Gut microbiota in autism and mood disorders Mangiola, Francesca; Ianiro, Gianluca; Franceschi, Francesco ...
World journal of gastroenterology : WJG,
01/2016, Letnik:
22, Številka:
1
Journal Article
Odprti dostop
The hypothesis of an important role of gut microbiotain the maintenance of physiological state into thegastrointestinal （GI） system is supported by severalstudies that have shown a qualitative and ...quantitativealteration of the intestinal flora in a number of gastrointestinaland extra-gastrointestinal diseases. Inthe last few years, the importance of gut microbiotaimpairment in the etiopathogenesis of pathology such asautism, dementia and mood disorder, has been raised.The evidence of the inflammatory state alteration,highlighted in disorders such as schizophrenia, majordepressive disorder and bipolar disorder, stronglyrecalls the microbiota alteration, highly suggestingan important role of the alteration of GI system alsoin neuropsychiatric disorders. Up to now, availableevidences display that the impairment of gut microbiotaplays a key role in the development of autism and mooddisorders. The application of therapeutic modulators ofgut microbiota to autism and mood disorders has beenexperienced only in experimental settings to date, withfew but promising results. A deeper assessment of therole of gut microbiota in the development of autismspectrum disorder （ASD）, as well as the advancementof the therapeutic armamentarium for the modulation ofgut microbiota is warranted for a better management ofASD and mood disorders.
Background
POEM has recently had a widespread diffusion, aiming at being the treatment of choice for esophageal achalasia. The results of ongoing RCTs against laparoscopic myotomy are not available, ...yet. We, therefore, designed this propensity score (PS) case-control study with the aim of evaluating how POEM compares to the long-standing laparoscopic Heller myotomy + Dor fundoplication (LHD) and verifying if it may really replace the latter as the first-line treatment for achalasia.
Methods
Two groups of consecutive patients undergoing treatment for primary achalasia from January 2014 to November 2017 were recruited in two high-volume centers, one with extensive experience with POEM and one with LHD. Patients with previous endoscopic treatment were included, whereas patients with previous LHD or POEM were excluded. A total of 140 patients in both centers were thus matched. LHD and POEM were performed following established techniques. The patients were followed with clinical (Eckardt score), endoscopic, and pH-manometry evaluations.
Results
The procedure was successfully completed in all the patients. POEM required a shorter operation time and postoperative stay compared to LHD (p < 0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (five mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p = 0.33). Two patients in the POEM group and one in the LHD were lost to follow-up. One patient in both groups died during the follow-up for unrelated causes. At a median follow-up of 24 months 15–30 for POEM and 31 months 15–41 for LHD (p < 0.05), 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p < 0.12). Four years after the treatment, the probability to have symptoms adequately controlled was > 90% for both groups (p = 0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; 24-h pH-monitoring showed however an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p < 0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p < 0.05).
Conclusion
POEM provides the same midterm results as LHD. This study confirms, however, a higher incidence of postoperative GERD with the former, even if its real significance needs to be further evaluated.
Glioblastoma multiforme (GBM) is a lethal disease characterized by an overall survival of about 1 year, making it one of the most aggressive tumours, with very limited therapeutic possibilities. ...Specific biomarkers for early diagnosis as well as innovative therapeutic strategies are urgently needed to improve the management of this deadly disease. In this work, we demonstrated that vesicular galectin‐3‐binding protein (LGALS3BP), a glycosylated protein overexpressed in a variety of human malignancies, is a potential GBM disease marker and can be efficiently targeted by a specific antibody–drug conjugate (ADC). Immunohistochemical analysis on patient tissues showed that LGALS3BP is highly expressed in GBM and, compared with healthy donors, the amount of vesicular but not total circulating protein is increased. Moreover, analysis of plasma‐derived extracellular vesicles from mice harbouring human GBM revealed that LGALS3BP can be used for liquid biopsy as a marker of disease. Finally, an ADC targeting LGALS3BP, named 1959‐sss/DM4, specifically accumulates in tumour tissue, producing a potent and dose‐dependent antitumor activity. In conclusion, our work provides evidence that vesicular LGALS3BP is a potential novel GBM diagnostic biomarker and therapeutic target deserving further preclinical and clinical validation.
