RBM33 directs the nuclear export of transcripts containing GC-rich elements.

Although splicing is a major driver of RNA nuclear export, many intronless RNAs are efficiently exported to the cytoplasm through poorly characterized mechanisms. For example, GC-rich sequences promote nuclear export in a splicing-independent manner, but how GC content is recognized and coupled to nuclear export is unknown. Here, we developed a genome-wide screening strategy to investigate the mechanism of export of NORAD, an intronless cytoplasmic long noncoding RNA (lncRNA). This screen revealed an RNA binding protein, RBM33, that directs the nuclear export of NORAD and numerous other transcripts. RBM33 directly binds substrate transcripts and recruits components of the TREX-NXF1/NXT1 RNA export pathway. Interestingly, high GC content emerged as the feature that specifies RBM33-dependent nuclear export. Accordingly, RBM33 directly binds GC-rich elements in target transcripts. These results provide a broadly applicable strategy for the genetic dissection of nuclear export mechanisms and reveal a long-sought nuclear export pathway for transcripts with GC-rich sequences.

Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro.

BACKGROUND: In this study the formulation of parthenolide (PN), an anticancer agent extracted from a natural product, into a liposome (PN-liposome), was examined. The surface of the PN-liposome was modified using chitosan (PN-chitosome). By using real-time quantitative PCR and flow cytometry, we examined the release of PN-chitosomes, cytotoxicity, and ability to induce apoptosis in vitro. METHODS AND RESULTS: According to the present study, PN-chitosomes had a size of 251 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. PN-chitosomes were confirmed to be spherical in shape and size through FESEM analysis. In terms of encapsulation efficiency, 94.5% was achieved. PN-chitosome possessed a zeta potential of 34.72 mV, which was suitable for its stability. According to the FTIR spectra of PN and PN-chitosome, PN was chemically stable due to the intermolecular interaction between the liposome and the drug. After 48 h, only 10% of the PN was released from the PN-chitosome in PBS (pH 7.4), and less than 20% was released after 144 h. CONCLUSION: In a dose-dependent manner, PN-chitosome exhibited anticancer properties that were more cytotoxic against cancer cells than normal cells. Moreover, the formulation activated both the apoptosis pathway and cytotoxic genes in real-time qPCR experiments. According to the cytotoxicity and activating apoptosis of the prepared modified particle, PN-chitosome may be helpful in the treatment of cancer.

Modeling the structural relationships between trauma exposure with substance use tendency, depression symptoms, and suicidal thoughts in individuals with earthquake trauma experience: the mediatory role of peritraumatic dissociation and experiential avoidance.

BACKGROUND: Despite the fact that studies indicate that earthquake trauma is associated with numerous psychological consequences, the mediating mechanisms leading to these outcomes have not been well-studied. Therefore, this study investigates the relationship between trauma exposure with substance use tendency, depression, and suicidal thoughts, with the mediating role of peritraumatic dissociation and experiential avoidance. METHODS: The descriptive-correlational approach was employed in this study. The participants were people who had experienced the Kermanshah earthquake in 2017. A total of 324 people were selected by convenient sampling method. The Traumatic Exposure Severity Scale, the Peritraumatic Dissociative Experiences Questionnaire, the Acceptance and Action Questionnaire, the Iranian Addiction Potential Scale, Beck's Depression Inventory [BDI-II], and Beck's Suicidal Thoughts Scale were used to collect data. The gathered data was analyzed| using structural equation modeling in |SPSS Ver. 24 and LISREL Ver. 24. RESULTS: The study findings indicated that the intensity of the trauma exposure is directly and significantly associated with depression symptoms, peritraumatic dissociation, and experiential avoidance. The severity of exposure to trauma had a significant indirect effect on the tendency to use substances through experiential avoidance. This is while the severity of the trauma experience did not directly correlate with substance use and suicidal thoughts. In addition, peritraumatic dissociation did not act as a mediator in the relationship between the severity of trauma exposure with substance use, depression, and suicidal thoughts. CONCLUSIONS: The severity of exposure to the earthquake was associated with symptoms of depression and these findings indicate the importance of experiential avoidance in predicting the tendency to use drugs. Hence, it is essential to design and implement psychological interventions that target experiential avoidance to prevent drug use tendencies and to establish policies that lower depression symptoms following natural disasters.

