Electrochemical microfluidic paper-based analytical devices for cancer biomarker detection: From 2D to 3D sensing systems.

Microfluidic paper-based analytical devices (µPADs) offer a unique possibility for a cost-effective portable and rapid detection of a wide range of small molecules and macromolecules and even microorganisms. In this line, electrochemical detection methods are key techniques for the qualitative analysis of different types of ligands. The electrochemical sensing µPADs have been devised for the rapid, accurate, and quantitative detection of oncomarkers through two-/three-dimensional (2D/3D) approaches. The 2D µPADs were first developed and then transformed into 3D systems via folding and/or twisting of paper. The microfluidic channels and connections were created within the layers of paper. Based on the fabrication methods, 3D µPADs can be classified into origami and stacking devices. Various fabrication methods and materials have been used to create hydrophilic channels in µPADs, among which the wax printing technique is the most common method in fabricating µPADs. In this review, we discuss the fabrication and design strategies of µPADs, elaborate on their detection modes, and highlight their applications in affinity-based electrochemical µPADs methods for the detection of oncomarkers.

Label-free electrochemical microfluidic biosensors: futuristic point-of-care analytical devices for monitoring diseases.

The integration of microfluidics with electrochemical analysis has resulted in the development of single miniaturized detection systems, which allows the precise control of sample volume with multianalyte detection capability in a cost- and time-effective manner. Microfluidic electrochemical sensing devices (MESDs) can potentially serve as precise sensing and monitoring systems for the detection of molecular markers in various detrimental diseases. MESDs offer several advantages, including (i) automated sample preparation and detection, (ii) low sample and reagent requirement, (iii) detection of multianalyte in a single run, (iv) multiplex analysis in a single integrated device, and (v) portability with simplicity in application and disposability. Label-free MESDs can serve an affordable real-time detection with a simple analysis in a short processing time, providing point-of-care diagnosis/detection possibilities in precision medicine, and environmental analysis. In the current review, we elaborate on label-free microfluidic biosensors, provide comprehensive insights into electrochemical detection techniques, and discuss the principles of label-free microfluidic-based sensing approaches.

Synergizing Functional Nanomaterials with Aptamers Based on Electrochemical Strategies for Pesticide Detection: Current Status and Perspectives.

Owing to the high toxicity and large-scale use of pesticides, it is imperative to develop selective, sensitive, portable, and convenient sensors for rapid monitoring of pesticide. Therefore, the electrochemical detection platform offers a promising analytical approach since it is easy to operate, economical, efficient, and user-friendly. Meanwhile, with advances in functional nanomaterials and aptamer selection technologies, numerous sensitivity-enhancement techniques alongside a widespread range of smart nanomaterials have been merged to construct novel aptamer probes to use in the biosensing field. Hence, this study intends to highlight recent development and promising applications on the functional nanomaterials with aptamers for pesticides detection based on electrochemical strategies. We also reviewed the current novel aptamer-functionalized microdevices for the portability of pesticides sensors. Furthermore, the major challenges and future prospects in this field are also discussed to provide ideas for further research.

Diabetes is associated with higher mortality and severity in hospitalized patients with COVID-19.

As a novel cause of pneumonia, coronavirus disease 2019 (COVID-19) has rapidly progressed worldwide. Previous studies have indicated COVID-19 patients with diabetes show higher mortality rates and more severe COVID-19 infection with an increased requirement for intensive care and hospital length of stay (LOS) compared to non-diabetic patients. The present study aimed to investigate the association of diabetes and COVID-19 outcome with severity of disease in hospitalized patients. The present case-control study included 268 patients diagnosed with COVID-19 who were hospitalized in Ayatollah Khoyi Hospital, Khoy, Iran. Diabetes was identified based on medical history and/or criteria of published documents. Out of 268 patients (median age of 59 years; 53.4 % male), 127 patients had diabetes (47 %). Diabetic patients had remarkably higher mortality rates (adjusted odds ratio, aOR: 3.36; confidence interval, CI: 1.17-9.66), requirement for invasive mechanical ventilation (IMV) (aOR: 4.59; CI: 1.38-15.25), and LOS (aOR: 1.13; CI: 1.06-1.24) compared to patients without diabetes. Inflammatory biomarkers including C-reactive protein (CRP), lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) were increased in patients with diabetes compared to non-diabetic patients (P < 0.05 for all the comparisons). In hospitalized patients with COVID-19, diabetes was correlated with increased disease severity and mortality.

