ABSTRACT
OBJECTIVE: Given the implications of concurrent human papilloma viral infection (HPV) in the prognostic course and implications on therapeutic approached of patients with oral squamous cell carcinoma (OSCC), we seek to investigate the implications that P16 expression has on the clinical course and pathological appearance of patients with OSCC and concurrent infection. METHODS: Using S-P immunohistochemistry, we examined the expression of P16 and Ki67 in 460 patients with OSCC. We compared the expression of the protein between the tumor cells and normal epithelial mucosa within the same patient. The clinical and pathological characteristics (including gender, age, histological grade, lymph node metastasis, clinical stage, clinical recurrence, tumor diameter, Ki67 proliferation index) were analyzed by stratification statistically. RESULTS: In total 460 cases of OSCC were identified and expression of P16 was significantly higher in the OSCC group compared to the normal mucosal epithelial group (X2 = 60.545, p = .000). There also appear to be a gender predilection as the expression was higher in females compared to males (0.218 vs. 0.144, X2 = 3.921, p = .048). Younger age also appears to be a predictive factor as those under 35 years old had higher expression of the protein compared to those over 35 years old (0.294 vs. 0.157, X2 = 4.230, p = .040). P16 positivity showed a significant positive correlation with histologic grade (X2 = 4.114, p = .043). In addition, the positive rate of P16 was higher in patients with ki67 over 85% (0.455 vs. 0.160, X2 = 6.667, p = .023). CONCLUSION: OSCC with HPV infection tends to occur more frequently in female patients and those under 35 years of age. HPV infection with expression of the P16 and ki67 protein may promote the proliferation and growth of OSCC at a higher frequency.
Subject(s)
Carcinoma, Squamous Cell , Cyclin-Dependent Kinase Inhibitor p16 , Ki-67 Antigen , Mouth Neoplasms , Papillomavirus Infections , Humans , Female , Male , Mouth Neoplasms/pathology , Mouth Neoplasms/virology , Mouth Neoplasms/metabolism , Middle Aged , Adult , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Ki-67 Antigen/metabolism , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Papillomavirus Infections/pathology , Papillomavirus Infections/metabolism , Papillomavirus Infections/virology , Aged , Papillomaviridae/isolation & purification , Immunohistochemistry , Sex Factors , Lymphatic Metastasis , Aged, 80 and over , Human Papillomavirus VirusesABSTRACT
BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.
ABSTRACT
Liver fibrosis is a pathological process that endangers human health, for which effective treatments remain elusive to date. Paeoniflorin (PAE), a pineane-type monoter penoid compound from the traditional Chinese medicine PaeoniaeRubra Radix, and metformin (MET), an oral biguanide hypoglycemic agent, both demonstrate anti-inflammatory and hepatoprotective effects. In current work, we first discovered that the combined treatment of PAE and MET synergistically inhibited the progression of liver fibrosis in two different animal models: therapeutic and preventive. This therapeutic effect is evidenced by a reduction in the expression levels of liver fibrosis markers and an improvement in histopathological characteristics. Mechanistic exploration further revealed that this combination therapy downregulated the expression of TGF-ß1 and p-Smad2, while upregulating Smad7 expression in both models. Importantly, we also found that this combinatorial approach significantly reduced hepatotoxicity and nephrotoxicity in both models. Our findings suggest an effective combination therapy for liver fibrosis and provide the possibility of therapeutic improvement for patients with liver fibrosis.
