Expression analysis of circulating miR-22, miR-122, miR-217 and miR-367 as promising biomarkers of acute lymphoblastic leukemia.

BACKGROUND: The role of serum-based biomarkers such as microRNAs in cancer diagnosis has been extensively established. This study aimed to determine the expression levels of bioinformatically selected miRNAs and whether they can be used as biomarkers or a new therapeutic target in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The expression levels of serum miR-22, miR-122, miR-217, and miR-367 in 21 ALL patients and 21 healthy controls were measured using quantitative real-time PCR. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) was used to assess candidate miRNAs' diagnostic value as a biomarker. RESULTS: The results showed that miR-217 was markedly decreased in patients with ALL compared to controls. Moreover, miR-22, miR-122, and miR-367 were found to be upregulated. Furthermore, ROC analysis showed that serum miR-217 and miR-367 could differentiate ALL patients from healthy individuals, while miR-22 has approximate discriminatory power that requires further investigation. CONCLUSION: These results provide promising preliminary evidence that circulating miR-217 and miR-367 could be considered potent diagnostic biomarkers and therapeutic goals in this disease.

MicroRNAs and proteolytic cleavage of receptors in cancers: A comprehensive review of regulatory interactions and therapeutic implications.

Cancer remains a challenging disease worldwide, necessitating innovative approaches to better comprehend its underlying molecular mechanisms and devise effective therapeutic strategies. Over the past decade, microRNAs (miRNAs) have emerged as crucial players in cancer progression due to their regulatory roles in various cellular processes. Moreover, the involvement of unwanted soluble receptors has gained increasing attention because they contribute to tumorigenesis or drug resistance by disrupting normal signaling pathways and neutralizing ligands. This comprehensive review explores the intricate interplay between miRNAs and unwanted-soluble receptors in the context of cancer biology. This study provides an analysis of the regulatory interactions between miRNAs and these receptors, elucidating how miRNAs can either suppress or enhance their expression. MiRNAs can directly target receptor transcripts, thereby regulating soluble receptor levels. They also modulate the proteolytic cleavage of membrane-bound receptors into soluble forms by targeting sheddases, such as ADAMs and MMPs. Furthermore, the review delves into the therapeutic potential of manipulating miRNAs to modulate unwanted soluble receptors. Various strategies, including synthetic miRNA mimics or anti-miRNAs, hold promise for restoring or inhibiting miRNA function to counteract aberrant receptor activity. Moreover, exploring miRNA-based delivery systems may provide targeted and precise therapies that minimizing off-target effects. In conclusion, this review sheds light on the intricate regulatory networks involving miRNAs and unwanted soluble receptors in cancer biology thereby uncovering novel therapeutic targets, and paving the way for developing innovative anti-cancer therapies.

Associations of perceived and common dyadic coping with self-care in older couples with cardiovascular disease: A dyadic analysis.

BACKGROUND: Dyadic engagement of patients and caregivers in self-care is essential for management of heart disease. However, little is known how dyadic coping at individual and partner levels is associated with self-care in couples living with cardiovascular disease. OBJECTIVE: This study examined whether dyadic coping at self, partner, and common levels was associated with patients' engagement in self-care and spouses' contribution to self-care in older couples living with cardiovascular disease. METHODS: In this cross-sectional study, 288 older patients and spouses were recruited from outpatient heart clinics in Qazvin, north of Iran. Data were collected using the Dyadic Coping Inventory, the Self-care of Coronary Heart Disease Inventory, and the Caregiver's Contribution to Self-care of Coronary Heart Disease. Dyadic data were analyzed using the actor-partner interdependence model. RESULTS: The results showed that patients' engagement in self-care maintenance was associated with partner dyadic coping in patients, self and common dyadic coping in spouses. Patients' engagement in self-care monitoring was only associated with self dyadic coping in spouses. Dyadic analysis also showed that self-care confidence in patients was only associated with by partner dyadic coping in spouses. CONCLUSIONS: This study revealed that self-care was associated with dyadic coping employed by each member of the dyad at self, partner and common levels. Findings of this study suggest that perceived and provided levels of dyadic coping can be employed for maintaining or restoring self-management in older couples living with cardiovascular disease.

