Publications by authors named "Arshad Zahoor"

14 Publications

  • Page 1 of 1

Reduced expression of MiR-125a-5p aggravates LPS-induced experimental acute kidney injury pathology by targeting TRAF6.

Life Sci 2021 May 25:119657. Epub 2021 May 25.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Aims: Patients with acute kidney injury (AKI) have higher mortality, and sepsis is among its main causes. MicroRNAs (miRNAs) are essential for regulating kidney function and could have curative potential. This study explored the possibility to treat AKI with miR-125a-5p and reveal the possible mechanism.

Materials And Methods: LPS-induced mouse model and LPS-induced RAW264.7 cell model of AKI were established and treated with miR-125a-5p mimics or inhibitors. Serum creatinine and blood urea were measured to evaluate kidney function. The pathological changes of kidney tissues were detected by H&E and PAS staining technique, and the infiltration of macrophages were observed by immunohistochemistry. RAW264.7 cell viability, TRAF6 and cytokines expressions under LPS stimulation were measured. The role and therapeutic potential of miR-125a-5p were verified in vivo and in vitro after given miR-125a-5p mimics or inhibitors.

Key Findings: LPS-induced mice had increasing serum creatinine and urea, and evident pathological changes, including severe tubular dilatation and macrophages infiltration. TRAF6 expression in the kidney was significantly higher, while miR-125a-5p expression was suppressed. MiR-125a-5p targeted TRAF6, and its overexpression deactivated NF-κB signaling pathway, reducing downstream TNF-α, IL-1β and IL-6 expressions. MiR-125a-5p mimics rescued LPS-induced kidney damage and suppressed pro-inflammatory cytokines expression through inhibiting TRAF6/NF-κB axis.

Significance: We highlighted that miR-125a-5p could inhibit LPS-induced acute inflammation in the kidney through targeting TRAF6/NF-κB axis. These results might contribute to the development of molecular therapy in AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119657DOI Listing
May 2021

MerTK negatively regulates Staphylococcus aureus induced inflammatory response via SOCS1/SOCS3 and Mal.

Immunobiology 2020 07 21;225(4):151960. Epub 2020 May 21.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Objective: Staphylococcus aureus (S. aureus), one of Gram-positive pathogen, is frequently associated with acute lung inflammation. The central feature of S. aureus acute lung inflammation are pulmonary dysfunctioning and impeded host defence response, which cause failure in inflammatory cytokines homeostasis and leads to serious tissue damage. However, the role of the Mer receptor tyrosine kinase (MerTK) in the lung following S. aureus infection remains elusive. Here, we investigate whether MerTK alleviates S. aureus induced uncontrolled inflammation through negatively regulating toll-like receptor 2 and 6 (TLR2/ TLR6) via suppressor of cytokine signalling 1, 3 (SOCS1/SOCS3).

Methods And Results: We found in mice lung tissues and RAW 264.7 macrophages upon S. aureus infection activates TLR2 and TLR6 driven mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signalling pathways, resulting in production of inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6). Furthermore, S. aureus-infection groups showed a significant up-regulation of MerTK which serves as mediator of SOCS1 and SOCS3. Subsequently, through feedback mechanism SOCS1/3 degrade Mal, resulting in inhibition of downstream TLR mediated inflammatory pathways. Moreover, MerTK mice lung tissues and silencing MerTK in RAW 264.7 inhibited the S. aureus-induced activation of MerTK, which significantly upregulated the phosphorylation of crucial protein in MAPKs (ERK, JNK, p38) and NF-κB (IĸBα, p65) signalling pathways, as well as the production of pro-inflammatory cytokines.

Conclusion: Collectively, these findings indicate the important role of MerTK in self-regulatory resolution of S. aureus-induced inflammatory pathways and cytokines through intrinsic SOCS1 and SOCS3 repressed feedback on TLR2, TLR6 both in vivo and in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imbio.2020.151960DOI Listing
July 2020

6-Gingerol exerts anti-inflammatory effects and protective properties on LTA-induced mastitis.

