scholarly journals A Combination Strategy of Solubility Enhancers for Effective Production of Soluble and Bioactive Human Enterokinase

2021 ◽  
Author(s):  
Jinhak Kwon ◽  
Hyeongjun Cho ◽  
Seungmin Kim ◽  
Yiseul Ryu ◽  
Joong-jae Lee
Keyword(s):  
Combination Strategy ◽  
Solubility Enhancers

scholarly journals A Combination Strategy of Solubility Enhancers for Effective Production of Soluble and Bioactive Human Enterokinase

2021 ◽  
Author(s):  
Jinhak Kwon ◽  
Hyeongjun Cho ◽  
Seungmin Kim ◽  
Yiseul Ryu ◽  
Joong-jae Lee
Keyword(s):  
Recombinant Proteins ◽  
Phosphoglycerate Kinase ◽  
Combinatorial Design ◽  
Peptide Sequence ◽  
Protein Digestion ◽  
Combination Strategy ◽  
Enhanced Solubility ◽  
Production Strategy ◽  
Solubility Enhancers ◽  
Specific Peptide

Enterokinase is one of the hydrolases that catalyze hydrolysis to regulate biological processes in intestinal visceral mucosa. Enterokinase plays an essential role in accelerating the process of protein digestion as it converts trypsinogen into active trypsin by accurately recognizing and cleaving a specific peptide sequence, (Asp)4-Lys. Due to its exceptional substrate specificity, enterokinase is widely used as a versatile molecular tool in various bioprocessing, especially in removing fusion tags from recombinant proteins. Despite its biotechnological importance, mass production of soluble enterokinase in bacteria still remains an unsolved challenge. Here, we present an effective production strategy of human enterokinase using tandemly linked solubility enhancers consisting of thioredoxin, phosphoglycerate kinase or maltose-binding protein. The resulting enterokinases exhibited significantly enhanced solubility and bacterial expression level while retaining enzymatic activity, which demonstrates that combinatorial design of fusion proteins has the potential to provide an efficient way to produce recombinant proteins in bacteria.

1295-P: Economic Evaluation of Drug Combination Strategy for Type 2 Diabetes in China

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1295-P
Author(s):  
SHUYAN GU ◽  
YI SHEN ◽  
LIZHENG SHI ◽  
HENGJIN DONG
Keyword(s):  
Type 2 Diabetes ◽  
Economic Evaluation ◽  
Drug Combination ◽  
Combination Strategy

Affinity Tags for Protein Purification

2020 ◽  
Vol 21 (8) ◽  
pp. 821-830
Author(s):  
Vibhor Mishra
Keyword(s):  
Protein Purification ◽  
Protein Complexes ◽  
Affinity Purification ◽  
Protein Domain ◽  
Affinity Tag ◽  
Small Peptides ◽  
Affinity Tags ◽  
C Terminus ◽  
Solubility Enhancers ◽  
As Solubility

The affinity tags are unique proteins/peptides that are attached at the N- or C-terminus of the recombinant proteins. These tags help in protein purification. Additionally, some affinity tags also serve a dual purpose as solubility enhancers for challenging protein targets. By applying a combinatorial approach, carefully chosen affinity tags designed in tandem have proven to be very successful in the purification of single proteins or multi-protein complexes. In this mini-review, the key features of the most commonly used affinity tags are discussed. The affinity tags have been classified into two significant categories, epitope tags, and protein/domain tags. The epitope tags are generally small peptides with high affinity towards a chromatography resin. The protein/domain tags often perform double duty as solubility enhancers as well as aid in affinity purification. Finally, protease-based affinity tag removal strategies after purification are discussed.

scholarly journals Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Adrián Flores-Romero ◽  
Vinnitsa Buzoianu-Anguiano ◽  
Elisa Garcia ◽  
Karla Soria-Zavala ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combination Strategy ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

scholarly journals CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5782
Author(s):  
Ashwini Makhale ◽  
Devathri Nanayakkara ◽  
Prahlad Raninga ◽  
Kum Kum Khanna ◽  
Murugan Kalimutho
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Triple Negative Breast Cancer ◽  
Combination Treatment ◽  
Triple Negative ◽  
Annexin V ◽  
Replication Stress ◽  
Breast Cancer Cell Lines ◽  
Combination Strategy

