scholarly journals Microbiota and Immune-Mediated Skin Diseases—An Overview

2019 ◽  
Vol 7 (9) ◽  
pp. 279 ◽  
Author(s):  
Adrian Catinean ◽  
Maria Adriana Neag ◽  
Andrei Otto Mitre ◽  
Corina Ioana Bocsan ◽  
Anca Dana Buzoianu
Keyword(s):  
Autoimmune Diseases ◽  
Beneficial Effect ◽  
Skin Diseases ◽  
Experimental Studies ◽  
Immune Mediated ◽  
The Impact ◽  
The Relationship

In recent years, increased attention has been paid to the relationship between microbiota and various diseases, especially immune-mediated diseases. Because conventional therapy for many autoimmune diseases is limited both in efficacy and safety, there is an increased interest in identifying nutraceuticals, particularly probiotics, able to modulate the microbiota and ameliorate these diseases. In this review, we analyzed the research focused on the role of gut microbiota and skin in immunity, their role in immune-mediated skin diseases (IMSDs), and the beneficial effect of probiotics in patients with this pathology. We selected articles published between 2009 and 2019 in PubMed and ScienceDirect that provided information regarding microbiota, IMSDs and the role of probiotics in these diseases. We included results from different types of studies including observational and interventional clinical trials or in vivo and in vitro experimental studies. Our results showed that probiotics have a beneficial effect in changing the microbiota of patients with IMSDs; they also influence disease progression. Further studies are needed to better understand the impact of new therapies on intestinal microbiota. It is also important to determine whether the microbiota of patients with autoimmune diseases can be manipulated in order to restore homeostasis of the microbiota.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals A Review on the Medicinal and Pharmacological Properties of Traditional Ethnomedicinal Plant Sonapatha, Oroxylum indicum

Sinusitis ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 71-89
Author(s):  
Ganesh Chandra Jagetia
Keyword(s):  
Glucose Transporter ◽  
Skin Diseases ◽  
Regulatory Element ◽  
Experimental Studies ◽  
Fatty Acid Synthetase ◽  
Preclinical Models ◽  
Oroxylin A ◽  
Oroxylum Indicum

Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. This review has been written by collecting the relevant information from published material on various ethnomedicinal and pharmacological aspects of Sonapatha by making an internet, PubMed, SciFinder, Science direct, and Google Scholar search. Various experimental studies have shown that Sonapatha scavenges different free radicals and possesses alkaloids, flavonoids, cardio glycosides, tannins, sterols, phenols, saponins, and other phytochemicals. Numerous active principles including oroxylin A, chrysin, scutellarin, baicalein, and many more have been isolated from the different parts of Sonapatha. Sonapatha acts against microbial infection, cancer, hepatic, gastrointestinal, cardiac, and diabetic disorders. It is useful in the treatment of obesity and wound healing in in vitro and in vivo preclinical models. Sonapatha elevates glutathione, glutathione-s-transferase, glutathione peroxidase, catalase, and superoxide dismutase levels and reduces aspartate transaminase alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxidation levels in various tissues. Sonapatha activates the expression of p53, pRb, Fas, FasL, IL-12, and caspases and inhibited nuclear factor kappa (NF-κB), cyclooxygenase (COX-2), tumor necrosis factor (TNFα), interleukin (IL6), P38 activated mitogen-activated protein kinases (MAPK), fatty acid synthetase (FAS), sterol regulatory element-binding proteins 1c (SREBP-1c), proliferator-activated receptor γ2 (PPARγ2), glucose transporter (GLUT4), leptin, and HPV18 oncoproteins E6 and E7 at the molecular level, which may be responsible for its medicinal properties. The phytoconstituents of Sonapatha including oroxylin A, chrysin, and baicalein inhibit the replication of SARS-CoV-2 (COVID-19) in in vitro and in vivo experimental models, indicating its potential to contain COVID-19 infection in humans. The experimental studies in various preclinical models validate the use of Sonapatha in ethnomedicine and Ayurveda.

