Age and sex-specific reference intervals for prooxidant-antioxidant balance, anti-heat-shock protein 27 (anti-hsp27), and routine laboratory tests in the middle-aged adult population.

INTRODUCTION: We aimed to define specific reference intervals (RIs) for 11 biomarkers including inflammatory and oxidative stress biomarkers, liver, and renal function tests in a healthy Iranian adult population for the first time. METHODS: CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as body mass index (BMI)-specific RIs. RESULTS: RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the BMI with a cutoff point of 25 kg/m2 , only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25: 0.51-7.85 mg/L and for BMI<25: 0.40-4.46 mg/L). RI for PAB and anti-hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35-65 years old. CONCLUSION: Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adults for improved monitoring of various diseases in the Iranian population.

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.

Targeting Nuclear Factor-Kappa B Signaling Pathway by Curcumin: Implications for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which involves an auto-immune mechanism that leads to perivascular demyelination. The role of nuclear factor-kappa B (NF-κB) signaling pathway in the pathogenesis of MS has been suggested by genome-wide association studies. Therefore, strategies targeting this pathway could be potentially beneficial. Curcumin is the active component of turmeric and a phenolic phytochemical. This phytochemical has anti-inflammatory properties and has been shown by multiple studies to downregulate NF-κB and its downstream gene targets including cyclooxygenase-2, tumor necrosis factor-α, interleukin-1, and interleukin-6. This review discusses the modulatory effects of curcumin on the NF-κB signaling pathway and its downstream effectors, and the therapeutic implications of this modulation on MS.

Controlled Gene Delivery Systems: Nanomaterials and Chemical Approaches.

Successful gene therapy depends on the design of effective gene delivery systems. A gene delivery system is considered a powerful tool for the release of genetic material within cells resulting in a change in cell functions and protein production. The release of genes in a controlled manner by using appropriate carriers facilitates their release without side effects and increases the expression of genes at the released site. It is expected that significant changes in the combination of several genes and drugs can be provided by developing treatment systems sensitive to different stimuli such as redox potential, pH variations, temperature gradients, light irradiation, and enzyme activity. The most important advantages for the release of genes and stimuli-responsive therapeutics include delivering vectors locally, reducing side effects and causing no toxicity to distant tissues while at the same time reducing the immune response to the vectors. In this review, we aim to discuss different types of gene carriers involved in the controlled transfer of nucleic acids (non-viral inorganic and organic nanoparticles (NPs) and virus-like particles (VLPs)) as well as the simultaneous transfer of several genes and/or drugs into cells or different tissues, providing for an efficient and safe treatment of numerous diseases.

Therapeutic Potential of Targeting Transforming Growth Factor-beta in Colorectal Cancer: Rational and Progress.

BACKGROUND: Colorectal cancer (CRC) is one of the most common types of cancer and is associated with an increasing rate of mortality. Transforming Growth Factor-Beta (TGF-ß) is often upregulated in CRC, and appears to play an important role in regulating cell proliferation, migration, immune surveillance, apoptosis, cell differentiation, drug-resistance and many cellular processes that may be involved in CRC, and therefore underscores its potential value as a therapeutic target in the treatment of CRC. An increased expression of the TGF- ß pathway has been associated with poor prognosis in several cancer types, including CRC. METHODS: Here, we describe the critical role of the TGF-ß pathway in CRC as well as the preclinical and clinical investigations on TGF-ß inhibitors, with particular emphasis on recent findings with small-molecule inhibitors in CRC. Several TGF-ß inhibitors (e.g., Trabedersen, Galunisertib, Gradalis, PF-03446962, NIS793) have been generated over the past decade for targeting this pathway. RESULTS: There is accumulating evidence of the therapeutic potential of this and other TGF-ß inhibitors for the treatment of other malignancies. These inhibitors might be used in combination with chemotherapy as well as with other biological agents, in order to overcome different resistance mechanisms. However, further studies are needed to identify determinants of the activity of TGF-ß inhibitors, through the analysis of genetic and environmental alterations affecting TGF-ß and parallel pro-cancer pathways. CONCLUSION: These studies will be critical to improving the efficacy and selectivity of current and future anticancer strategies targeting TGF-ß.

The Impact of Statin Therapy on the Survival of Patients with Gastrointestinal Cancer.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins affect several potential pathways, including cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk.