Genetic polymorphisms as potential pharmacogenetic biomarkers for platinum-based chemotherapy in non-small cell lung cancer.

Platinum-based chemotherapy (PBC) is a widely used treatment for various solid tumors, including non-small cell lung cancer (NSCLC). However, its efficacy is often compromised by the emergence of drug resistance in patients. There is growing evidence that genetic variations may influence the susceptibility of NSCLC patients to develop resistance to PBC. Here, we provide a comprehensive overview of the mechanisms underlying platinum drug resistance and highlight the important role that genetic polymorphisms play in this process. This paper discussed the genetic variants that regulate DNA repair, cellular movement, drug transport, metabolic processing, and immune response, with a focus on their effects on response to PBC. The potential applications of these genetic polymorphisms as predictive indicators in clinical practice are explored, as are the challenges associated with their implementation.

Dendrimers as nanoscale vectors: Unlocking the bars of cancer therapy.

Chemotherapy is the first choice in the treatment of cancer and is always preferred to other approaches such as radiation and surgery, but it has never met the need of patients for a safe and effective drug. Therefore, new advances in cancer treatment are now needed to reduce the side effects and burdens associated with chemotherapy for cancer patients. Targeted treatment using nanotechnology are now being actively explored as they could effectively deliver therapeutic agents to tumor cells without affecting normal cells. Dendrimers are promising nanocarriers with distinct physiochemical properties that have received considerable attention in cancer therapy studies, which is partly due to the numerous functional groups on their surface. In this review, we discuss the progress of different types of dendrimers as delivery systems in cancer therapy, focusing on the challenges, opportunities, and functionalities of the polymeric molecules. The paper also reviews the various role of dendrimers in their entry into cells via endocytosis, as well as the molecular and inflammatory pathways in cancer. In addition, various dendrimers-based drug delivery (e.g., pH-responsive, enzyme-responsive, redox-responsive, thermo-responsive, etc.) and lipid-, amino acid-, polymer- and nanoparticle-based modifications for gene delivery, as well as co-delivery of drugs and genes in cancer therapy with dendrimers, are presented. Finally, biosafety concerns and issues hindering the transition of dendrimers from research to the clinic are discussed to shed light on their clinical applications.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches.

Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Video Abstract.

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

The influence of omega-3 supplementation on vitamin D levels in humans: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans. METHODS: We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model. RESULTS: Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was ˂20 ng/ml. Moreover, omega-3 intake ≤1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day. CONCLUSION: In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages ≤1000 mg/day and intervention durations >8 weeks.

Antimicrobial peptides as potential therapeutics for breast cancer.

Breast cancer is the most common and deadliest cancer in women worldwide. Although notable advances have been achieved in the treatment of breast cancer, the overall survival rate of metastatic breast cancer patients is still considerably low due to the development of resistance to breast cancer chemotherapeutic agents and the non-optimal specificity of the current generation of cancer medications. Hence, there is a growing interest in the search for alternative therapeutics with novel anticancer mechanisms. Recently, antimicrobial peptides (AMPs) have gained much attention due to their cost-effectiveness, high specificity of action, and robust efficacy. However, there are no clinical data available about their efficacy. This warrants the increasing need for clinical trials to be conducted to assess the efficacy of this new class of drugs. Here, we will focus on the recent progress in the use of AMPs for breast cancer therapy and will highlight their modes of action. Finally, we will discuss the combination of AMP-based therapeutics with other breast cancer therapy strategies, including nanotherapy and chemotherapy, which may provide a potential avenue for overcoming drug resistance.

The effect of fasting and energy restricting diets on markers of glucose and insulin controls: a systematic review and meta-analysis of randomized controlled trials.

Inconsistencies exist with regard to influence of fasting and energy-restricting diets on markers of glucose and insulin controls. To address these controversial, this study was conducted to determine the impact of fasting diets on fasting blood sugars (FBSs), insulin, homeostatic model assessment insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) levels. A comprehensive systematic search was carried out in electronic databases, i.e., Scopus, PubMed, and Web of Science through June 2019 for RCTs that investigated the impact of fasting and energy-restricting diets on circulating FBS, insulin, HOMA-IR and HbA1c levels from. Weighted mean difference (WMD) with the 95% CI were used for estimating combined effect size. The subgroup analysis was applied to specify the source of heterogeneity among articles. Pooled results from 30 eligible articles with 35 arms demonstrated a significant decrease in FBS (WMD): -3.376 mg/dl, 95% CI: -5.159, -1.594, p < 0.001), insulin (WMD: -1.288 µU/ml, 95% CI: -2.385, -0.191, p = 0.021), HOMA-IR (WMD: -0.41 mg/dl, 95% CI: -0.71, -0.10, p = 0.01) levels following fasting or energy-restricting diets. Nevertheless, no significant changes were observed in serum HbA1c levels. The subgroup analyses showed that overweight or obese people with energy restricting diets and treatment duration >8 weeks had a greater reduction in FBS, insulin and HOMA-IR level compared with other subgroups. The evidence from available studies suggests that the fasting or energy-restricting diets leads to significant reductions in FBS, insulin and HOMA-IR level and has modest, but, non-significant effects on HbA1c levels.

