Molecular Origin of the Anomalous pH Effect in Blue Proteorhodopsin

Author(s):  
Mizuki Sumikawa ◽  
Rei Abe-Yoshizumi ◽  
Takayuki Uchihashi ◽  
Hideki Kandori
Keyword(s):  
Author(s):  
Debanjan Kundu ◽  
Vikash Kumar Dubey

Abstract:: Various neurodegenerative disorders have molecular origin but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.


2021 ◽  
Author(s):  
Mario Milazzo ◽  
Alessio David ◽  
Gang Seob Jung ◽  
Serena Danti ◽  
Markus J. Buehler

Bone is mineralized tissue constituting the skeletal system, supporting and protecting body organs and tissues. In addition to such fundamental mechanical functions, bone also plays a remarkable role in sound...


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 557
Author(s):  
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Nishant Biswas ◽  
Molly S. Adam ◽  
...  

Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet. ASD tablets achieved similar area under the plasma drug concentration–time curve (AUC) at low and high gastric pH and outperformed Calquence capsules 2.4-fold at high gastric pH in beagle dogs. In vitro multicompartment dissolution testing conducted a priori to the in vivo study successfully predicted the improved formulation performance. In addition, ASD tablets were 60% smaller than Calquence capsules and demonstrated good laboratory-scale manufacturability, physical stability, and chemical stability. ASD dosage forms are attractive for improving patient compliance and the efficacy of acalabrutinib and other weakly basic drugs that have pH-dependent absorption.


Author(s):  
Francis Canon ◽  
Christine Belloir ◽  
Eric Bourillot ◽  
Hélène Brignot ◽  
Loïc Briand ◽  
...  

ACS Omega ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 3017-3023
Author(s):  
Song Deng ◽  
Dingkun Ling ◽  
Binbin Zhou ◽  
Yu Gong ◽  
Xin Shen ◽  
...  

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