Supramolecular Aggregation of Carbon Nanodots.

Supramolecular aggregation has provided the archetype concept to understand the variants in an emerging systems property. Herein, we have achieved the supramolecular assembly of carbon nanodots (CDs) for the first time and employ supramolecular aggregation to understand their alteration in photophysical properties. In detail, we have employed the CDs as a block to construct the supramolecular assembly of aggregates in the CDs' antisolvent of ethanol. The CD-based aggregates exhibit complex and organized morphologies with another long-wavelength excitation-dependent emission band. The experimental results and density functional theoretical calculations reveal that the supramolecular assembly of CDs can decrease the energy gap between the ground and excited states, contributing to the new long-wavelength excitation-dependent emission. The supramolecular aggregation can be employed as one universal strategy to manipulate and understand the luminescence of CDs. These findings cast new light to build the emerging systems and understand the light emission of CDs through supramolecular chemistry.

Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines.

Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.

Chemiluminescent carbon nanodots for dynamic and guided antibacteria.

Advanced antibacterial technologies are needed to counter the rapid emergence of drug-resistant bacteria. Image-guided therapy is one of the most promising strategies for efficiently and accurately curing bacterial infections. Herein, a chemiluminescence (CL)-dynamic/guided antibacteria (CDGA) with multiple reactive oxygen species (ROS) generation capacity and chemiexcited near-infrared emission has been designed for the precise theranostics of bacterial infection by employing near-infrared emissive carbon nanodots (CDs) and peroxalate as CL fuels. Mechanistically, hydrogen peroxide generated in the bacterial microenvironment can trigger the chemically initiated electron exchange between CDs and energy-riched intermediate originated from the oxidized peroxalate, enabling bacterial induced inflammation imaging. Meanwhile, type I/II photochemical ROS production and type III ultrafast charge transfer from CDs under the self-illumination can inhibit the bacteria proliferation efficiently. The potential clinical utility of CDGA is further demonstrated in bacteria infected mice trauma model. The self-illuminating CDGA exhibits an excellent in vivo imaging quality in early detecting wound infections and internal inflammation caused by bacteria, and further are proven as efficient broad-spectrum antibacterial nanomedicines without drug-resistance, whose sterilizing rate is up to 99.99%.

Molecular characterization of a teleost-specific toll-like receptor 22 (tlr22) gene from yellow catfish (Pelteobagrus fulvidraco) and its transcriptional change in response to poly I:C and Aeromonas hydrophila stimuli.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that can recognize pathogen-associated molecular patterns (PMPs) and play important roles in the innate immune system in vertebrates. In this study, we identified a teleost-specific tlr22 gene from yellow catfish (Pelteobagrus fulvidraco) and its immune roles in response to different pathogens were also determined. The open reading frame (ORF) of the tlr22 was 2892 bp in length, encoding a protein of 963 amino acids. Multiple protein sequences alignment, secondary and three-dimensional structure analyses revealed that TLR22 is highly conserved among different fish species. Phylogenetic analysis showed that the phylogenetic topology was divided into six families of TLR1, TLR3, TLR4, TLR5, TLR7 and TLR11, and TLR22 subfamily was clustered into TLR11 family. Meanwhile, synteny and gene structure comparisons revealed functional and evolutionary conservation of the tlr22 gene in teleosts. Furthermore, tlr22 gene was shown to be widely expressed in detected tissues except barbel and eye, with highest expression level in liver. The transcription of tlr22 was significantly increased in spleen, kidney, liver and gill tissues at different timepoints after Poly I:C infection, suggesting TLR22 plays critical roles in defensing virus invasion. Similarly, the transcription of tlr22 was also dramatically up-regulated in spleen, kidney and gill tissues with different patterns after Aeromonas hydrophila infection, indicating that TLR22 is also involved in resisting bacteria invasion. Our findings will provide a solid basis for the investigation the immune functions of tlr22 gene in teleosts, as well as provide useful information for disease control and treatment for yellow catfish.

