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Lyophilization of Protein Pharmaceuticals
Published in Kenneth E. Avis, Vincent L. Wu, Biotechnology and Biopharmaceutical Manufacturing, Processing, and Preservation, 2020
John F. Carpenter, Byeong S. Chang
In the storage study with interleukin-1 receptor antagonist, it appears that, in addition to an environment permissive to chemical degradation, the glassy state also allowed sufficient mobility for further structural alterations in, and intermolecular interactions between, unfolded protein molecules. In samples prepared with ≤ 1 percent sucrose, the infrared spectra after 6 months of storage at 50°C were greatly altered relative to those for the protein immediately after lyophilization (Chang et al. in press). The appearance of bands at 1620 cm−1 and 1695 cm−1, which are due to the intermolecular beta sheet, indicate that protein aggregation was arising during storage in the dried solid. These interactions were not seen in the preparations containing 5 percent and 10 percent sucrose, in which the initial lyophilization-induced protein unfolding was inhibited.
Current and Rising Concepts in Immunotherapy: Biopharmaceuti cals versus Nanomedicines
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Immune cells produce a huge spectrum of compounds named cytokines acting on other cell types and tissues, which constitutes a major part of humoral immunity. Serum cytokine levels are important in diagnostics as they represent potential indicators of organ injury. There is evidence that cancerogenesis is influenced by different MΦ subsets, but the roles of the subsets are not fully understood. Several reports demonstrated that M2-polarized MΦ are frequent in cancer, which can be designated as type 2 tumor-associated macrophages (TAM2). The TAM2 and other immune cells exhibit immunosuppressive functions, such as myeloid-derived suppressor cells, T helper 2 (Th2) cells, and regulatory T (TReg) cells, which are overrepresented in many types of cancer allowing for immune evasion of tumors [17]. Similar to M2-MΦ and TAM2, also TReg produce large amounts of interleukin 10 (IL10) [18]. M2-MΦ additionally produce many other anti-inflammatory cytokines such as the CC chemokine ligand 18 (CCL18), transforming growth factor β (TGF-β), or interleukin 1 receptor antagonist (IL1RA), depending on the subset of M2-MΦ [19]. Currently our unpublished research in experimental liver cancer has demonstrated that in addition to the TAM2, there are also inflammatory TAM, which one might term TAM1, which are highly distinctive from TAM2 and from MDSC in mRNA profiles.
Treatment of Rheumatoid Arthritis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Stuart Weisman, Arthur Kavanaugh
In rheumatoid arthritis, IL-lβ is present in large quantities in the synovial fluid and synovial tissue.47 Interleukin-1 β can stimulate metalloproteinase expression, adhesion molecule expression, secretion of other cytokines, and prostaglandin production. Interleukin 1 receptor antagonist is a naturally occurring competitive inhibitor for IL-la and IL-lβ. IL-1 Ra binds to the IL-1R1 (interleukin-1 receptor) without transducing a signal, thus blocking the ability of interleukin la or 1 β to bind to the receptor. In November 2001, anakinra was approved for the treatment of rheumatoid arthritis. Anakinra is a recombinant form of the naturally occurring interleukin-1 receptor antagonist (ILl-Ra) produced using E. coli.
The roadmap towards cure of chronic hepatitis B virus infection
Published in Journal of the Royal Society of New Zealand, 2022
TLR-8 is a transmembrane receptor counsellor located in the endosomal membrane of a subset of immune cells and recognises single-stranded RNA. TLR-8 activates innate and adaptive effector cells. GS-9688 is the first oral TLR8 agonist. Once-weekly dosing of oral GS-9688 induced dose-dependent increase in serum interferon-gamma (IFN-γ), interleukin-12 (IL-12) and interleukin-1 receptor antagonist (IL-1RA) in cynomolgus monkeys and Functional Cure in the woodchucks (Daffis et al. 2017). In phase II studies, weekly dosing of GS-9688 for 24 weeks in patients with chronic HBV induced dose-dependent cytokine and PD responses, as well as shifts in peripheral immune cell subsets. Profound HBsAg suppression and isolated HBeAg and HBsAg loss were observed in isolated patients (Gane, Zhao, et al. 2019). Ongoing studies are now evaluating TLR-8 agonists in combination with other novel therapies.
Optimizing the biodegradability and osteogenesis of biogenic collagen membrane via fluoride-modified polymer-induced liquid precursor process
Published in Science and Technology of Advanced Materials, 2023
Xiyan Li, Chuangji Li, Mengxi Su, Xinyi Zhong, Yihan Xing, Zhengjie Shan, Shoucheng Chen, Xingchen Liu, Xiayi Wu, Quan Liu, Ye Li, Shiyu Wu, Zhuofan Chen
Cells were stimulated with the conditioned medium of collagen membranes for 24 h. Total RNA was extracted using TRIzol reagent (Life Technologies, U.S.A.) following the manufacturer’s instructions. RNA was reverse-transcribed into single-stranded cDNA using the TaKaRa PrimeScriptTM Master Mix (Perfect Real Time Kit; Takara, Japan). RT-PCR was performed on an equivalent quantity of cDNA using Hieff® qPCR SYBR Green Master Mix (No Rox; Yeasen, Shanghai, China) according to the manufacturer’s instructions. The relative mRNA expression of inflammation-related genes [interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6), nuclear factor kappa-B1 (NFκB1), and interleukin 1 receptor antagonist (IL-1rn)], osteoclastogenesis-related genes [macrophage colony-stimulating factor (MCSF)], angiogenic factors [vascular endothelial growth factor (VEGF)], osteogenesis- and fibrosis-related genes [transforming growth factor-β1 (TGF-β1) and TGF-β3)], and collagenase [matrix metalloprotein 9, (MMP9)] were detected in the F-mBCM and blank groups. The relative mRNA expression of inflammation-related genes (IL-1β, TNF-α, IL-6, NFκB1, and IL-1rn), osteoclastogenesis-related genes (MCSF), osteogenesis- and fibrosis-related genes [TGF-β1, TGF-β3, and oncostatin M, (OSM)], and collagenase (MMP9) were detected in the SF25 and blank groups. The 2−ΔΔCt method was used to calculate relative gene expression after normalization against the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Primers used in this study are listed in Supplementary Table S1.
The effects of a multi-day cross-country mountain bike race on myocardial function, stress, inflammation and cardiac biomarkers in amateur master athletes
Published in Research in Sports Medicine, 2022
Einat Kodesh, Dalya Navot-Mintzer, Liora Livshitz, Idit Shub, Tsafrir Or
The biomarker panels for tracking changes in individuals following exercise have been previously described (Hackney et al., 2016; Jorres et al., 2021; Konig et al., 2007; Lee et al., 2017) and included biomarkers for stress (Cortisol, Prolactin), cardiac (Troponin, NT-Pro BNP) muscle damage (Creatine Phosphokinase-CPK) hydration status (Blood urea nitrogen-BUN, Creatinine and BUN/Creatinine ratio) inflammatory biomarkers (C-reactive protein-CRP, interleukin-1 receptor antagonist-IL1ra, IL6, tumour necrosis factor α-TNFα) and Hormones (Testosterone, Insulin-like growth factor 1-IGF1, Growth hormone-GH).