Copper complexes as antitumor agents: in vitro and in vivo evidences

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucia M. Balsa ◽  
Enrique J. Baran ◽  
Ignacio E. León
Keyword(s):  
Copper Complexes ◽  
Antitumor Agents ◽  
Essential Element ◽  
Design Synthesis ◽  
Copper Compounds ◽  
Comprehensive Knowledge ◽  
The Relationship

: Copper is an essential element for most aerobic organisms, with an important function as a structural and catalytic cofactor, and in consequence, it is implicated in several biological actions. The relevant aspects of chemistry and biochemistry and the importance of copper compounds in medicine give us a comprehensive knowledge of the multifaceted applications of copper in physiology and physiopathology. In this review, we present an outline of the chemistry and the antitumor properties of copper complexes on breast, colon, and lung cancer cells focus on the role of copper in cancer, the relationship between structure-activity, molecular targets, and the study of the mechanism of action involved in its anticancer activity. This overview is expected to contribute to understanding the design, synthesis, uses of copper complexes as antitumor agents in the most common cancers.

scholarly journals Cerebrospinal Fluid Pulsation Stress Promotes the Angiogenesis of Tissue-Engineered Laminae

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Linli Li ◽  
Yiqun He ◽  
Han Tang ◽  
Wei Mao ◽  
Haofei Ni ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cerebrospinal Fluid ◽  
Engineering Technology ◽  
Expression Levels ◽  
Fluid Pulsation ◽  
Endothelial Growth Factor ◽  
The Impact

Background. Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. Methods. For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. Results. The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. Conclusion. CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique.

scholarly journals Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies

2019 ◽  
Vol 20 (11) ◽  
pp. 2675 ◽  
Author(s):  
Nicholas Wilson ◽  
Robert Steadman ◽  
Ilaria Muller ◽  
Mohd Draman ◽  
D. Aled Rees ◽  
...  
Keyword(s):  
Stem Cell Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Synthesis Inhibitor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inhibitory Role ◽  
The Impact

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.

scholarly journals The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice

Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 501-515 ◽  
Author(s):  
Kunpeng Wu ◽  
Yan Yuan ◽  
Huihui Yu ◽  
Xin Dai ◽  
Shu Wang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Macrophage Polarization ◽  
Short Chain Fatty Acids ◽  
Inflammasome Activation ◽  
Microbial Metabolites ◽  
M1 Macrophage ◽  
The Impact

Abstract The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow–derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage’s response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.

scholarly journals MicroRNA-28-5p Regulates Liver Cancer Stem Cell Expansion via IGF-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Qing Xia ◽  
Tao Han ◽  
Pinghua Yang ◽  
Ruoyu Wang ◽  
Hengyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Critical Role ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Background. MicroRNAs (miRNAs) play a critical role in the regulation of cancer stem cells (CSCs). However, the role of miRNAs in liver CSCs has not been fully elucidated. Methods. Real-time PCR was used to detect the expression of miR-miR-28-5p in liver cancer stem cells (CSCs). The impact of miR-28-5p on liver CSC expansion was investigated both in vivo and in vitro. The correlation between miR-28-5p expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results. Our data showed that miR-28-5p was downregulated in sorted EpCAM- and CD24-positive liver CSCs. Biofunctional investigations revealed that knockdown miR-28-5p promoted liver CSC self-renewal and tumorigenesis. Consistently, miR-28-5p overexpression inhibited liver CSC’s self-renewal and tumorigenesis. Mechanistically, we found that insulin-like growth factor-1 (IGF-1) was a direct target of miR-28-5p in liver CSCs, and the effects of miR-28-5p on liver CSC’s self-renewal and tumorigenesis were dependent on IGF-1. The correlation between miR-28-5p and IGF-1 was confirmed in human HCC tissues. Furthermore, the miR-28-5p knockdown HCC cells were more sensitive to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-28-5p may predict sorafenib benefits in HCC patients. Conclusion. Our findings revealed the crucial role of the miR-28-5p in liver CSC expansion and sorafenib response, rendering miR-28-5p an optimal therapeutic target for HCC.

scholarly journals Alpha 1-antichymotrypsin contributes to stem cell characteristics and enhances tumorigenicity of Glioblastoma

2020 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Natanael Zarco ◽  
Anna Carrano ◽  
Jordan Phillipps ◽  
Emily S Norton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Brain Tumor ◽  
Primary Cultures ◽  
Cellular Migration ◽  
Tumor Initiating Cells ◽  
The Impact