ABSTRACT
Transition metal carbides modified by Au nanoparticles (Au/Ti3C2) were synthesized and developed as a colorimetric sensor for the determination of H2O2 and ampicillin. The surface electrical properties of Ti3C2 were changed, and Au nanoparticles (AuNPs) and gold growth solution were synthesized simultaneously. Au/Ti3C2 was obtained by seed growth method with AuNPs modified on the surface of transition metal carbides, nitrides or carbon-nitrides (Ti3C2 MXenes). The synthesized AuNPs and Ti3C2 had no peroxidase-like activity, but Au/Ti3C2 had. The peroxidase catalytic mechanism was due to electron transfer. The peroxidase activity of Au/Ti3C2 can be utilized for the determination of H2O2. The linear range of Au/Ti3C2 for H2O2 was 1-60 µM, and the detection limit was 0.12 µM (S/N = 3). A colometric sensor for ampicillin detection based on Au/Ti3C2 was further constructed since S in ampicillin formed an Au-S bond with Au/Ti3C2, leading to the weakening of its peroxidase-like property. The change of peroxidase-like property attenuated oxidation of TMB, and the ampicillin content was inversely proportional to the concentration of oxidized TMB, and the blue color of solution faded, which enabled the determination of ampicillin. The linear range for ampicillin was 0.005-0.5 µg mL- 1, and the detection limit was 1.1 ng mL- 1 (S/N = 3). The sensor was applied to the detection of ampicillin in milk and human serum.
Subject(s)
Gold , Metal Nanoparticles , Humans , Gold/chemistry , Colorimetry/methods , Hydrogen Peroxide/chemistry , Metal Nanoparticles/chemistry , Titanium , Peroxidase/chemistry , PeroxidasesABSTRACT
S-adenosylmethionine (SAM) was a methyl donor for modifying histones, which had crucial roles in lipid accumulation, tissue injury, and immune responses. SAM fluctuation might be linked to variations in histone methylation. However, the underlying molecular mechanisms of whether the SAM diet influenced the immune response via histone modification remained obscure. In this study, we utilized the Caenorhabditis elegans as a model to investigate the role of SAM diet in innate immunity. We found that 50 µM SAM increased resistance to Gram-negative pathogen Pseudomonas aeruginosa PA14 by reducing the bacterial burden in the intestine. Furthermore, through the genetic screening in C. elegans, we found that SAM functioned in germline to enhance innate immunity via an H3K4 methyltransferase complex to upregulate the immune response genes, including irg-1 and T24B8.5. Intriguingly, SAM also protected mice from P. aeruginosa PA14 infection by reducing the bacterial burden in lung. These findings provided insight into the mechanisms of molecular connections among SAM diet, histone modifications and innate immunity.
Subject(s)
Caenorhabditis elegans Proteins , Histones , Animals , Mice , Caenorhabditis elegans/genetics , Caenorhabditis elegans/microbiology , S-Adenosylmethionine , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Immunity, Innate , DietABSTRACT
The evolutionarily conserved insulin/IGF-1 signaling pathway plays a central role in aging and aging related diseases such as neurodegeneration diseases. Inhibition of insulin/IGF-1 signaling pathway has been proposed as an effective way to extend lifespan and delay neurodegeneration diseases in different organisms. Cynaroside (Cyn), a flavonoid contained in many medical plants and in vegetables, had been shown to exhibit pharmacological properties such as anti-inflammatory, anti-tumor, and anti-oxidant effects. The study demonstrated that lifespan extension and neurodegeneration diseases improving could be achieved by targeting evolutionarily conserved insulin/IGF-1 pathway through using pharmacological interventions. Via using this approach in tractable model Caenorhabditis elegans, we found that 10 µM Cynaroside significantly promoted the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Cynaroside acted on IGF-1-R /DAF-2, which was followed by the activation of transcription factor DAF-16/FOXO to extend the healthy lifespan. Intriguingly, Cynaroside also improved neurodegeneration diseases such as Alzheimer's and polyglutamine disease by suppressing insulin/IGF-1 signaling pathway. Our work suggests that Cynaroside may be a promising candidate for the prevention and treatment of aging and neurodegeneration diseases.
Subject(s)
Caenorhabditis elegans , Insulin-Like Growth Factor I , Insulin , Longevity , Signal Transduction , Animals , Caenorhabditis elegans/drug effects , Insulin-Like Growth Factor I/metabolism , Signal Transduction/drug effects , Longevity/drug effects , Insulin/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/prevention & control , Aging/drug effects , Aging/physiology , Luteolin/pharmacology , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/geneticsABSTRACT
Constitutive activation of STAT3 plays important role in the pathogenesis of colorectal cancer (CRC). Inhibition of STAT3 has been proposed as a reasonable strategy to suppress CRC. Gamabufotalin (Gam), an effective bioactive compound of ChanChu, has been used for cancer therapy due to its desirable metabolic stability and less adverse effect. However, its effect on CRC is still unclear. In this study, we found that Gam significantly inhibited the CRC in vitro and vivo. Furthermore, Gam induced apoptosis to inhibit the viability of HCT-116 and HT-29 cell lines in dose-dependent manner by suppressing the transcription factor STAT3. In addition, Gam was also found to inhibit carcinogenesis of colitis-associated cancer (CAC) in AOM/DSS mice model by inhibiting STAT3. Our findings suggest that Gam may be an effective way to prevent occurrence and development of CRC and CAC.
Subject(s)
Bufanolides , Colitis-Associated Neoplasms , Colitis , Colorectal Neoplasms , Animals , Mice , Colitis/complications , Colitis/drug therapy , Colitis/metabolism , Transcription Factors/metabolism , Signal Transduction , Cell Proliferation , Colorectal Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Dextran Sulfate/pharmacology , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
Schizandrin A (SA), also known as deoxyschizandrin, is one of the most biologically active lignans isolated from the traditional Chinese medicine Fructus schisandrae chinensis. Schisandrin A has proven benefits for anti-cancer, anti-inflammation, hepatoprotection, anti-oxidation, neuroprotection, anti-diabetes. But the influence of Schisandrin A to the innate immune response and its molecular mechanisms remain obscure. In this study, we found that Schisandrin A increased resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogen Listeria monocytogenes. Meanwhile, Schisandrin A protected the animals from the infection by enhancing the tolerance to the pathogens infection rather than by reducing the bacterial burden. Through the screening of the conserved immune pathways in Caenorhabditis elegans, we found that Schisandrin A enhanced innate immunity via p38 MAPK pathway. Furthermore, Schisandrin A increased the expression of antibacterial peptide genes, such as K08D8.5, lys-2, F35E12.5, T24B8.5, and C32H11.12 by activation PMK-1/p38 MAPK. Importantly, Schisandrin A-treated mice also enhanced resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Thus, promoted PMK-1/p38 MAPK-mediated innate immunity by Schisandrin A is conserved from worms to mammals. Our work provides a conserved mechanism by which Schisandrin A enhances innate immune response and boosts its therapeutic application in the treatment of infectious diseases.
Subject(s)
Caenorhabditis elegans Proteins , Cyclooctanes , Lignans , Polycyclic Compounds , Animals , Mice , p38 Mitogen-Activated Protein Kinases/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/microbiology , Immunity, Innate , MammalsABSTRACT
Mitochondria play roles in the resistance of Caenorhabditis elegans against pathogenic bacteria by regulating mitochondrial unfolded protein response (UPRmt). Caffeic acid (CA) (3,4-dihydroxy cinnamic acid) is a major phenolic compound present in several plant species, which exhibits biological activities such as antioxidant, anti-fibrosis, anti-inflammatory, and anti-tumor properties. However, whether caffeic acid influences the innate immune response and the underlying molecular mechanisms remains unknown. In this study, we find that 20 µM caffeic acid enhances innate immunity to resist the Gram-negative pathogen Pseudomonas aeruginosa infection in C. elegans. Meanwhile, caffeic acid also inhibits the growth of pathogenic bacteria. Furthermore, caffeic acid promotes host immune response by reducing the bacterial burden in the intestine. Through genetic screening in C. elegans, we find that caffeic acid promotes innate immunity via the transcription factor ATFS-1. In addition, caffeic acid activates the UPRmt and immune response genes for innate immune response through ATFS-1. Our work suggests that caffeic acid has the potential to protect patients from pathogen infection.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Caffeic Acids , Animals , Humans , Caenorhabditis elegans/microbiology , Caenorhabditis elegans Proteins/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Mitochondria/metabolismABSTRACT
The unfolded protein response (UPR) is an evolutionarily conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen during bacterial infection. The IRE-1/XBP-1 pathway is a major branch of the UPRER that has been conserved from yeast to human. Dioscin, a steroidal saponin exhibits a broad spectrum of properties. However, whether dioscin influences the immune response and the underlying molecular mechanisms remain obscure. We find that dioscin increases resistance to Gram-negative pathogen Pseudomonas aeruginosa. Furthermore, dioscin also inhibits the growth of pathogenic bacteria. Meanwhile, dioscin enhances the resistance to pathogens by reducing bacterial burden in the intestine. Through genetic screening, we find that dioscin activates the UPRER to promote innate immunity via IRE-1/XBP-1 pathway. Intriguingly, dioscin requires the neural XBP-1 for immune response. Our findings suggest that dioscin may be a viable candidate for the treatment of infectious diseases.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Diosgenin/analogs & derivatives , Animals , Humans , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Unfolded Protein Response , Immunity, Innate , Bacteria , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/metabolism , Carrier Proteins/metabolismABSTRACT