The Effect of the Persian Gulf Jellyfish (Cassiopea andromeda) Venom on the Expression of P15, P21, P53, DNMT1, and Bcl-2 in Acute Lymphoblastic Leukemia Jurkat Cells.

Background: One of the acute hematologic malignancies is acute lymphoblastic leukemia (ALL), which is formed in B or T lymphocyte stem cells. Regarding the increasing tendency to herbal and marine studies and unclear characteristics of Cassiopea andromeda Venom, this study was performed to determine its effects on Jurkat cells as a model for T-ALL. Materials and Methods: In this experimental study, the cells were treated with a variety of concentrations of Cassiopea andromeda venom at different periods and times. Growth inhibition and toxic effects of Cassiopea andromeda Venom were evaluated by methyl thiazole tetrazolium salt reduction (MTT test). The flow cytometry analysis was carried out using 7-aminoactinomycin D (7AAD) and Annexin V stains to evaluate the venom's effect on apoptotic pathways. Besides, Real-Time PCR was performed to evaluate the relative gene expression. Results: Cassiopea andromeda venom inhibited the growth of Jurkat cells in a concentration and time manner. Jurkat cell growth was inhibited by 48.9% after 72 hours of treatment with 250µg/mL Cassiopea andromeda venom. The venom increased the apoptotic process through the upregulation of p15INK4b and P53 proteins and downregulation of Bcl-2, p21 WAF1/CIP1, and DNMT1 in the Jurkat cell line. Conclusion: Considering the growth inhibitory property of Cassiopea andromeda Venom, we recommend it as a part of combinational medication for treating ALL in animal trials and for other leukemias in vitro studies.

Efficacy of 15% azelaic acid in psoriasis vulgaris: a randomized, controlled clinical trial.

BACKGROUND: Psoriasis is a common disorder affecting 1-3 percent of the general global population. Many therapeutic modalities have been suggested for treatment of this condition, but still there is no definite treatment for this disease. The objective in this study was to evaluate the efficacy of topical azelaic acid gel versus placebo in the treatment of psoriasis vulgaris. PATIENTS, MATERIALS AND METHODS: This study was a single-blinded randomized clinical trial. Overall, 31 patients were selected and the left or right sided lesions of the patients were randomized to receive either 15% azelaic acid or gel twice daily for a one-month period. Two symmetrical lesions with almost similar severity in every patient were selected and considered as index lesions to evaluate lesion response to treatment. The severity of erythema, scaling, hyperkeratosis and pruritus of the index lesions were scored in range of 0-3 for each lesion by the investigator at the baseline and follow up visits. The percent of involvement of each side of body was also measured using rule of nines. The collected data were analyzed using statistical tests including Mann-Whitney and ANOVA tests. RESULTS: There was no significant difference between the two groups before treatment (P > 0.05). After treatment, however, except pruritus, there was significant difference between the two groups (P < 0.05). There was no significant difference regarding total psoriasis score between the two groups before treatment (P > 0.05). After treatment, however, there was significant difference between the two groups (P < 0.05) in favor of more efficacy for azelaic acid. There was no significant difference regarding percent of body involvement between the two groups before treatment (P > 0.05). After treatment, however, there was a significant difference between the two groups (P < 0.05) in favor of more efficacy on the part of azelaic acid gel. DISCUSSION: The results of our study showed that 15% azelaic acid gel was effective in reduction of purities, scaling and hyperkeratosis of psoriasis plaques. This treatment was also effective in reduction of skin involvement with psoriasis. It is recommended that a longer study be performed that can better evaluate the efficacy of this treatment against plaque-type psoriasis.