Abstract Background Glioblastomas (GBMs) are the most common primary brains tumors in adults with almost 100% recurrence rate. Patients with lateral ventricle proximal GBMs (LV-GBMs) exhibit worse survival compared to distal locations for reasons that remain unknown. One potential explanation is the proximity of these tumors to the cerebrospinal fluid (CSF) and its contained chemical cues that can regulate cellular migration and differentiation. We therefore investigated the role of CSF on GBM gene expression and the role of a CSF-induced gene, SERPINA3, in GBM malignancy in vitro and in vivo. Methods We utilized patient-derived CSF and primary cultures of GBM brain tumor initiating cells (BTICs). We determined the impact of SERPINA3 expression in glioma patients using TCGA database. SERPINA3 expression changes were evaluated at both the mRNA and protein levels. The effects of knockdown (KD) and overexpression (OE) of SERPINA3 on cell behavior were evaluated by transwell assay (for cell migration), and alamar blue and Ki67 (for viability and proliferation respectively). Stem cell characteristics on KD cells were evaluated by differentiation and colony formation experiments. Tumor growth was studied by intracranial and flank injections. Results GBM CSF induced a significant increase in BTIC migration accompanied by upregulation of the SERPINA3 gene. In patient samples and TCGA data we observed SERPINA3 to correlate directly with brain tumor grade and indirectly with GBM patient survival. Silencing of SERPINA3 induced a decrease in cell proliferation, migration, invasion, and stem cell characteristics, while SERPINA3 overexpression increased cell migration. In vivo, mice orthotopically-injected with SERPINA3 KD BTICs showed increased survival. Conclusions SERPINA3 plays a key role in GBM malignancy and its inhibition results in a better outcome using GBM preclinical models.

scholarly journals Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

2019 ◽  
Vol 16 (10) ◽  
pp. 1799 ◽  
Author(s):  
Marta Camacho-Cardenosa ◽  
Alba Camacho-Cardenosa ◽  
Rafael Timón ◽  
Guillermo Olcina ◽  
Pablo Tomas-Carus ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Experimental Studies ◽  
Hormonal Responses ◽  
Hypoxia Exposure ◽  
Ambient Oxygen ◽  
The Impact

Among other functions, hypoxia-inducible factor plays a critical role in bone–vascular coupling and bone formation. Studies have suggested that hypoxic conditioning could be a potential nonpharmacological strategy for treating skeletal diseases. However, there is no clear consensus regarding the bone metabolism response to hypoxia. Therefore, this review aims to examine the impact of different modes of hypoxia conditioning on bone metabolism. The PubMed and Web of Science databases were searched for experimental studies written in English that investigated the effects of modification of ambient oxygen on bone remodelling parameters of healthy organisms. Thirty-nine studies analysed the effect of sustained or cyclic hypoxia exposure on genetic and protein expression and mineralisation capacity of different cell models; three studies carried out in animal models implemented sustained or cyclic hypoxia; ten studies examined the effect of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. Different modes of hypoxic conditioning may have different impacts on bone metabolism both in vivo and in vitro. Additional research is necessary to establish the optimal cyclical dose of oxygen concentration and exposure time.

scholarly journals Transcriptome Analysis of the Barley–Deoxynivalenol Interaction: Evidence for a Role of Glutathione in Deoxynivalenol Detoxification

2010 ◽  
Vol 23 (7) ◽  
pp. 962-976 ◽  
Author(s):  
Stephanie A. Gardiner ◽  
Jayanand Boddu ◽  
Franz Berthiller ◽  
Christian Hametner ◽  
Robert M. Stupar ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Phytopathogenic Fungi ◽  
Glutathione Depletion ◽  
Host Responses ◽  
Application Site ◽  
Nuclear Magnetic Resonance Analysis ◽  
The Impact

Trichothecenes are a major group of toxins produced by phytopathogenic fungi, including Fusarium graminearum. Trichothecenes inhibit protein synthesis in eukaryotic cells and are toxicologically relevant mycotoxins for humans and animals. Because they promote plant disease, the role of host responses to trichothecene accumulation is considered to be an important aspect of plant defense and resistance to fungal infection. Our overall objective was to examine the barley response to application of the type B trichothecene deoxynivalenol (DON). We found that DON is diluted by movement from the application site to acropetal and basipetal florets. A susceptible barley genotype converted DON to DON-3-O-glucoside, indicating that UDP-glucosyltransferases capable of detoxifying DON must exist in barley. RNA profiling of DON-treated barley spikes revealed strong upregulation of gene transcripts encoding ABC transporters, UDP-glucosyltransferases, cytochrome P450s, and glutathione-S-transferases. We noted that transcripts encoding cysteine synthases were dramatically induced by DON, and that toxin-sensitive yeast on glutathione- or cysteine-supplemented media or carrying a gene that encodes a cysteine biosynthetic enzyme exhibit DON resistance, suggesting that preventing glutathione depletion by increasing cysteine supply could play a role in ameliorating the impact of DON. Evidence for nonenzymatic formation of DON-glutathione adducts in vitro was found using both liquid chromatography–mass spectrometry and nuclear magnetic resonance analysis, indicating that the formation of DON-glutathione conjugates in vivo may reduce the impact of trichothecenes. Our results indicate that barley exhibits multiple defense mechanisms against trichothecenes.

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