In Situ Confining Citric Acid-Derived Carbon Dots for Full-Color Room-Temperature Phosphorescence.

Room-temperature phosphorescence has received much attention owing to its potential applications in information encryption and bioelectronics. However, the preparation of full-color single-component-derived phosphorescent materials remains a challenge. Herein, a facile in situ confining strategy is proposed to achieve full-color phosphorescent carbon dots (CDs) through rapid microwave-assisted carbonization of citric acid in NaOH. By tuning the mass ratio of citric acid and NaOH, the obtained CDs exhibit tunable phosphorescence wavelengths ranging from 483 to 635 nm and alterable lifetimes from 58 to 389 ms with a synthesis yield of up to 83.7% (>30 g per synthesis). Theoretical calculations and experimental results confirm that the formation of high-density ionic bonds between cations and CDs leads to efficient afterglow emission via the dissociation of CD arrangement, and the evolution of the aggregation state of CDs results in redshifted phosphorescence. These findings provide a strategy for the synthesis of new insights into achieving and manipulating room-temperature phosphorescent CDs, and prospect their applications in labeling and information encryption.

Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.

INTRODUCTION: The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP). METHODS: Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. RESULTS: In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. CONCLUSIONS: These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.

Conserved Role of mTORC1 Signaling in B Cell Immunity in Teleost Fish.

Mammalian studies have demonstrated that B cell immune responses are regulated by mechanistic target of rapamycin complex 1 (mTORC1) signaling. Teleost fish represent the oldest living bony vertebrates that contain bona fide B cells. So far, whether the regulatory mechanism of mTORC1 signaling in B cells occurred in teleost fish is still unknown. In this study, we developed a fish model by using rapamycin (RAPA) treatment to inhibit mTORC1 signaling and demonstrated the role of mTORC1 signaling in teleost B cells. In support, we found inhibition of mTORC1 signaling by RAPA decreased the phagocytic capacity, proliferation, and Ig production of B cells. Critically, Flavobacterium columnare induced specific IgM binding in serum, and these titers were significantly inhibited by RAPA treatment, thus decreasing Ab-mediated agglutination of F. columnare and significantly increasing the susceptibility of fish upon F. columnare reinfection. Collectively, our findings elucidated that the mTORC1 pathway is evolutionarily conserved in regulating B cell responses, thus providing a new point for understanding the B cells functions in teleost fish.

Study on the cohesive shear characteristics and intrinsic modelling of the root-tailing soil interface of Amorpha fruticosa.

To study the soil consolidation effect of shrub plant roots on tailings soil and to explore the frictional characteristics of plant roots on tailings soil, three experimental conditions of the root-soil interface were established by using a modified indoor direct shear instrument with binders such as liquid sodium silicate and cyanoacrylate to conduct direct shear frictional tests at the root-soil interface using the roots of the typical slope protection plant Amorpha fruticosa. The Gompertz improved curve model was established by using the relationship between shear stress and shear displacement and the trend of the root-soil interface parameter index. The results were compared between the improved Gompertz curve model and the Clough-Duncan hyperbolic model, and a two-factor coupled improved Gompertz interfacial intrinsic structure model with normal stress and cohesive strength factor was established. The results showed that the interface shear stress and shear displacement showed strain hardening characteristics at different normal pressures for cohesive strength ratios of 1.5 and 1.7 at the root-tailing soil interface. At a cohesive strength ratio of 1.6, strain-softening was observed from 100 to 300 kPa and strain hardening was observed at 400 kPa. The improved Gompertz curve model predicts the shear stress and shear displacement curves at the root-soil interface with different cohesive strengths more reasonably than the Clough-Duncan hyperbolic model, and the maximum accuracy can be improved by nearly 40%. The two-factor coupled improved Gompertz curve model can fit the shear stress versus shear displacement relationship at the A. fruticosa root-tailing soil interface.

The Microbial Mechanisms of a Novel Photosensitive Material (Treated Rape Pollen) in Anti-Biofilm Process under Marine Environment.