LGALS3BP is overexpressed in glioblastoma multiforme (GBM) and is highly enriched in GBM‐derived extracellular vesicles. We established a panel of patient‐derived GBM cell lines and developed a cell‐derived xenograft preclinical model. Our data reported that extracellular LGALS3BP can be used as a potential liquid biopsy GBM marker and can be efficiently targeted by a specific antibody–drug conjugate.
The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM ...resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion. In the current study, we assessed the effects of Hes1-targeted shRNA, a Notch1 gene target, specifically on GBM CSC refractory to GSI-X. Depletion of Hes1 protein induces major changes in cell morphology, cell growth rate and in the invasive ability of shHes1-CSC in response to growth factor EGF. shHes1-CSC show a decrease of the stemness marker Nestin concurrently to a marked increase of neuronal marker MAP2 compared to pLKO.1-CSC. Those effects correlated with repression of EGFR protein and modulation of Stat3 phosphorylation at Y705 and S727 residues. In the last decade Stat3 has gained attention as therapeutic target in cancer but there is not yet any approved Stat3-based glioma therapy. Herein, we report that exposure to a Stat3/5 inhibitor, induced apoptosis either in shHes1-CSC or control cells. Taken together, Hes1 seems to be a favorable target but not sufficient itself to target GBM efficaciously, therefore a possible pharmacological intervention should provide for the use of anti-Stat3/5 drugs either alone or in combination regimen.
Abstract
Background
We designed this study with the aim of comparing POEM and laparoscopic Heller myotomy+Dor fundoplication (LHD) by matching 2 groups of consecutive patients, treated in 2 ...high-volume Centers, with the propensity score (PS).
Methods
Patients undergoing treatment for achalasia from 2014 to 2017 were selected: by applying the PS, 140 patients in both centers were matched. LHD and POEM were performed following established techniques. Patients were followed with clinical, endoscopic and pH-manometry evaluations.
Results
POEM required a shorter operation time (47 min 35-57) and postoperative stay (2 days 2-2) compared to LHD (95 min 85-105 and 3 days 3-3, respectively, p<0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (5 mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p=0.33). At a median follow up of 24 mos. 15-30 for POEM and 31 mos. 15-41 for LHD (p<0.05), the median Eckardt score did not differ: moreover, 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p <0.12). Four years after the treatment, the probability to be symptom free was > 90% for both groups (98.2% for POEM and 93.9% for LHD, p=0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; however, 24-h pH-monitoring showed an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p<0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p<0.05). Finally, the need for PPI therapy was higher in the POEM group (38.8%) compared to the LHD group (15.1%), p<0.001.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
50.
A New Method of Estimating Intracranial Elastance Anile, Carmelo, MD; De Bonis, Pasquale, PhD; Mangiola, Annunziato, MD ...
Interdisciplinary neurosurgery : Advanced techniques and case management,
06/2014, Letnik:
1, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract Objective Current methods of calculating Intracranial Elastance Index (IEI) depend from CSF pulse-wave, whose shape may deeply change during ICP rising. The main aim of this study was to ...evaluate the reliability and specificity of a novel method to calculate IEI (method C), based on the integral of the CSF pulse-wave area. Method Twenty ventricular infusion-tests of patients with idiopathic NPH were re-evaluated. We have compared method C with the most widely used methods to calculate IEI: a modified Szewczykowski method (diastolic ICP against CSF pulse-wave amplitude-method A) and a modified Czosnyka method (diastolic ICP against the fundamental harmonic-method B). R-squared (R2 ) was calculated for each test. Means were compared through ANOVA and t-test. Results Mean R2 values for methods A, B and C were 0.91 ± 0.06, 0.9 ± 0.06 and 0.96 ± 0.03, respectively. Mean R2 values obtained through method A vs C and through method B vs C were significantly different (p = .006 and p = .001, respectively), while values obtained through method A vs B were not (p = 1). Analysis of ICP tracks demonstrated that 9 patients showed no different shape of the ICP wave during the infusion test, while the remaining 11 did. The mean R2 values obtained through method A vs C and through method B vs C were significantly different (p < .001 for both) for patients showing a different shape of the ICP wave during the infusion test. Conclusions Method C seems to be the most reliable method to calculate IEI, as it is independent from CSF pulse wave modifications.
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