 25. Response to immune stimulation was examined by challenging larvae with polyriboinosinic polyribocytidylic acid (pIC) to mimic viral infection and elicit an immune reaction. R-qPCR revealed that the expression of IRF7 significantly increased in pIC-treated groups relative to that in the control groups, in a time-dependent manner, with peak responses at 48 and 72 h after pIC-treatment. These results show that IRF7 is expressed in various tissues of adult fish and larvae and is sensitive to viral infection, suggesting that it plays a role in antiviral immune defense in G. macrocephalus.

Fluorescent DNA-Protected Silver Nanoclusters for Ligand-HIV RNA Interaction Assay.

Studying ligand-biomacromolecule interactions provides opportunities for creating new compounds that can efficiently regulate specific biological processes. Ribonucleic acid (RNA) molecules have become attractive drug targets since the discovery of their roles in modulating gene expression, while only a limited number of studies have investigated interactions between ligands and functional RNA molecules, especially those based on nanotechnology. DNA-protected silver nanoclusters (AgNCs) were used to investigate ligand-RNA interactions for the first time in this study. The anthracycline anticancer drug mitoxantrone (MTX) was found to quench the fluorescence of AgNCs. After adding human immunodeficiency virus trans-activation responsive region (TAR) RNA or Rev-response element (RRE) RNA to AgNCs-MTX mixtures, the fluorescence of the AgNCs recovered due to interactions between MTX with RNAs. The binding constants and number of binding sites of MTX to TAR and RRE RNA were determined through theoretical calculations. MTX-RNA interactions were further confirmed in fluorescence polarization and mass spectrometry experiments. The mechanism of MTX-based fluorescence quenching of the AgNCs was also explored. This study provides a new strategy for ligand-RNA binding interaction assay.

[Expression and distribution of SDF-1 in the soft tissue healing of tooth extraction].

PURPOSE: To observe the expression and distribution of stromal cell derived factor -l (SDF-1) in the soft tissues after tooth extraction, in order to provide new ideas to promote wound healing of tooth extraction. METHODS: Thirty male Wistar rats were randomly divided into 10 groups. After extracting the first molar of left mandibular respectively, immunohistochemistry and RT-PCR technique were used to evaluate the distribution and expression of SDF-1 1, 2, 4, 7 and 10 days after extraction. Data processing was performed using SPSS 12.0 software package. RESULTS: Immunohistochemical staining showed the SDF-1 protein was strongly expressed at the gingival tissues around tooth extraction wound at early stage, mainly in the cytoplasm and intercellular substance of the stratum spinosum and stratum basale, and stained more obviously closer to the stratum basale. Four days after tooth extraction, the expression of SDF-1 in the stratum basale became more evident, and it is also positive inside endothelial cells of granulation tissues. Seven days after tooth extraction, the staining became uniform in the gingival epithelium, and a few positive staining of vascular endothelial cells could be found in lamina propria; Ten days after tooth extraction, the staining characteristics were similar to the normal gingiva. RT-PCR results showed that SDF-1mRNA underwent a biphasic expression change during gingival wound healing. SDF-1 mRNA level reached peak at day 1 after tooth extraction (P<0.01) but decreased by day 2. However, the SDF-1 mRNA level increased again to a peak at day 4 and then returned to a normal level by day 10 (P>0.05). CONCLUSIONS: SDF-1 is involved in the early soft tissue healing process, and may play a role as a promoter in tooth extraction healing. Supported by Young Scientists Award Fund of Shangdong Province(BS2013YY056) and Sci-tech Development Planning Program of Jinan City (2013-60).

Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.