Association of IGF-1 and IGFBP-3 levels with gastric cancer: A systematic review and meta-analysis.

PURPOSE: Many studies have investigated the association between serum IGF-1 and IGFBP levels with gastric cancer (GC), but the results remained inconclusive. In this work, we performed a systematic review and meta-analysis to examine the precise association of serum levels of IGF-1 and IGFBP with GC. METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE databases for (nested) case-control studies that reported the levels of IGF-1 and IGFBP in GC cases and healthy controls, from inception until October 2020. Weighted mean difference (WMD) was calculated for estimating combined effect size. Subgroup analysis was performed to identify the source of heterogeneity among studies. RESULTS: We found eight and five eligible studies (with 1541 participants) which provided data for IGF-1 and IGFBP, respectively. All studies on IGFBP reported the IGFBP-3 isoform. The pooled results indicate that GC patients had significantly lower serum IGF-1 [WMD = -26.21 ng/mL (95% CI, -45.58 to -6.85; P = .008)] and IGFBP-3 [WMD = -0.41 ng/mL (95% CI, -0.80 to -0.01; P = .04; I2  = 89.9%; P < .001)] levels than those in healthy subjects. Significant heterogeneity was observed in the association, which could be attributed to the sample size of the studies. CONCLUSIONS: In conclusion, our study reveals a significantly lower level of IGF-1 and IGFBP-3 in GC patients compared with healthy control subjects.

Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis.

The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.

Adherence to Alternative Healthy Eating Index (AHEI-2010) is not associated with risk of stroke in Iranian adults: A case-control study.

Background: Stroke is a major global health problem that contributes to a significant burden of morbidity and mortality. The association of several foods and nutrients with stroke has been well-established. However, the effect of the whole diet on stroke is poorly understood. In this work, we aimed to examine the association between the quality of whole diet, as measured using Alternate Healthy Eating Index-2010 (AHEI-2010), and risk of stroke in Iranian adults. Methods: In this hospital-based case-control study, 193 stroke patients (diagnosed based on clinical and brain CT findings) and 193 controls with no history of cerebrovascular diseases or neurologic disorders were included. The participants' dietary intakes were examined using a validated 168-item semi-quantitative food frequency questionnaire. AHEI-2010 was constructed based on earlier studies. Participants were classified according to tertiles of AHEI-2010 scores and multivariate logistic regression was used to evaluate the association between whole diet quality and risk of stroke. Results: Individuals with greater adherence to AHEI-2010 had a higher intake of fruits, vegetables, nuts and legumes, whole grains and carbohydrate, and a lower intake of trans-fatty acids, sugar-sweetened beverages, total energy and fat (P < 0.05). After adjusting for potential confounders, adherence to AHEI-2010 was not significantly associated with a reduced risk of stroke (OR: 0.92; 95% CI: 0.56-1.51). Conclusion: We found that adherence to AHEI-2010 was not associated with risk of stroke in Iranian adults. Further prospective studies are warranted to validate this finding and clarify the relationship between whole diet and stroke.

Association between body mass index and urinary tract infection: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND AND OBJECTIVE: Very few studies have investigated the relationship between body mass index (BMI) and risk of urinary tract infection (UTI), and conclusions from these available studies have been inconsistent. To resolve this inconsistency, we performed a systematic review and meta-analysis to precisely examine the association between BMI and UTI. METHODS: This meta-analysis was performed based on the PRISMA recommendations. PubMed, Web of Science, Scopus, Embase, and Google Scholar databases were searched for all published observational studies that reported the risk of UTI based on BMI categories up to March 2020. RESULTS: Fourteen (n = 14) articles comprising 19 studies in different populations met our inclusion criteria. The overall analysis showed a significant increased risk of UTI in subjects affected by obesity vs. individuals without obesity (RR = 1.45; 95% CI: 1.28 - 1.63; I2 = 94%), and a non-significant increased risk of UTI in subjects who were overweight (RR = 1.03; 95% CI: 0.98 - 1.10; I2 = 49.6%) and underweight (RR = 0.99; 95% CI: 0.81 - 21; I2 = 0.0%) when compared to subjects who had normal weight. In the stratified analysis, we showed that obesity increased the risk of UTI in females (RR = 1.63; 95% CI: 1.38 - 1.93) and in subjects below 60 years old (RR = 1.53; 95% CI: 1.33 - 1.75). CONCLUSION: This systematic review and meta-analysis recognized a significant relationship between BMI and incidence of UTI in obese vs. non-obese subjects, as well as in females and in individuals below 60 years old.

