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Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1276
Author(s):  
Louay Bachnak ◽  
Jean Sparks ◽  
Daniel E. Newmire ◽  
Xavier F. Gonzales ◽  
Felix O. Omoruyi

Background: Type 2 diabetes (T2D) is a chronic illness associated with resistance to or defective insulin secretion. This study investigates the effects of thermotherapy on cell viability, gene expression and inflammation in skeletal muscle cell lines. Methods: Healthy and T2D human skeletal muscle cell lines (HSMM and D-HSMM, respectively) were subjected to acute or chronic thermo-therapy (AT or CT, respectively). CT consisted of a 30 min exposure to 40 °C, three times a week for three weeks; AT was a one-time exposure. Results: A significant decrease in D-HSMM cell viability percentage followed AT; however, no significant change occurred in CT. HSMM yielded the highest elevations of genes following CT. In D-HSMM, both treatments yielded gene upregulation. Both treatments significantly down-regulated IL-1β, IL-6, IL-10 and TNF-α in HSMM. AT significantly decreased IL-1β, IL-6 and upregulated IL-10 and TNF-α levels in D-HSMM, while CT yielded a reduction in IL-4, TNF-α and an upregulation of IL-6 and IL-10. Conclusions: An increase in gene expression indicates actin activity and cellular responses, suggesting an increase in transcriptional regulation. The upregulation of IL-6 and IL-10 in D-HSMM negatively correlated with a decrease in TNF-α and IL-1β, indicating improved adverse inflammatory effects associated with the disease.


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1136
Author(s):  
Mostafa Abdel-Salam ◽  
Bárbara Pinto ◽  
Geovanni Cassali ◽  
Lilian Bueno ◽  
Gabriela Pêgas ◽  
...  

Cationic anticancer peptides have exhibited potent anti-proliferative and anti-inflammatory effects in neoplastic illness conditions. LyeTx I-b is a synthetic peptide derived from Lycosa erythrognatha spider venom that previously showed antibiotic activity in vitro and in vivo. This study focused on the effects of LyeTxI-b on a 4T1 mouse mammary carcinoma model. Mice with a palpable tumor in the left flank were subcutaneously or intratumorally injected with LyeTx I-b (5 mg/kg), which significantly decreased the tumor volume and metastatic nodules. Histological analyses showed a large necrotic area in treated primary tumors compared to the control. LyeTxI-b reduced tumor growth and lung metastasis in the 4T1 mouse mammary carcinoma model with no signs of toxicity in healthy or cancerous mice. The mechanism of action of LyeTx I-b on the 4T1 mouse mammary carcinoma model was evaluated in vitro and is associated with induction of apoptosis and cell proliferation inhibition. Furthermore, LyeTx I-b seems to be an efficient regulator of the 4T1 tumor microenvironment by modulating several cytokines, such as TGF-β, TNF-α, IL-1β, IL-6, and IL-10, in primary tumor and lung, spleen, and brain. LyeTx I-b also plays a role in leukocytes rolling and adhesion into spinal cord microcirculation and in the number of circulating leukocytes. These data suggest a potent antineoplastic efficacy ofLyeTx I-b.


Author(s):  
Ige Francis Olaoye ◽  
Babatunde Joseph Oso ◽  
Adepeju Aberuagba

Background: A large body of literature suggests that the extracts of Ocimum gratissimum (O. gratissimum) and Thymus vulgaris (T. vulgaris) play protective roles against various inflammatory disorders. However, the possible mechanism of action with reference to the interactions of their respective phytochemical compositions with pro-inflammatory mediators as the indication of their therapeutic effects is less clear. Therefore, the immunomodulatory properties of O. gratissimum and T. vulgaris were investigated in this study. Methods: The in vitro lipoxygenase inhibitory potentials of methanolic extracts of the selected plants were assessed through colorimetric analysis. The pharmacokinetics of some identified compounds in the botanicals were investigated via the Swiss ADME server while the molecular interactions of the compounds with lipoxygenase, IL-1, IL-6, TNF-α, IL-8, and CCL-2 were performed through molecular docking. Results: The assessment of the lipoxygenase inhibition revealed the extracts could possess anti-inflammatory agents. The pharmacokinetic results of some selected compounds identified in the botanicals showed moderate toxic effects compared to indomethacin. The molecular docking study substantiated the report of the in vitro analysis as indicated in the binding score of all the selected compounds compared to indomethacin. Conclusion: The phytochemical components of the extracts of O. gratissimum and T. vulgaris could be effective as anti-inflammatory agents that could be explored in preventing disorders associated with excessive activities of pro-inflammatory mediators.