Retention and Clinical Performance of Zirconia Crowns: A Comprehensive Review.

Zirconia has been used for rehabilitation of edentulous spaces approximately for a decade, and there have been several reports regarding the clinical performance and retention of zirconia crowns. Outstanding mechanical properties, biocompatibility, and excellent aesthetics make zirconia-based crowns as a popular crown among the current all-ceramic crowns in restorative dentistry. However, restoration with a zirconia crown is a challenging treatment. The goal of this study was to assess the current literature to summarize the studies reporting the effective risk factors on retention of zirconia crowns to provide clinicians with a useful point of view in the decision-making process for use of these restorations. Literature based-search was performed to find related articles until August 2020 using EMBASE, Google Scholar, and MEDLINE. Search terms used were "zirconia restorations properties," "zirconia crowns clinical performance," "zirconia crown survival," "biological complications," and "zirconia crown retention." Results were limited to papers available in English. The references of all related literature were also searched for further citations. Overall, although clinical long-term and follow-up studies are a vital requirement to conclude that zirconia has great reliability, it seems that zirconia crown restorations are both well tolerated and sufficiently resistant.

Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate.

PURPOSE: This study is designed to evaluate and compare follicular phase parameters during ovarian stimulation with the clomiphene citrate (CC) and letrozole (LET) in unexplained infertile patients who failed to get pregnant following frequent CC-treated cycles. METHODS: A total of 64 unexplained infertile women who failed to get pregnant following frequent CC-treated cycles were studied for one CC-treated cycle (100 mg/day), 2 washout cycles, and then 1 LET-treated cycle (5 mg/day). Number of follicles over 14 mm in diameter, diameter of the largest follicles, endometrial thickness, serum estradiol (E2) and LH levels were measured when one mature follicle over 18 mm in diameter detected during transvaginal ultrasonography. RESULTS: The mean value of the largest follicle diameter, number of developed follicles >14 mm, endometrial thickness and LH in LET-treated cycle was significantly higher than CC-treated cycle (P values were 0.007, <0.001, <0.001, and 0.004, respectively), whereas mean level of E2 showed a significantly lower level during LET-treated cycle (P < 0.001). CONCLUSIONS: About 5 mg/day of LET is associated with better follicular phase parameters, endometrial development, serum E2 and LH levels in women with unexplained infertility who failed to get pregnant following frequent CC-treated cycles.

Antimicrobial and physical properties of alginate impression material incorporated with silver nanoparticles.

BACKGROUND: Self-disinfecting impression materials would reduce time and energy needed for impression disinfecting process in clinic. The aim of this study was to evaluate the antimicrobial effect of alginate mixed with nanosilver solution at a concentration of 500 ppm and 1000 ppm on common oral microorganisms and assess changes in working time, setting time, and surface detail reproduction. MATERIALS AND METHODS: In this in vitro study, three groups were assigned. The first group was alginate, the second group was alginate mixed with 500 ppm nanosilver, and the third group was alginate mixed with 1000 ppm nanosilver. Antimicrobial effect on Escherichia coli, Staphylococcus aureus, and Candida albicans was studied using direct contact test in each group (n = 10). Working time (n = 10), setting time (n = 10), and surface detail reproduction (n = 10) were evaluated separately using the ISO 21563 protocol. Descriptive tables were used to describe the data. Kruskal-Wallis test used to determine significant differences in the number of colonies was counted in antimicrobial test (α = 0.05). RESULTS: No adverse effects observed in working time, setting time, and surface detail reproduction of alginate impressions. Alginate mixed with silver nanoparticles showed no inhibitory effect on S. aureus and C. albicans, but the number of E. coli colonies were counted in the group 1000 ppm was significantly lower than 500 ppm (P = 0.001). CONCLUSION: Antimicrobial effect of alginate mixed with silver nanoparticles is not clinically indicated. Nevertheless, its physical features did not change significantly.