Phytomedicine 2020 May 26;76:153248. Epub 2020 May 26.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Background: Mastitis has a severe impact on human health and breastfeeding. Gram-positive bacteria are one of the most common pathogens, of which lipoteichoic acid (LTA) serves as the main pathogenic factor. Bio-active extractions from herbs is regarded as an alternative method to antibiotics. 6-Gingerol is used for the treatment of tumors and inhibition of inflammation in liver and gallbladder.

Purpose: To determine whether 6-gingerol can be used as a therapeutic medicine for mastitis.

Results: In this article, we used mice as the animal model and RAW264.7/PMECs as cell models. Western blot was for detecting the expression of proteins in NF-κB/MAPK signaling pathways and MMPs/TIMPs. MPO was for the detection of the amount of immune cells. H&E, immunohistochemistry and immunofluorescence were used for locating and detecting the expression of proteins. The detection of inflammatory cytokines was conducted by ELISA and RT-qPCR. We found that the NF-κB/MAPK signaling pathways, formation of ECM, production of inflammatory cytokines and injury to mammary gland cells were attenuated both in vivo and in vitro when 6-gingerol was administered.

Conclusion: We discovered the function and efficacy of 6-gingerol as a therapeutic compound in LTA-induced mastitis and its probable mechanism of action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2020.153248DOI Listing
May 2020

MerTK negatively regulates Staphylococcus aureus induced inflammatory response via Toll-like receptor signaling in the mammary gland.

Mol Immunol 2020 Apr 2;122:1-12. Epub 2020 Apr 2.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Mastitis is the most commonly diagnosed infectious disease reducing milk yield and quality and is accompanied by mammary tissue damage in both humans and animals. Mastitis incurs welfare and economic costs as well as environmental concerns regarding treatment. Staphylococcus aureus (S. aureus) is a prevalent Gram-positive bacteria and a major cause of mastitis, however, pathogenesis of the intrinsic anti-inflammatory response in mammary tissues is still principally unknown. Our aim, in combatting the S. aureus induced inflammatory response in mammary tissues, was to elucidate the intrinsic anti-inflammatory role of MerTK signaling. Here, we demonstrate that Mer receptor tyrosine kinase (MerTK) regulates an intrinsic negative feedback to balance the over-reaction of the host defense system. S. aureus elicits toll-like receptors 2 and 6 (TLR2/TLR6) signaling pathways, subsequently recruiting TRAF6, whose ubiquitination is intricate to the downstream signaling including MAPKs and NF-κB. We observed that TLR2/TLR6 activation, in response to S. aureus, was concomitant with induced MerTK activation, leading to raised expression of suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) in wild type mice mammary tissues and epithelial cells. Meanwhile, S. aureus infection in MerTK mice showed significant increased phosphorylation of p65, IκBα, p38, JNK and ERK along with production of pro-inflammatory cytokines. Moreover, MerTK evidently inhibited S. aureus induced phosphorylation of STAT1 and subsequent SOCS1/SOCS3 expression which are pivotal in the negative feedback mechanism for targeting TRAF6 to inhibit the TLR2/TLR6 mediated immune response. Taken together, our findings demonstrate the importance of MerTK in the regulation of the intrinsic feedback during the inflammatory response induced by S. aureus through STAT1/SOCS1/SOCS3 in mice mammary tissues and mice mammary epithelial cells (MMECs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2020.03.007DOI Listing
April 2020

Upregulated-gene expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) via TLRs following NF-κB and MAPKs in bovine mastitis.

