Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

Objective Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. Methods High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Results Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Conclusion Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population

Knowledge, attitude and practices of pregnant women for antenatal care during COVID-19 pandemic

Background: The antenatal care had suffered across the globe during COVID-19 pandemic. This study was undertaken to elicit knowledge, attitude and practices adopted by pregnant women for antenatal care during the pandemic. Methods: A cross-sectional survey was undertaken (N=126) at a purposively selected community health center Nalagarh of Solan district in north India. Self-administered pilot tested standardized questionnaire was employed. Results: 46 percent of women were in age group of 21-25 years and had secondary level of education. 60 percent were primigravida. 47 percent of pregnant women significantly undertook antenatal care from civil hospital and 33 percent availed these services from the public health facility of the level of Primary Health Centre or Community Health Centre, χ2 (1, N=126) =7.7, p=0.02. All pregnant women had taken complete antenatal care for four times and as per schedule. Only one tested positive for the disease COVID-19. Majority of the pregnant women studied were asymptomatic. The participants had the knowledge about symptoms of disease and COVID-19 appropriate behavior. About 25 percent also had difficulty in approaching the public health sector due to lack of accessible transportation. 18 and 33 percent of pregnant women suffered from stress and anxiety respectively. All undertook iron and folic acid along with tetanus prophylaxis. 21 and 18 percent practiced wearing of face mask and frequent hand washing with soap respectively. Conclusions: COVID pandemic did not hinder antenatal care adopted by pregnant women. Lockdown and isolation were important perceived worrisome aspects of the disease

Implications of Biosecurity in Food Safety

Owing to growing population of world, efforts are being made to maximise food production. Food safety should not be compromised to meet the food requirement of increasing population. Biosecurity is the imperative approach to ensure food safety. This is a holistic approach that interlinks health, environment, security and trade. Increased incidents of foodborne diseases led to promotion of biosecurity as a major priority policy worldwide to curtail such incidents and ensure food safety. Microbial risk management is an essential component of food safety. National biosecurity programmes are essentially required to identify the prospective modes of introduction and spread of a disease in a country or region and to specify the control measures to curtail the risk associated with the disease. International standards for various biosecurity sectors are set mainly by Codex Alimentarius Commission, the World Organisation for Animal Health and Commission on Phytosanitary Measures, which are implemented through the Sanitary and Phytosanitary Agreement, 1995 of World Trade Organisation. Agricultural biosecurity is of utmost importance in the countries that are large crop and animal producers, and these countries are at risk from alien pests and pathogens. Adequate biosecurity programmes are essential in all the countries to protect global environment, agriculture and biodiversity. Developing countries, particularly with large populations aiming maximised food production require stringent biosecurity approaches to provide safe and nutritious food to the people

Detection of Fecal DNA Methylation for Colorectal Neoplasia : Does It Lead to an Optimal Screening Test?

Aberrant promoter methylation, an 'epigenetic' form of genomic instability that leads to transcriptional silencing of tumor suppressor genes, is increasingly being recognized as a crucial component in the evolution of human cancers. With our limited knowledge of the molecular basis and timing of the initiation of altered methylation events in the stepwise progression of cancers, the biggest challenge we currently face is to identify novel biomarkers and technologies for the timely screening of patients carrying such alterations. One such strategy would be to develop tests for the detection of fecal DNA methylation patterns that will improve the sensitivity of noninvasive screening tests for colorectal neoplasia, and moreover, will decrease both mortality and the incremental costs of treating colorectal cancers

LAMC2 promotes gemcitabine resistance in PDAC

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. Gemcitabine remains an effective option for the majority of PDAC patients. Unfortunately, currently no reliable prognostic and predictive biomarkers of therapeutic response are available for the patients with PDAC. Laminin γ2 (LAMC2) is overexpressed in several cancers, and its high expression facilitates cancer development and chemoresistance. However, its functional role in PDAC remains unclear, and a better understanding of this will likely help improve the prognosis of PDAC patients. This study aimed to elucidate the clinical and biological role of LAMC2 in PDAC. We first analyzed the expression levels of LAMC2 by real-time reverse transcription PCR in a cohort of 114 PDAC patients. Interestingly, higher expression of LAMC2 significantly correlated with poor survival in PDAC cohort. In addition, elevated LAMC2 expression served as a potential prognostic marker for survival. Subsequently, functional characterization for the role of LAMC2 in PDAC was performed by small interfering RNA (siRNA) knockdown in pancreatic cancer (PC) cell lines. Interestingly, inhibition of LAMC2 in PC cells enhanced the gemcitabine sensitivity and induction of apoptosis. Moreover, it inhibited colony formation ability, migration, and invasion potential. Furthermore, LAMC2 regulated the expression of epithelial-mesenchymal transition (EMT) phenotype. In addition, LAMC2 significantly correlated with genes associated with the expression of ATP-binding cassette (ABC) transporters in PC cells and PDAC patients. In conclusion, these results suggest that LAMC2 regulates gemcitabine sensitivity through EMT and ABC transporters in PDAC and may be a novel therapeutic target in PDAC patients

Biological Warfare Agents

There is a long historic record of use of biological warfare (BW) agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC) in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures