Prevention Of Multiple Diseases Research Articles

Design and Optimization of a Two-Component TorRST-Based Biosensor for Detection and Degradation of Trimethylamine N-Oxide.

In mammals, Trimethylamine N-oxide (TMAO) is involved in various physiological processes, and is considered a biomarker for multiple diseases. As a natural molecule found in marine organisms, TMAO is also an important indicator of seafood freshness. In this study, a TMAO biosensor was developed in Escherichia coli harnessing TorRST two-component system. By using a cascade amplification circuit based on HrpRS-PhrpL, the biosensor's dynamic range was increased from 4.1- to 10.3-fold. By optimizing the affinity between the regulatory protein TorR and DNA binding sites in promoters, the concentration for 50% of maximal effect (EC50) value was reduced from 1008 to 141 μM. The biosensor was successfully used for aquatic sample detection. By introducing an exogenous TMAO degradation pathway into E. coli Nissle 1917, a probiotic chassis capable of TMAO detection, transportation, and degradation was constructed, providing an effective tool for rapid detection of TMAO and prevention of multiple diseases.

Unraveling the potential contribution of DHHC2 in cancer biology via untargeted metabolomics.

DHHC-mediated protein-S-palmitoylation is recognized as a distinct and reversible lipid modification, playing a pivotal role in the progression and prevention of multiple diseases, including cancer and neurodegenerative disorders. Over the past decade, growing evidence indicates the crucial role of DHHC2 in preventing tumorigenesis by palmitoylation of various protein substrates. However, a comprehensive understanding of the specific impact of DHHC2 on cancer cell metabolic regulation remains unclear. To investigate the metabolites change by DHHC2, we conducted untargeted metabolomic profiling on the HEK-293 T cell line with DHHC2- Knockdown (DHHC2-KD), DHHC2-Overexpression (DHHC2-OE) and empty vector control (Ctrl) conditions via LC-MS/MS-based analysis. Our dataset revealed the identification of a total of 73 metabolites encompassing all the conditions, with only 22 showing significant differences in univariate analysis. Furthermore, we performed pathway analysis with metabolites having VIP ≥ 0.7, P value ≤0.05, and fold change (FC) > 2 in DHHC2-OE (upregulated) and FC < 0.5 in DHHC2-OE or FC > 2 in DHHC2-KD condition (downregulated). We unveiled significant expression of the pyrimidine metabolism, urea cycle, and aspartate metabolism due to the abundance of onco-metabolites such as glutamine, uridine, and glutamic acid in the DHHC2-KD condition. However, DHHC2 overexpression resulted in a higher expression of metabolites previously reported to be associated with anti-cancer activity, such as betaine and 5'-methylthioadenosine (5'-MTA). Overall, this study sheds light on the changes mediated by DHHC2 in a cancer cell metabolome and suggests avenues for further investigation into other DHHC isoforms and their metabolic aspects.

Mechanisms of Toll-like receptor tolerance induced by microbial ligands

Some microorganisms can develop tolerance. On the one hand, it allows pathogenic microbes to escape immune surveillance, on the other hand, it provides the possibility to microbiota representatives to colonize different biotopes and build a symbiotic relationship with the host. Complex regulatory interactions between innate and adaptive immune systems as well as stimulation by antigens help microbes control and maintain immunological tolerance. An important role in this process belongs to innate immune cells, which recognize microbial components through pattern-recognition receptors. Toll-like receptors (TLRs) represent the main class of these receptors. Despite the universality of the activated signaling pathways, different cellular responses are induced by interaction of TLRs with microbiota representatives and pathogenic microbes, and they vary during acute and chronic infection. The research on mechanisms underlying the development of TLR tolerance is significant, as the above receptors are involved in a wide range of infectious and noninfectious diseases; they also play an important role in development of allergic diseases, autoimmune diseases, and cancers. The knowledge of TLR tolerance mechanisms can be critically important for development of TLR ligand-based therapeutic agents for treatment and prevention of multiple diseases.

Chili pepper intake and all-cause and disease-specific mortality.

Background: Chili pepper has been used for the treatment and prevention of multiple diseases. This may be due to its abundance of bioactive components, such as carotenoids, which are well known for their antioxidant properties. To date, several prospective cohort studies have examined the association between chili pepper intake and mortality, but the results have not been consistent. This study aimed to clarify the association between chili pepper intake and all-cause and disease-specific mortality using a meta-analysis. Methods: PubMed, Embase, and ISI Web of Science databases were searched up to December 20, 2020, and reference lists of included studies were manually reviewed. All prospective cohort studies on the association between chili pepper intake and all-cause, cardiovascular disease (CVD)-specific, and cancer-specific mortality were included in this study. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the meta-analysis. Between-study heterogeneity was assessed using I2 statistic and Q test. Results: A total of 4 cohort studies (N=564,748; all four studies had adjusted for important potential confounders such as demographic variables, dietary intake, and physical activity) were ultimately included in this meta-analysis. Among them, 31,527 died due to all causes, 10,184 died due to CVD, and 9,868 died due to cancer. Compared to none or rare consumption of chili pepper, consumption of chili pepper (ever or more than once a week) could significantly reduce the risk of all-cause mortality (summary adjusted HR: 0.87, 95% CI: 0.85, 0.90), CVD-specific mortality (summary adjusted HR: 0.89, 95% CI: 0.85, 0.93), and cancer-specific mortality (summary adjusted HR: 0.92, 95% CI: 0.88, 0.97). There was no significant between-study heterogeneity in the analyses (all-cause mortality: I2=0.7%, P=0.389; CVD-specific mortality: I2=21.8%, P=0.280; cancer-specific mortality: I2=0.0%, P=0.918). Conclusions: The present meta-analysis confirmed that chili pepper intake could reduce the risk of all-cause, CVD-specific, and cancer-specific mortality, suggesting that chili pepper may be a beneficial ingredient in the diets in prolonging life.

Testing a breast cancer prevention and a multiple disease prevention weight loss programme amongst women within the UK NHS breast screening programme\u2014a randomised feasibility study

BackgroundExcess weight and unhealthy behaviours (e.g. sedentariness, high alcohol) are common amongst women including those attending breast screening. These factors increase the risk of breast cancer and other diseases. We tested the feasibility and acceptability of a weight loss/behaviour change programme framed to reduce breast cancer risk (breast cancer prevention programme, BCPP) compared to one framed to reduce risk of breast cancer, cardiovascular disease (CVD) and diabetes (T2D) (multiple disease prevention programme, MDPP).MethodsWomen aged 47-73 years with overweight or obesity (n = 1356) in the NHS Breast Screening Programme (NHSBSP) were randomised (1:2) to be invited to join a BCPP or a MDPP. The BCPP included personalised information on breast cancer risk and a web and phone weight loss/behaviour change intervention. The MDPP also included an NHS Health Check (lipids, blood pressure, HbA1c and personalised feedback for risk of CVD [QRISK2] and T2D [QDiabetes and HbA1c]). Primary outcomes were uptake and retention and other feasibility outcomes which include intervention fidelity and prevalence of high CVD and T2D risk. Secondary outcomes included change in weight.ResultsThe BCPP and MDPP had comparable rates of uptake: 45/508 (9%) vs. 81/848 (10%) and 12-month retention; 33/45 (73%) vs. 53/81 (65%). Both programmes had a high fidelity of delivery with receipt of mean (95% CI) 90 (88-98% of scheduled calls, 91 (86-95%) of scheduled e-mails and 89 (76-102) website entries per woman over the 12-month period. The MDPP identified 15% of women with a previously unknown 10-year CVD QRISK2 of ≥ 10% and 56% with 10-year Qdiabetes risk of ≥ 10%. Both groups experienced good comparable weight loss: BCPP 26/45 (58%) and MDPP 46/81 (57%) with greater than 5% weight loss at 12 months using baseline observation carried forward imputation.ConclusionsBoth programmes appeared feasible. The MDPP identified previously unknown CVD and T2D risk factors but does not appear to increase engagement with behaviour change beyond a standard BCPP amongst women attending breast screening. A future definitive effectiveness trial of BCPP is supported by acceptable uptake and retention, and good weight loss.Trial registrationISRCTN91372184, registered 28 September 2014.

Flavonoid/Polyphenol Ratio in Mauritia flexuosa and Theobroma grandiflorum as an Indicator of Effective Antioxidant Action.

Studies on polyphenols and flavonoids in natural products reveal benefits in the prevention of multiple diseases. Proper extraction, treatment of extracts, and quantification of polyphenols and flavonoids demand attention from the scientific community in order to report more specific biological action. Total polyphenol content (TPC) and total flavonoid content (TFC) (measured at three different times) of ethanol, methanol and acetone extracts of Mauritia flexuosa (aguaje) and Theobroma grandiflorum (copoazú) fresh pulp, from the Colombian Amazon region, were evaluated with the purpose of focusing in the polyphenol/flavonoid proportion and its effective antioxidant activity. This objective could help to explain specific flavonoid biological action based on higher flavonoid proportion rather than higher total polyphenol content. Differences in extracting solvents resulted in statistically significant different yields; the highest TPC was observed with acetone 70% in Mauritia flexuosa and ethanol 80% for T. grandiflorum. The best flavonoid/polyphenol ratio in M. flexuosa was about 1:2.4 and 1:12.8 in T. grandiflorum and the antioxidant efficacy was proportionally higher for flavonoids extracted from T. grandiflorum. HPLC analysis revealed 54 µg/g of the flavonoid kaempferol in M. Flexuosa and 29 µg/g in T. grandiflorum. Further studies evaluating this proportionality, in seeds or peel of fruits, as well as, other specific biological activities, could help to understand the detailed flavonoid action without focusing on the high total polyphenol content.

Chili Pepper Carotenoids: Nutraceutical Properties and Mechanisms of Action.

Chili pepper is a prominent cultivated horticultural crop that is traditionally used for food seasoning and is applied for the treatment and prevention of multiple diseases. Its beneficial health properties are due to its abundance and variety of bioactive components, such as carotenoids, capsaicinoids, and vitamins. In particular, carotenoids have important nutraceutical properties, and several studies have focused on their potential in the prevention and treatment of human diseases. In this article, we reviewed the state of knowledge of general aspects of chili pepper carotenoids (biosynthesis pathway, types and content in Capsicum spp., and the effects of processing on carotenoid content) and recent findings on the effects of carotenoid nutraceuticals, such as antioxidant, cancer preventive, anti-inflammatory, cardiovascular disorder preventive, and anti-obesity effects.

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Huajuhong (Exocarpium Citri grandis, ECG) is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years. Recently, ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 (sixth edition) in China. To date, the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed. In this paper, the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant, improving lung function, alleviating acute lung injury, attenuating pulmonary fibrosis, and enhancing antiviral immune response, so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases, including coronavirus disease 2019.

Developing a Health Risk Evaluation Method for Triple H.

The development of a health evaluation system from human-related data is an important issue in preventive medicine. Previously, most studies have focused on disease assessment and prevention in patients. However, even if certain risk factors are all within normal ranges, individuals may not necessarily be completely healthy. This study focused on healthy individuals to develop a new index to assess health risks; this index can be used for the prevention of multiple diseases in healthy people. The kernel density technique was proposed to estimate the distribution of common risk factors and to develop a health risk index. A dataset of hypertension, hyperlipidemia, and hyperglycemia (Triple H) data from the National Health Insurance Research Database in Taiwan was used to demonstrate the proposed analytical process. The results of risk factor changes after six weeks of exercise were used to calculate the health risk index. The results showed that the subjects experienced a 7.29% reduction in their health risk index after the exercise intervention. This finding demonstrates the potential impact of an important reference index on quantifying the effect of maintenance in healthy people.

Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets

Flavonoids constitute the largest class of dietary phytochemicals, adding essential health value to our diet, and are emerging as key nutraceuticals. Cellular targets for dietary phytochemicals remain largely unknown, posing significant challenges for the regulation of dietary supplements and the understanding of how nutraceuticals provide health value. Here, we describe the identification of human cellular targets of apigenin, a flavonoid abundantly present in fruits and vegetables, using an innovative high-throughput approach that combines phage display with second generation sequencing. The 160 identified high-confidence candidate apigenin targets are significantly enriched in three main functional categories: GTPase activation, membrane transport, and mRNA metabolism/alternative splicing. This last category includes the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2), a factor involved in splicing regulation, mRNA stability, and mRNA transport. Apigenin binds to the C-terminal glycine-rich domain of hnRNPA2, preventing hnRNPA2 from forming homodimers, and therefore, it perturbs the alternative splicing of several human hnRNPA2 targets. Our results provide a framework to understand how dietary phytochemicals exert their actions by binding to many functionally diverse cellular targets. In turn, some of them may modulate the activity of a large number of downstream genes, which is exemplified here by the effects of apigenin on the alternative splicing activity of hnRNPA2. Hence, in contrast to small-molecule pharmaceuticals designed for defined target specificity, dietary phytochemicals affect a large number of cellular targets with varied affinities that, combined, result in their recognized health benefits.