The resonant magnetoelectric (ME) effect of Fe78Si9B13/Pb(Zr,Ti)O3 (FeSiB/PZT) composites with a surface-modified Fe78Si9B13 amorphous alloy has been studied. The surface-modified FeSiB can improve the ME coefficient at the resonant frequency by optimizing the magnetomechancial power conversion efficiency. The maximum ME coefficient of the surface-modified ribbons combined with soft PZT (PZT5) is two-thirds larger than that of the composites with fully amorphous ribbons. Meanwhile, the maximum value of the ME coefficient with surface-modified FeSiB ribbons and hard PZT (PZT8) is one-third higher compared with the fully amorphous composites. In addition, experimental results of magnetomechanical coupling properties of FeSiB/PZT composites with or without piezoelectric layers indicate that the power efficiency of the composites first decreases and then increases with the increase in the number of FeSiB layers. When the surface crystalline FeSiB ribbons are combined with a commercially available hard piezoelectric ceramic plate, the maximum magnetoelectric coupling coefficient of the ME composite reaches 5522 V/(Oe*cm), of which the electromechanical resonant frequency is 23.89 kHz.
ABSTRACT
Increasing evidence indicate that the expression of defense genes at the right place and the right time are regulated by host-defense transcription factors. However, the precise mechanisms of this regulation are not well understood. Homeodomain transcription factors, encoded by homeobox genes, play crucial role for the development of multicellular eukaryotes. In this study, we demonstrated that homeodomain transcription factor CEH-37 (known as OTX2 in mammals) was a key transcription factor for host defense in Caenorhabditis elegans. Meanwhile, CEH-37 acted in the intestine to protect C. elegans against pathogen infection. We further showed that the homeodomain transcription factor CEH-37 positively regulated PMK-1/ p38 MAPK activity to promote the intestinal immunity via suppression phosphatase VHP-1. Furthermore, we demonstrated that this function was conserved, because the human homeodomain transcription factor OTX2 also exhibited protective function in lung epithelial cells during Pseudomonas aeruginosa infection. Thus, our work reveal that CEH-37/OTX2 is a evolutionarily conserved transcription factor for defense against pathogen infection. The finding provides a model in which CEH-37 decreases VHP-1 phosphatase activity, allowing increased stimulation of PMK-1/p38 MAPK phosphorylation cascade in the intestine for pathogen resistance.
Subject(s)
Caenorhabditis elegans Proteins , Transcription Factors , Animals , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Phosphoric Monoester Hydrolases/metabolism , Immunity, Innate , DNA-Binding Proteins/metabolism , Mammals/metabolism , Dual-Specificity PhosphatasesABSTRACT
Morphologically controllable ALG@ε-PL water-in-water microspheres were successfully prepared using a two-step method through precise control of the two-phase flow rate. Through further interfacial coagulation, the ALG@ε-PL microspheres possess a dense surface structure and good permeability. The sensor based on PtS2@ALG@ε-PL microspheres was constructed by encapsulating PtS2 nanosheets with peroxidase-like properties in ALG@ε-PL water-in-water microspheres. PtS2 nanosheets catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce blue oxTMB. The strong reducing property of the model analyte dopamine (DA) can reduce oxTMB, thus causing the blue color to fade and successfully achieving colorimetric detection of DA. The linear range of the assay is 2.0-200 µM, and the detection limit is 0.22 µM. The recoveries of DA in serum samples were determined by the spik method, and the results were reproducible.
