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PCSK9 and cancer: Rethinking the link
Biomed Pharmacother. 2021 May 28;140:111758. doi: 10.1016/j.biopha.2021.111758. Online ahead of print.ABSTRACTBACKGROUND: Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells including prostate, breast, and colorectal carcinomas. However, the importance of cholesterol in carcinogenesis and thereby the role of cholesterol homeostasis as a therapeutic target is still a debated area in cancer therapy...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - May 31, 2021 Category: Drugs & Pharmacology Authors: Khadijeh Mahboobnia Matteo Pirro Ettore Marini Francesco Grignani Evgeny E Bezsonov Tannaz Jamialahmadi Amirhossein Sahebkar Source Type: research

Fight Aging! Newsletter, June 19th 2017
This study is the first to show that downregulation of PAPP-A expression in adult mice can significantly extend life span. Importantly, this beneficial longevity phenotype is distinct from the dwarfism of long-lived PAPP-A KO, Ames dwarf, Snell dwarf and growth hormone receptor (GHR) KO mice with germ-line mutations. Thus, downregulation of PAPP-A expression joins other treatment regimens, such as resveratrol, rapamycin and dietary restriction, which can extend life span when started in mice as adults. In a recent study, inducible knockdown of the GHR in young adult female mice increased maximal, but not median, lif...
Source: Fight Aging! - June 18, 2017 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

Strain-Specific Altered Regulatory Response of Rab7a and Tau in Creutzfeldt-Jakob Disease and Alzheimer’s Disease
In this study, we performed a targeted search for endocytic pathway proteins in the different regions of the brain. We found late endosome marker Rab7a which was significantly upregulated in the frontal cortex region in the rapid progressive CJD form (MM1) and rapid progressive AD (rpAD) forms. However, Rab9 expression was significantly downregulated only in CJD-MM1 brain frontal cortex region. In the cerebellum, Rab7a expression showed significant upregulation in both subtype MM1 and VV2 CJD forms, in contrast to Rab9 which showed significant downregulation in both subtype MM1 and VV2 CJD forms at terminal stage of the di...
Source: Molecular Neurobiology - January 14, 2016 Category: Neurology Source Type: research

Fight Aging! Newsletter, February 19th 2018
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - February 18, 2018 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, March 29th 2021
Discussion of Systemic Inflammation and its Contribution to Dementia Fisetin Reduces D-Galactose Induced Cognitive Loss in Mice Reprogramming Cancer Cells into Normal Somatic Cells Considering Longevity Medicine and the Education of Physicians Researchers Generate Thyroid Organoids Capable of Restoring Function in Mice In Search of Transcriptional Signatures of Aging A Pace of Aging Biomarker Correlates with Manifestations of Aging Targeting Tissues with Extracellular Vesicles Calorie Restriction Slows Aging of the Gut Microbiome in Mice Mitochondrial DNA Heteroplasmy in the Aging Heart Evidence for Hea...
Source: Fight Aging! - March 28, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

RNA interference targeting E637K mutation rescues hERG channel currents and restores its kinetic properties
Conclusion: Our findings illustrated that siRNA can effectively inhibit E637K-hERG protein expression and rescue the dominant-negative effect of this mutation by restoring the kinetic properties of hERG protein channel. It has potential clinical implications with regard to the possibility of using siRNA in the treatment of LQTS.
Source: Heart Rhythm - September 28, 2012 Category: Cardiology Authors: Xiaoli Lu, Xi Yang, Xiaoyan Huang, Chen Huang, Huan Huan Sun, Lihua Jin, Weifeng Xu, Haiyan Mao, Junming Guo, Jianqing Zhou, Jiangfang Lian Tags: Experimental Genetic Source Type: research

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
Conclusion In conclusion, the present study demonstrated that autophagy was involved in relieving the effects of TSF against NAFLD, which were mediated by the AMPK/SIRT1 pathway (Figure 7D). These findings may improve our current understanding of the role of TSF in treating hepatic steatosis and provide an experimental basis for the clinical application of TSF in NAFLD and its related metabolic syndrome. Ethics Statement This study was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Ethics Co...
Source: Frontiers in Physiology - April 25, 2019 Category: Physiology Source Type: research

