Effect of the F129L Mutation in Alternaria solani on Fungicides Affecting Mitochondrial Respiration

Isolates of Alternaria solani previously collected from throughout the Midwestern United States and characterized as being azoxystrobin sensitive or reduced sensitive were tested for sensitivity to the Quinone outside inhibitor (QoI) fungicides famoxadone and fenamidone and the carboxamide fungicide boscalid. All three fungicides affect mitochondrial respiration: famoxadone and fenamidone at complex III, and boscalid at complex II. A. solani isolates possessing reducedsensitivity to azoxystrobin also were less sensitive in vitro to famoxadone and fenamidone compared with azoxystrobin-sensitive isolates, but the shift in sensitivity was of lower magnitude, approximately 2- to 3-fold versus approximately 12-fold for azoxystrobin. The in vitro EC50 values, the concentration that effectively reduces germination by 50% relative to the untreated control, for sensitive A. solani isolates were significantly lower for famoxadone and azoxystrobin than for fenamidone and boscalid; whereas, for reduced-sensitive isolates, famoxadone EC50 values were significantly lower than all other fungicides. Isolates of A. solani with reducedsensitivity to azoxystrobin were twofold more sensitive in vitro to boscalid than were azoxystrobin-sensitive wild-type isolates, displaying negative cross-sensitivity. All isolates determined to have reduced-sensitivity to azoxystrobin also were determined to possess the amino acid substitution of phenylalanine with leucine at position 129 (F129L mutation) using real-time polymerase chain reaction. In vivo studies were performed to determine the effects of in vitro sensitivity shifts on early blight disease control provided by each fungicide over a range of concentrations. Reduced-sensitivity to azoxystrobin did not significantly affect disease control provided by famoxadone, regardless of the wide range of in vitro famoxadone EC50 values. Efficacy of fenamidone was affected by some azoxystrobin reduced-sensitive A. solani isolates, but not others. Boscalid controlled azoxystrobin-sensitive and reduced-sensitive isolates with equal effectiveness. These results suggest that the F129L mutation present in A. solani does not convey cross-sensitivity in vivo among all QoI or related fungicides, and that two- to threefold shifts in in vitro sensitivity among A. solani isolates does not appreciably affect disease control.

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Phytochemistry and Pharmacology of the Genus Pedicularis Used in Traditional Chinese Medicine

The American Journal of Chinese Medicine ◽

10.1142/s0192415x14500670 ◽

2014 ◽

Vol 42 (05) ◽

pp. 1071-1098 ◽

Cited By ~ 13

Author(s):

Mao-Xing Li ◽

Xi-Rui He ◽

Rui Tao ◽

Xinyuan Cao

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Chemical Constituents ◽

Iridoid Glycosides ◽

In Vivo Studies ◽

Chemical Components ◽

Wide Range ◽

Phenylpropanoid Glycosides

In the present review, the literature data on the chemical constituents and biological investigations of the genus Pedicularis are summarized. Some species of Pedicularis have been widely applied in traditional Chinese medicine. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides (PhGs), lignans glycosides, flavonoids, alkaloids and other compounds have been isolated and identified from the genus Pedicularis. In vitro and in vivo studies indicated some monomer compounds and extracts from the genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscle, nootropic effect and other activities.

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Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Biology ◽

10.3390/biology9070161 ◽

2020 ◽

Vol 9 (7) ◽

pp. 161

Author(s):

Séverine André ◽

Lionel Larbanoix ◽

Sébastien Verteneuil ◽

Dimitri Stanicki ◽

Denis Nonclercq ◽

...

Keyword(s):

Ldl Receptor ◽

Density Lipoprotein ◽

Therapeutic Agents ◽

In Vivo Studies ◽

Phage Display Technology ◽

Brain Penetration ◽

Wide Range ◽

The Brain

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.

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Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽

10.3390/cells9051232 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1232

Author(s):

Stefania D’Adamo ◽

Silvia Cetrullo ◽

Veronica Panichi ◽

Erminia Mariani ◽

Flavio Flamigni ◽

...

