A simple bypass assay for DNA polymerases shows hypermutating variants associated with cancer show mechanistic differences in vitro

Errors made by DNA polymerases contribute to both natural variation and, in extreme cases, to genome instability and its associated diseases. Recently the importance of polymerase misincorporation in disease has been highlighted by the identification of cancer-associated polymerase variants and the recognition that a subgroup of these variants have a hypermutation phenotype in tumours. We have developed a bypass assay to rapidly determine the tendency of a polymerase to misincorporate in vitro. We have used the assay to compare misincorporation by wild-type, exonuclease defective and two hypermutating DNA polymerase e variants, P286R and V411L. The assay clearly distinguished between the misincorporation rates of wild type, exonuclease dead and P286R polymerases. However, the V411L polymerase showed different misincorporation characteristics to P286R, suggesting that these variants cause hypermutation by different mechanisms. Using this assay misincorporation opposite a templated C nucleotide was consistently higher than for other nucleotides, and this caused predominantly C to T transitions. This is consistent with the observation that C to T transitions are commonly seen in POLE mutant tumours.

Protective effects of Bacteroides fragilis against lipopolysaccharide-induced systematic inflammation and their potential functional genes

Bacteroides fragilis, one of the potential next generation of probiotics, has been demonstrated to alleviate inflammation-associated diseases. In this study, we compare the anti-inflammatory effects of six Bacteroides fragilis strains...

Influence of 8-week daily consumption of a new product combining green coffee hydroxycinnamates and beta-glucans on polyphenol bioavailability in subjects with overweight and obesity

Nutraceuticals based on plant extracts rich in polyphenols, as well as dietary fibres, are new strategies to fight overweight/obesity and associated diseases. However, to understand the potential effects of polyphenols...

Autophagy facilitates age-related cell apoptosis—a new insight from senile cataract

Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.

STATUS OF SANITATION FACILITIES AND ITS IMPACTS ON HEALTH IN MAINPURI CITY OF UTTAR PRADESH, INDIA

Nearly 60 million people in urban areas lack access to improved sanitation arrangements, and more than two-thirds of wastewater is let out untreated into the environment, polluting land and water bodies. Urban sanitation in India faces many challenges. To respond to these environmental and public health challenges, urban India will need to address the full cycle of sanitation, i.e., universal access to toilets, with safe collection, conveyance and treatment of human excreta. There has been a significant increase in waste generation because of rapid population growth and economic development. Thus, waste management and sanitation became major environmental and health problem. In rainy season condition gets worse. This paper outlines these concerns, and highlights the need for focusing on access to water and the full cycle of sanitation for the urban poor, as fundamental to addressing the sanitation challenge. In this paper an attempt has been made to identify the sanitation related risk factors and its relationship with associated diseases in Mainpuri city. The study is based on primary sources of data collected through household surveys in Mainpuri city. Households belong to different income groups. The total sample size consists of 1836 households. The result showed that the sanitation condition and associated diseases or living standards and health conditions are related to each other. In this paper typhoid fever, cholera, malaria, etc. diseases were observed. The lower income group households are most vulnerable. They suffer most because of their poor sanitation conditions.

Low Molecular Weight Sulfated Chitosan Efficiently Reduces Infection Capacity of Porcine Circovirus Type 2 (PCV2) In PK15 Cells

Background Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to vaccines, the availability of antiviral polymers provides an efficient and safe option for reducing the impact of these diseases. By virtue of their molecular weight and repetitious structure, polymers possess properties not found in small-molecule drugs. In this perspective, we focus on chitosan, a ubiquitous biopolymer, that adjusts the molecular weight and sulfated-mediated functionality could act as a efficient antiviral polymer by mimicking PCV2-cell receptor interactions. Methods Sulfated chitosan (Chi-S) polymers of two molecular weights were synthesized and characterized by FTIR, SEM-EDS and elemental analysis. The Chi-S solutions were tested against PCV2 infection in PK15 cells in vitro and antiviral activity was evaluated by measuring the PCV2 copy number upon application different molecular weights, sulfate functionalization, and concentration of polymer. In addition, to explore the mode of action of the Chi-S against PCV2 infection, experiments were designed to clarify whether the antiviral activity of the Chi-S would be influenced by when it was added to the cells, relative to the time and stage of viral infection. Results Chi-S significantly reduced genomic copies of PCV2, showing specific antiviral effects depending on its molecular weight, concentration, and chemical functionalization. Assays designed to explore the mode of action of Chi-S revealed that exerted antiviral activity through impeding viral attachment and penetration into cells. Conclusions These findings help better understanding PCV2-porcine cells interaction and reinforce the idea that sulfated polymers, such as Chi-S, represent a promising candidate for uses in antiviral therapies against PCV2-associated diseases.

Damage to the musculoskeletal system during eradication therapy of Helicobacter pylori with levofloxacin

Eradication therapy is the mainstay of treatment for H. pylori-associated diseases. A case of the development of tendinitis of the left patellar ligament proper during eradication therapy using a triple regimen with levofoloxacin for 14 days for exacerbation of duodenal ulcer is presented.