Marine biofouling is a worldwide problem in coastal areas and affects the maritime industry primarily by attachment of fouling organisms to solid immersed surfaces. Biofilm formation by microbes is the main cause of biofouling. Currently, application of antibacterial materials is an important strategy for preventing bacterial colonization and biofilm formation. A natural three-dimensional carbon skeleton material, TRP (treated rape pollen), attracted our attention owing to its visible-light-driven photocatalytic disinfection property. Based on this, we hypothesized that TRP, which is eco-friendly, would show antifouling performance and could be used for marine antifouling. We then assessed its physiochemical characteristics, oxidant potential, and antifouling ability. The results showed that TRP had excellent photosensitivity and oxidant ability, as well as strong anti-bacterial colonization capability under light-driven conditions. Confocal laser scanning microscopy showed that TRP could disperse pre-established biofilms on stainless steel surfaces in natural seawater. The biodiversity and taxonomic composition of biofilms were significantly altered by TRP (p < 0.05). Moreover, metagenomics analysis showed that functional classes involved in the antioxidant system, environmental stress, glucose−lipid metabolism, and membrane-associated functions were changed after TRP exposure. Co-occurrence model analysis further revealed that TRP markedly increased the complexity of the biofilm microbial network under light irradiation. Taken together, these results demonstrate that TRP with light irradiation can inhibit bacterial colonization and prevent initial biofilm formation. Thus, TRP is a potential nature-based green material for marine antifouling.

PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1.

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

Au25 Nanoclusters Incorporating Three-Dimensionally Ordered Macroporous In2O3 for Highly Sensitive and Selective Formaldehyde Sensing.

Detection of formaldehyde (FA) in the atmosphere is of significant importance because exposure to FA may cause serious health problems such as sick-house syndrome, leukemia, and cancer. Modifying metal oxide semiconductors (MOSs) with noble metal nanoparticles (NPs) is an efficient method to enhance FA-sensing properties. Herein, a series of Au25 nanocluster (NC)-decorated three-dimensionally ordered macroporous In2O3 materials (Au25/3DOM In2O3) is created, and the loading amount of Au25 NCs was optimized based on FA responses. To reveal the effect of gold size on FA responses, we constructed Au144 NC-loaded 3DOM In2O3 and Au NP (2.9 nm)-modified 3DOM In2O3 and compared their gas-sensing properties with the optimal Au25/3DOM In2O3. The results show that in comparison with its counterparts, the optimal Au25/3DOM In2O3 presents higher sensitivity, shorter response/recovery times, better selectivity, and excellent reproducibility. More attractively, the responses to FA are dependent on the size of Au particles loaded on In2O3. We suggest that the enhanced FA responses for the optimal material are mainly attributed to the electronic and chemical-sensitization effects of Au25 NCs, and the size-dependent effect of FA responses is ascribed to the size of Au NPs affecting the formation of oxygen-adsorbing species. This work provides an efficient way for fabricating noble metal NP-loaded MOSs with tunable gas-sensing properties.

Diketopiperazine and enterotoxin analogues from the mangrove derived-soil Streptomyces sp. SCSIO 41400 and their biological evaluation.

A new diketopiperazine, cyclo-(d-8-acetoxyl-Pro-l-Leu) (1), together with eight known compounds (2-9) including three enterotoxins (2-4), four diketopiperazines (5-8) and maltol (9), were isolated from the mangrove derived-soil Streptomyces sp. SCSIO 41400. The planar structures of all compounds were determined from analysis of NMR spectra, MS, optical rotation and comparing with literature data. The absolute configuration of compound 1 was assigned by electronic circular dichroism (ECD). The isolated compounds (1-9) were tested for their acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Among them, the new diketopiperazine (1) displayed preferable PL enzyme inhibitory activity with IC50 value of 27.3 µg/mL, while compounds 2, 5 and 6 showed weak PL enzyme inhibitory activity. Further molecular docking simulation exhibited that compound 1 could be well bind with the catalytic pocket of the PL. Besides, compound 9 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with MIC value of 12.5 µg/mL, which was comparable to that of the positive control ampicillin with MIC value of 3.125 µg/mL.

