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1.
Pharmacol Res ; 195: 106891, 2023 09.
Article in English | MEDLINE | ID: mdl-37586618

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves environmental factors, genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cell (MSC) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies. However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis are not clear. METHODS: The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal microbiota composition was evaluated by 16S rRNA amplicon sequencing. RESULTS: iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2 expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of Tregs and IFN-γ+CD8+ T cells in the MLNs while decreasing the IL-4+Th2 response. It also ameliorated intestinal dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance, while reducing Alistipes and Turicibacter, genera associated with inflammation. CONCLUSION: Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal dysbiosis, supporting the use of MSCs for the treatment of IBD.


Subject(s)
Colitis-Associated Neoplasms , Colitis , Inflammatory Bowel Diseases , Mesenchymal Stem Cells , Humans , Mice , Animals , Colitis-Associated Neoplasms/complications , Colitis-Associated Neoplasms/pathology , Interleukin-6 , Mice, Inbred C57BL , Dysbiosis/complications , CD8-Positive T-Lymphocytes , RNA, Ribosomal, 16S , Phosphatidylinositol 3-Kinases , Colitis/pathology , Inflammation , Colon/pathology , Inflammatory Bowel Diseases/pathology , Immunity , Dextran Sulfate , Disease Models, Animal
2.
Sci Rep ; 12(1): 3268, 2022 02 28.
Article in English | MEDLINE | ID: mdl-35228596

ABSTRACT

Parkinson's disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships.


Subject(s)
Parkinson Disease , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Cholinergic Agents/metabolism , Cholinergic Neurons/metabolism , Disease Models, Animal , Dopamine/metabolism , Parkinson Disease/metabolism
3.
BMC Surg ; 17(1): 41, 2017 Apr 19.
Article in English | MEDLINE | ID: mdl-28424067

ABSTRACT

BACKGROUND: Parastomal hernia is a very common complication after stoma formation. Current surgical techniques for repairing parastomal hernia have unsatisfactory results. We aim to assess our preliminary experience with prophylactic mesh placement at the time of stoma formation. METHODS: Data were prospectively recorded. A specifically designed mesh made of polyvinyl fluoride with central conduit (Dynamesh IPST®) was fixed using an intra-peritoneal onlay technique. Safety was evaluated by means of surgical data and frequency of mesh-related complications, efficacy by the rate of parastomal hernias. RESULTS: Thirty-four patients were included in the study. Three of them died before a year of follow up (not related to the stoma), so they were excluded. The other 31 patients (11 women and 20 men) were prospectively followed up after different pathologies resulting in a permanent colostomy. Twelve months after surgery CT-Scan imaging revealed two (6.4%) parastomal hernias, one of them already clinically suspected. During the follow up, 29% of the patients (n = 9) developed another type of hernia (incisional, inguinal or both). In five patients (16.1%) a light stomal retraction of the otherwise slightly prominent ostomy was observed. Median clinical follow-up was 17.5 months (range 12-34). CONCLUSION: Prophylactic parastomal mesh placement might be a safe and effective procedure with a potential to reduce the risk of parastomal hernia. Routine use of this technique should be further analysed.


Subject(s)
Colostomy/adverse effects , Hernia, Ventral/prevention & control , Herniorrhaphy/instrumentation , Polyvinyls , Surgical Mesh , Surgical Stomas/adverse effects , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Hernia, Ventral/diagnostic imaging , Hernia, Ventral/etiology , Humans , Male , Middle Aged , Tomography, X-Ray Computed
5.
J Altern Complement Med ; 16(11): 1191-200, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21058885

ABSTRACT

OBJECTIVE: The objective of this study was to determine the effects of a 3-month Biodanza intervention in women with fibromyalgia (FM). DESIGN: This was a controlled trial. SETTING/LOCATION: The study was conducted at a university research laboratory and social center. SUBJECTS: The study comprised 59 women with FM recruited from a local association of patients with FM. Participants were allocated to the Biodanza intervention group (n = 27) or usual-care group (n = 32). INTERVENTION: The Biodanza intervention was carried out once a week for 3 months. OUTCOME MEASURES: The outcome measures included the following: Pain threshold, body composition (body-mass index and estimated body fat percentage), physical fitness (30-second chair stand, handgrip strength, chair sit and reach, back scratch, blind flamingo, 8 feet up and go, and 6-minute walk test) and psychologic outcomes (Fibromyalgia Impact Questionnaire [FIQ], Short-Form Health Survey 36, Vanderbilt Pain Management Inventory, Hospital Anxiety and Depression Scale, General Self-Efficacy Scale, and Rosenberg Self-Esteem Scale). RESULTS: We observed a significant interaction effect (group*time) for pain threshold of several tender points (left [L] and right [R] side of the anterior cervical and supraspinatus, trapezius L and lateral epicondyle R, algometer score, tender points count), body fat percentage, and FIQ total score. In the intervention group, post hoc analysis revealed a significant improvement in pain threshold of the anterior cervical R and L and supraspinatus R and L tender points (all p < 0.05), algometer score (p = 0.008), tender point count (p = 0.002), body fat percentage (p = 0.001), and FIQ total score (p = 0.003). CONCLUSIONS: A 3-month (one session per week) Biodanza intervention shows improvements on pain, body composition, and FM impact in female patients.


Subject(s)
Body Composition , Dance Therapy , Fibromyalgia/therapy , Pain Management , Adult , Female , Fibromyalgia/physiopathology , Fibromyalgia/psychology , Humans , Middle Aged , Pain/etiology , Pain Threshold , Treatment Outcome
8.
Surg Laparosc Endosc Percutan Tech ; 17(1): 49-51, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17318056

ABSTRACT

The aim of this study was to evaluate the role of laparoscopic decapsulation in the management of splenic cysts. Cystic disease of spleen is an infrequent entity. Laparoscopic surgery should be considered as the method of choice for the greater of patients diagnosed with a splenic cyst. We provide 2 new cases of splenic cysts treated with partial laparoscopic decapsulation using harmonic scalpel. The patients were examined 5 years later and no cysts recurrence was found.


Subject(s)
Cysts/surgery , Laparoscopy/methods , Splenic Diseases/surgery , Adult , Cysts/diagnostic imaging , Cysts/pathology , Female , Humans , Male , Splenic Diseases/diagnostic imaging , Splenic Diseases/pathology , Tomography, X-Ray Computed , Treatment Outcome
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