JMJD6 Shapes a Pro-tumor Microenvironment via ANXA1-Dependent Macrophage Polarization in Breast Cancer.

Breast cancer is the most common type of cancer in women worldwide, with the luminal subtype being the most widespread. Although characterized by better prognosis compared with other subtypes, luminal breast cancer is still considered a threatening disease due to therapy resistance, which occurs via both cell- and non-cell-autonomous mechanisms. Jumonji domain-containing 6, arginine demethylase and lysine hydroxylase (JMJD6) is endowed with a negative prognostic value in luminal breast cancer and, via its epigenetic activity, it is known to regulate many intrinsic cancer cell pathways. So far, the effect of JMJD6 in molding the surrounding microenvironment has not been explored.Here, we describe a novel function of JMJD6 showing that its genetic inhibition in breast cancer cells suppresses lipid droplet formation and ANXA1 expression, via estrogen receptor alpha and PPARα modulation. Reduction of intracellular ANXA1 results in decreased release in the tumor microenvironment (TME), ultimately preventing M2-type macrophage polarization and tumor aggressiveness. IMPLICATIONS: Our findings identify JMJD6 as a determinant of breast cancer aggressiveness and provide the rationale for the development of inhibitory molecules to reduce disease progression also through the remodeling of TME composition.

Variations of HRV and skin conductance reveal the influence of CV4 and Rib Raising techniques on autonomic balance: A randomized controlled clinical trial.

INTRODUCTION: The aim of the present study was to evaluate whether Fourth Ventricle Compression Technique (CV4) and Rib Raising (RR) osteopathic techniques influence Autonomic Nervous System (ANS) activity, as measured by Heart Rate Variability (HRV) and Skin Conductance (SC). METHOD: A randomized-controlled clinical trial has been performed from June 2010 to January 2011. 32 healthy adults (33.9 ± 14 years, and 72% female) were selected. Subjects were randomized in three groups: CV4 group, RR group and Placebo group. Each subject of each group underwent respective technique only once. HRV and SC were continuously recorded during the session. All data analysis was performed using SPSS statistical software (version 21.0) and the significance level was considered at p ≤ 0.05. RESULTS: RR technique intra-group subject analysis showed a significant decrease in LF/HF ratio (F = 25.18; p < 0.001), a statistically significant decrease of LF (F = 27.09; p < 0.001), and increase of HF, both at the end of treatment (F = 27.09; p < 0.001). CV4 technique intra-group subject analysis showed a significant reduction of the LF/HF ratio (F = 81.15; p < 0.001), a significant decrease in LF (F = 38.29; p < 0.001) and a significant increase of HF, at the end of treatment (F = 38.28; p < 0.001). Between-group analysis showed only a significant difference in LF/HF ratio between CV4 and PL groups (F = 3.44; p = 0.042). DISCUSSION: Our results suggest that the application of CV4 and RR techniques favors a shift in the autonomic balance towards a parasympathetic predominant state. Thus, their use within OMT protocol, as holistic approach, might improve the outcome of the treatment of clinical neuro-vegetative conditions.

Osteopathic Manipulative Treatment in a Paediatric Patient with Oesophageal Atresia and Tracheo-Oesophageal Fistula.

This study is aimed to evaluate the effectiveness of osteopathic manipulative treatment (OMT) in dysphagia symptoms and aspiration risk. This is a clinical case report on a 40-day-old infant with a diagnosis of oesophageal atresia and tracheo-oesophageal fistula. The patient received one OMT every 15 days for 7 times. The clinical outcome was the clinical changes in dysphagia symptoms assessed by the Paediatric Eating Assessment Tool-10 (PEDI-EAT-10). At the first osteopathic evaluation (T0), the total score of the PEDI-EAT-10 was 7, at the fourth osteopathic evaluation (T1), the total score was 3, and at the seventh osteopathic evaluation (T2), the total score was 1. OMT was effective and safe in reducing dysphagia symptoms and aspiration risk.

Tellurium epigenetic transgenerational effects on behavioral expression of coping behavior in rats.

An increasing interest has been developed in the past 15 years in the relationship between trace elements and cell functioning. In the present work the possibility of transgenerational effects of Te was investigated in rats. F1 generation exposed to K2TeO3 (1.55nM) from day 1 of pregnancy until litters were 30 day old, these animals with no other treatment than tap water and food were let to reach 60-70 day old. At this age, female rats were mated with normal untreated male rats. The F2 generation also without any Te treatment was allowed to grow until 30 days of age. At this age, behavioral tests measuring exploration induced by novelty, lateralized exploration, social interaction and survival behavior were applied. Results showed that head-dipping, rearing, lateralized exploration, social interaction, and survival behaviors, affected by Te treatment in F1 generation, also were modified in the same manner in F2 generation. These data show that Te effects on coping behavior in rats are preserved epigenetically in the next generation.

Osteopathic Manipulative Treatment Effect on Pain Relief and Quality of Life in Oncology Geriatric Patients: A Nonrandomized Controlled Clinical Trial.

PURPOSE: The aim of present study was to study the effect of osteopathic manipulation on pain relief and quality of life improvement in hospitalized oncology geriatric patients. METHODS: A nonrandomized controlled clinical trial was performed in the Oncology Rehabilitation Unit, Milan, Italy, from September 2015 to March 2016. Twenty-three older cancer patients were enrolled and allocated in 2 experimental groups: the study group (OMT group, N = 12) underwent osteopathic manipulative treatment in addition to physiotherapy, and the control group (PT group, N = 12) underwent only physiotherapy. At enrollment (T0), 24 recruited oncology patients completed the sociodemographic forms and were evaluated for pain intensity and quality of life by an external examiner. All patients were revaluated every week (T1, T2, T3, and T4) for pain intensity and at the end of the study treatment (T4) for quality of life. A standard level of significance was set at α < .05. RESULTS: The 2 groups did not significantly differ in age ( P = .682), body mass index ( P = .413), or gender ( P = 1). The osteopathic manipulative treatment added to physiotherapy produced a significant reduction in Numeric Rating Scale (NRS) scores both at T2 ( P = .004) and T4 ( P = .002). The difference in quality of life improvements between T0 and T4 was not statistically significant. NRS improved in the PT group at T4. Between-group analysis of NRS and quality of life with the Mann-Whitney test did not show any significant difference between the 2 treatments. CONCLUSIONS: Our study showed a significant improvement in pain relief and a nonsignificant improvement in quality of life in hospitalized geriatric oncology patients during osteopathic manipulative treatment. TRIAL REGISTRATION: Protocol registered on Clinicaltrials.gov (NCT03142386).