Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria

Bed bugs are globally important pests and there is an ongoing need for the development and improvement of bed bug control tools. Though promising against other insect pests, the exploration of biological methods for bed bug control is limited. Previously, we identified several species of bacteria that have entomopathogenic effects against bed bugs when ingested. We also described the conservation of several antibacterial responses in bed bugs, including the expression of immune effector genes regulated by NF-kB transcription factors through the Toll and immune deficiency (IMD) signaling pathways. Accordingly, we predicted that chemical inhibition of NF-kB signaling could reduce bed bug resistance to orally provisioned entomopathogenic bacteria, potentially improving their effectiveness as biological control agents. In the present study, we administered four small molecule inhibitors of NF-kB signaling (BMS345541, IKK16, IMD0354, Takinib) to bed bugs by feeding them in a blood meal. We then quantified basal mortality and mortality in response to oral infection with two different entomopathogenic bacteria (Pseudomonas entomophila and Bacillus thuringiensis israelensis). None of the NF-kB signaling inhibitors tested increased mortality above control levels when administered alone, suggesting a lack of direct toxicity. However, one inhibitor (IKK16) significantly enhanced the rate of mortality from oral infection with P. entomophila. Enhanced mortality was independent of direct effects of IKK16 on P. entomophila growth in vitro but was associated with higher bacterial loads in vivo (i.e., reduced resistance). Together, these results provide new insight into the regulation of the bed bug immune system and suggest that administration of entomopathogens in combination with inhibition of immune signaling pathways to reduce infection resistance may be effective for biological control of bed bugs.

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Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20102500 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2500 ◽

Cited By ~ 3

Author(s):

Vrathasha Vrathasha ◽

Hilary Weidner ◽

Anja Nohe

Keyword(s):

Signaling Pathways ◽

Treatment Options ◽

Time Frame ◽

Bmp Signaling ◽

C2c12 Cells ◽

Molecular Sequence ◽

Sequence Of Events ◽

Protein Receptor

Background: Osteoporosis is a degenerative skeletal disease with a limited number of treatment options. CK2.3, a novel peptide, may be a potential therapeutic. It induces osteogenesis and bone formation in vitro and in vivo by acting downstream of BMPRIA through releasing CK2 from the receptor. However, the detailed signaling pathways, the time frame of signaling, and genes activated remain largely unknown. Methods: Using a newly developed fluorescent CK2.3 analog, specific inhibitors for the BMP signaling pathways, Western blot, and RT-qPCR, we determined the mechanism of CK2.3 in C2C12 cells. We then confirmed the results in primary BMSCs. Results: Using these methods, we showed that CK2.3 stimulation activated OSX, ALP, and OCN. CK2.3 stimulation induced time dependent release of CK2β from BMPRIA and concurrently CK2.3 colocalized with CK2α. Furthermore, CK2.3 induced BMP signaling depends on ERK1/2 and Smad1/5/8 signaling pathways. Conclusion: CK2.3 is a novel peptide that drives osteogenesis, and we detailed the molecular sequence of events that are triggered from the stimulation of CK2.3 until the induction of mineralization. This knowledge can be applied in the development of future therapeutics for osteoporosis.

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Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

Scientific Reports ◽

10.1038/s41598-020-79450-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jakob Weglage ◽

Friederike Wolters ◽

Laura Hehr ◽

Jakob Lichtenberger ◽

Celina Wulz ◽

...

Keyword(s):

Signaling Pathways ◽

Colorectal Carcinogenesis ◽

Sub Saharan Africa ◽

Interleukin 4 ◽

Health Burden ◽

Sub Saharan ◽

Considerable Morbidity ◽

First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

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The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽

10.3390/cancers13040855 ◽

2021 ◽

Vol 13 (4) ◽

pp. 855

Author(s):

Paola Serrano Martinez ◽

Lorena Giuranno ◽

Marc Vooijs ◽

Robert P. Coppes

Keyword(s):

Signaling Pathways ◽

Progenitor Cells ◽

Tissue Regeneration ◽

Normal Tissue ◽

Cellular Response ◽

Adult Tissue ◽

Tissue Specific ◽

Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

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Anti-Cancer Properties of Theaflavins

Molecules ◽

10.3390/molecules26040987 ◽

2021 ◽

Vol 26 (4) ◽

pp. 987

Author(s):

Eric J. O’Neill ◽

Deborah Termini ◽

Alexandria Albano ◽

Evangelia Tsiani

Keyword(s):

Signaling Pathways ◽

Cancer Progression ◽

Treatment Strategies ◽

B Cell Lymphoma ◽

Black Tea ◽

Phosphorylated Akt ◽

Phenolic Components ◽

Anti Cancer

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.

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SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters

Cell Death and Disease ◽

10.1038/s41419-021-04009-8 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Heyun Zhang ◽

Zhangyu Zheng ◽

Rongqin Zhang ◽

Yongcong Yan ◽

Yaorong Peng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathways ◽

Histone Methylation ◽

Cell Growth And Migration ◽

Histone 3 ◽

Sphingosine 1 Phosphate ◽

And Migration ◽

Proliferation And Migration

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

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Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer

Cancer Biomarkers ◽

10.3233/cbm-200540 ◽

2021 ◽

pp. 1-16

Author(s):

Yang Wang ◽

Bo He ◽

Yan Dong ◽

Gong-Jin He ◽

Xiao-Wei Qi ◽

...