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapy. Here, we evaluated the anti-cancer activity of APR-246, a P53 activator, and CX-5461, a RNA polymerase I inhibitor, in the treatment of TNBC cells. We tested the efficacy of individual and combination therapy of CX-5461 and APR-246 in vitro, using a panel of breast cancer cell lines. Using publicly available breast cancer datasets, we found that components of RNA Pol I are predominately upregulated in basal-like breast cancer, compared to other subtypes, and this upregulation is associated with poor overall and relapse-free survival. Notably, we found that the treatment of breast cancer cells lines with CX-5461 significantly hampered cell proliferation and synergistically enhanced the efficacy of APR-246. The combination treatment significantly induced apoptosis that is associated with cleaved PARP and Caspase 3 along with Annexin V positivity. Likewise, we also found that combination treatment significantly induced DNA damage and replication stress in these cells. Our data provide a novel combination strategy by utilizing APR-246 in combination CX-5461 in killing TNBC cells that can be further developed into more effective therapy in TNBC therapeutic armamentarium.

scholarly journals An Effective Adaptive Combination Strategy for Distributed Learning Network

2021 ◽  
Vol 11 (12) ◽  
pp. 5723
Author(s):  
Chundong Xu ◽  
Qinglin Li ◽  
Dongwen Ying
Keyword(s):  
Minimum Variance ◽  
Iteration Scheme ◽  
Estimation Problem ◽  
Lms Algorithm ◽  
Unbiased Estimation ◽  
Mean Square ◽  
Least Mean Square ◽  
Combination Strategy ◽  
Adaptive Combination ◽  
Diffusion Networks

In this paper, we develop a modified adaptive combination strategy for the distributed estimation problem over diffusion networks. We still consider the online adaptive combiners estimation problem from the perspective of minimum variance unbiased estimation. In contrast with the classic adaptive combination strategy which exploits orthogonal projection technology, we formulate a non-constrained mean-square deviation (MSD) cost function by introducing Lagrange multipliers. Based on the Karush–Kuhn–Tucker (KKT) conditions, we derive the fixed-point iteration scheme of adaptive combiners. Illustrative simulations validate the improved transient and steady-state performance of the diffusion least-mean-square LMS algorithm incorporated with the proposed adaptive combination strategy.

scholarly journals Successful combination strategy of preoperative placement of an endoscopic nasopancreatic drainage catheter and pancreas preservation surgery for pancreatic injury with major pancreatic duct disruption: a case report

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Kenji Kandori ◽  
Wataru Ishii ◽  
Ryoji Iizuka
Keyword(s):  
Pancreatic Duct ◽  
Pancreatic Resection ◽  
Pancreatic Injury ◽  
Combination Strategy ◽  
Pancreatic Body ◽  
First Case ◽  
Endoscopic Nasopancreatic Drainage ◽  
Pancreas Preservation ◽  
Nasopancreatic Drainage ◽  
Grade Iii

Abstract Background The guidelines recommend pancreatic resection for grade III and IV pancreatic injuries. On the other hand, organ preservation is an important issue. Herein, we present the first case of pancreatic injury with major pancreatic duct (MPD) disruption that was treated with the combination of preoperative placement of endoscopic nasopancreatic drainage (ENPD) catheter and pancreas preservation surgery after endoscopic pancreatic stenting (EPS) failure. Case presentation A 70-year-old female diagnosed with pancreatic injury was admitted to our hospital. She was hemodynamically stable. ERP revealed MPD disruption, and EPS failed. An ENPD catheter was placed preoperatively at the site of injury. During laparotomy, we identified a partial-thickness laceration in the pancreatic body. At the site of injury, the tip of the ENPD catheter was found; therefore, the patient was diagnosed with grade III pancreatic body injury with MPD disruption. The extent of crush was not severe, and we had no difficulty in identifying the distal MPD segment. We inserted the ENPD catheter into the distal MPD segment. The ruptured MPD and the laceration was sutured, then pancreatic resection was prevented. She was discharged on POD 56. Conclusion The treatment strategy incorporated ERP, placement of an ENPD catheter preoperatively, and a simple surgery in a hemodynamically stable patient with pancreatic injury allows the pancreas and spleen to be preserved.

scholarly journals Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model

2021 ◽  
Author(s):  
Hai-Jun Hu ◽  
Xiu Liang ◽  
Hai-Lang Li ◽  
Huai-Yuan Wang ◽  
Jin-Fa Gu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Mouse Model ◽  
Immune Checkpoint Blockade ◽  
Oncolytic Adenovirus ◽  
Immunocompetent Mouse ◽  
Combination Strategy ◽  
Obvious Effect ◽  
Immune Infiltration ◽  
Synergistic Inhibition ◽  
Recent Treatment

AbstractAlthough the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

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