Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.     

Management of hydatid disease (echinococcosis) in pregnancy

Hydatid disease, manifesting as single or multiple hydatid cysts and caused by Echinococcus granulosus, is common in many parts of the world, especially the tropical countries. Although rare, this disease can also present during pregnancy, especially in endemic areas. Although much has been written about hepatic hydatidosis, there are only a few articles (mainly case reports) on hydatid disease in association with pregnancy. A literature search was done through Medline/PubMed and Medscape independently by the authors from 1950 to 2007 for key words "echinococcosis" and "pregnancy" and "management." All retrieved articles were reviewed. Manual cross-referencing was also done with inclusion of all relevant articles. In this review, we have attempted to summarize the presentation and available management approaches to hydatid disease, and have suggested evidence-based guidelines for its management during pregnancy.     

A new non-hormonal antifertility drug DL 111-IT: II. Effects on testicular hyaluronidase activity in male rats

Effects of DL-111, [3-(2-ethylphenyl)-5-(3-methoxyphenyl-1H-1,2,4-triazole] a non-hormonal antifertility agent, on testicular hyaluronidase activity, an accurate biochemical marker for testicular function, were evaluated in male rats. Treatment of 21-day-old rats with DL-111 sc for 7 or 15 days resulted in a significant fall in testicular weight and complete suppression of hyaluronidase activity. During the 30-day post-treatment the enzyme activity was restored to normal levels. Treatment of 40-day-old rats for 7 or 15 days also produced a significant decrease in testicular weight and hyaluronidase activity. Simultaneous administration of LH, PMSG or T with DL-111 to 21-day-old rats blocked the inhibitory activity of the drug as the enzyme activity was restored to untreated control levels. Administration of FSH along with DL-111 had no effect on suppressive action of the drug. These results suggest that in male rats DL-111 inhibits testicular activity by reducing LH levels, thereby reducing T levels as observed by reduced weights of testes and accessory glands of reproduction and hyaluronidase activity.     

Evolution of Treatment of Fistula in Ano

Background  

Fistula-in-ano is a common medical problem affecting thousands of patients annually. In the past, the options for treatment of fistula-in-ano were limited to fistulotomy and/or seton placement. Current treatment options also include muscle-sparing techniques such as a dermal island flap, endorectal advancement flap, fibrin sealent injection, anal fistula plug, and most recently ligation of the intersphincteric fistula tract (procedure). This study seeks to evaluate types and time trends for treatment of fistula-in-ano.     

Hepatic Resection for Colorectal Metastasis: Impact of Tumour Size

Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions.     

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

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