Disorders of proteolytic homeostasis in the liver of rats with hyperhomocysteinemia

2021-07-30T22:10:54+00:00

Introduction: The liver is a key organ of the body that is responsible for maintaining homeostasis. It helps regulate almost all biochemical pathways associated with metabolism, nutrition, energy supply, and the formation of immunity. Consequently, impaired liver function can contribute to the progression of hyperhomocysteinemia and the development of associated complications. The present study aims to investigate the level and activity of metal-dependent and serine proteases in the liver of rats with hyperhomocysteinemia.

Methods: A total of 60 albino nonlinear male rats were used in this study. Hyperhomocysteinemia was induced by intragastric administration of DL-homocysteine thiolactone. Total proteolytic activity was measured using casein as a substrate. To determine the activity of metal-dependent and serine proteases, ethylenediaminetetraacetic acid and phenylmethylsulfonyl fluoride were used. The levels of MMP-1, MMP-2, and MMP-3 were studied by enzyme-linked immunosorbent assay. The fraction of serine proteases was isolated by affinity chromatography on the benzamidine sepharose column. The composition of serine protease fraction was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Results: The pathogenesis of hyperhomocysteinemia was found to be accompanied by a proteolytic imbalance manifested in the increase in the total proteolytic activity, the activity of serine proteases and especially the activity of metal-dependent enzymes. The increase in the levels of MMP-1, MMP-2, and MMP-3 indicates the involvement of these enzymes in the amplification of proteolysis mediated by metal-dependent enzymes. Despite a significant increase in the content of the serine proteases, their activity did not increase significantly. This may be because of the proteolytic degradation of serine proteases, which was confirmed by changes in their qualitative composition. The accumulation of low-molecular-weight proteins and the decrease in the part of proteins with a molecular weight of greater than 50 kDa in the fraction of serine proteases were revealed.

Conclusion: Collectively, our observations indicate that impaired proteolysis in the liver may be an important determinant in the development of hyperhomocysteinemia-associated disorders.

Clinical data analysis of dengue fever severity identification

2021-07-30T23:41:16+00:00

Introduction: The dynamic nature of dengue fever demands rapid and repeated clinical detection based on the vital signs variables, blood profile, and symptoms for providing timely clinical treatment. Patients with or without warning signs are at risk of contracting the severe dengue; thus, this study aims to identify the vital signs and blood profile variables that would differentiate the severity levels of dengue fever among dengue patients.

Methods: The patients were aged between 15 and 60 years and diagnosed with dengue infection. The infections were confirmed through laboratory tests positive either for the NS1 antigen or the dengue IgM antibody. The patients had no premorbid conditions.

Results: Our results show that dengue fever without warning signs and severe dengue can be differentiated using the pulse rate on day 3 (p = 0.008), day 4 (p = 0.004), day 5 (p = 0.005), and day 6 (p = 0.011) and the white blood cell count (p = 0.008) on day 7 of illness. Statistically significant parameters on day 6 of illness, such as systolic blood pressure (p = 0.001), pulse rate (p = 0.001), and hematocrit (p = 0.001), distinguished dengue fever with warning signs from the severe dengue category. Hematocrit (p = 0.000) was also found to be statistically significant in dengue fever with warning signs versus severe dengue on day 8 of illness. In conclusion, pulse rate was found to be a common marker for day 3 to day 6 even though other parameters were found to be significant. However, for day 7 and day 8, pulse rate was not found to be a contributor, instead, white blood cells and hematocrit were significant factors.

Conclusion: As the results of this study are based on a limited number of patients, it is recommended to further study the validity of the findings with a larger number of patients in the future.

Biomedical Research and Therapy

Disorders of proteolytic homeostasis in the liver of rats with hyperhomocysteinemia

Clinical data analysis of dengue fever severity identification