Author(s):  
Ahmad Shamabadi ◽  
Alireza Hasanzadeh ◽  
Shahin Akhondzadeh

Besides concerns about the increasing prevalence of psychiatric disorders and the significant burdens and costs, there are concerns about its validity. The dilemma of validity went so far that studies described the diagnoses in psychiatry as scientifically worthless. We suggest integrating psychiatry and medical biotechnology and using biotechnological products in psychiatric aspects help psychiatry become more precise, strengthen its position among other sciences, and increase its scientific credibility by giving examples. For this matter, we need different inputs to choose between the vast outputs. The most common inputs are clinical symptoms, cognitive function, individual and environmental risk factors, molecular markers, genetic markers, neuroimaging signs, and big data. Some molecular markers have been shown to have a relationship with psychiatric disorders such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α). Genetic studies might evolve the most accurate part of precision psychiatry. Currently, and through the developments in technology, genome-wide association studies have become available. In neuroimaging signs, psychiatric disorders are associated with generalized rather than focal brain network dysfunction, and functional magnetic resonance imaging could be performed to study them. It would exhibit different aberrancies in various psychiatric disorders. In big data, the constitution of predictive models and movement toward precision psychiatry can be led by using artificial intelligence and machine learning.


2021 ◽  
Vol 12 ◽  
Author(s):  
Li'ang Li ◽  
Ran Xu ◽  
Lingfeng Jiang ◽  
Elvis Genbo Xu ◽  
Man Wang ◽  
...  

Compared with marine organisms, research on microplastics (MPs) in freshwater organisms is still less although MPs have been widely found in the freshwater ecosystem. Hypoxia is a ubiquitous issue in freshwater aquaculture, and under such scenarios, the toxic effects of MPs on typical aquaculture fish need to be clarified. In this study, we studied the effects of MPs (polystyrene) on specific growth rate (SGR), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interferon (IFN) in the yellow catfish (Pelteobagrus fulvidraco) under hypoxic conditions. After 15 days of exposure, the SGR was not affected by MPs or hypoxia. MPs significantly increased the expressions of HIF-1α and TNF-α but inhibited the expression of IFN at high concentration MPs under normoxia. However, hypoxia significantly inhibited the expression of IL-8 and TNF-α under high MP concentration and low MP concentration, respectively. In addition, MPs had significant concentration-dependent inhibitory effects on IFN under hypoxia. Surprisingly, a positive correction between HIF-1α and TNF-α was found in fish. Although hypoxia might alleviate the effects of MPs with low concentrations, the interaction of hypoxia and MPs aggravated the negative effects of MPs on immune factors at high concentration MPs. This study provided new insight into the complex effects of hypoxia and MPs on aquatic organisms, and future studies should focus on the cellular pathways of immune cells in fish. Given that MPs could induce the immune response in fish, considerations should be paid to the impacts of MPs on freshwater aquaculture, and hypoxia should be taken into consideration when evaluating the effects of MPs.


2021 ◽  
Author(s):  
Mingming Yin ◽  
Jinlong Hu ◽  
Zhongxu Yuan ◽  
Guangyi Luo ◽  
Jiaming Yao ◽  
...  

Abstract Purpose: This article focused on STING agonist role in breast cancer (BCa) immunotherapy.Methods: Clinical samples were collected from 37 BCa patients'. Xenograft tumor model was established by injecting 4T1 cells into mammary fat pad of mice. STING agonist and Atezolizumab were injected into mice with 2 times a week for 2 weeks. Peripheral blood, xenograft tumor, lung, liver, brain-cortex and kidney of mice were collected. Anti-IFNAR1 was used to treat 4T1 cells. Quantitative reverse transcription-polymerase chain reaction and Western blot were used for mRNA and proteins expression. Enzyme-linked immunosorbent assay, immunohistochemistry and hematoxylin-eosin staining were performed. Results: Tumor tissues of BCa patients exhibited lower STING and high PD-1 and PD-L1 protein expression. STING agonist inhibited 4T1 cells growth in mice (P < 0.001). STING agonist increased IFNβ level and the phosphorylation of STING, TBK1, IRF3 and STAT1 in xenograft tumor (P < 0.001). STING agonist synergized with Atezolizumab to inhibit 4T1 cells growth in mice, and increase TNF-α, IFN-β and IL-10 level in peripheral blood and xenograft tumor (P < 0.01). STING agonist synergized with Atezolizumab to increase CD8+ cytotoxic T cells and decrease FOXP3+ Tregs cells in xenograft tumor. STING agonist was non-toxic to lung, liver, brain-cortex and kidney. Anti-IFNAR1 reversed STING agonist promotion on TBK1, IRF3 and STAT1 phosphorylation in 4T1 cells (P < 0.01).Conclusion: STING agonist enhances the efficacy of Atezolizumab in BCa immunotherapy by activating the IFNβ signaling pathway.


2021 ◽  
Author(s):  
Sara Khan ◽  
Pinki Mishra ◽  
Rizwana Parveen ◽  
Ram Bajpai ◽  
Mohd Ashif Khan ◽  
...  