The Changes of Brain Edema and Neurological Outcome, and the Probable Mechanisms in Diffuse Traumatic Brain Injury Induced in Rats with the History of Exercise.

Since no definitive treatment has been suggested for diffuse traumatic brain injury (TBI), and also as the effect of exercise has been proven to be beneficial in neurodegenerative diseases, the effect of endurance exercise on the complications of TBI along with its possible neuroprotective mechanism was investigated in this study. Our objective was to find out whether previous endurance exercise influences brain edema and neurological outcome in TBI. We also assessed the probable mechanism of endurance exercise effect in TBI. Rats were randomly assigned into four groups of sham, TBI, exercise + sham and exercise + TBI. Endurance exercise was carried out before TBI. Brain edema was assessed by calculating the percentage of brain water content 24 h after the surgery. Neurological outcome was evaluated by obtaining veterinary coma scale (VCS) at - 1, 1, 4 and 24 h after the surgery. Interleukin-1ß (IL-1ß), total antioxidant capacity (TAC), malondialdehyde (MDA), protein carbonyl and histopathological changes were evaluated 24 h after the surgery. Previous exercise prevented the increase in brain water content, MDA level, histopathological edema and apoptosis following TBI. The reduction in VCS in exercise + TBI group was lower than that of TBI group. In addition, a decrease in the level of serum IL-1ß and the content of brain protein carbonyl was reported in exercise + TBI group in comparison with the TBI group. We suggest that the previous endurance exercise prevents brain edema and improves neurological outcome following diffuse TBI, probably by reducing apoptosis, inflammation and oxidative stress.

Epigenetic modulation of BRCA-1 and MGMT genes, and histones H4 and H3 are associated with breast tumors.

Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = -0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy.

Atorvastatin, losartan and captopril may upregulate IL-22 in hypertension and coronary artery disease; the role of gene polymorphism.

AIMS: Interleukin-22 (IL-22) may be considered as an important cytokine in maintenance and progression of hypertension and coronary artery disease (CAD). The aim of the present study was to investigate the effect of treatment of hypertension and CAD on serum levels of IL-22 and the possible association of IL-22-rs1179251 gene polymorphism with hypertension and CAD. MATERIALS AND METHODS: A total of 286 subjects with suspected CAD were enrolled. Serum levels and gene polymorphism of IL-22 were investigated in hypertensive patients with no CAD (H-Tens), hypertensive patients with CAD (CAD + H-Tens); 3), CAD patients with no hypertension (CAD); and non-hypertensive with no CAD subjects as a control group (Ctr). The patients received routine medications for hypertension and CAD. Serum IL-22 levels and IL-22-rs1179251 gene polymorphism were evaluated using ELISA and RFLP-/PCR techniques, respectively. KEY FINDINGS: Findings demonstrated that there were significantly higher levels of IL-22 in case groups (H-Tens, CAD + H-Tens, and CAD) compared to the Ctr group (P = 0.001, P = 0.014, and P < 0.001, respectively). Moreover, atorvastatin, losartan and captopril were administered significantly more in patients compared to the Ctr group. The results indicated a decreased risk of CAD + H-Tens of rs1179251 dominant genetic model (OR = 0.324; 95% CI = 0.121-0.873; P = 0.026). SIGNIFICANCE: Atorvastatin, losartan and captopril may be led to upregulation of IL-22 in CAD and hypertensive patients. Meanwhile, higher levels of circulating IL-22 could contribute to alleviating the hypertension and CAD conditions. The G allele of IL-22 rs1179251 may be a protective factor for concomitant hypertension and CAD.

Elevated levels of DNA methylation at the OPRM1 promoter region in men with opioid use disorder.