A pilot study of polymorphism of adrenergic Beta-2 receptor and mild asthma: a clinical and pharmacogenetic study.

Glycine allele at codon 16 has previously been associated with the increase in asthma severity, bronchial hyperresponsiveness and also the increase in inhaled corticosteroid dependence. This study was designed to evaluate the genetic alleles in mild asthma. Thirty-four patients with diagnosis of mild asthma (FEV1 ≥ 80%, positive methacholine test) and body mass index (BMI ≤ 30 Kg/m(2)) were included in the study. They could only use short acting beta-2 agonists for asthma control. Smoking, infection, occupational sensitizers' exposure, gastroesophageal reflux, diabetes mellitus and heart failure were also considered as exclusion criteria. All patients were genotyped at 16(th) and 27(th) codons. Among all, 20 (58.8%) Arg/Gly, 14 (41.2%) Arg/Arg and no Gly/Gly genotype were detected at codon 16. Genotyping at codon 27 revealed 2 (5.9%) Glu/Glu, 13 (38.2%) Glu/Gln and 18 Gln/Gln (52.9%). Based on the obtained results, Arg/Gly mutation had a higher rate among the studied subjects compared to Arg/Arg polymorphism. This is a pilot study which shows a probable usefulness of genotyping for predicting of asthma severity.

The effect of polymorphisms of beta2 adrenoceptors on response to long-acting beta2 agonists in Iranian asthmatic patients.

The results of many studies suggested possible relationship between polymorphism at codons 16 and 27 and development of tolerance to beta-2 adrenoceptor agonist responses as well as disease severity in asthmatic patients. This study was designed to evaluate the effect of polymorphism of beta2 adrenoceptors on response to salmeterol and fluticasone (as inhaled Seretide).Sixty-four patients with either mild or moderate-severe asthma were evaluated in this study. A four-week therapy with Seretide was conducted in moderate-severe asthmatics. The respiratory parameters and asthma score (based on GINA guidelines) were measured before and after run in period. Blood samples were genotyped at codons 16 and 27.No significant difference was observed in genotypes neither at codon 16 nor at codon 27 between mild and moderate-severe asthma groups. However, Patients in Arg/Arg (n = 8) category showed significant improvement in asthma control parameters and lung function compared with Arg/Gly genotype (n =20).These results suggest that genotyping may be useful in some asthmatic patients in order to better tailor asthma treatment plan.

Evaluation of mutagenicity of mebudipine, a new calcium channel blocker.

Mebudipine is a new dihydropyridine calcium channel blocker, synthesized in our laboratory, for treatment of hypertension. It has shown a better efficacy than other drugs in this group. For assessing the risks of this drug, certain safety tests in the preclinical stage have been performed. In this study mutagenic effect of mebudipine was evaluated using Ames assay that could assess the mutagenicity of drugs and their metabolites using liver enzymes (S-9 mix). This procedure is approved as a predictive test, with a high predictive value. Salmonella TA102 (Ames assay) was used with and without S-9 in this study. For preparing S-9 mix, rat liver enzymes induced by phenobarbital were separated in KCl 0.154 M (0.154 M), as the solvent. Mebudipine was dissolved in polyethylenglycol 400. Mutagenicity test was performed in 6 doses from 39 µg to 1250 µg per every plate, in the presence and absence of the S-9 mix. The positive control sodium azide was dissolved in a dose of 5 µg/plate dissolved in polyethylenglycol 400 and negative control was polyethylenglycol 400 with no added agent. The colony counts of all doses in plates with S-9 were between 200-400 and in plates without S9 was between100-300. The colony counts in both states (with and without S-9) of all doses were in the range suggested by Ames assay for the safe drugs and were different from the positive control groups and equal to the negative controls. Mebudipine and its metabolites were not found to be mutagen on Salmonella TA102, based on Ames assay.