Integrated Genomic and Functional Characterization of the Anti-diabetic Potential of Arthrobacter sp. SW1.

For decades, bacterial natural products have served as valuable resources for developing novel drugs to treat several human diseases. Recent advancements in the integrative approach of using genomic and functional tools have proved beneficial in obtaining a comprehensive understanding of these biomolecules. This study presents an in-depth characterization of the anti-diabetic activity exhibited by a bacterial isolate SW1, isolated from an effluent treatment plant. As a primary screening, we assessed the isolate for its potential to inhibit alpha-amylase and alpha-glucosidase enzymes. Upon confirmation, we further utilized LC-MS, ESI-MS/MS, and NMR spectroscopy to identify and characterize the biomolecule. These efforts were coupled with the genomic assessment of the biosynthetic gene cluster involved in the anti-diabetic compound production. Our investigation discovered that the isolate SW1 inhibited both α-amylase and α-glucosidase activity. The chemical analysis suggested the production of acarbose, an anti-diabetic biomolecule, which was further confirmed by the presence of biosynthetic gene cluster "acb" in the genome. Our in-depth chemical characterization and genome mining approach revealed the potential of bacteria from an unconventional niche, an effluent treatment plant. To the best of our knowledge, it is one of the first few reports of acarbose production from the genus Arthrobacter.

Albumin Cobalt Binding or Ischaemia Modified Albumin: a Test of Great Prognostic Value in Malaria.

BACKGROUND: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria in a medical college setting. METHODS: Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. RESULTS: 100 consecutive patients (50 with vivax and 50 with falciparum malaria) were evaluated. The reference range for ACB assay was established using 50 adult healthy (25 male and 25 female) individuals. 16 out of 50 p. Falciparum-Infected developed complicated malaria. None of the P Vivax patients developed complicated malaria. All malaria infected patients had high ACB levels (P<0.0001). There was a stepwise increase in ACB levels from healthy volunteers to different categories of malaria (P<0.0001) without any overlap. CONCLUSION: ACB has the potential to be used as a robust simple and inexpensive prognostic marker for organ dysfunction in severe malaria even if an evaluation at multiple sites with a bigger number of patients should be initiated for final recommendation.

Antioxidant enzymes and lipid peroxidation in different stages of breast cancer.

Oxidative stress resulting from an imbalance between pro-oxidants and anti-oxidants seems to play an important role in human breast carcinogenesis. There are conflicting reports regarding the tissue levels of malondialdehyde (MDA), ascorbic acid and superoxide dismutase (SOD) in breast cancer patients whereas few blood values have been reported. The present study was carried out to observe the changes in serum MDA, serum SOD and plasma ascorbic acid with the stage-wise progression of the disease. Serum MDA and serum SOD levels were found to be increased gradually from Stage I to Stage IV as compared to control group (p < 0.001). The maximum rise was in Stage IV patients. In contrast, mean plasma ascorbic acid levels were low in all stages compared to control group (p < 0.001). The decrease was more pronounced in Stage III and Stage IV. The study would be of immense help for establishing blood based biochemical marker in breast cancer patients.

Alteration in the activities of the membrane-integrated enzymes of polymorphonuclear leukocytes in obesity.

Oubain sensitive and insensitive adenosine triphosphatase showed decrease in their activities in the polymorphonuclear leukocytes of obese patients while the activity of acetylcholinesterase was found to be increased significantly. The contents of sodium, potassium and magnesium were found to be significantly decreased in polymorphonuclear leukocytes of obese patients. Polymorphonuclear leukocytes obtained from treated obese patients showed considerable restoration.

Leukocyte lipid profile in chronic alcoholics.

Polymorphonuclear leukocytic (PNML) lipid content was studied in chronic alcoholic and normal control subjects. Chronic alcoholic subjects showed abnormal liver function and abnormal serum lipid profile. PMNL obtained from chronic alcoholic subjects exhibited decreased free cholesterol and phospholipid contents, with a significant increase in cholesterol to phospholipid ratio. Although, there was no change in the free fatty acids, the levels of triglycerides were significantly elevated.

Sex variation in ascorbic acid catabolism.

Male and female albino rats of same age and body weight were pair fed with laboratory stock diet and ascorbic acid, dehydroascorbic acid and diketogulonic acid were determined in the liver and urine, while in blood only ascorbic acid was estimated. Male rats had concentration higher of ascorbic acid in liver and urine as compared with females, while there were no significant variations in the contents of dehydroascorbic acid and diketogulonic acid. Hepatic and renal 2, 3-diketoaldonate decarboxylase, and hepatic dehydroascorbatase were also found to be significantly higher in male rats. Similar sex variations were also observed in ascorbic acid catabolism in guinea pigs without any differences in urinary ascorbic acid contents.

Polymorphonuclear leukocytic sialic acid and sialidase activity in obesity.

The level of sialic acid in the obese polymorphonuclear leukocytes (PMNL) was found to be significantly reduced as compared to normal. Activity of sialic acid degrading enzyme, sialidase, was found to be increased in the obese state. Restoration in both sialic acid content and sialidase activity was also evidenced in the PMNL of treated obese patients.

Ascorbic acid in thyroidectomized rats. II) Ascorbic acid status of the storage tissues and hepatic biosynthesis of glucuronic acid.

Depletion of ascorbic acid from adrenals, brain and epididymis along with loss in weight were noticed in the state of thyroidectomy. This decrease appears to be due to an effect of thyroidectomy on the membrane integrity since the membrane bound sialic acid was found to be significantly lowered in these tissues as a consequence of the elevated activity of sialidase. Thyroidectomy was also found to cause an adverse effect on the activities of hepatic UDP-glucuronyl transferase and beta-glucuronidase with no alteration in UDP-glucose dehydrogenase.

Ascorbic acid in thyroidectomized rats. I) Biosynthesis and catabolism.

Thyroidectomized rats showed a decrease in ascorbic acid and dehydroascorbic acid, with almost no alterations in the diketogulonic acid in liver and kidney. Total ascorbic acid in urine was found to be increased, whereas glucuronic acid in urine decreased significantly. There were no significant changes in the activities of ascorbic acid synthesizing enzymes. Activities of the degrading enzymes were found to increase significantly in the liver, with no remarkable change in their activities in kidney. Daily administration of thyroxine for 10 days to thyroidectomized rats normalized the activities of dehydroascorbatase and 2,3 diketoaldonate decarboxylase in the liver, whereas single administration of thyroxine on the 7th day after thyroidectomy could not bring about such restoration. It seems that thyroxine has no direct role on ascorbic acid metabolism in rats.