Keyword(s):

Lung Cancer ◽

Signaling Pathways ◽

Cox Regression ◽

Prognostic Significance ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Feature ◽

Diagnostic Biomarker

BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.

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KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways

Cancer Biomarkers ◽

10.3233/cbm-201045 ◽

2021 ◽

pp. 1-15

Author(s):

Ping Xu ◽

Xiao Mo ◽

Ruixue Xia ◽

Long Jiang ◽

Chengfei Zhang ◽

...

Keyword(s):

Potassium Channels ◽

Lung Adenocarcinoma ◽

Potassium Channel ◽

Signaling Pathways ◽

Epithelial To Mesenchymal Transition ◽

Tumor Biology ◽

Erk Signaling ◽

Mesenchymal Transition

BACKGROUND: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology. OBJECTIVE: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer. METHODS: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models. RESULTS: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells. CONCLUSIONS: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.

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Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

BioMed Research International ◽

10.1155/2018/8584136 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Lingyu Yang ◽

Dehai Xian ◽

Xia Xiong ◽

Rui Lai ◽

Jing Song ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Metabolic Diseases ◽

Low Cost ◽

Natural Agents ◽

Molecular Damage ◽

And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

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Virulence and Genetic Characterization of Six Baculovirus Strains Isolated From Different Populations of Spodoptera Frugiperda (Lepidoptera: Noctuidae)

10.21203/rs.3.rs-988050/v1 ◽

2021 ◽

Author(s):

Ingrid Zanella-Saenz ◽

Elisabeth A. Herniou ◽

Jorge E. Ibarra ◽

Ma.Cristina Del Rincón-Castro ◽

Ilse Alejandra Huerta-Arredondo

Keyword(s):

Biological Control ◽

Cell Cultures ◽

Spodoptera Frugiperda ◽

Fall Armyworm ◽

The United States ◽

Infection Mechanisms ◽

Different Populations

Abstract Fall armyworm (FAW), Spodoptera frugiperda (Smith, 1797), is a polyphagous, voracious, and economically important agricultural pest. Biological control of FAW is a strategy that must be further explored. This study evaluated six baculovirus strains isolated from infected FAW larvae from Mexico, Argentina, Honduras, and the United States. Five alphabaculoviruses (SfNPV-An2, SfNPV-Arg, SfNPV-Fx, SfNPV-Ho and SfNPV-Sin) and one betabaculovirus (SfGV-RV), were tested against FAW larvae, showing a wide diversity of virulence levels among strains when their estimated LC50s were compared, being SfNPVArg, SfNPV-Ho and SfNPV-Fx more virulent than SfNPV-An 2 , SfNPV-Sin and SfGV-RV. To determine any virulence difference in vitro studies of these isolates, Sf9 cell cultures were used. Interestingly, only ODVs from four of the test SfNPV strains showed infectivity on Sf9 cell cultures, and some differences in virulence were observed. Genomic restriction analyses and partial sequences of lef-8, lef-9 , and polh/granulin genes showed little variability among alphabaculoviruses, both, among them and with previously reported sequences. However, sequences from SfGV-RV were closer to previously reported sequences from the SfGVVG008 strain than the SfGV-Arg and SfGV-VG014 strains. The great difference in the in vivo virulence was not correlated with great similarity among the isolates. The characterization of these six baculoviruses isolates offers the basis for exploring their potential as biological control agents against S. frugiperda, as well the initial studies on their specific infection mechanisms, evolution, and ecology.

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In vitro and in vivo Assay for Assessment of the Biological Control Potential of Streptomyces sp. KT

Journal of Plant Studies ◽

10.5539/jps.v7n1p10 ◽

2017 ◽

Vol 7 (1) ◽

pp. 10

Author(s):

Tatsuya Ohike ◽

Minori Maeda ◽

Tetsuya Matsukawa ◽

Masahiro Okanami ◽

Shin’ichiro Kajiyama ◽

...

Keyword(s):

Biological Control ◽

Suppressive Effect ◽

Phytopathogenic Fungi ◽

Dual Culture ◽

Biological Control Agents ◽

Bipolaris Oryzae ◽

Biological Control Potential ◽

Dual Culture Assay

Rhizoctonia solani is fungal plant pathogen that infects many different host plants. Recently, biological control agents that are friendly to the environment and ecosystems have attracted much attention as an alternative to the use of chemical fungicide which have been used worldwide to control soil borne pathogens including R. solani. In this study, 53 strains of actinomycetes isolated from environmental soils, and antifungal activities of them were assessed by the dual culture assay. Strain KT showed strong inhibitory activities against 8 phytopathogenic fungi. A great suppressive effect on R. solani growth was observed in the inoculation test of plants using cucumber and chin-geng-sai. In addition, infection of Bipolaris oryzae also could be suppressed in the detached leaf assay using oats. As a result of genetic analysis, it was shown that KT was a species closely related to Streptomyces lavenduligriseus NRRL B-3173T. However, as far as we know, there is no report for biological control agents using S. lavenduligriseus. This study suggests that the strain KT may useful as biological control agents to suppress various crop diseases.

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