Citrinin and α-pyrone derivatives with pancreatic lipase inhibitory activities from Penicillium sp. SCSIO 41302.

One new citrinin monomer derivative (1), and two new natural products α-pyrone analogues (2a and 2b), were isolated from the sponge derived fungus Penicillium sp. SCSIO 41302. Their structures were determined by extensive spectroscopic analysis, chiral-phase HPLC analysis, modified Mosher's method, ECD calculations, and X-ray single-crystal diffraction. Bioactivity screening showed that compounds 2b and 8 exhibited obvious inhibitory activities against pancreatic lipase and acetyl cholinesterase with IC50 values of 48.5 and 4.8 µM, respectively, which indicated that different chiral center between enantiomers (2a and 2b) might result in different biological activities (IC50 value against PL for 2a >100 µg/ml).

Bioinformatics analyses of gene expression profile identify key genes and functional pathways involved in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.

Atorvastatin inhibits malignant behaviors and induces apoptosis in human glioma cells by up-regulating miR-146a and inhibiting the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells.@*METHODS@#Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway.@*RESULTS@#AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05).@*CONCLUSION@#AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.

Characterization of MRF genes and their tissue distributions and analysis of the effects of starvation and refeeding on the expression of these genes in Acipenser dabryanus muscle.

The purpose of the study was to clone the sequences of myogenic regulatory factors in Acipenser dabryanus and explore the changes in their expression during starvation and refeeding in A. dabryanus muscle. One hundred twenty fish (60.532 ± 0.284 g) were randomly assigned to four groups (fasted for 0, 3, 7 or 14 d and then refed for 14 d). Our predictions showed that the coding sequences of myod1, myf5, myog and myf6 in A. dabryanus encoded 275, 248, 248 and 243 amino acids, respectively, and the expression of the four genes was the highest in muscle. During fasting, the expression of myod1 in muscle was significantly decreased in the 14 d group. The expressions of myf5 and myf6 were increased significantly at first and then decreased with prolonged starvation time. The expression of myog in the 14 d group was significantly decreased compared with other groups (P < 0.05). During refeeding, the highest values of myod1 and myf6 expression were found in the 3 d group (P < 0.05).The expressions of myf5 and myog in 0 d and 3 d group were significantly higher than those in 7 d and 14 d group (P < 0.05). These results indicate that myogenic regulatory factors (MRFs) play important roles in muscle growth and development in A. dabryanus. The inhibition of long-term starvation (14 d) on the expression of myogenic regulatory factors is probably one of the reasons why it can not achieve full compensation for growth.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Analysis of radiation force on a uniaxial anisotropic sphere by dual counter-propagating Gaussian beams.

Based on Maxwell's stress tensor and the generalized Lorenz-Mie theory, a theoretical approach is introduced to study the radiation force exerted on a uniaxial anisotropic sphere illuminated by dual counter-propagating (CP) Gaussian beams. The beams propagate with arbitrary direction and are expanded in terms of the spherical vector wave functions (SVWFs) in a particle coordinate system using the coordinate rotation theorem of the SVWFs. The total expansion coefficients of the incident fields are derived by superposition of the vector fields. Using Maxwell stress tensor analysis, the analytical expressions of the radiation force on a homogeneous absorbing uniaxial anisotropic sphere are obtained. The accuracy of the theory is verified by comparing the radiation forces of the anisotropic sphere reduced to the special cases of an isotropic sphere. In order to study the equilibrium state, the effects of beam parameters, particle size parameters, and anisotropy parameters on the radiation force are discussed in detail. Compared with the isotropic particle, the equilibrium status is sensitive to the anisotropic parameters. Moreover, the properties of optical force on a uniaxial anisotropic sphere in a single Gaussian beam trap and Gaussian standing wave trap are compared. It indicates that the CP Gaussian beam trap may more easily capture or confine the anisotropic particle. However, the radiation force exerted on an anisotropic sphere exhibits very different properties when the beams do not propagate along the primary optical axis. The influence of the anisotropic parameter on the radiation force by CP Gaussian beams is different from that of a single Gaussian beam. In summary, even for anisotropic particles, the Gaussian standing wave trap also exhibits significant advantages when compared with the single Gaussian beam trap. The theoretical predictions of radiation forces exerted on a uniaxial anisotropic sphere by dual Gaussian beams provide effective ways to achieve the improvement of optical tweezers as well as the capture, suspension, and high-precision delivery of anisotropic particles.