Subject(s)
Nanoparticles , Peroxidase , Peroxidase/chemistry , Colorimetry/methods , Microspheres , Hydrogen Peroxide/chemistry , Polylysine , Oxidoreductases , Coloring Agents/chemistry , WaterABSTRACT
Understanding the growth mechanisms of III-nitride nanowires is of great importance to realise their full potential. We present a systematic study of silane-assisted GaN nanowire growth on c-sapphire substrates by investigating the surface evolution of the sapphire substrates during the high temperature annealing, nitridation and nucleation steps, and the growth of GaN nanowires. The nucleation step - which transforms the AlN layer formed during the nitridation step to AlGaN - is critical for subsequent silane-assisted GaN nanowire growth. Both Ga-polar and N-polar GaN nanowires were grown with N-polar nanowires growing much faster than the Ga-polar nanowires. On the top surface of the N-polar GaN nanowires protuberance structures were found, which relates to the presence of Ga-polar domains within the nanowires. Detailed morphology studies revealed ring-like features concentric with the protuberance structures, indicating energetically favourable nucleation sites at inversion domain boundaries. Cathodoluminescence studies showed quenching of emission intensity at the protuberance structures, but the impact is limited to the protuberance structure area only and does not extend to the surrounding areas. Hence it should minimally affect the performance of devices whose functions are based on radial heterostructures, suggesting that radial heterostructures remain a promising device structure.
ABSTRACT
Although extensively studied, it is unknown what is the major cellular energy driving tumor metastasis after anti-cancer radiotherapy. Metabolic reprogramming is one of the fundamental hallmarks in carcinogenesis and tumor progression featured with the increased glycolysis in solid tumors. However, accumulating evidence indicates that in addition to the rudimentary glycolytic pathway, tumor cells are capable of reactivating mitochondrial OXPHOS under genotoxic stress condition to meet the increasing cellular fuel demand for repairing and surviving anti-cancer radiation. Such dynamic metabolic rewiring may play a key role in cancer therapy resistance and metastasis. Interestingly, data from our group and others have demonstrated that cancer cells can re-activate mitochondrial oxidative respiration to boost an annexing energy to meet the increasing cellular fuel demand for tumor cells surviving genotoxic anti-cancer therapy with metastatic potential.
ABSTRACT
Hydrogen peroxide (H2O2) is produced in living organisms and is involved in a variety of redox-regulated processes. Therefore, the detection of H2O2 is important for tracing the molecular mechanisms of some biological events. Here, we demonstrated for the first time the peroxidase activity of PtS2-PEG NSs under the physiological conditions. PtS2 NSs were synthesized by mechanical exfoliation followed by functionalization with polyethylene glycol amines (PEG-NH2) to improve their biocompatibility and physiological stability. Fluorescence was generated by catalyzing the oxidation of o-phenylenediamine (OPD) by H2O2 in the presence of the PtS2 NSs. The proposed sensor had a limit of detection (LOD) of 248 nM and a detection range of 0.5-50 µM in the solution state, which was better than or comparable to previous reports in the literature. The developed sensor was further applied for the detection of H2O2 released from cells as well as for imaging studies. The results show that the sensor is promising for future applications in clinical analysis and pathophysiology.
Subject(s)
Fluorescent Dyes , Hydrogen Peroxide , Fluorescence , Hydrogen Peroxide/analysis , Limit of Detection , Oxidation-Reduction , Peroxidases , Platinum/chemistry , Sulfides/chemistry , Polyethylene Glycols/chemistry , NanostructuresABSTRACT
Delay aging, especially in healthy life extension, brought the most interest to the medical field. Searching for anti-aging drugs with relative safety profiles bring natural products in hotspot. In this study, we find that dioscin promotes the health span extension in wild-type Caenorhabditis elegans. Through the genetic screening in C. elegans, we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPRER transcription factor XBP-1 to upregulate transcription of the Δ9 desaturase FAT-5 and FAT-7, resulting in increased monounsaturated fatty acid content which requires for healthy life span extension. Intriguingly, through tissue-specific knockdown, we find that dioscin modulates the health span by activating SBP-1 in the intestine. Unexpectedly, dietary supplementation of POA and OA rescues XBP-1, SBP-1 mutants-induced shortened life span phenotype. Considering the conservation of MUFAs metabolism, dioscin may promote health span in other species, including mammals. Our work suggests that dioscin might be a promising candidate for developing anti-aging agent.
