Long noncoding RNA MALAT1 is dynamically regulated in leader cells during collective cancer invasion.

Cancer cells collectively invade using a leader-follower organization, but the regulation of leader cells during this dynamic process is poorly understood. Using a dual double-stranded locked nucleic acid (LNA) nanobiosensor that tracks long noncoding RNA (lncRNA) dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that the lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is dynamically regulated in the invading fronts of cancer cells and patient-derived spheroids. MALAT1 transcripts exhibit distinct abundance, diffusivity, and distribution between leader and follower cells. MALAT1 expression increases when a cancer cell becomes a leader and decreases when the collective migration process stops. Transient knockdown of MALAT1 prevents the formation of leader cells and abolishes the invasion of cancer cells. Taken together, our single-cell analysis suggests that MALAT1 is dynamically regulated in leader cells during collective cancer invasion.

Altered expression of serum lncRNA CASC2 and miRNA-21-5p in COVID-19 patients.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has a high incidence of spread. On January 30, 2020, the World Health Organization proclaimed a public health emergency of worldwide concern. More than 6.9 million deaths and more than 768 million confirmed cases had been reported worldwide as of June 18, 2023. This study included 51 patients and 50 age- and sex-matched healthy subjects. The present study aimed to identify the expression levels of lncRNA CASC2 and miRNA-21-5p (also known as miRNA-21) in COVID-19 patients and their relation to the clinicopathological characteristics of the disease. The expression levels of noncoding RNAs were measured by RT-PCR technique. Results detected that CASC2 was significantly downregulated while miRNA-21-5p was significantly upregulated in COVID-19 patients compared to healthy subjects. A significant negative correlation was found between CASC2 and miRNA-21-5p. ROC curve analysis used to distinguish COVID-19 patients from controls. MiRNA-21-p serum expression level had a significant positive association with temperature and PO2 (p = 0.04 for each). These findings indicate that CASC2 and miRNA-21-p might be used as potential diagnostic and therapeutic biomarkers in COVID-19.

Efficacy and Safety of 577-nm Yellow Laser in the Treatment of Pigmented Epidermal Lesions.

OBJECTIVES: Freckles and lentigines are common pigmented problems which not only cause substantial cosmetic morbidity but also create psychosocial concern. The available modalities for the treatment of pigmented lesions are often unsatisfactory for patients, require a long treatment period, and often cause skin irritation. With the advent of lasers, safe and effective treatment options for epidermal pigmentation have become more varied for different Fitzpatrick skin types. We aimed to evaluate the efficacy and safety of 577-nm yellow laser in the treatment of pigmented epidermal lesions. METHODS: This study was carried out on 50 patients presented with pigmented epidermal lesions (25 presented with freckles and 25 presented with lentigines). Each patient received four treatment sessions with a 577-nm diode laser at 2-week intervals. RESULTS: There was significant improvement in freckles and lentigines, as 23 out of 50 patients showed marked improvement, 11 patients showed moderate improvement, 10 patients showed mild improvement, and only six patients had no changes. Moreover, 23 patients were very satisfied, 18 patients were satisfied, and nine patients were not satisfied. As regards the safety of the 577-nm yellow laser, there was no significant adverse effect among patients except pain, erythema, and hyperpigmentation, which resolved within one month after treatment. CONCLUSIONS: This study showed that the 577-nm yellow laser is an effective, safe, and well-tolerated device in the treatment of freckles and lentigines.

Expression of miR-34a, RASSF1A and E-cadherin in relation to PRB in endometrioid carcinoma and its precursor.

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC.

The effect of two different contemporary chelating agents on vital pulp therapy in mature permanent teeth with irreversible pulpitis using bioceramic material: randomized clinical trial.

BACKGROUND: Vital pulp therapy maintained functionality, vitality, and asymptomatic teeth. Compared to normal root canal treatment, pulpotomy was more helpful for irreversible pulpitis in adult permanent teeth. The research was aimed to assess effectiveness of vital pulp therapy using mineral trioxide aggregate with Apple Vinegar and Ethylene diamine tetra acetic acid (17%) for five minutes in adult carious exposed pulp of permanent teeth. METHODS: Forty patients between 18 and 50 years old with a clinical diagnosis of symptomatic irreversible pulpitis but no periapical radiolucency were then divided randomly into two groups based on the irrigation method; ethylene diamine tetraacetic acid or apple vinegar. If pulpal bleeding could not be managed in less than six minutes, the assigned procedure was abandoned. After mineral trioxide aggregate application as a pulpotomy agent, glass ionomer and composite restoration were placed. Using a visual analogue scale, the pre and post-operative pain were recorded after 2,6,24,48, and 72 h. Success was assessed using radiographic and clinical examination data at three, six, and twelve months. RESULTS: The success rate was discovered to be non-statistically significant in both groups after a year follow-up. Apple vinegar had a lower mean value than ethylene diamine tetra acetic acid at the preoperative baseline pain level, which was significant.Postoperatively, the ethylene diamine tetraacetic acid group reported the greatest mean value after two hours while Apple vinegar group reported the lowest mean values after 48 h (P < 0.05). After 72 h, pain level recorded insignificant difference. CONCLUSION: Apple vinegar yielded a marginally successful outcome but substantially improved pain alleviation. TRIAL REGISTRATION: The trial was registered in Clinical trials.gov with this identifier NCT05970536 on 23/7/2023.

The plaque hypothesis: understanding mechanisms of plaque progression and destabilization, and implications for clinical management.

PURPOSE OF REVIEW: Major adverse cardiac events (MACE) typically arise from nonflow-limiting coronary artery disease and not from flow-limiting obstructions that cause ischemia. This review elaborates the current understanding of the mechanism(s) for plaque development, progression, and destabilization and how identification of these high-risk features can optimally inform clinical management. RECENT FINDINGS: Advanced invasive and noninvasive coronary imaging and computational postprocessing enhance an understanding of pathobiologic/pathophysiologic features of coronary artery plaques prone to destabilization and MACE. Early investigations of high-risk plaques focused on anatomic and biochemical characteristics (large plaque burden, severe luminal obstruction, thin cap fibroatheroma morphology, and large lipid pool), but more recent studies underscore that additional factors, particularly biomechanical factors [low endothelial shear stress (ESS), high ESS gradient, plaque structural stress, and axial plaque stress], provide the critical incremental stimulus acting on the anatomic substrate to provoke plaque destabilization. These destabilizing features are often located in areas distant from the flow-limiting obstruction or may exist in plaques without any flow limitation. Identification of these high-risk, synergistic plaque features enable identification of plaques prone to destabilize regardless of the presence or absence of a severe obstruction (Plaque Hypothesis). SUMMARY: Local plaque topography, hemodynamic patterns, and internal plaque constituents constitute high-risk features that may be located along the entire course of the coronary plaque, including both flow-limiting and nonflow-limiting regions. For coronary interventions to have optimal clinical impact, it will be critical to direct their application to the plaque area(s) at highest risk.

Bronchodilator reversibility testing in morbidly obese non-smokers: fluticasone/salmeterol efficacy versus salbutamol bronchodilator.

A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn't accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects.The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal (< 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI ≥ 30). Spirometry measurements were performed before and after salbutamol or fluticasone/salmeterol administration.The study included 415 (49.9% male) patients with a mean age of 40.92 ± 10.86 years. Obese subjects showed a high prevalence of restrictive patterns (23.4%), with non-significantly lower spirometric values compared to normal and overweight subjects (p > 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively.Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population.

Effect of Liraglutide on Osteoporosis in a Rat Model of Type 2 Diabetes Mellitus: A Histological, Immunohistochemical, and Biochemical Study.

Diabetic osteoporosis (DOP) is a diabetic complication associated with a significant disability rate. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug for type 2 diabetes mellitus (T2DM), with potential therapeutic implications for bone disorders. This investigation examined the impact of liraglutide on osteoporosis in rats with T2DM and studied the influence of vitamin D receptor Bsm1 polymorphism on liraglutide-induced outcomes. Thirty rats were divided into control, T2DM induced by a combination of a high-fat diet and 25 mg/kg streptozotocin, and T2DM-liraglutide (T2DM treated with 0.4 mg/kg/day liraglutide) groups. After 8 weeks of liraglutide treatment, femurs and blood samples were obtained from all rats for subsequent investigations. Diabetes induced a remarkable rise in the serum levels of receptor activator of nuclear factor kappa B ligand (RANKL) and C-telopeptide of type I collagen (CTX-1) associated with a remarkable decline in osteocalcin and osteoprotegerin (OPG). Impaired bone architecture was also demonstrated by light and scanning electron microscopic study. The immune expression of OPG was down-regulated, while RANKL was up-regulated. Interestingly, the administration of liraglutide ameliorated the previous changes induced by diabetes mellitus. In conclusion, liraglutide can prevent DOP, mostly due to liraglutide's ability to increase bone growth, while inhibiting bone resorption.

Application Of Health Belief Model About Cervical Cancer Screening Among Female Officer Employees In Kafr-El Sheikh University, Egypt.

Objectives: To assessthe impact of a health educational programme on knowledge and health beliefs of female office workers regarding cervical cancer screening. Method: The quasi-experimental study was conducted at Kafrelsheikh University, Egypt, from March to September 2021, and comprised all female employees at the university regardless of department or professional status. After baseline assessment using a self-designed questionnaire, an educational session was conducted through small focussed groups having 1-5 participants in their own office environments. Post-intervention change in knowledge and beliefs was assessed using the same questionnaire 1 month after the intervention. Data was analysed using SPSS 22. RESULTS: Of the total 492 female employees, 360(73.2%) completed the study. Of them, 256(71.1%) were aged 30-40 years, 283(78.6%) were ever-married, 206(57.2%) were from urban communities, 322(89.4%) had university educational, 280(77.8%) had sufficient income, and 214(59.4%) had high socioeconomic status. The mean totalscores for knowledge and health beliefs increased significantly post-intervention (p<0.0001). CONCLUSIONS: The use of health belief model to change knowledge of and perceptions towards cervical cancer and its screening was found to be effective.

Optimizing locked nucleic acid modification in double-stranded biosensors for live single cell analysis.

Double-stranded (ds) biosensors are homogeneous oligonucleotide probes for detection of nucleic acid sequences in biochemical assays and live cell imaging. Locked nucleic acid (LNA) modification can be incorporated in the biosensors to enhance the binding affinity, specificity, and resistance to nuclease degradation. However, LNA monomers in the quencher sequence can also prevent the target-fluorophore probe binding, which reduces the signal of the dsLNA biosensor. This study investigates the influence of LNA modification on dsLNA biosensors by altering the position and amount of LNA monomers present in the quencher sequence. We characterize the fluorophore-quencher interaction, target detection, and specificity of the biosensor in free solution and evaluate the performance of the dsLNA biosensor in 2D monolayers and 3D spheroids. The data indicate that a large amount of LNA monomers in the quencher sequence can enhance the specificity of the biosensor, but prevents effective target binding. Together, our results provide guidelines for improving the performance of dsLNA biosensors in nucleic acid detection and gene expression analysis in live cells.