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International Journal of Molecular... Dec 2023Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was...
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the and genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, = 2.6 × 10; R = -0.21, = 0.015) and cg21886367 (R = -0.45, = 7.3 × 10; R = -0.24, = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated . To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.
Topics: Humans; Triple Negative Breast Neoplasms; Cell Line, Tumor; Epigenomics; Receptors, Leukotriene
PubMed: 38139172
DOI: 10.3390/ijms242417343 -
Journal of Clinical Medicine Dec 2023Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this...
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.
PubMed: 38137814
DOI: 10.3390/jcm12247745 -
Frontiers in Medicine 2023Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of...
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies.
PubMed: 38098840
DOI: 10.3389/fmed.2023.1295777 -
Heliyon Dec 2023This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut...
This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8 g/kg/d), and montelukast sodium treatment (MAS) group (1 mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with but inversely correlated with ; propanoic acid was positively associated with but negatively associated with ; butanoic acid exhibited positive correlations with and , but negative correlations with , , and ; Additionally, TNF-α was inversely linked to , while IL-8 was positively related to and . In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.
PubMed: 38094068
DOI: 10.1016/j.heliyon.2023.e22782 -
Iranian Journal of Allergy, Asthma, and... Oct 2023Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children. This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission. In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge. The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.
Topics: Child; Humans; Anti-Asthmatic Agents; Iran; Asthma; Acetates; Quinolines; Double-Blind Method
PubMed: 38085143
DOI: 10.18502/ijaai.v22i5.13990 -
BMC Pulmonary Medicine Dec 2023This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in... (Meta-Analysis)
Meta-Analysis
An efficacy and safety evaluation of montelukast + fluticasone propionate vs. fluticasone propionate in the treatment of cough variant asthma in children: a meta-analysis.
PURPOSE
This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.
METHODS
Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I statistics, followed by sensitivity analysis and publication bias evaluation.
RESULTS
Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group.
CONCLUSION
Mon + Flu is effective and safe for the treatment of CVA in children.
Topics: Child; Humans; Acetates; Anti-Asthmatic Agents; Asthma; Cough; Cyclopropanes; Fluticasone; Quinolines
PubMed: 38053076
DOI: 10.1186/s12890-023-02721-z -
Heliyon Nov 2023Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses...
Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.
PubMed: 38034763
DOI: 10.1016/j.heliyon.2023.e21842 -
Health Science Reports Nov 2023To reduce death rates for critical patients hospitalized in intensive care units (ICUs), coronavirus (COVID-19) lacks proven and efficient treatment methods. This...
BACKGROUND AND AIMS
To reduce death rates for critical patients hospitalized in intensive care units (ICUs), coronavirus (COVID-19) lacks proven and efficient treatment methods. This cross-sectional study aims to evaluate how physicians treat severe and suspected COVID-19 patients in the ICU department in the absence of an established approach, as well as assess the rational use of the medication in the ICU department.
METHODS
Between June 16, 2021, and December 10, 2022, a total of 428 prescriptions were randomly gathered, including both suspected (yellow zone) and confirmed (red zone) COVID-19 patients. For data management, Microsoft Excel 2021 was utilized, while STATA 17 provided statistical analysis. To find associations between patients' admission status and demographic details, exploratory and bivariate analyses were conducted.
RESULTS
Of the 428 patients admitted to the ICU, 228 (53.27%) were in the yellow zone and 200 (46.73%) were in the verified COVID-19 red zone. The majority of patients were male (54.44%), and the age range from 41 to 60 was the most common (41.82%). No significant deviation was detected to the yellow and red groups' prescription patterns. A total of 4001 medicines (mean 9.35/patient) were prescribed. Antiulcerants, antibiotics, respiratory, analgesics, anticoagulants, vitamins and minerals, steroids, cardiovascular, antidiabetic drugs, antivirals, antihistamines, muscle relaxants, and antifungal treatments were widely prescribed drugs. Enoxaparin (67.06%) appeared as the most prescribed medicine, followed by montelukast (60.51%), paracetamol (58.41%), and dexamethasone (51.64%).
CONCLUSION
The prescription patterns for the yellow and red groups were comparable and mostly included symptomatic treatment. Respiratory drugs constituted the most frequent therapeutic class. Polypharmacy should be taken under considerations. In ICU settings, the outcomes emphasize the need of correct diagnosis, cautious antibiotic usage, suitable therapy, and attentive monitoring.
PubMed: 38028685
DOI: 10.1002/hsr2.1711 -
Frontiers in Pharmacology 2023Adenoidal hypertrophy (AH) is one of the most common causes of upper airway obstruction in children. Drug and surgical treatment are the typical treatment of AH. The...
Adenoidal hypertrophy (AH) is one of the most common causes of upper airway obstruction in children. Drug and surgical treatment are the typical treatment of AH. The study on the inflammatory mechanism of AH in children provides a new idea for preoperative intervention and non-surgical treatment with anti-inflammatory drugs such as montelukast sodium (a cysteine leukotriene receptor antagonist). The aim of this study is to evaluate the effect of montelukast sodium on adenoidal lymphoid tissue pathology in children with AH under light microscope. To study whether there is any change in pathology of the adenoidal lymphoid tissue under the light microscope compared with the control group in children with moderate to severe simple AH treated with montelukast sodium for 1 month before operation. Twenty patients (8 males, 12 females, 3-8 years old) with moderate to severe AH who were prepared for surgical treatment were selected. All the patients were examined by Nasopharyngeal CT and hemocyte analysis before operation. 20 subjects were randomly divided into two groups: One group was given montelukast chewable tablets 5 mg/d, qn, for 4 weeks; The control group was given placebo 5 mg/d, qn, for 4 weeks. After 4 weeks, the adenoids were removed and examined histopathology. Compared with the control group, the number of lymphocytes in the blood cell analysis of the study group was significantly reduced, with a statistically significant difference ( < 0.05). And the number of germinal centers in adenoid tissue of the study group was relatively reduced, no small cyst was found in the epithelium, and the degree of inflammatory cell infiltration was reduced, with a statistically significant difference ( < 0.05). Montelukast can reduce the number of reactive cells, the number of lymphocytes in blood cells and blood vessels in adenoid lymphoid tissue, which can provide a new idea for preoperative intervention and non-surgical treatment of adenoid hypertrophy in children. However, this is only a pilot study and a longer treatment period is needed to assess the long-term effects of montelukast sodium on adenoid lymphoid tissue. : www.Chictr.org.cn, identifier ChiCTR2300075040.
PubMed: 38026964
DOI: 10.3389/fphar.2023.1285647 -
Qatar Medical Journal 2023Obstructive sleep apnea (OSA) affects 1% to 5% of all children, with the most significant prevalence between ages 2 and 8. Correlations between OSA and Adenoid...
BACKGROUND
Obstructive sleep apnea (OSA) affects 1% to 5% of all children, with the most significant prevalence between ages 2 and 8. Correlations between OSA and Adenoid hypertrophy (AH) have been well-demonstrated in children. If untreated, OSA can cause growth impairment, neuro-cognitive and behavioral problems, and cardiovascular complications. Allergy was reported to be a vital risk factor for AH, among other inflammatory processes mentioned.
OBJECTIVES
To demonstrate that the combination of nasal steroids and ani leukotriene reduces the number of adenectomies in children with OSA and adenoid hypertrophy in Saudi children.To demonstrate the positive Correlation between allergic sensitization and OSA caused by adenoid hypertrophy Methods: This retrospective study included 60 children with moderate/severe OSA attending a Pediatric Allergy Clinic in Saudi Arabia diagnosed using Sleep-Related Breathing Disorder Scale (pediatrics-related items). We had children with adenoid hypertrophy confirmed by soft neck tissue x-ray or both; children who suffer from obesity were excluded. Sensitization was defined as positive specific IgE and/or skin prick for food and/or inhaled allergens; allergic comorbidities were enumerated.
RESULTS
Combination of nasal steroid and anti-leukotriene reduces adenectomy by 58.3 % in children with OSA caused by AH. 71.7% of Them were sensitized to inhaled food or both allergens.
CONCLUSION
Anti-inflammatory treatment with a combination of nasal steroids and anti-leukotriene remarkably reduces the adenectomy rate in children with OSA caused by AH. Our findings suggest that allergic sensitization, regardless of the allergen, increases children's susceptibility to AH through the inflammatory process. This may be why nasonex and montelukast are effective treatments for OSA in children with AH.
PubMed: 38025327
DOI: 10.5339/qmj.2023.sqac.31