ABSTRACT
Objective: Investigate the influence of miR-107 on breast cancer cell growth and death through the PTEN/AKT signaling pathway. Method: As study subjects, the human breast cancer cell line MCF-7 and the normal breast cell line Hs 578Bst were chosen, and MCF-7 cells were, respectively, transfected with control miRNA and miR-107 inhibitor. CCK-8, flow cytometry, scratch assay, and Transwell assay were used to analyze the proliferation, apoptosis, and invasion, and in order to identify the proteins associated with apoptosis in each of the three categories, we used western blot analysis. Bcl-2, cleaved caspase-3, and cleaved caspase-9 expression, as well as PTEN/AKT signaling pathway-associated protein expression, are correlated. Result: The expression of miR-107 in MCF-7 cells was significantly greater than that in Hs 578Bst cells, with a P < 0.05 difference; compared to the blank and miRNA control groups, the miR-107 inhibitor group had a P < 0.05 difference. P < 0.05 showed a decrease in proliferation (42.52) but no difference in proliferation between the blank and miRNA control groups (P > 0.05); the miR-107 inhibitor group had higher apoptosis (38.96) with P < 0.05 than the blank group (4.85) and the miRNA control group (5.89); there was no difference in apoptosis between the blank and miRNA groups (P > 0.05). There was no significant difference between the blank group and the miRNA control group with P > 0.05; compared with the blank group, the miR-107 inhibitor group had a lower expression of Bcl-2 protein (0.18), in addition to the degraded paradigms (0.73) and caspase-9 protein concentrations (0.79), respectively. Conclusion: The PTEN/AKT signaling pathway may be regulated by miR-107 to limit breast cancer cell growth and increase apoptosis, which suggests that miR-107 may be exploited as a tumor marker for therapeutic therapy.
ABSTRACT
The DAF-2/DAF-16 insulin-like signaling pathway was an evolutionarily conserved pathway, which regulated many aspects of organismal physiology, such as pathogen resistance, metabolism, stress response, longevity. Luteolin, a flavone contained in many medical plants and in vegetables, had been shown to exhibit activities such as anti-tumor, anti-oxidant and neuroprotective effects. However, whether the Luteolin influenced the immune response and the underlying molecular mechanisms remained obscure. We found that Luteolin increased resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus in dose dependent manner. Meanwhile, Luteolin promoted host immune response via inhibiting the growth of pathogenic bacteria. Through the genetic screening in C. elegans, we found that Luteolin promoted innate immunity via DAF-2/DAF-16 insulin-like signaling pathway rather than p38 MAPK pathway and SKN-1. Furthermore, Luteolin activated the DAF-16/FOXO transcription factor for innate immune response. Our work suggested that Luteolin had the potential of improving the patients with pathogen infection.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Humans , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Insulin/metabolism , Luteolin/pharmacology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Signal Transduction , Immunity, Innate/genetics , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptor, Insulin/pharmacologyABSTRACT
The conserved p38/PMK-1 pathway that is an evolutionarily conserved module used by mammals and nematodes in immune response against bacterial infections. Brevilin A (BA), a sesquiterpene lactone compound of Centipeda minima has been shown to exhibit activities such as anti-tumor, anti-bacterial and anti-protozoal. However, whether the Brevilin A influences the immune response and the underlying molecular mechanisms remain obscure. We find that 10 µM Brevilin A increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcusfaecalis and Staphylococcus aureus. Meanwhile, Brevilin A enhances the resistance to pathogens by reducing the bacterial burden in the intestine. Through the genetic screening in C. elegans, we find that Brevilin A promotes innate immunity via p38 MAPK pathway. Furthermore, Brevilin A activates the p38/PMK-1 in the intestine for innate immune response. In addition, we also find that Brevilin A increases the resistance of oxidative stress and extends lifespan through p38 MAPK pathway. Our work suggests that Brevilin A may be a viable candidate for the treatment of infectious diseases.