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Total 60 results found since Jan 2013.

Delivery Strategies for mRNA Vaccines
AbstractThe therapeutic potential for messenger RNA (mRNA) in infectious diseases and cancer was first realized almost three decades ago, but only in 2018 did the first lipid nanoparticle-based small interfering RNA (siRNA) therapy reach the market with the United States Food and Drug Administration (FDA) approval of patisiran (Onpattro ™) for hereditary ATTR amyloidosis. This was largely made possible by major advances in the formulation technology for stabilized lipid-based nanoparticles (LNPs). Design of the cationic ionizable lipids, which are a key component of the LNP formulations, with an acid dissociation constan...
Source: Pharmaceutical Medicine - January 30, 2022 Category: Drugs & Pharmacology Source Type: research

Drug repurposing of dextromethorphan as a cellular target for the management of influenza
ConclusionInfluenza viruses continue to emerge and cause infection (including pandemics) in humans, so there remains a critical need to advance the understanding of influenza treatment. Our results demonstrated reduced hospitalization rates for influenza patients treated with DM. Further research on cellular targets and / or DM are warranted for the treatment of influenza.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - August 24, 2021 Category: Drugs & Pharmacology Authors: Tammy H. Cummings, Joseph Magagnoli, James W. Hardin, S. Scott Sutton Tags: ORIGINAL RESEARCH ARTICLE Source Type: research

Delivery of Thrombospondin-2 Small Interfering RNA for Suppression of Intimal Hyperplasia
Treatments of peripheral arterial disease, which affects>8.5 million individuals in the United States, include angioplasty and stenting and graft bypass. However, these have been limited by the pervasive development of intimal hyperplasia, which leads to in-stent restenosis and reduced graft patency. We propose a novel technique to suppress the progression of intimal hyperplasia using bioengineered hydrogels (ClickGels) for localized small interfering RNA (siRNA) delivery and suppression of thrombospondin-2 (TSP2), an upregulated gene of intimal hyperplasia, in an in vivo rat carotid angioplasty model.
Source: Journal of Vascular Surgery - August 24, 2021 Category: Surgery Authors: Jennifer R. Li, Kimberly Piper, Patric Liang, Max Zhu, Mauricio Contreras, Alexander Stafford, David Mooney, Leena Pradhan-Nabzdyk, Frank Logerfo Tags: PC: Poster Competition Source Type: research

Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells.
The objective of this study was to determine whether NOTCH signaling regulates goblet cell differentiation in response to cigarette smoke. Primary human bronchial epithelial cells (HBECs) from nonsmokers and COPD smokers were differentiated in vitro on air-liquid interface and exposed to cigarette smoke extract (CSE) for 7 days. NOTCH signaling activity was modulated using (1) the NOTCH/γ-secretase inhibitor Dibenzazepine (DBZ), (2) lentiviral over-expression of the NOTCH3-intracellular domain (NICD3) or (3) NOTCH3-specific siRNA. Cell differentiation and response to CSE were evaluated by qPCR, Western blotting, immunosta...
Source: Am J Respir Cell Mol... - January 14, 2021 Category: Respiratory Medicine Authors: Bodas M, Moore AR, Subramaniyan B, Georgescu C, Wren JD, Freeman WM, Brown BR, Metcalf JP, Walters MS Tags: Am J Respir Cell Mol Biol Source Type: research

E2F7, regulated by miR ‑30c, inhibits apoptosis and promotes cell cycle of prostate cancer cells.
In conclusion, the present study suggested that E2F7 may be positively associated with PCa cell proliferation by inhibiting p21, whereas E2F7 is in turn under regulation by miR‑30c. These observations suggest the miR‑30c/E2F7/p21 axis to be a viable therapeutic target for PCa. PMID: 32582990 [PubMed - as supplied by publisher]
Source: Oncology Reports - June 27, 2020 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

EZH2 Downregulation Augments the Effect of Irradiation in Reducing Pancreatic Cancer Cell Proliferation in vitro.
CONCLUSIONS: EZH2 downregulation in combination with irradiation reduces PANC-1 and MIA PaCa-2 cell proliferation more than irradiation alone. This study affirms the role of EZH2 downregulation for radiosensitization in pancreatic cancer treatment. PMID: 32161011 [PubMed - in process]
Source: Annals of Clinical and Laboratory Science - December 31, 2019 Category: Laboratory Medicine Authors: Agrawal R, Chen M, Bukhari Z, Ogunwobi OO, Haseeb MA, Martello LA Tags: Ann Clin Lab Sci Source Type: research

Study identifies therapeutic target for high blood pressure in the lungs
This study was supported by grants from the National Institutes of Health and the American Heart Association; and by the Foundation for Anesthesia Education and Research.
Source: UCLA Newsroom: Health Sciences - October 1, 2019 Category: Universities & Medical Training Source Type: news

Porcine deltacoronavirus enters cells via two pathways: A protease-mediated one at the cell surface and another facilitated by cathepsins in the endosome Microbiology
Porcine deltacoronavirus (PDCoV) is a pathogen belonging to the genus Deltacoronavirus that in 2014 caused outbreaks of piglet diarrhea in the United States. To identify suitable therapeutic targets, a more comprehensive understanding of the viral entry pathway is required, particularly of the role of proteases. Here, we identified the proteases that activate the viral spike (S) glycoprotein to initiate cell entry and also pinpointed the host-cellular pathways that PDCoV uses for entry. Our results revealed that cathepsin L (CTSL) and cathepsin B (CTSB) in lysosomes and extracellular trypsin in cell cultures independently ...
Source: Journal of Biological Chemistry - June 20, 2019 Category: Chemistry Authors: Jialin Zhang, Jianfei Chen, Da Shi, Hongyan Shi, Xin Zhang, Jianbo Liu, Liyan Cao, Xiangdong Zhu, Ye Liu, Xiaobo Wang, Zhaoyang Ji, Li Feng Tags: Microbiology Source Type: research

miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration
Conclusion In conclusion our results evidenced that 3D-COL/hPDLSCs/PEI-EVs may be an efficacious strategy to induce bone regeneration and vascularization of bone defects, thanks to its capacity to increase the levels of VEGF. Ethics Statement The study was performed in accordance with the guidelines of the Helsinki Declaration (2013). The written approval for the human periodontal ligament collection performed in this study has been obtained from the Medical Ethics Committee at the Medical School, “G. d’Annunzio” University of Chieti–Pescara, Chieti, Italy (n°266/17.04.14, Principal in...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research