MiR-499a-5p promotes 5-FU resistance and the cell proliferation and migration through activating PI3K/Akt signaling by targeting PTEN in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) can be considered a representative cancer type of the human body. As demonstrated by some studies, microRNA (miR)-499 is dysregulated in various cancer types including PC, for which chemotherapy involving 5-fluorouracil (5-FU) has long been considered the first-line therapy. However, there are complex and comprehensive mechanisms related to 5-FU, which have not been fully elucidated. This study thus aimed to examine the molecular mechanisms of 5-FU resistance through miR-499a-5p in PC. METHODS: The expression of miR-499a-5p in PC was measured using quantitative polymerase chain reaction (PCR). MiR-499a-5p was examined in-vivo for its effects on the malignant phenotypes of PC cells. RESULTS: The results of the present study demonstrated miR-499a-5p to be upregulated in PC and 5-FU resistant PC tissues. According to in vitro assays in PC cells (PANC1/FR), miR-499a-5p was found to affect adenosine triphosphate (ATP) binding cassette subfamily B member 1 (P-gp), ATP binding cassette subfamily C member 1 (MRP1), and ATP binding cassette subfamily G member 2 (BCRP), thereby facilitating 5-FU resistance in PC cells. Functions assays indicated that suppressed miR-499a-5p expression inhibited the proliferation and migration of cells but facilitated apoptosis in the PC cell line; by contrast, miR-499a-5p overexpression triggered the inverse phenotypic changes of cells. Concerning the mechanisms involved, miR-499a-5p increased PI3K/Akt signaling by targeting phosphatase and tensin homolog (PTEN). CONCLUSIONS: Taken together, these findings demonstrate that miR-499a-5p can be potentially applied to PC therapy.

IgT Plays a Predominant Role in the Antibacterial Immunity of Rainbow Trout Olfactory Organs.

The olfactory organs (OOs) of vertebrates play important roles in their extraordinary chemosensory capacity, a process during which they are continuously exposed to environmental pathogens. Nasopharynx-associated lymphoid tissue (NALT) contains B cells and immunoglobulins (Igs), which function as the first defense line against antigens in mammals and also exist in teleosts. However, the immune responses of teleost NALT B cells and Igs during bacterial infection remain largely uncharacterized. In this study, rainbow trout were infected with Flavobacterium columnare via continuous immersion, after which the adaptive immune responses within NALT were evaluated. F. columnare could invade trout nasal mucosa and cause histopathological changes in trout OO. Moreover, the accumulation of IgT+ B cells in trout nasal mucosa was induced by bacterial challenge, which was accompanied by strong bacteria-specific IgT responses in the nasal mucus. Importantly, our study is the first to report local nasal-specific immune responses in teleosts during bacterial challenge by characterizing the local proliferation of IgT+ B cells and generation of bacteria-specific IgT in trout OOs after F. columnare infection. In addition to the strong IgT and IgT+ B cells responses in OO, bacteria-specific IgT and IgM were also detected in serum following bacterial challenge. Taken together, our findings suggest that IgT functions as an important mucosal Ig in teleost NALT and mediates local adaptive immunity during bacterial infection, which is similar to their protective role during parasitic infection.