The effects of astaxanthin supplementation on obesity, blood pressure, CRP, glycemic biomarkers, and lipid profile: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Previous studies lack consistent conclusions as to whether astaxanthin is actually linked to various health benefits as claimed. Here, we attempt to unravel the association of astaxanthin consumption with selected health benefits by performing a systematic review and meta-analysis. METHODS: Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups. RESULTS: 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319-2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease. CONCLUSION: In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.

The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis.

BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis.

Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03-1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1<0.001; Coef2 = -0.0932, p2<0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02-1.31, I2: 19 %). Interestingly, no comparable relationship was uncovered between hormone therapy as a whole and Parkinson's disease (OR 1.14, 95 % CI 0.95-1.38, I2: 65 %); however, sub-group analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23-9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34-1.65). Indeed, this association was also found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04). This study reveals a significant direct relationship between the use of certain hormonal therapies and Alzheimer's disease, all-cause dementia, and Parkinson's disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer's disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.

Effects of dehydroepiandrosterone (DHEA) supplementation on the lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has gained attention in individuals with adrenal insufficiency, and as a tool for increasing androgens and estrogens whereby is proposed to improve the accretion of muscle and bone mass. However, DHEA supplementation has demonstrated negative effects on the lipid profile and, thus, we aimed to analyze the body of evidence in this regard. METHODS AND RESULTS: A systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) was performed employing in Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar, then including relevant articles that addressed the effects of DHEA supplementation on the lipid profile, up to February 2020. Combined findings were generated from 23 eligible articles. Hence, total cholesterol (TC) (weighted mean difference (WMD): -3.5 mg/dl, 95% confidence interval (CI): -8.5 to 1.6)), low-density lipoprotein-cholesterol (LDL-C) (WMD: 0.34 mg/dl, 95% CI: -3 to 3.7) and triglycerides (TG) levels (WMD: -2.85 mg/dl, 95% CI: -9.3 to 3.6) did not alter in DHEA group compared to the control, but HDL-C levels significantly reduced in DHEA group (WMD: -3.1 mg/dl, 95% CI: -4.9 to -1.3). In addition, a significant reduction in HDL-C values was observed in studies comprising women (WMD: -5.1 mg/dl, 95% CI: -7.2 to -3) but not in males (WMD: 0.13 mg/dl, 95% CI: -1.4 to 1.7). CONCLUSIONS: Overall, supplementation with DHEA did not change circulating values of TC, LDL-C and TG, whereas it may decrease HDL-C levels. Further long-term RCTs are required to investigate the effects of DHEA particularly on major adverse cardiac events.

Sudden Cardiac Death (SCD) - risk stratification and prediction with molecular biomarkers.

Sudden cardiac death (SCD) is a sudden, unexpected death that is caused by the loss of heart function. While SCD affects many patients suffering from coronary artery diseases (CAD) and heart failure (HF), a considerable number of SCD events occur in asymptomatic individuals. Certain risk factors for SCD have been identified and incorporated in different clinical scores, however, risk stratification using such algorithms is only useful for health management rather than for early detection and prediction of future SCD events in high-risk individuals. In this review, we discuss different molecular biomarkers that are used for early detection of SCD. This includes genetic biomarkers, where the majority of them are genomic variants for genes that encode for ion channels. Meanwhile, protein biomarkers often denote proteins that play roles in pathophysiological processes that lead to CAD and HF, notably (i) atherosclerosis that involves oxidative stress and inflammation, as well as (ii) cardiac tissue damage that involves neurohormonal and hemodynamic regulation and myocardial stress. Finally, we outline existing challenges and future directions including the use of OMICS strategy for biomarker discovery and the multimarker panels.

Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition.

Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. Identification of high-frequency, low-penetrance genetic polymorphisms associated with the cancer has therefore emerged as an important approach which can potentially aid prediction of colorectal cancer risk. However, the overwhelming amount of genetic epidemiology data generated over the past decades has made it difficult for one to assimilate the information and determine the exact genetic polymorphisms that can potentially be used as biomarkers for colorectal cancer. This review comprehensively consolidates, based primarily on results from meta-analyses, the recent progresses in the search of colorectal cancer-associated genetic polymorphisms, and discusses the possible mechanisms involved.

Identification of Optimal Reference Genes for Normalization of RT-qPCR Data in Cancerous and Non-Cancerous Tissues of Human Uterine Cervix.

This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.