Acta Trop 2020 Jul 31;207:105458. Epub 2020 Mar 31.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Mastitis is the inflammation of mammary glands which causes huge economic loss in dairy cows. Inflammation, any tissue injury and pathogens in cow udder activate Toll-like Receptors (TLRs). Staphylococcus aureus (S. aureus) is the major cause of mastitis. In mastitis, activated TLRs initiate the NF-κB/MAPKs pathways which further trigger the gene expression associated with mastitis followed by innate immune response. In this study, pathogenic-induced gene expression profile of pro-inflammatory cytokines in mammary gland tissues, was investigated in mastitis. The Hematoxylin and Eosin (H & E) results indicated severe histopathological changes in infected tissues. Western blot results suggested the over expressions of TLR2/TLR4 with NF-κB/MAPKs pathways activation in infected tissues. qRT-PCR results revealed the gene expression associated with TLR2/TLR4-mediated NF-κB/MAPKs pathways in infected tissues in comparison with non-infected. Statistical analysis of mRNA and relative protein expression levels indicated the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in infected tissues rather than non-infected tissues. These results suggested that the up-regulation of gene expression levels implicated the underlying regulatory pathways for proper immune function in mammary glands. In conclusion, our study might give new insights for investigation and better understanding of mammary gland pathophysiology and TLRs and NF-κB/MAPKs-mediated gene expression of pro-inflammatory cytokines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actatropica.2020.105458DOI Listing
July 2020

Ginsenoside Rb 1: A novel therapeutic agent in Staphylococcusaureus-induced Acute Lung Injury with special reference to Oxidative stress and Apoptosis.

Microb Pathog 2020 Jun 12;143:104109. Epub 2020 Mar 12.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Acute lung injury (ALI) is considered as an uncontrolled inflammatory response that can leads to acute respiratory distress syndrome (ARDS), which limits the therapeutic strategies. Ginsenosides Rb1 (Rb1), an active ingredient obtained from Panax ginseng, possesses a broad range of pharmacological and medicinal properties, comprising the anti-inflammatory, anti-oxidant, and anti-tumor activities. Therefore, the purpose of the present study was to investigate the protective effects of Rb1 against S. aureus-induced (ALI) through regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial-mediated apoptotic pathways in mice (in-vivo), and RAW264.7 cells (in-vitro). For that purpose, forty Kunming mice were randomly assigned into four treatment groups; (1) Control group (phosphate buffer saline (PBS); (2) S. aureus group; (3) S. aureus + Rb1 (20 mg/kg) group; and (4) Rb1 (20 mg/kg) group. The 20 μg/mL dose of Rb1 was used in RAW264.7 cells. In the present study, we found that Rb1 treatment reduced ALI-induced oxidative stress via suppressing the accumulation of malondialdehyde (MDA) and myeloperoxidase (MPO) and increase the antioxidant enzyme activities of superoxidase dismutase 1 (SOD1), Catalase (CAT), and glutathione peroxidase 1 (Gpx1). Similarly, Rb1 markedly increased messenger RNA (mRNA) expression of antioxidant genes (SOD1, CAT and Gpx1) in comparison with ALI group. The histopathological results showed that Rb1 treatment ameliorated ALI-induced hemorrhages, hyperemia, perivascular edema and neutrophilic infiltration in the lungs of mice. Furthermore, Rb1 enhanced the antioxidant defense system through activating the Nrf2 signaling pathway. Our findings showed that Rb1 treated group significantly up-regulated mRNA and protein expression of Nrf2 and its downstream associated genes down-regulated by ALI in vivo and in vitro. Moreover, ALI significantly increased the both mRNA and protein expression of mitochondrial-apoptosis-related genes (Bax, caspase-3, caspase-9, cytochrome c and p53), while decreased the Bcl-2. In addition, Rb1 therapy significantly reversed the mRNA and protein expression of these mitochondrial-apoptosis-related genes, as compared to the ALI group in vivo and in vitro. Taken together, Rb1 alleviates ALI-induced oxidative injury and apoptosis by modulating the Nrf2 and mitochondrial signaling pathways in the lungs of mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2020.104109DOI Listing
June 2020

Gas6 negatively regulates the Staphylococcus aureus-induced inflammatory response via TLR signaling in the mouse mammary gland.