A machine learning approach for predicting and localizing the failure and damage point in sewer networks due to pipe properties.

As a basic infrastructure, sewers play an important role in the innards of every city and town to remove unsanitary water from all kinds of livable and functional spaces. Sewer pipe failures (SPFs) are unwanted and unsafe in many ways, as the disturbance that they cause is undeniable. Sewer pipes meet manholes frequently, unlike water distribution systems, as in sewers, water movement is due to gravity and manholes are needed in every intersection as well as through pipe length. Many studies have been focused on sewer pipe failures and so on, but few investigations have been done to show the effect of manhole proximity on pipe failure. Predicting and localizing the sewer pipe failures is affected by different parameters of sewer pipe properties, such as material, age, slope, and depth of the sewer pipes. This study investigates the applicability of a support vector machine (SVM), a supervised machine learning (ML) algorithm, for the development of a prediction model to predict sewer pipe failures and the effects of manhole proximity. The results show that SVM with an accuracy of 84% can properly approximate the manhole effects on sewer pipe failures.

Improvement photothermal property of MoS2/Fe3O4/GNR nanocomposite in cancer treatment.

The objective of the present study was to develop a novel molybdenum disulfide/iron oxide/gold nanorods (MoS2/Fe3O4/GNR) nanocomposite (MFG) with different concentrations of AgNO3 solution (MFG1, MFG2, and MFG3) for topical doxorubicin (DOX) drug delivery. Then, these nanocomposites were synthesized and characterized by Fourier transform infrared (FTIR), Transmission electron microscopy (TEM), Dynamic light scattering (DLS), and Ultraviolet-visible (UV-Vis) spectroscopies to confirm their structural and optical properties. Cytotoxicity of samples on Hela cell was determined using MTT assay. Results indicated that nanocomposites possess little cytotoxicity without NIR laser irradiation. Also, the relative viabilities of Hela cells decreased when the concentration of AgNO3 solution increased in this nanocomposite. Using NIR irradiation, the relative viabilities of Hela cells decreased when the concentration of samples increased. Acridine orange/propidium iodide (PI) staining, flow cytometry were recruited to evaluate the effect of these nanocomposites on apoptosis of Hela cells. Finally, results revealed when DOX loading increased in nanocomposite, then cell viability was decreased in it. Therefore, these properties make MFG3 nanocomposite a good candidate for photothermal therapy and drug loading.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Utilization of the internal mammary perforators as the recipient vessels for microsurgical breast reconstruction: A systematic review and meta-analysis of the literature.

BACKGROUND: The selection of reliable recipient vessels is essential for successful free tissue transfer. The use of internal mammary intercostal perforators (IMAPs), instead of the internal mammary vessels as the recipient vessels, has been described in breast reconstruction. Debates exist regarding the reliability of these perforators as recipient vessels because of their variability in location and caliber. The aim of this paper was to conduct a systematic literature review and meta-analysis to determine the reliability of the IMAPs as recipient vessels. METHODS: A systematic literature review was performed on the "PubMed," "Medline," "Ovid," and "Cochrane library" databases for articles published from January 1990 to March 2021. Exclusion criteria were non-English studies, reports with case number less than 5, cadaveric or animal studies, and studies with incomplete postoperative outcomes. The reliability of using IMAPs for breast reconstruction was determined by assessing the reported rates of partial or complete flap failure and other complications (fat necrosis, skin necrosis, and requirement for revision surgery). RESULTS: Three hundred and sixteen cases in 13 studies were included for further analysis with more than 85% of the IMAPs suitable for anastomosis being located in the second and third intercostal spaces. Partial or total flap failure was reported in three of 316 patients (0.95%). The rate of other complications such as fat necrosis, skin necrosis, and requirement for revision surgery were all less than 5%. CONCLUSION: With deliberate preoperative planning, delicate perioperative manipulation, and meticulous microvascular anastomosis, the internal mammary perforators can be used as reliable recipient vessels in microvascular breast reconstruction.