Purpose: Literature suggests association of inflammatory markers with the severity and mortality related to COVID-19, but there are varying conclusions available. We aimed to provide an overview of the association of inflammatory markers with the severity and mortality of COVID-19 patients. Methods: We searched Medline (via PubMed), Cochrane, Clinicaltrials.gov databases until Sept 1, 2020. Results: A total of 21 studies comprising 4023 patients with COVID-19 were included in our analysis. Levels of IL-6 (WMD=18.17 95%CI 3.38 to 32.96, p=0.016), IL-8 (WMD=12.09 95%CI 4.41 to 19.77, p=0.002), MCP-1 (WMD=146.66 95%CI 88.16 to 205.16, p<0.001), CRP (WMD=31.09 95%CI 10.08 to 52.10, p=0.004), PCT (WMD= -31.23 95%CI -37.70 to -24.76, p<0.001), IL-2R (WMD=861.93 95%CI 275.45 to 1448.41, p=0.004), ferritin (WMD= 1083.34 95%CI 431.99 to 1734.70, p=0.001) were found significantly higher in the severe group compared with the non-severe group of COVID-19 patients. Moreover, non-survivors had a higher levels of IL-2R (WMD= -666.06 95%CI -782.54 to -549.59, p<0.001), IL-8 (WMD= -26.63 95%CI -33.031 to -20.236, p<0.001), IL-10 (WMD= -7.60 95%CI -8.93 to -6.26, p<0.001), TNF-α (WMD= -4.60 95%CI -5.71 to -3.48, p<0.001), IL- 1β (WMD=22.66 95%CI 8.13 to 37.19, p=0.002), CRP (WMD= -96.40 95%CI -117.84 to -74.97, p<0.001), and ferritin (WMD= -937.60 95%CI -1084.15 to -791.065, p<0.001) when compared to the non-survivor group. Conclusion: This meta-analysis highlights the association of inflammatory markers with the severity and mortality of COVID-19 patients. Measurement of these inflammatory markers may assist clinicians to monitor and evaluate the severity and prognosis of COVID-19 thereby reducing the mortality rate. Keywords: inflammatory markers, cytokine storm, interleukin, disease severity, COVID-19


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qiu-Yue Wang ◽  
Na Zhang ◽  
Shu-Yu Liu ◽  
Xi-Hong Jiang ◽  
Shu-Min Liu

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1β, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1β, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1β, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.


2021 ◽  
Author(s):  
Xinchi Shang ◽  
Bo Wang ◽  
Qingsong Sun ◽  
Yue Zhang ◽  
Yuting Lu ◽  
...  

Abstract Mercury (Hg) is a global pollutant that affects the health of humans and ecosystems. Selenium (Se) is an essential trace element for many organisms including humans. Bacillus subtilis is widely distributed in nature, is one of the main probiotics used in aquaculture, and has a certain adsorption effect on heavy metals. The interaction between Hg and Se was rigorously studied, especially due to the observation of the protective effect of Se on Hg toxicity. The common carp was exposed to Hg (0.03 mg/L), and 105 cfu/g Se-rich B. subtilis was added to the feed. After 30 days of feeding, samples were taken to evaluate the growth performance, serological response, inflammatory response, and intestinal microbial changes. In this study, when fish were exposed to Hg, the growth performance of the Se-rich B. subtilis plus 0.03 mg/L Hg fish group was lower than that of the control group and higher than 0.03 mg/L Hg; The levels of LZM and IgM decreased, but after supplementation with Se-rich B. subtilis, the levels of LZM and IgM increased; Hg treatment significantly up-regulated the mRNA expression of IL-1β, IL-8, TNF-α and NF-κB P65, but down-regulated the mRNA expression of IL-10, TGF-β and IkBα. However, compared with the Hg group, the Se-rich B. subtilis plus Hg group can significantly increase the mRNA expression levels of IL-1β, IL-8, TNF-α and NF-κB P65, but reduce the regulation of IL-10, TGF-β and IkBα expression. At the genus level, the abundance of Aeromonas in the intestines of common carp in the Hg treatment group increased, and Se-rich B. subtilis could reduce the abundance of Aeromonas (pathogenic bacteria). Through the analysis of the species, we found that the Hg group was mainly composed of Aeromonas sobria and Aeromonas hydrophila. However, in the Se-rich B. subtilis treatment group, we found that Aeromonas sobria was significantly less than the Hg group. Because Aeromonas (pathogenic bacteria) is harmful to the fish, it can induce inflammation in the fish and make the fish sick. Through microbiological analysis, it is found that Se-rich B. subtilis improves Hg-induced intestinal microbial changes, alleviates the abundance of Aeromonas, and alleviates the inflammation of the fish.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hisanori Muto ◽  
Takanori Ito ◽  
Taku Tanaka ◽  
Shinya Yokoyama ◽  
Kenta Yamamoto ◽  
...  

AbstractNon-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.


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