Biology, Engineering, Medicine and Science Reports

Protein Binding and Differential Distribution of Calcitonin in the Sub-compartments of Blood: An in vitro Study

Alex Bryan, Arun HS Kumar — Wed, 11 May 2022 00:00:00 -0400

The pharmacodynamics effects of therapeutically administered calcitonin is observed for extended duration much beyond its reported short half-life. The rationale for this pharmacodynamic-pharmacokinetics mismatch of calcitonin is not known. Hence in this study the hypothesis on sub-compartmentalization of calcitonin in blood to explain the extended pharmacodynamics effects of calcitonin was evaluated in vitro using the sheep blood model. A relatively higher proportion of calcitonin concentration was observed in the WBC compartment. The partition coefficient analysis showed levels of calcitonin to be higher on WBC membrane compared to intracellular. Molecular modelling to assess the binding of calcitonin with protein in plasma and WBC membranes indicated physiologically relevant higher affinity with beta-2-microglobulin’s in plasma and glycoproteins (CD44), sushi domains (CD25), fibronectins (CD206) and siglecs (CD22) on WBC membrane. The physiologically relevant higher affinity with several proteins on WBC membrane and plasma can be responsible for extended pharmacodynamics effects observed for therapeutically administered calcitonin.

Network Profiling of Hepatocellular Carcinoma Targets for Evidence Based Pharmacological Approach to Improve Clinical Efficacy

Bhavya Manchukonda, Arun HS Kumar — Wed, 11 May 2022 00:00:00 -0400

Introduction: Hepatocellular Carcinoma (HCC) is the most prevalent malignancy of the liver with limited clinical efficacy of currently used drugs such as sorafenib. Hence in this study we assessed the network proteins of HCC targets to identify the target/s which can achieve optimal clinical efficacy. Materials and Methods: The reported HCC targets and their network proteins were identified in the string database. The interactions of the network proteins based on the number of hydrogen bonds formed were evaluated using the chimera software and used to merit the network protein interactions. The merit of network protein interactions in clinical efficacy was assessed based on the expression pattern of the network proteins and corelating their targeting by sorafenib. Results: 22 potential HCC targets were identified along with their 152 unique network proteins. The following HCC targets; PDGFRB, IFNA2, VEGFR2, PD1, C-MET, RAR and IGF1R were observed to be among the top networks with the most number of hydrogen bond interactions between them. Among these, C-MET, RAR and IGF1R were significantly expressed in hepatocytes, making them relevant HCC targets. PD-1 and PD-L1, which are immune checkpoint regulators and hence used as part of immune therapy, were observed to form higher numbers of hydrogen bonds with HCC network proteins. Conclusion: Our analysis suggest that selectively targeting IGF1R, C-MET and RAR in hepatocytes together with immunotherapy will result in optimal clinical efficacy in the management of HCC.

A Perspective on the Newtonian Gravity Paradox

Anushka Saini — Wed, 11 May 2022 00:00:00 -0400

There are four branches of mechanics i.e., classical, relativistic, quantum and the quantum field theory, which are fundamentally based on dichotomised parameter (speed and size of the object). Since many years Physicists have made efforts to establish the “Theory of Everything” by correlating between each of these mechanics. In this report I provide my perspective on the correlation between Classical and Relativistic mechanics by proving that mass is proportional to velocity³ x time.

Surgical Management of Congenital Unilateral Entropion in a Labrador Pup Using Modified Hotz-Celsus Technique

Rahul Kumar Udehiya, Dayamon David Mathew, Naresh Kumar Singh — Wed, 11 May 2022 00:00:00 -0400

A two-month-old male Labrador retriever pup was presented with a history of unilateral blepharospasm, and epiphora. The case was diagnosed with congenital unilateral entropion on physical and ophthalmic examination. The entropion condition was corrected surgically using modified Hotz-Celsus technique. Excellent recovery was observed, and no complication was recorded following treatment up to three monthspost surgery.