Circulating miR-221/222 expression as microRNA biomarker predicting tamoxifen treatment outcome: a case-control study.

The high mortality rate in breast cancer (BC) patients is generally due to metastases resistant to systemic therapy. Two causes of systemic therapy resistance in BC patients are circulating miRNAs-221 and miR-222, leading to improved BC cell proliferation, survival, and reduced cell apoptosis. This study investigated the miRNA expression changes associated with cancer cell resistance to tamoxifen therapy and is expected to be clinically meaningful before providing endocrine therapy to luminal-type BC patients who express them. Methods: This case-control research included individuals with the luminal subtype of BC who had received tamoxifen medication for around one year. Furthermore, the case group contained 15 individuals with local recurrence or metastases, while the control group comprised 19 patients without local recurrence or metastases. Plasma miR-221/222 quantification was performed with real-time PCR using transcript-specific primers. Results: A significant difference was found in circulating miR-221 expression between cases and controls (P=0.005) but not in miR-222 expression (P=0.070). There were no significant differences between miR-221/222 expression, progesterone receptor, Ki67 protein levels, lymphovascular invasion, and stage. However, receiver operator characteristic curve analyses showed miR-221/222 expressions predictive of tamoxifen resistance (P=0.030) with a sensitivity of 60.00 and a specificity of 83.33%. Conclusion: The use of circulating miR-221/222 expression can predict relapse as well as resistance to tamoxifen treatment in BC patients, and their testing is recommended for luminal subtype BC patients who will undergo tamoxifen therapy to determine their risk of tamoxifen resistance early, increasing treatment effectiveness.

Effect of folinic acid on serum homocysteine, TNFα, IL-10, and HMGB1 gene expression in head injury model.

BACKGROUND: Head injury or traumatic brain injury is the leading cause of mortality and morbidity. Many modalities of neuroprotection had been developed in brain injury but there was no much information regarding folinic acid's effect on neuroinflammation associated with homocysteine, TNFα, IL-10, and HMGB1. OBJECTIVE: This study aimed to investigate whether folinic acid has improving effect on head injury model. METHOD: This study was done in the rat's head injury model using modified Marmarou weight drop model. Fifteen rats were randomized and grouped into 3 groups: Group A: Folinic acid (+), head injury (-); Group B: Folinic acid (-), head injury (+); Group C: Folinic acid (+), head injury (+). Folinic acid was administered intraperitoneally with a dose of 60 mg/m2. Blood samples were taken immediately after head injury (H0), 12 h (H12), and 24 h (H24) after head injury from the lateral vein of tail. Serum level of homocysteine, TNFα, and IL-10 were measured using ELISA, and HMGB1 gene expression was measured with Real-Time RT-PCR. RESULTS: This study found serum level of homocysteine, TNFα, IL-10 and HMGB1 gene expression were markedly increased at all time points after head injury. Significantly lower level of serum homocysteine, TNFα, IL-10 and HMGB1 gene expression were found after 24 h treatment with folinic acid in group C compared to those in group B. CONCLUSION: Folinic acid may have anti-inflammatory properties in traumatic brain injury by inhibition of serum level of homocysteine, TNFα, IL-10 and HMGB1 gene expression.

Immunomodulatory properties of high mobility group box 1 and its potential role in brain injury: Review article.

BACKGROUND: Human mobility group box 1 (HMGB1) is a novel biomolecular agent which has a major part in inflammation process. HMGB1 has been known to be a strong pro-inflammatory factor as damage associated molecular pattern (DAMP) which its interaction with its receptor, the receptor of advanced glycation end products (RAGE), will cause positive amplification of inflammation signalling pathway.Brain injury is one of the major contributors for disability and death which neuroinflammation has a major role in its pathogenesis and influencing its outcome. In neuroinflammation, it has been described that HMGB1 may have a pivotal role in the process. OBJECTIVE: The objective of this article is to review the role HMGB1 in brain injury and its immunomodulatory properties. METHODS: A comprehensive search of literature was conducted in PubMed (NIH), Scopus, EMBASE, and Google Scholar database using keyword combinations of the medical subject headings (MeSH) of "HMGB1" and "Brain Injury" and relevant reference lists were also manually searched. All relevant articles of any study design published from year 1990 till June 2020, were included and narratively discussed in this review. RESULTS: Twenty-four articles were shortlisted and reviewed in this article. Through these articles, we synthesis information on the function and metabolism of HMGB1, immunomodulatory effect of HMGB1, clinical findings and other potential treatment involving HMGB1, and role of HMGB1 protein in brain injury. CONCLUSION: HMGB1 has a strong pro-inflammation property which predominantly acts through RAGE pathways.Review registration number reviewregistry966 in www.researchregistry.com.

Hyperbaric Oxygen Therapy for Second-Degree Burn Healing: An Experimental Study in Rabbits.

BACKGROUND: The wound healing process includes inflammation, proliferation, and remodelling phases, the main features of which are inflammation, neoangiogenesis, and epithelialization. Hyperbaric oxygen therapy (HBOT) is one modality postulated to improve wound healing. The objective of this study was to determine whether HBOT could improve selected features of burn wound healing in an experimental rabbit model. METHODS: Researchers conducted an experimental study with 36 rabbits given second-degree burns. Subjects were separated into two groups: a control group (n = 18) and an intervention group that was given HBOT at 2.4 atmospheres absolute for 6 days (n = 18). The main outcome measure was wound healing. RESULTS: Compared with the control group, the HBOT group showed more robust inflammatory cells (P = .025) and epithelialization (P = .024), but no significant difference in angiogenesis (P = .442). CONCLUSIONS: The authors conclude that HBOT may improve second-degree burn healing by increasing inflammatory cell migration and re-epithelialization.

Association between asthma control and Interleukin-17F expression levels in adult patients with atopic asthma.

OBJECTIVES: To investigate the correlation between Interleukin 17 (IL-17F) and the level of asthma control. METHODS: This is a cross-sectional study of 40 subjects who were diagnosed with atopic asthma. All participants were recruited from the Allergy and Immunology Clinic, Prof. R.D. Kandou General Hospital, Manado, Indonesia, between April 2015 and April 2016. Total serum IL-17F measured by using Enzyme-Linked Immunosorbent Assay methods; and mRNA IL-17F was obtained by using real-time reverse transcriptase polymerase chain reaction. Level of asthma control was quantified by using asthma control test (ACT) scoring system. The correlation between IL-17F, mRNA, and level of asthma control was analyzed by using Pearson's correlation coefficient (r). RESULTS: There is a strong positive correlation between IL-17F serum level and Nathan's ACT-score (r=0.969) which is statistically significant (p less than 0.001). Analysis of the correlation between mRNA IL-17F serum level and Nathan's ACT-score revealed a strong positive correlation (r=0.963), which is statistically significant (p less than 0.001). CONCLUSION: These findings suggest that IL-17F plays an important role in asthma control. However, the role played by IL-17F in asthma pathogenesis are still questions to be answered.

Cortisol dynamics are associated with electrocardiographic abnormalities following the aneurysmal subarachnoid hemorrhage.

CONTEXT: Electrocardiographic (ECG) abnormalities are common following subarachnoid hemorrhage (SAH). It probably represents cardiovascular stress after SAH. AIMS: The purpose of this study was to assess cortisol dynamics in relation to the ECG abnormality and disease course of SAH. SETTINGS AND DESIGN: The study follows a consecutive cohort of aneurysmal SAH patients, who underwent surgery within 72 hours of onset, and they were followed up for 10 days. MATERIALS AND METHODS: Serum cortisols, cortisol-binding globulin (CGB), adenocorticotropic hormone were measured (between 08.00-09.00 hours) preoperatively and then on postoperative days (PODs) 2, 4, 7, and 10. Electrocardiographs (ECG) were recorded on initial assessment and after surgery on daily basis in ICU. ECG abnormalities will be followed up by measurement of cardiac troponin T to quantify the myocyte necrosis. STATISTICAL ANALYSIS USED: Logistic regression analysis using commercial available software STATA 9. RESULTS: A total of 44 patients (20 M and 24 F) were eligible for the cohort analysis. Average patient age is 52.02 years (52.02 ± 11.23), and 86% (6/44) arrived with World Federation of Neurosurgical Society Scale grade 3 or better. The ECG abnormality was found in 10 cases (22.7%), but the abnormal TnT (>1 µg/l) were found in eight cases, and two cases contribute to the mortality. The ECG abnormalities are significantly associated with total cortisol on day 4 (P < 0.05) and free cortisol on day 2 (P = 0.0065). CONCLUSIONS: Elevated levels of morning cortisol within the first four days after surgery are associated with the ECG abnormality.