scholarly journals Silencing lncRNA TUG1 Alleviates LPS-Induced Mouse Hepatocyte Inflammation by Targeting miR-140/TNF

Author(s):  
Qing-Min Liu ◽  
Li-Li Liu ◽  
Xi-Dong Li ◽  
Ping Tian ◽  
Hao Xu ◽  
...  

Hepatitis is a major public health problem that increases the risk of liver cirrhosis and liver cancer. Numerous studies have revealed that long non-coding RNAs (lncRNAs) exert essential function in the inflammatory response of multiple organs. Herein, we aimed to explore the effect of lncRNA TUG1 in LPS-induced hepatocyte inflammation response and further illuminate the underlying mechanisms. Mice were intraperitoneally injected with LPS, and the liver inflammation was evaluated. Microarray showed that lncRNA TUG1 was upregulated in LPS-induced hepatocyte inflammation. qRT-PCR and immunofluorescence assay indicated a significant increase of TUG1 in mice with LPS injection. Functional analysis showed that si-TUG1 inhibited LPS-induced inflammation response in mice liver, inhibited apoptosis level, and protected liver function. Then, we knock down TUG1 in normal human hepatocyte AML12. Consistent with in vivo results, si-TUG1 removed the injury of LPS on AML12 cells. Furthermore, TUG1 acted as a sponge of miR-140, and miR-140 directly targeted TNFα (TNF). MiR-140 or si-TNF remitted the beneficial effects of TUG1 on LPS-induced hepatocyte inflammation response both in vitro and in vivo. Our data revealed that deletion of TUG1 protected against LPS-induced hepatocyte inflammation via regulating miR-140/TNF, which might provide new insight for hepatitis treatment.

Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 501
Author(s):  
Wenjing Tao ◽  
Geng Wang ◽  
Jintao Wei

Metabolic syndrome, a cluster of metabolic disorders including central obesity, insulin resistance, hyperglycemia, dyslipidemia, and hypertension, has become a major public health problem worldwide. It is of great significance to develop natural products to prevent and treat metabolic syndrome. Chitosan oligosaccharide (COS) is an oligomer of chitosan prepared by the deacetylation of chitin, which is the second most abundant polymer in nature. In recent years, COS has received widespread attention due to its various biological activities. The present review will summarize the evidence from both in vitro and in vivo studies of the beneficial effects of COS on obesity, dyslipidemia, diabetes mellitus, hyperglycemia, and hypertension, and focus attention on possible mechanisms of the prevention and treatment of metabolic syndrome by COS.


2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Chanon Piamsiri ◽  
Chayodom Maneechote ◽  
Natthaphat Siri-Angkul ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn

AbstractCardiovascular diseases (CVDs) are considered the predominant cause of morbidity and mortality globally. Of these, myocardial infarction (MI) is the most common cause of CVD mortality. MI is a life-threatening condition which occurs when coronary perfusion is interrupted leading to cardiomyocyte death. Subsequent to MI, consequences include adverse cardiac remodeling and cardiac dysfunction mainly contribute to the development of heart failure (HF). It has been shown that loss of functional cardiomyocytes in MI-induced HF are associated with several cell death pathways, in particular necroptosis. Although the entire mechanism underlying necroptosis in MI progression is still not widely recognized, some recent studies have reported beneficial effects of necroptosis inhibitors on cell viability and cardiac function in chronic MI models. Therefore, extensive investigation into the necroptosis signaling pathway is indicated for further study. This article comprehensively reviews the context of the underlying mechanisms of necroptosis in chronic MI-induced HF in in vitro, in vivo and clinical studies. These findings could inform ways of developing novel therapeutic strategies to improve the clinical outcomes in MI patients from this point forward.


2020 ◽  
Author(s):  
Ozgun Kocabiyik ◽  
Valeria Cagno ◽  
Paulo Jacob Silva ◽  
Yong Zhu ◽  
Laura Sedano ◽  
...  

AbstractInfluenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6’sialyl-N-acetyllactosamine (6’SLN) or 3’SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Hersant ◽  
Mounia Sid-Ahmed ◽  
Laura Braud ◽  
Maud Jourdan ◽  
Yasmine Baba-Amer ◽  
...  

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.


Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 609 ◽  
Author(s):  
Amjad Khan ◽  
Muhammad Ikram ◽  
Jong Ryeal Hahm ◽  
Myeong Ok Kim

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.


2020 ◽  
Vol 21 (18) ◽  
pp. 6541
Author(s):  
Dong Wook Choi ◽  
Sang Woo Cho ◽  
Seok-Geun Lee ◽  
Cheol Yong Choi

The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus. However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms.


2018 ◽  
Vol 18 (5) ◽  
pp. 667-674 ◽  
Author(s):  
Didem Sohretoglu ◽  
Shile Huang

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.


2016 ◽  
Vol 21 (4) ◽  
pp. NP98-NP102 ◽  
Author(s):  
Sedighe Albakhit ◽  
Shahram Khademvatan ◽  
Monir Doudi ◽  
Masoud Foroutan-Rad

Leishmaniasis is considered as a major public health problem worldwide. Current drugs in treatment of leishmaniasis have some limitations; thus, the current study was aimed to assess the methanolic extracts of pit and fruit of Phoenix dactylifera against Leishmania major promastigotes. L major promastigotes were cultured in RPMI 1640 and incubated at 25°C ± 1°C for 24, 48, and 72 hours. For obtaining the IC50 (half maximal inhibitory concentration) value, MTT assay was employed. Furthermore, promastigotes were examined in terms of morphology under light microscope. About 48 hours after treatment, IC50s were estimated 23 μg/mL and 500 mg/mL for methanolic extracts of pit and fruit of P dactylifera, respectively. Both extracts exhibited a dose and time-dependent antileishmanial activity against L major parasites. Also, some visible morphological changes were seen. This finding revealed both date fruit and pit, are effective against L major promastigotes. Further studies should be designed in future based on apoptosis induction in vitro and in vivo.


2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Qingqi Meng ◽  
Zhiteng Chen ◽  
Qingyuan Gao ◽  
Liqiong Hu ◽  
Qilong Li ◽  
...  

Background. Neurodegenerative diseases, such as Alzheimer’s disease, and traumatic brain and spinal cord injury (SCI) are prevalent in clinical practice. Inhibition of hyperactive inflammation and proliferation of endogenous neural stem cells (NSCs) is a promising treatment strategy for SCI. Our previous studies demonstrated the beneficial effects of rosiglitazone (Rosi) on SCI, but its roles in inflammation inhibition and proliferation of NSCs are unknown. Methods. SCI in a rat model was established, and the effects of Rosi on motor functions were assessed. The effects of Rosi on NSC proliferation and the underlying mechanisms were explored in details. Results. We showed that Rosi ameliorated impairment of moto functions in SCI rats, inhibited inflammation, and promoted proliferation of NSCs in vivo. Rosi increased ATP production through enhancing glycolysis but not oxidative phosphorylation. Rosi reduced mitophagy by downregulating PTEN-induced putative kinase 1 (PINK1) transcription to promote NSC proliferation, which was effectively reversed by an overexpression of PINK1 in vitro. Through KEGG analysis and experimental validations, we discovered that Rosi reduced the expression of forkhead box protein O1 (FOXO1) which was a critical transcription factor of PINK1. Three FOXO1 consensus sequences (FCSs) were found in the first intron of the PINK1 gene, which could be potentially binding to FOXO1. The proximal FCS (chr 5: 156680169–156680185) from the translation start site exerted a more significant influence on PINK1 transcription than the other two FCSs. The overexpression of FOXO1 entirely relieved the inhibition of PINK1 transcription in the presence of Rosi. Conclusions. Besides inflammation inhibition, Rosi suppressed mitophagy by reducing FOXO1 to decrease the transcription of PINK1, which played a pivotal role in accelerating the NSC proliferation.


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