A Novel Anticoagulation Method Based on Electrochemical Characteristics of Blood: An in vitro Study.

This in vitro experimental investigation aimed to provide a novel method for preventing blood clotting based on the electrochemical characteristics of blood. Using this method in cases such as dialysis can minimize the risk of blood clots and also avoid hemorrhagic risk for patients. Blood samples were collected from 13 sheep (45 kg) (25 mL), and the clotting time (CT) was measured using a 20-min cutoff after they were separated into control and experimental samples. The test blood sample was put in a cell designed with two aluminum electrodes (positive pole/anode) located in a container containing 0.9% sodium chloride (as a salt bridge) and a platinum (negative pole/cathode) linked to a power supply (-3.5 V, 1 mA/cm2). Biochemical and hematological tests to check blood damage and clotting were performed. The control sample coagulated after 8 min, while the electrified blood did not, even at the end of the cutoff time. Among hematologic and biochemical tests, the average time of prothrombin time (PT) and partial thromboplastin time (PTT) was significantly different between the control and test samples (p = 0.001). Our findings on electrified blood with expanding CT, PT, and PTT times revealed that the electric current passing through the blood enhanced the CT. Furthermore, no change in biochemical or hematological factors demonstrated that this current had no detrimental effect on the blood.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

LEVEL OF EVIDENCE: III.

Assessing land use changes' effect on river water quality in the Dez Basin using land change modeler.

Changes in land use due to urbanization, industrialization, and agriculture will adversely affect water quality at all scales. This study examined the possible effects of future land use on the water quality of the Dez River located in Iran. The QUAL2Kw dynamic model was used to simulate the water quality of the Dez River. Data and information available in July 2019 and 2013 were used for calibration and validation. According to the comparison of the RMSE, RMSE%, and percent bias error indices for the model during the calibration and validation period, the QUAL2Kw model of Dez River had high accuracy with acceptable values of errors. The land use changes in the Dez river basin were modeled and predicted by the LCM model after simulating water quality. The images from Landsat 8/OLI were used for 2013, 2016, and 2019, respectively. Based on the accurate evaluation of classified images, Kappa coefficients for 2013, 2016, and 2019 were 88.19, 87.46, and 89.91, respectively. Modeling land use and land cover changes was conducted to predict 2030. As a result of the study, agricultural and built-up areas and water bodies will increase in 2030. The possible effects of land use changes in 2030 on river water quality were examined as a final step. Based on the results of the water quality simulation in 2030, biochemical oxygen demand, chemical oxygen demand, and NO3 parameters exceeded the maximum permissible level of drinking standard. This study recommends frequent water quality monitoring and LULC planning and management to reduce pollution in river basins.

PTH/PTHrP Receptor Signaling Restricts Arterial Fibrosis in Diabetic LDLR-/- Mice by Inhibiting Myocardin-Related Transcription Factor Relays.

RATIONALE: The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR-/- mice. OBJECTIVE: To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR-/- mice (PTH1R-VKO) and Cre-negative controls. METHODS AND RESULTS: Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. PTH1R-VKO cohorts exhibited increased aortic collagen accumulation in vivo, and VSM cultures from PTH1R-VKO mice elaborated more collagen (2.5-fold; P=0.01) with elevated Col3a1 and Col1a1 expression. To better understand these profibrotic responses, we performed mass spectrometry on nuclear proteins extracted from Cre-negative controls and PTH1R-VKO VSM. PTH1R deficiency reduced Gata6 but upregulated the MADS (MCM1, Agamous, Deficiens, and Srf DNA-binding domain)-box transcriptional co-regulator, Mkl-1 (megakaryoblastic leukemia [translocation] 1). Co-transfection assays (Col3a1 promoter-luciferase reporter) confirmed PTH1R-mediated inhibition and Mkl-1-mediated activation of Col3a1 transcription. Regulation mapped to a conserved hybrid CT(A/T)6GG MADS-box cognate in the Col3a1 promoter. Mutations of C/G in this motif markedly reduced Col3a1 transcriptional regulation by PTH1R and Mkl-1. Upregulation of Col3a1 and Col1a1 in PTH1R-VKO VSM was inhibited by small interfering RNA targeting Mkl1 and by treatment with the Mkl-1 antagonist CCG1423 or the Rock (Rho-associated coiled-coil containing protein kinase)-2 inhibitor KD025. Chromatin precipitation demonstrated that VSM PTH1R deficiency increased Mkl-1 binding to Col3a1 and Col1a1, but not TNF, promoters. Proteomic studies of plasma extracellular vesicles and VSM from PTH1R-VKO mice identified C1r (complement component 1, r) and C1s (complement component 1, s), complement proteins involved in vascular collagen metabolism, as potential biomarkers. VSM C1r protein and C1r message were increased with PTH1R deficiency, mediated by Mkl-1-dependent transcription and inhibited by CCG1423 or KD025. CONCLUSIONS: PTH1R signaling restricts collagen production in the VSM lineage, in part, via Mkl-1 regulatory circuits that control collagen gene transcription. Strategies that maintain homeostatic VSM PTH1R signaling, as reflected in extracellular vesicle biomarkers of VSM PTH1R/Mkl-1 action, may help mitigate arteriosclerosis and vascular fibrosis.

Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells.

Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5-6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX. Graphical abstract.

Analysis of Volatile Compounds by Advanced Analytical Techniques and Multivariate Chemometrics.

Smelling is one of the five senses, which plays an important role in our everyday lives. Volatile compounds are, for example, characteristics of food where some of them can be perceivable by humans because of their aroma. They have a great influence on the decision making of consumers when they choose to use a product or not. In the case where a product has an offensive and strong aroma, many consumers might not appreciate it. On the contrary, soft and fresh natural aromas definitely increase the acceptance of a given product. These properties can drastically influence the economy; thus, it has been of great importance to manufacturers that the aroma of their food product is characterized by analytical means to provide a basis for further optimization processes. A lot of research has been devoted to this domain in order to link the quality of, e.g., a food to its aroma. By knowing the aromatic profile of a food, one can understand the nature of a given product leading to developing new products, which are more acceptable by consumers. There are two ways to analyze volatiles: one is to use human senses and/or sensory instruments, and the other is based on advanced analytical techniques. This work focuses on the latter. Although requirements are simple, low-cost technology is an attractive research target in this domain; most of the data are generated with very high-resolution analytical instruments. Such data gathered based on different analytical instruments normally have broad, overlapping sensitivity profiles and require substantial data analysis. In this review, we have addressed not only the question of the application of chemometrics for aroma analysis but also of the use of different analytical instruments in this field, highlighting the research needed for future focus.

Resveratrol supplementation improves DNA integrity and sperm parameters in streptozotocin-nicotinamide-induced type 2 diabetic rats.

Reproductive dysfunction is one of the diabetes complications. Resveratrol, a polyphenol compound, shows antidiabetic and antioxidant effects. The aim of the present study was to investigate the protective effects of resveratrol on sperm parameters and chromatin quality in experimentally induced type 2 diabetes by streptozotocin and nicotinamide. Forty male adult Wistar rats were grouped into normal control, diabetic control and resveratrol-treated diabetic groups (1, 5 and 10 mg/kg orally treated for 30 days). Type 2 diabetes was induced using a single dose of streptozotocin and nicotinamide by intraperitoneal injection. Then, the different parameters and chromatin condensation of the epididymal extracted spermatozoon were studied using aniline blue (AB), acridine orange (AO) and toluidine blue (TB) staining. The sperm parameters including count, motility and viability had significant reduction in diabetic rats (p < 0.05). Resveratrol increased count, motility and viable spermatozoa relative to the diabetic group (p < 0.05). The mean percentage of AB, AO and TB staining positive spermatozoa was increased in diabetic groups compared to control (p < 0.001) and decreased after treatment with 1 and 5 mg/kg resveratrol (p < 0.001). The results of AO and TB staining showed that resveratrol did not have any beneficial effect on chromatin condensation and denatured DNA at the dose of 10 mg/kg.

Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl4-induced liver fibrosis in rats.

Objectives: In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX).Materials and methods: The six-week old Wistar rats received carbon tetrachloride (CCl4) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured.Results: Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together.Conclusion: The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.

Study of Insulin-Loaded Chitosan Nanoparticle Effects on TGF-ß1 and Fibronectin Expression in Kidney Tissue of Type 1 Diabetic Rats.

In diabetes, the increasing blood glucose levels through oxidative stress, with increase in inflammatory cytokines and growth factors, such as TGF-ß1, can cause long-term complications, including nephropathy. Subcutaneous injection of insulin is a common method used to treat Type 1 diabetes, which can lead to problems such as hypoglycemia and edema. In the present study, we examined the effect of insulin in its two injectable and oral forms on the expression of TGF-ß1 and fibronectin in kidney tissue of STZ diabetic rats. A total of 25 male Wistar rats were randomly divided into 5 groups: C: normal control, D: diabetic control, D+NP, oral insulin-loaded trimethyl chitosan nanoparticles (8 IU/kg), and subcutaneously injected insulin (8 IU/kg). The groups were treated from 8th to 10th weeks. After 10 weeks, FBS was measured. Also, the TGF-ß1 and fibronectin mRNA expression and serum TGF-ß1 protein were examined in the kidney tissue. Structural changes in the kidney tissue were studied using H&E staining. After 10 weeks of diabetes induction, the rats showed significant change in blood glucose, weight, serum TGF-ß1, Fibronectin and TGF-ß1 expression of kidney in diabetic groups (p < 0.05). Oral insulin-loaded trimethyl chitosan nanoparticles treatment, similar to injected insulin, significantly ameliorate blood glucose and rats' weight (p < 0.05). However, the reduction in fibronectin and TGF-ß1 expression and serum TGF-ß1 protein by both treatments was not statistically significant (p > 0.05). These data showed that oral insulin-loaded trimethyl chitosan nanoparticles were better therapeutic intervention than injected insulin for Type 1 diabetes.

Hepatoprotective Effects of Silymarin on Liver Injury via Irisin Upregulation and Oxidative Stress Reduction in Rats with Type 2 Diabetes.

BACKGROUND: Diabetes is one of the most prevalent metabolic diseases. Irisin (FNDC5 protein) is involved in the new strategy of combating type 2 diabetes. In the liver, the antidiabetic mechanism of silymarin at the molecular level is unknown. This study investigated the effects of silymarin on irisin and the related gene expression and oxidative stress status in the liver of type 2 diabetic rats. METHODS: Thirty-six rats were divided into 6 groups (n=6 each) by simple randomization: control, control+silymarin (60 mg/kg daily in normal saline orally for 60 days), control+silymarin (120 mg/kg daily in normal saline orally for 60 days), diabetic, diabetic+silymarin (60 mg/kg daily for 60 days), and diabetic+silymarin (120 mg/kg daily for 60 days). Biochemical parameters were measured by spectrophotometric and immunoassay methods, and quantitative polymerase chain reaction was used to evaluate gene expression. The data were analyzed by one-way ANOVA, followed by the Tukey test, using SPSS software, version 16.0. The results were considered statistically significant at a P value less than 0.05. RESULTS: In the diabetic rats treated with silymarin (60 and 120 mg/kg), by comparison with the diabetic group, body weight (P=0.04 and P=0.02), insulin (P<0.001), expression of PGC-1α (P=0.04 and P=0.02), expression of FNDC5 (P=0.03 and P=0.01), and concentration of irisin in the liver (P=0.02 and P=0.01) and serum (P<0.001) were significantly increased, whereas the levels of glucose (P<0.001), HOMA-IR (P=0.03 and P=0.01), and liver injury markers (P<0.001) were significantly reduced. Oxidative stress status and histopathological changes were improved in the treated groups. CONCLUSION: These results suggest that silymarin because of its ability to upregulate irisin and antioxidant effects can be considered an antidiabetic agent.

MicroRNA: Relevance to stroke diagnosis, prognosis, and therapy.

Stroke is a life-threatening disease that accounts for a considerable burden of mortality in both developing and developed world. Identification of specific biomarkers for stroke and its outcomes can greatly contribute to improved care of patients. MicroRNAs (miRNAs) are known as novel biomarkers that could be used as diagnostic, prognostic, and therapeutic biomarkers. Various studies have shown that miRNAs have key roles in the pathogenesis of stroke, and its complications and outcomes. In addition, there is evidence showing that mesenchaymal stromal cell-derived exosomes containing miRNAs can be used for monitoring and treatment of various diseases such as stroke. Here, we summarized various aspects of miRNA applications in different stages of stroke.

State of the art in microRNA as diagnostic and therapeutic biomarkers in chronic lymphocytic leukemia.

Early diagnostic is one of the most important steps in cancer therapy which helps to design and choose a better therapeutic approach. The finding of biomarkers in various levels including genomics, transcriptomics, and proteomics levels could provide better treatment for various cancers such as chronic lymphocytic leukemia (CLL). The CLL is the one of main lymphoid malignancies which is specified by aggregation of mature B lymphocytes. Among different biomarkers (e.g., CD38, chromosomes abnormalities, ZAP-70, TP53, and microRNA [miRNA]), miRNAs have appeared as new diagnostic and therapeutic biomarkers in patients with the CLL disease. Multiple lines of evidence indicated that deregulation of miRNAs could be associated with pathological events which are present in the CLL. These molecules have an effect on a variety of targets such as Bcl2, c-fos, c-Myc, TP53, TCL1, and STAT3 which play critical roles in the CLL pathogenesis. It has been shown that expression of miRNAs could lead to the activation of B cells and B cell antigen receptor (BCR). Moreover, exosomes containing miRNAs are one of the other molecules which could contribute to BCR stimulation and progression of CLL cells. Hence, miRNAs and exosomes released from CLL cells could be used as potential diagnostic and therapeutic biomarkers for CLL. This critical review focuses on a very important aspect of CLL based on biomarker discovery covers the pros and cons of using miRNAs as important diagnostics and therapeutics biomarkers for this deadly disease.

Salivary and Serum Antioxidant and Oxidative Stress Markers in Dental Caries.

Dental caries is the most common, chronic, noncommunicable, preventable oral disease worldwide. Oxidation may play an important role in dental caries initiation and progression. Antioxidants in body fluids protect cells. The aim of this study was to evaluate salivary and serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in dental caries. A total of 118 healthy caries-free and caries-active male and female students participated. Caries was detected clinically. Unstimulated whole-saliva samples and blood samples were obtained. Sialochemical analysis was carried out by spectrophotometric assay. Data were analyzed with the Student t test using STATA 11. Salivary and serum TAC levels in the case and control groups did not show any significant differences. Mean salivary MDA levels in the case and control groups were 0.71 ± 0.1 and 0.35 ± 0.06 nmol/mL, respectively. The results showed significantly higher levels of salivary and serum MDA in the case group compared to the healthy control group. The oxidative stress marker was significantly higher in the caries group compared to the healthy control group. Antioxidants were not significantly different between the two groups. MDA can be produced by dental caries, resulting in a decrease in antioxidant levels, causing disease progression. Further studies are necessary to determine whether MDA is the cause or effect of the disease.