Advances and challenges of the cell-based therapies among diabetic patients.

Diabetes mellitus is a significant global public health challenge, with a rising prevalence and associated morbidity and mortality. Cell therapy has evolved over time and holds great potential in diabetes treatment. In the present review, we discussed the recent progresses in cell-based therapies for diabetes that provides an overview of islet and stem cell transplantation technologies used in clinical settings, highlighting their strengths and limitations. We also discussed immunomodulatory strategies employed in cell therapies. Therefore, this review highlights key progresses that pave the way to design transformative treatments to improve the life quality among diabetic patients.

MicroRNA-382 as a tumor suppressor during tumor progression.

Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients.

Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Cardiac Function in Pediatric Patients with MIS-C Using Speckle Tracking and Conventional Echocardiography: A Longitudinal, Single-Center Study.

Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children's Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases.

Unlocking G-Quadruplexes as Antiviral Targets.

Guanine-rich DNA and RNA sequences can fold into noncanonical nucleic acid structures called G-quadruplexes (G4s). Since the discovery that these structures may act as scaffolds for the binding of specific ligands, G4s aroused the attention of a growing number of scientists. The versatile roles of G4 structures in viral replication, transcription, and translation suggest direct applications in therapy or diagnostics. G4-interacting molecules (proteins or small molecules) may also affect the balance between latent and lytic phases, and increasing evidence reveals that G4s are implicated in generally suppressing viral processes, such as replication, transcription, translation, or reverse transcription. In this review, we focus on the discovery of G4s in viruses and the role of G4 ligands in the antiviral drug discovery process. After assessing the role of viral G4s, we argue that host G4s participate in immune modulation, viral tumorigenesis, cellular pathways involved in virus maturation, and DNA integration of viral genomes, which can be potentially employed for antiviral therapeutics. Furthermore, we scrutinize the impediments and shortcomings in the process of studying G4 ligands and drug discovery. Finally, some unanswered questions regarding viral G4s are highlighted for prospective future projects. SIGNIFICANCE STATEMENT: G-quadruplexes (G4s) are noncanonical nucleic acid structures that have gained increasing recognition during the last few decades. First identified as relevant targets in oncology, their importance in virology is now increasingly clear. A number of G-quadruplex ligands are known: viral transcription and replication are the main targets of these ligands. Both viral and cellular G4s may be targeted; this review embraces the different aspects of G-quadruplexes in both host and viral contexts.

Evaluating the protective effect of metformin against diclofenac-induced oxidative stress and hepatic damage: In vitro and in vivo studies.

Diclofenac (DIC) is one of the most commonly prescribed non-steroidal anti-inflammatory drugs and has been shown to cause oxidative stress and liver injury. The current study investigated protective effects of metformin against DIC-induced hepatic toxicity in both in vitro and in vivo models. For the in vitro study, HepG2 cells were exposed to DIC in the presence or absence of metformin. The effect of metformin on cell viability was evaluated by MTT assay. Oxidative stress parameters (malondialdehyde (MDA), total thiol molecules (TTM), and total antioxidant capacity (TAC)) were assessed. For the in vivo study, thirty-six male Wistar rats were randomly divided into 6 groups. These groups were normal saline, metformin (200 mg/kg), DIC (50 mg/kg/day), DIC + metformin (50, 100, and 200 mg/kg/day). Histopathological studies and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), albumin, direct and total bilirubin were measured. Also, oxidative stress parameters were assessed in liver tissue. Furthermore, expression of glutathione peroxidase (GPX)-1, -3, and -4, catalase (CAT), superoxide dismutase (SOD)-1, and -3 was examined using the real-time PCR method in hepatic tissue. In the in vitro study, metformin significantly prevented DIC-induced loss in cell viability in HepG2 cells. Metformin markedly reduced DIC-induced elevation of MDA levels and increased the TAC and TTM levels. In the in vivo study, metformin significantly prevented DIC-induced changes in hematological and histological markers. Administration of metformin significantly improved oxidative stress parameters in liver tissue. In addition, metformin increased the expression of antioxidant enzymes. Our results suggest that metformin exerts a significant protective effect against DIC-induced hepatic toxicity.

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study.