J Cell Physiol 2020 10 13;235(10):7081-7093. Epub 2020 Feb 13.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.

Staphylococcus aureus (S. aureus)-induced mastitis is the most frequent, pathogenic, and prevalent infection of the mammary gland. The ligand growth arrest-specific 6 (Gas6) is a secretory protein that binds to and activates Tyro3, Axl, and MerTK receptors. This study explored the role of Gas6 in S. aureus-induced mastitis. Our results revealed that TLR receptors initiate the innate immune response in mammary gland tissues and epithelial cells and that introducing S. aureus activates TLR2 and TLR6 to drive multiple intracellular mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways. Moreover, S. aureus also induces Gas6, which then activates the TAM receptor kinase pathway, which is related to the inhibition of TLR2- and TLR6-mediated inflammatory pathways through SOCS1 and SOCS3 induction. Gas6 absence alone was found to be involved in the downregulation of TAM receptor-mediated anti-inflammatory effects by inducing significantly prominent expression of TRAF6 and low protein and messenger RNA expression of SOCS1 and SOCS3. S. aureus-induced MAPK and NF-ĸB p65 phosphorylation were also dependent on Gas6, which negatively regulated the production of Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in S. aureus-treated mammary tissues and mammary epithelial cells. Our in vivo and in vitro study uncovered the Gas6-mediated negative feedback mechanism, which inhibits TLR2- and TLR6-mediated MAPK and NF-ĸB signaling by activating TAM receptor kinase (MerTK, Axl, and Tyro3) through the induction of SOCS1/SOCS3 proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.29604DOI Listing
October 2020

Hederacoside-C Inhibition of Staphylococcus aureus-Induced Mastitis via TLR2 & TLR4 and Their Downstream Signaling NF-κB and MAPKs Pathways In Vivo and In Vitro.

Inflammation 2020 Apr;43(2):579-594

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Hederacoside-C (HDC) is a biological active ingredient, extracted from the leaves of Hedera helix. It has been reported to have anti-inflammatory properties. However, the effects of HDC on Staphylococcus aureus (S. aureus)-induced mastitis have not been reported yet. Here, we evaluated the anti-inflammatory effects of HDC on S. aureus-induced mastitis both in vivo on mammary gland tissues and in vitro on RAW 264.7 cells. The ascertained histopathological changes and MPO activity revealed that HDC defended mammary glands from tissue destruction and inflammatory cell infiltration induced by S. aureus. The results of ELISA, western blot, and qRT-PCR indicated that HDC significantly inhibited the expressions IL-6, IL-1β, and TNF-α and enhanced the IL-10 by downregulating and upregulating their relevant genes, respectively. Furthermore, HDC markedly suppressed the TLR2 and TLR4 expressions by attenuating the MAPKs (p38, ERK, JNK) and NF-κB (p65 and IκBα) pathways followed by decreasing the phosphorylation of p38, ERK, JNK, p65, and IκBα. The above parameters enhanced the mammary gland defense and reduced inflammation. These findings suggested that HDC may have the potential to be an effective anti-inflammatory drug for the S. aureus-induced mice mastitis and in RAW 264.7 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10753-019-01139-2DOI Listing
April 2020

Anti-inflammatory effects of Hederacoside-C on Staphylococcus aureus induced inflammation via TLRs and their downstream signal pathway in vivo and in vitro.

Microb Pathog 2019 Dec 30;137:103767. Epub 2019 Sep 30.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Acute lung inflammation is one among the top of infectious diseases. It is a pulmonary dysfunctional disease. It breaks the physiological coordination in the structures and functions of respiratory system. There are a few effective treatments to minimize the mortality of acute lung inflammation. It was induced by Staphylococcus aureus (S. aureus) via nasal instillation of mice. The common ivy (Hedera helix) is the most significant medicinal plant and considered as a traditional medicinal plant. The most active ingredient in the extract of ivy plant was Hederacoside-C (HDC). The purpose of this study was to investigate its anti-inflammatory effects on induced acute lung inflammation in vivo and (RAW 264.7 cells) in vitro and to elucidate its anti-inflammatory mechanisms. HDC was administered intraperitoneally 1 h after infection until 24 h. The dose was repeated every 8 h for three successful doses. Mice treated with HDC significantly reduced the pulmonary edema, white blood cells, wet-dry ratio (W/D) and myeloperoxidase (MPO) activity. HDC attenuated protein expression levels of MAPKs including p38, ERK, JNK and NF-κB including p65 and IκB-α pathways analyzed by ELISA. HDC also suppressed the protein expressions of TLR2 & TLR4 detected by Western blot. HDC also downregulated the gene expression of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α, but upregulated the gene expression of an anti-inflammatory cytokine IL-10 analyzed by qRT-PCR. In conclusion, our results stated that HDC could inhibit the S. aureus induced acute lung inflammation and it may be a potential therapeutic drug against acute lung inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2019.103767DOI Listing
December 2019

MicroRNA-188-5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c.

J Cell Physiol 2020 03 20;235(3):2389-2402. Epub 2019 Sep 20.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.29144DOI Listing
March 2020

MiR-142a-3p alleviates Escherichia coli derived lipopolysaccharide-induced acute lung injury by targeting TAB2.

Microb Pathog 2019 Nov 5;136:103721. Epub 2019 Sep 5.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease, leading to an extremely high mortality. The pathogenesis of ALI is suggested to be a consequence of uncontrolled inflammation. Lipopolysaccharide (LPS)-induced ALI mice model is often used for the mechanism. Studies show that TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response. Furthermore, microRNA-142a-3p (miR-142a-3p) has been observed to be involved in inflammation-induced disease. Thus, we investigated the role of miR-142a-3p and TAB2 on LPS-induced ALI, which involved the TLR4/TAB2/NF-κB signaling. ALI and normal lung tissues were collected to access the relative expression of pro-inflammatory cytokines and miR-142a-3p. Histopathological examination and Wet to Dry weight ratios of lung tissues were used to access the establishment of ALI models. Raw264.7 cells were transfected with si-TAB2 or miR-142a-3p mimics to elucidate the role of TAB2 or miR-142a-3p in the inflammatory cascade in ALI. Additionally, the relationship between miR-142a-3p and TAB2 was validated by dual-luciferase report system. Our study discovered that miR-142-3p was up-regulated both in LPS-induced ALI mice model and RAW264.7 cells model. MiR-142a-3p mimics group experienced significant decrease in the secretion of pro-inflammatory cytokines as a result of the inhibition of NF-κB signaling pathway. Bioinformatics database showed that the adaptor protein, TAB2, was critical in this pathway and it is the target gene of miR-142a-3p. Their relation was first confirmed by us via dual-luciferase report system. Results of our study demonstrated that miR-142a-3p exerts as a protective role in LPS-induced ALI through down-regulation of NF-κB signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2019.103721DOI Listing
November 2019

Ginsenoside Rb1 ameliorates Staphylococcus aureus-induced Acute Lung Injury through attenuating NF-κB and MAPK activation.

Microb Pathog 2019 Jul 4;132:302-312. Epub 2019 May 4.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. Electronic address:

Acute lung injury (ALI) is clinically characterized by excessive inflammation leading to acute respiratory distress syndrome (ARDS), having high morbidity and mortality both in human and animals. Ginsenoside Rb1 (Rb1) is a major primary bioactive component extracted by Panax ginseng, which has numerous pharmacological functions such as anti-cancer, anti-inflammatory, and antioxidant. However, the anti-inflammatory effects of Rb1 in Staphylococcus aureus (S. aureus)-induced ALI in mice have not been investigated. The aim of the current study was to determine the anti-inflammatory influence of Rb1 on S. aureus-induced ALI in mice, and to explore its possible underlying principle mechanisms in RAW 264.7 macrophage cells. The results of physical morphology, histopathological variation and wet-to-dry weight ratio of lungs revealed that Rb1 significantly attenuated S. aureus-induced lung injury. Furthermore, qPCR results displayed that Rb1 inhibited IL-1β, IL-6 and TNF-α production both in vivo and in vitro. The activation of Toll-like receptor 2 (TLR2) by S. aureus was inhibited by application of Rb1 as confirmed by results of immunofluorescence assay. The expression of NF-kB and MAPK signaling proteins revealed that Rb1 significantly attenuated the phosphorylation of p65, ERK, as well as JNK. Altogether, the results of this experiment presented that Rb1 has ability to protect S. aureus-induced ALI in mice by attenuating TLR-2-mediated NF-kB and MAPK signaling pathways. Consequently, Rb-1 might be a potential medicine in the treatment of S. aureus-induced lung inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2019.05.003DOI Listing
July 2019

MiR-128 mediates negative regulation in Staphylococcus aureus induced inflammation by targeting MyD88.

Int Immunopharmacol 2019 May 22;70:135-146. Epub 2019 Feb 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address:

Acute lung injury (ALI) is a common clinical syndrome of excessive uncontrolled inflammatory response in lung tissues with high mortality rates and limited therapeutic approaches. MicroRNAs (miRNAs) are a class of small non-coding RNAs which attach at 3'UTR of mRNA for further regulation of diverse proteins. MiRNAs are a current focus in regulating the inflammatory processes. The extent of pro-inflammatory gene activated against Staphylococcus aureus (S. aureus) is still unclear. Myeloid differentiation primary response 88 (MyD88) is involved in gram positive bacteria-induced lung inflammation by Toll-like receptors (TLRs). Then MyD88 activates NF-κB through IRAKs which are in charge of inflammation. Target prediction analyses revealed MyD88, a result of projections from multiple bio-websites, to be a putative target of miR-128. Here we probe the expression of the MyD88 and miRNA in mode of inflammation. We found up-regulated expression of MyD88 and down-regulation of miR-128 after S. aureus infection in mouse lung tissues and RAW264.7 cells via qPCR and western blotting (WB) analysis. Moreover, MyD88-miR-128 interaction was validated by luciferase assays. Then, we proved that miR-128 expression caused a reduction in IκBα and p65 phosphorylation and resulted in significant reduction in secretion of inflammatory cytokines, being consistent with the deletion of MyD88 in macrophages. It revealed that miR-128 specifically blocked the further development of inflammation through MyD88 down-regulation. Finally, we demonstrated a novel role of miR-128 that it mediates negative regulation in S. aureus induced inflammation by targeting MyD88.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2018.11.024DOI Listing
May 2019

Effects of medetomidine on serum glucose in cattle calves.

Pak J Pharm Sci 2016 May;29(3):941-4

Department of Animal Health, Faculty of Animal Husbandry and Veterinary Sciences, The University of Agriculture, Peshawar, KPK, Pakistan.

An experimental study was carried out to compare physiological effects (serum glucose level) of medetomidine in Red Sindhi cattle calves at three different doses i.e. 8, 10 and 12µg/kg body weight intravenously. Medetomidine produced a dose dependent significant (P<0.01) increase in serum glucose level with a maximum increase observed at 30 minutes with 8µg/kg, 10μg/kg and 12μg/kg body weight respectively. Start of sedation, degree of sedation and total duration of sedation were all dose dependent and the values obtained were significantly (P<0.01) different from each other. It was observed that the sedation was rapid, deep and longer with the higher doses of medetomidine i.e. 12μg/kg. The results of the present study shows that medetomidine is a very effective and safest drug use as sedative for calves which in lower doses (8μg/kg) can be used as a pre-anesthetic and for restraining of the animal, while higher calculated doses (10μg/kg, 12μg/kg) can be used to execute the minor surgical procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2016
-->