Synergistic effect of STAT3 ‑targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo.
Synergistic effect of STAT3‑targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo. Mol Med Rep. 2019 Aug 21;: Authors: Liu Q, Wang L, Li D, Zhao J, Chen S, Li J Abstract The aim of this study was to explore the synergistic effect of signal transducer and activator of transcription 3 (STAT3)‑targeted small interfering (si)RNA and AZD0530 against glioblastoma in vitro and in vivo. Glioblastoma cell lines U87 and U251 were divided into four groups and treated with control, LV‑STAT3 siRNA, AZD0530, and combined LV‑STAT3 siRNA with AZD0530, respectively. The proli...
Source: Molecular Medicine Reports - September 7, 2019 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Preliminary experimental study of urethral reconstruction with tissue engineering and RNA interference techniques.
This study investigated the feasibility of replacing urinary epithelial cells with oral keratinocytes and transforming growth factor-β1 (TGF-β1) small interfering RNA (siRNA)-transfected fibroblasts seeded on bladder acellular matrix graft (BAMG) in order to reconstruct tissue-engineered urethra. Constructed siRNAs, which expressed plasmids targeting TGF-β1, were transfected into rabbit fibroblasts. The effective siRNA was screened out by RT-PCR and was transfected into rabbit fibroblasts again. Synthesis of type I collagen in culture medium was measured by enzyme-linked immuno sorbent assay (ELISA). Autologous oral ker...
Source: Asian Journal of Andrology - May 1, 2013 Category: Urology & Nephrology Authors: Li C, Xu YM, Li HB Tags: Asian J Androl Source Type: research

Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.
Authors: Gao P, Zhang X, Wang H, Zhang Q, Li H, Li Y, Duan Y Abstract Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2...
Source: Oncotarget - December 5, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 15, 2019 Category: Microbiology Source Type: research

Target gene delivery from targeting ligand conjugated chitosan–PEI copolymer for cancer therapy
In this study, we designed a novel carrier which was having low cytotoxicity, site-specific target function, and high transfection efficiency using low molecular weight water soluble O-carboxymethyl chitosan (OCMCh), branched low molecular weight poly(ethyleneimine) (bPEI), and targeting ligand (epitope type, HER-2/neu). OCMCh/bPEI/targeting ligand, HPOCP copolymer, and targeting ligand-modified polyamphoteric polymer, and were prepared by chemical reaction and characterized by 1H NMR and FT-IR. The binding affinity, protecting efficiency, and releasing ability of gene/HPOCP polyplex were confirmed by gel retardation assay...
Source: Carbohydrate Polymers - September 9, 2015 Category: Biomedical Science Source Type: research

Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance to Subsequent Stimulation With Lipopolysaccharides
Conclusion: Bypass of tolerance by DAMPs might be a phenomenon as important as TI, since it could explain how chronic inflammation can be maintained in spite of an environment with multiple TLR2/TLR4-ligands. In RA monocytes, a PRDM8-dependent TI mechanism could be responsible for sustained chemokine/cytokines levels. Introduction Monocytes and macrophages play a central role in the pathophysiology of inflammation. For instance, in rheumatoid arthritis (RA), activated monocytes massively infiltrate synovial tissues and produce tumor necrosis factor-α (TNFα) (1–3). Accordingly, therapies aime...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research

Silencing TNF-α in macrophages and dendritic cells for arthritis treatment.
Conclusions: Suppression of TNF-α expression in macrophages and DCs by RVG-9R-mediated siRNA delivery could potentially be a clinically viable strategy for treatment of arthritis. PMID: 23582054 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Rheumatology - April 14, 2013 Category: Rheumatology Authors: Ye C, Bhan A, Deshpande V, Shankar P, Manjunath N Tags: Scand J Rheumatol Source Type: research