BACKGROUND: Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population. METHODS: ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS. RESULTS: Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference. CONCLUSIONS: Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.

Non-HDL cholesterol and long-term follow-up outcomes in patients with metabolic syndrome.

BACKGROUND: Non-high-density lipoprotein-cholesterol (non-HDL-C) has been identified as a potential biomarker for metabolic syndrome (MetS). However, its predictive capability for MetS varies among different ethnic groups, necessitating further investigation. This study aimed to assess the role of non-HDL-C in the early diagnosis of MetS in the Iranian population through a longitudinal study with a 10-year follow-up period. METHODS: Our study enrolled 4684 individuals from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorder) cohort who were followed for 10 years to examine the association between non-HDL-C and the incidence of MetS. Additionally, the contribution of individual MetS components to the overall burden was evaluated. RESULTS: A total of 1599 subjects developed MetS, while 3085 did not. Non-HDL-C levels ≥ 130 were associated with a 42% higher risk of developing MetS (relative risk (RR), 1.42; 95% confidence interval (CI), 1.25-1.62). Regarding MetS components, elevated waist circumference (WC) showed the strongest association with MetS incidence (RR, 2.32; 95% CI, 1.45-2.9), whereas triglyceride (TG) levels ≥ 150 mg/dL demonstrated the weakest association (RR, 1.23; 95% CI, 1.04-1.46). Additionally, higher HDL-C levels were reported to be 20% protective against the risk of MetS (RR, 0.8; 95% CI, 0.73-0.86). Moreover, fasting blood glucose (FBG) levels ≥ 100 mg/dL were not significantly linked to MetS burden, while systolic blood pressure (BP) levels ≥ 130 mmHg or diastolic BP levels ≥ 85 mmHg increased the risk of MetS incidence (RR, 1.25; 95% CI: 1.11-1.41). CONCLUSIONS: Elevated non-HDL-C and increased WC serve as significant predictors of MetS in Iranians. Strategies targeting non-HDL-C levels and weight loss should be emphasized to mitigate the risk of MetS development.

Cell cycle related long non-coding RNAs as the critical regulators of breast cancer progression and metastasis.

Cell cycle is one of the main cellular mechanisms involved in tumor progression. Almost all of the active molecular pathways in tumor cells directly or indirectly target the cell cycle progression. Therefore, it is necessary to assess the molecular mechanisms involved in cell cycle regulation in tumor cells. Since, early diagnosis has pivotal role in better cancer management and treatment, it is required to introduce the non-invasive diagnostic markers. Long non-coding RNAs (LncRNAs) have higher stability in body fluids in comparison with mRNAs. Therefore, they can be used as efficient non-invasive markers for the early detection of breast cancer (BCa). In the present review we have summarized all of the reported lncRNAs involved in cell cycle regulation in BCa. It has been reported that lncRNAs mainly affect the cell cycle in G1/S transition through the CCND1/CDK4-6 complex. Present review paves the way of introducing the cell cycle related lncRNAs as efficient markers for the early detection of BCa.

Radioprotective Effect of Zinc Nanoparticles on Ionizing Radiation-induced Nephrotoxicity in Mice.

INTRODUCTION: Ionizing radiation (IR) causes oxidative stress in kidneys and subsequently disrupts renal function. The use of green synthesized zinc nanoparticles (Zn NPs) with antioxidant properties may reduce the damage caused by IR. METHODS: Thirty-six mice were kept in a standard situation and divided into 6 groups: 1: Control; 2-4: receiving 5 mg/kg, 10 mg/kg, and 25 mg/kg of Zn NPs with IR; 5: receiving 5 mg/kg of ZnSO4 with IR; and 6: IR. After 15 days, half of the animals in each group were sacrificed and their blood samples isolated to evaluate the plasma urea and creatinine levels. The kidneys were kept for evaluating the glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels; on 21st day, the rest of the animals were sacrificed and their kidneys removed for histological assessments. RESULTS: IR decreased GSH content, increased MDA level, and reduced SOD and CAT activity. On the other hand, Zn NPs at 10 and 25 mg/kg doses increased GSH, decreased MDA, and enhanced SOD and CAT activities. Zn NPs treatment at 10 and 25 mg/kg doses decreased the plasma urea and creatinine levels induced by IR. Moreover, Zn NPs significantly decreased the level of urea and creatinine in irradiated mice in comparison with IR alone (p < 0.05). The main histopathological results were tubular and glomerular atrophy and interstitial fibrosis in irradiated mice, while tubular degeneration and atrophy were less frequent in Zn NPs + IR group than in IR group alone. CONCLUSION: Zn NPs treatment, especially at 25 mg/kg dose, attenuates the side effect of IR on kidneys through reducing oxidative stress factors, biochemical, and histopathological changes.

The impact of probiotic cell-free metabolites in MDR Pseudomonas aeruginosa: antibacterial properties and effect on antibiotic resistance genes expression.

There is a significant demand for novel antibacterial agents against multidrug-resistant (MDR) gram-negative bacteria. Recently, probiotics have been noted for their antibacterial properties against various pathogens. This study aimed to investigate the effects of probiotic cell-free supernatants on MDR Pseudomonas aeruginosa. Clinical isolates demonstrating the highest degree of antibiotic resistance were chosen, and the antibacterial effect of probiotic metabolites was evaluated using an agar-well diffusion assay. In addition, the effect of probiotics on the expression of resistance genes was evaluated using real-time PCR. The CFS was assessed using GC-MS to determine the antibacterial compounds. The supernatants inhibited the growth of the isolates (P < 0.0001); however, there was no noticeable difference in the effectiveness of the probiotics. In addition, the supernatants decreased the expression levels of mexD, mexB, mexF, and ampC, and an increase in oprD was observed in some groups. After the assessment of Lactobacillus acidophilus by GC-MS, antibacterial compounds, such as acetamide, nonadecane, 9-methyl, and tetradecane, were determined. Our findings showed that probiotic metabolites can effectively inhibit the growth of MDR P. aeruginosa. Gene expression analysis also revealed that the mechanism of antibacterial action was most likely related to the regulation of efflux pumps.

Rapid and sensitive detection of SARS-CoV-2 virus in human saliva samples using glycan based nanozyme: a clinical study.

A highly sensitive colorimetric method (glycan-based nano(e)zyme) was developed for sensitive and rapid detection of the SARS-CoV-2 virus based on N-acetyl neuraminic acid (sialic acid)-functionalized gold nanoparticles (SA-Au NZs). A number of techniques were used to characterize the prepared nanomaterials including XRD, FT-IR, UV-vis, DLS, and TEM. DLS analysis indicates an average hydrodynamic size of 34 nm, whereas TEM analysis indicates an average particle size of 15.78 nm. This observation confirms that water interacts with nanoparticle surfaces, resulting in a large hydrodynamic diameter. The peroxidase-like activity of SA-Au NZs was examined with SARS-CoV-2 and influenza viruses (influenza A (H1N1), influenza A (H3N2), and influenza B). UV-visible spectroscopy was used to monitor and record the results, as well as naked eye detection (photographs). SA-Au NZs exhibit a change in color from light red to purple when SARS-CoV-2 is present, and they exhibit a redshift in their spectrum. N-acetyl neuraminic acid interacts with SARS-CoV-2 spike glycoprotein, confirming its ability to bind glycans. As a result, SA-Au NZs can detect COVID-19 with sensitivity and specificity of over 95% and 98%, respectively. This method was approved by testing saliva samples from 533 suspected individuals at Ghaem Hospital of Mashhad, Mashhad, Iran. Sensitivity and specificity were calculated by comparing the results with the definitive results. The positive results were accompanied by a color change from bright red to purple within five minutes. Statistical analysis was performed based on variables such as age, gender, smoking, diabetes, hypertension, and lung involvement. In clinical trials, it was demonstrated that this method can be used to diagnose SARS-CoV-2 in a variety of places, such as medical centers, hospitals, airports, universities, and schools.

Investigating the protective role of metformin on lithium-induced hypothyroidism.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

Clinical, laboratory and imaging characteristics, and outcomes of hospitalized children with suspected COVID-19 infection: A report from Isfahan-Iran.

Background: The aim of this study was to evaluate the clinical, laboratory and imaging characteristics, and outcomes of hospitalized children with suspected COVID-19 infection in Isfahan. Materials and Methods: In this cross-sectional study, all children aged < 15 years, who hospitalized as suspected case of COVID-19 were enrolled. During this study, all demographic, clinical, laboratory, and imaging characteristics as well as follow-up data and outcomes of the hospitalized children were recorded by pediatric residents using a questionnaire. The findings of studied populations in the two groups of definite/or suspected and negative COVID-19 patients were compared. Results: During 6 months' period, 137 children with suspected COVID-19 infection were evaluated. Mean age of studied population was 4.3 (0.38) years. The most common symptoms in order were fever, cough, dyspnea and diarrhea. The most common computed tomography scan findings were bilateral ground glass and subpleural involvements. The rate of mortality was 7.3%. COVID-19 polymerase chain reaction test was positive in 22% of the patients. Based on the specialist's diagnosis, 30/25 patients were definite/or suspected to COVID-19 and reminder (79) were negative. O2 saturation <90%, was significantly higher in children with definite/or suspected diagnosis for COVID-19 (46.7% vs. 22.4%, P < 0.05). Dyspnea and shivering were significantly higher in children with definite/or suspected diagnosis for COVID-19 than those negative for COVID-19(P < 0.05). Mean duration of hospitalization was significantly associated with level of lactate dehydrogenase (P < 0.05). Conclusion: The clinical, laboratory, and imaging findings of our studied population were similar to other studies, but outcome was not similar which may be due to our studied population (inpatients cases). It is suggested that a better understanding of the infection in children may give important insights into disease pathogenesis, health-care practices, and public health policies.

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.

The effects of nano-curcumin supplementation on glycemic control, blood pressure, lipid profile, and insulin resistance in patients with the metabolic syndrome: A randomized, double-blind clinical trial.

Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic ß cell function (HOMA-ß) and lipid profile-were assessed at the baseline and the end of the study. Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p < .05) and HOMA-ß (-5.7 ± 48.2 vs. -4.01 ± 16.9; p < .05). But there were no significant differences in anthropometric measurements, blood pressure and biochemical factors-including FBS, HbA1c, HOMA-IR, HOMA-ß, and lipid profile variables include (total cholesterol, LDL-C, and HDL-C) at the end of the study. In conclusion, supplementation with nano-micelle curcumin significantly improved serum TG in MetS patients.

Successful treatment of plasmapheresis followed by interferon beta-1a in a child with severe COVID-19.

COVID-19 outbreak has become a global health concern due to challenges in treatment and high mortality rate; therefore, its therapeutic approaches play an important role in reducing the mortality rate and resolving this concern. Different therapies have been introduced, including interferon beta-1a and purification methods, for instance, plasmapheresis. In this article, we reported a child with severe COVID-19 who fully recovered after receiving plasmapheresis and interferon beta-1a.

Role of tyrosine kinases in bladder cancer progression: an overview.

BACKGROUND: Bladder cancer (BCa) is a frequent urothelial malignancy with a high ratio of morbidity and mortality. Various genetic and environmental factors are involved in BCa progression. Since, majority of BCa cases are diagnosed after macroscopic clinical symptoms, it is required to find efficient markers for the early detection. Receptor tyrosine-kinases (RTKs) and non-receptor tyrosine-kinases (nRTKs) have pivotal roles in various cellular processes such as growth, migration, differentiation, and metabolism through different signaling pathways. Tyrosine-kinase deregulations are observed during tumor progressions via mutations, amplification, and chromosomal abnormalities which introduces these factors as important candidates of anti-cancer therapies. MAIN BODY: For the first time in present review we have summarized all of the reported tyrosine-kinases which have been significantly associated with the clinicopathological features of BCa patients. CONCLUSIONS: This review highlights the importance of tyrosine-kinases as critical markers in early detection and therapeutic purposes among BCa patients and clarifies the molecular biology of tyrosine-kinases during BCa progression and metastasis. Video abstract.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

INTRODUCTION: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran. MATERIAL AND METHODS: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence. RESULTS: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05). CONCLUSION: In the present study, TC baseline level was significantly associated with the risk of MI among men.