BACKGROUND: The mu-opioid receptor, encoded by mu-opioid receptor gene (OPRM1), has an important role in the development of addiction to opioids. Its aberrant reduction on the cell membrane is responsible, at least in part, for tolerance and physical dependence. OBJECTIVES: The present study was designed to identify the relationship between opium consumption and epigenetic mechanisms involved in opium addiction. METHODS: Genomic DNA was extracted from the peripheral blood of 66 men with opium use disorder and 57 healthy men as a control group. Genomic DNAs were treated with sodium bisulfite to convert the un-methylated cytosine to uracil, while methylated cytosine remained unaffected. Nested methylation-specific PCR (MSP) was used for analyses of region 1 (R1) and region 2 (R2) of the OPRM1 promoter DNA methylation. RESULTS: All participants were 19-56 years old, and there was no significant difference in the mean age of both groups (P = 0.082). After Bonferroni correction, results showed that the DNA methylation status significantly increased the risk of opium addiction in the R2 region compared with un-methylation status (OR = 3.80, 95%CI = 1.77-8.17, P = 0.001). However, we found no significant difference in the R1 region DNA methylation between case and control groups (21.2% and 21.1%, respectively) (P = 1). CONCLUSION: Our findings demonstrated DNA hypermethylation of the R2 region of the OPRM1 promoter in leukocytes of opium use disorder. In peripheral tissues such as blood, changes of epigenetic endpoints with substance use can be considered as potentially clinically useful biomarkers in identifying individuals who may warrant further diagnostic assessment of a substance use disorder.

Evaluation of serum arsenic and its effects on antioxidant alterations in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Environmental factors that are involved in the development of autoimmune diseases include bacteria, viruses, and xenobiotics such as chemicals, drugs, and metals. Regarding the metals, a number of studies have demonstrated that oxidative stress is one of the well-directed pathways of arsenic-induced tissue damages. This study was designed to explore the serum concentrations of arsenic and its correlation with markers associated with oxidative stress in relapsing-remitting MS (RRMS) patients. METHODS: This case-controlled study comprised 50 patients with RRMS and 50 healthy subjects. Serum arsenic levels, total antioxidant potential, malondialdehyde (MDA), and lactate levels were measured. RESULTS: The arsenic value, MDA, and lactate levels were elevated meaningfully while FRAP level significantly was decreased in RRMS patients with respect to healthy subjects (P <0.05). Furthermore, arsenic serum levels were positively correlated with serum concentrations of MDA and lactate. In contrast, serum levels were negatively correlated to FRAP values in RRMS patients. CONCLUSION: Taken together, the association between arsenic level and oxidative stress parameters supports the hypothesis that high serum arsenic levels may play a critical role in the pathogenesis of MS progression.

Evaluation of lithium serum level in multiple sclerosis patients: A neuroprotective element.

INTRODUCTION: It has been claimed that continuous and high production of nitric oxide (NO) and its metabolites may be involved in the pathogenesis of several neurological disorders such as multiple sclerosis. A number of studies have demonstrated that lithium regulates NO levels in disorders of the central nervous system. The aim of this study was to investigate whether NO as a marker of disease activity is correlated with lithium deficiency in relapsing remitting multiple sclerosis (RR-MS). METHODS: This case-controlled study comprised 44 patients with RR-MS and 43 healthy subjects matched by age, gender, smoking status, and body mass index. The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in serum. In addition serum lithium levels were measured using atomic absorption spectrometry method. The mean serum NO concentrations in the groups RR-MS and the control were 18.5 ± 3.1µM and 15.5 ± 2.9µM, respectively. Data analysis showed a statistically significant difference between subjects with RR-MS and the control group (p < 0.05). Furthermore, serum lithium concentrations in RR-MS (0.57 ± 0.2) were remarkably lower in RR-MS patients than the controls (2.29 ± 0.7) (p < 0.05). CONCLUSION: The present findings suggest that lithium deficiency may upregulates NO production in RR-MS. Further studies with larger samples are needed to confirm the effects of lithium treatment on NO pathway and its association with synaptic plasticity in RR-MS patients.