Keyword(s):

Signaling Pathways ◽

Antioxidant Activities ◽

Synergistic Effects ◽

National Health System ◽

Bioactive Molecules ◽

Joint Disease ◽

In Vivo Studies ◽

Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

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Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽

10.3390/molecules25030596 ◽

2020 ◽

Vol 25 (3) ◽

pp. 596 ◽

Cited By ~ 3

Author(s):

María del Carmen Villegas-Aguilar ◽

Álvaro Fernández-Ochoa ◽

María de la Luz Cádiz-Gurrea ◽

Sandra Pimentel-Moral ◽

Jesús Lozano-Sánchez ◽

...

Keyword(s):

Energy Metabolism ◽

Phenolic Compounds ◽

Molecular Mechanisms ◽

Biological Effects ◽

Biological Properties ◽

In Vivo Studies ◽

Wide Range ◽

High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

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Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

10.20944/preprints201809.0459.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Vinicius Cruzat ◽

Marcelo Macedo Rogero ◽

Kevin Noel Keane ◽

Rui Curi ◽

Philip Newsholme

Keyword(s):

Amino Acid ◽

The Body ◽

Glutamine Metabolism ◽

In Vivo Studies ◽

Glutamine Supplementation ◽

Bacterial Killing ◽

Nutrition Supplementation ◽

Wide Range

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

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Gold Nanoparticles and Nanorods in Nuclear Medicine: A Mini Review

Applied Sciences ◽

10.3390/app9163232 ◽

2019 ◽

Vol 9 (16) ◽

pp. 3232 ◽

Cited By ~ 10

Author(s):

Daria Maccora ◽

Valentina Dini ◽

Chiara Battocchio ◽

Ilaria Fratoddi ◽

Antonella Cartoni ◽

...

Keyword(s):

Gold Nanoparticles ◽

Nuclear Medicine ◽

Nuclear Imaging ◽

Engineered Nanomaterials ◽

In Vivo Studies ◽

Wide Range ◽

Engineered Systems ◽

Radiometabolic Therapy

In the last decade, many innovative nanodrugs have been developed, as well as many nanoradiocompounds that show amazing features in nuclear imaging and/or radiometabolic therapy. Their potential uses offer a wide range of possibilities. It can be possible to develop nondimensional systems of existing radiopharmaceuticals or build engineered systems that combine a nanoparticle with the radiopharmaceutical, a tracer, and a target molecule, and still develop selective nanodetection systems. This review focuses on recent advances regarding the use of gold nanoparticles and nanorods in nuclear medicine. The up-to-date advancements will be shown concerning preparations with special attention on the dimensions and functionalizations that are most used to attain an enhanced performance of gold engineered nanomaterials. Many ideas are offered regarding recent in vitro and in vivo studies. Finally, the recent clinical trials and applications are discussed.

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Are Fe-Based Stenting Materials Biocompatible? A Critical Review of In Vitro and In Vivo Studies

Journal of Functional Biomaterials ◽

10.3390/jfb11010002 ◽

2019 ◽

Vol 11 (1) ◽

pp. 2

Author(s):

Eleonora Scarcello ◽

Dominique Lison

Keyword(s):

In Vivo Studies ◽

Design Strategies ◽

Indirect Contact ◽

Cardiovascular Stents ◽

In Vivo Experiments ◽

Local Toxicity ◽

Wide Range ◽

Fe Toxicity

Fe-based materials have increasingly been considered for the development of biodegradable cardiovascular stents. A wide range of in vitro and in vivo studies should be done to fully evaluate their biocompatibility. In this review, we summarized and analyzed the findings and the methodologies used to assess the biocompatibility of Fe materials. The majority of investigators drew conclusions about in vitro Fe toxicity based on indirect contact results. The setup applied in these tests seems to overlook the possible effects of Fe corrosion and does not allow for understanding of the complexity of released chemical forms and their possible impact on tissue. It is in particular important to ensure that test setups or interpretations of in vitro results do not hide some important mechanisms, leading to inappropriate subsequent in vivo experiments. On the other hand, the sample size of existing in vivo implantations is often limited, and effects such as local toxicity or endothelial function are not deeply scrutinized. The main advantages and limitations of in vitro design strategies applied in the development of Fe-based alloys and the correlation with in vivo studies are discussed. It is evident from this literature review that we are not yet ready to define an Fe-based material as safe or biocompatible.

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CSNK2 in cancer: Pathophysiology and translational applications.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15594 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15594-e15594

Author(s):

Scott Strum ◽

Laszlo Gyenis ◽

David W Litchfield

Keyword(s):

Current Knowledge ◽

Human Cancer ◽

Prognostic Significance ◽

Response To Treatment ◽

In Vivo Studies ◽

Protein Activity ◽

Oncology Research ◽

Wide Range

e15594 Background: Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase whose expression levels are frequently elevated in solid and hematologic malignancies. CSNK2 has been discovered to hold prognostic and therapeutic significance across multiple cancers and is an excellent target for oncology research. This systematic review summarizes the current knowledge from in vitro and in vivo studies on the biology of this kinase in cancer alongside pre-clinical/clinical investigations from 24 different human cancer types. Methods: PRISMA methodology was used to generate a study protocol and building-block search strategy, from which a total of 796 publications in PubMed were retrieved across 24 human cancers. 245 of these publications met both screening and inclusion criteria. Data was then systematically extracted, including information about CSNK2 subunit mRNA/protein/activity levels, phosphorylation targets, phenotypic changes, in vivo studies, and prognostic/therapeutic data. The data was thereafter summarized and analyzed. Results: Five targets phosphorylated by CSNK2 were identified in at least 4 cancers: AKT, STAT3, RELA, PTEN, and TP53. The most heavily cited was AKT, identified in 15 cancers. Phenotypically, behaviors influenced by CSNK2 that were reported in 11 or more cancers included: evasion of apoptosis, enhancement of proliferation, enhancement of invasion/metastasis, and cell cycle control. Interestingly, these pathways correlated heavily with the most commonly cited CSNK2 targets. From a clinical perspective, CSNK2 held prognostic significance in 17 of the cancers. Additionally, xenograft experiments were found to have been performed in 13 cancers where CSNK2 inhibition resulted in a positive response to treatment. Lastly, early studies have shown promising results through the clinical application of CSNK2-specific inhibitors, with several clinical trials now underway for further assessment. Conclusions: Overall, our analysis supports CSNK2 as an attractive target for cancer therapy and points to specific areas where additional investigation is critical to advance our understanding of CSNK2 biology. The design of targeted therapies by exploiting the pathophysiology of CSNK2 has the potential to generate impactful treatment strategies across a wide range of cancers, promising exciting new discoveries scientifically and clinically.

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Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Nutrients ◽

10.3390/nu12030789 ◽

2020 ◽

Vol 12 (3) ◽

pp. 789 ◽

Cited By ~ 4

Author(s):

Mattia Bellan ◽

Laura Andreoli ◽

Chiara Mele ◽

Pier Paolo Sainaghi ◽

Cristina Rigamonti ◽

...

Keyword(s):

Vitamin D ◽

Immune System ◽

Autoimmune Diseases ◽

Convincing Evidence ◽

In Vivo Studies ◽

Human Immune System ◽

Therapeutic Implications ◽

Wide Range

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

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Transcriptional regulation of CCSP by interferon-γ in vitro and in vivo

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00186.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. L108-L118 ◽

Cited By ~ 13

Author(s):

P. L. Ramsay ◽

Z. Luo ◽

S. M. Magdaleno ◽

S. K. Whitbourne ◽

X. Cao ◽

...

Keyword(s):

Inflammatory Responses ◽

Interferon Γ ◽

Clara Cell ◽

In Vivo Studies ◽

Deletion Mapping ◽

Induced Expression ◽

Wide Range ◽

Ifn Γ

Interferon γ (IFN-γ), a potent cytokine inducing a wide range of immunologic activities, is increased in the airway secondary to viral infection or during an inflammatory response. This increase in IFN-γ concentration may alter the expression of specific airway epithelial cell genes that regulate adaptation of airway inflammatory responses. One protein induced by IFN-γ is Clara cell secretory protein (CCSP), which may contribute to the attenuation of airway inflammation. This study was done to investigate the molecular mechanism by which IFN-γ stimulates the expression of the CCSP gene in mouse transformed Clara cells and transgenic mice. Deletion mapping and linker-scanning mutations demonstrated that IFN-γ-induced expression of CCSP was regulated, in part, at the level of transcription. In vitro and in vivo studies verified that the minimal IFN-γ-responsive segment was localized to the proximal 166 bp of the 5′-flanking region. Additionally, IFN-γ-induced expression of CCSP was mediated indirectly through an interferon regulatory factor-1-mediated increase in hepatocyte nuclear factor-3β.

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