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1.
BMC Med ; 21(1): 178, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170273

RESUMEN

BACKGROUND: Early-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes. METHODS: We undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices. RESULTS: As opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species. CONCLUSIONS: We confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Estudios Prospectivos , Disbiosis/inducido químicamente , Calidad de Vida , Proteómica , Inflamación/inducido químicamente , Aumento de Peso , Heces/química , Heces/microbiología , Antineoplásicos/efectos adversos , Complejo de Antígeno L1 de Leucocito/análisis , Complejo de Antígeno L1 de Leucocito/uso terapéutico
2.
Molecules ; 27(9)2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35566122

RESUMEN

Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the important therapeutic strategies to keep the disease in remission. As there is no permanent cure for IBD except for chronic long-term treatment or surgery, it is therefore imperative to investigate plant-based agents that are receiving attention for their therapeutic benefits to overcome the debilitating clinical conditions of IBD. Lycopodium (LYCO), a plant of tropical and subtropical origin and known by numerous names such as ground pine, club moss, or devil's claw, has been popularly used for centuries in traditional medicine including Chinese and Indian medicines. In the present study, the effect of LYCO has been investigated in an acetic acid (AA)-induced colitis model in Wistar rats. LYCO was orally administered at the dose of 50 mg/kg/day either 3 days before or 30 min after the induction of IBD and continued for 7 days by intrarectal administration of AA. The changes in body weight and macroscopic and microscopic analysis of the colon of rats of different experimental groups were observed on days 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), reduced glutathione (GSH), and malondialdehyde (MDA) were measured. AA caused a significant reduction in body weight and increased macroscopic and microscopic ulcer scores along with a significant decline in antioxidant enzymes, superoxide dismutase (SOD), and catalase and antioxidant substrate, glutathione (GSH). There was a concomitant increased formation of malondialdehyde (MDA), a marker of lipid peroxidation, and raised myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with LYCO significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. AA also caused the release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-23 (IL-23). Furthermore, AA also increased the levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. LYCO treatment significantly reduced the release of calprotectin and proinflammatory cytokines. The results demonstrate that LYCO treatment has the potential to improve disease activity by inhibiting oxidative stress, lipid peroxidation, and inflammation along with histological preservation of colonic tissues.


Asunto(s)
Colitis Ulcerosa , Colitis , Enfermedades Inflamatorias del Intestino , Lycopodium , Ácido Acético/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/metabolismo , Peso Corporal , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Complejo de Antígeno L1 de Leucocito/metabolismo , Complejo de Antígeno L1 de Leucocito/farmacología , Complejo de Antígeno L1 de Leucocito/uso terapéutico , Malondialdehído/metabolismo , Estrés Oxidativo , Peroxidasa/metabolismo , Ratas , Ratas Wistar
3.
Minerva Gastroenterol (Torino) ; 68(2): 216-222, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35262307

RESUMEN

BACKGROUND: Symptomatic uncomplicated diverticular disease (SUDD) is a recognized clinical condition characterized by abdominal pain and changes in bowel habits, attributed to diverticula but without macroscopic signs of diverticulitis. There is no consensus about the management of these patients. Enteroflegin®, an association of natural active ingredients, could be effective in the treatment of those patients. METHODS: We conducted a retrospective observational study to evaluate the performances of Enteroflegin® in patients with SUDD. Patients were treated with Enteroflegin® 2 cp/day for 10 days per month for 6 months. Primary endpoint was the clinical remission rate, defined as the absence of any symptoms; secondary endpoints were the impact of the treatment on reduction of symptoms, on fecal calprotectin (FC) expression, and the prevention of acute diverticulitis. RESULTS: Three hundred and fifty patients were retrospectively enrolled (183 males, median age 64 years, IQR 54-70). Enteroflegin® was effective in inducing remission in 9.34% and 17.64% of patients at 3 and 6 months respectively (P<0.001). Reduction of symptoms occurred in 92.3% and in 85.3% of patients at 3 and 6 months respectively (P<0.001), and symptoms' recurrence or worsening was recorded in only 1.71% of patients during the follow-up. FC expression dropped from 181.3 µg/g at baseline to 100.2 µg/g (P<0.001) and to 67.9 µg/g (P<0.001) at 3 and 6 months of follow-up respectively. No adverse event was recorded during the follow-up. Finally, acute diverticulitis occurred in just 2% of patients during the follow-up. CONCLUSIONS: Enteroflegin® seems to be an effective nutraceutical compound in obtaining remission and symptom relief in SUDD patients. Further randomized, placebo-controlled clinical trials are needed to confirm these preliminary data.


Asunto(s)
Enfermedades Diverticulares , Diverticulitis , Anciano , Suplementos Dietéticos , Enfermedades Diverticulares/diagnóstico , Enfermedades Diverticulares/tratamiento farmacológico , Femenino , Humanos , Complejo de Antígeno L1 de Leucocito/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
4.
Indian J Exp Biol ; 52(2): 103-11, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24597142

RESUMEN

Role of herbal drugs and medicinal plant extracts in the successful treatment of urolithiasis, classified as the third most common urinary tract diseases is well documented. Ayurvedic plants and their components mediate antilithogenic effects by altering ionic composition of urine, being diuretic, antioxidant or having antimicrobial activity. Therapeutic peptides and proteins have unique place in pharmaceutical biotechnology due to their critical roles in cell biology. The innovation in antilithiatic proteins is that they are anionic, rich in acidic amino acids which make oxalate unavailable by interacting with calcium and have EF Hand domain which is a characteristic feature of various calcium binding protein like calgranulin, osteopontin. The review provides a background on the pathogenesis of urolithiasis and medical treatments. It focusses on the present research evaluating the scientific basis of antilithiatic potential of various plants and role of plant proteins as therapeutic agents thus opening new vista in the management of urolithiasis. Further investigations are required to fully decipher the mode of action of the potent biomolecules so as to exploit their preventive and therapeutic potential.


Asunto(s)
Medicina Ayurvédica , Fitoterapia , Extractos Vegetales/uso terapéutico , Urolitiasis/tratamiento farmacológico , Humanos , Complejo de Antígeno L1 de Leucocito/uso terapéutico , Osteopontina/uso terapéutico , Extractos Vegetales/química , Urolitiasis/patología
5.
Exp Dermatol ; 21(10): 778-82, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23078400

RESUMEN

The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an ageing population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments that exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins and cathelicidins as well as novel synthetic peptides. Among fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach.


Asunto(s)
Antifúngicos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Dermatomicosis/tratamiento farmacológico , Animales , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Defensinas/uso terapéutico , Dermatomicosis/microbiología , Hexosaminidasas/uso terapéutico , Histatinas/uso terapéutico , Humanos , Lactoferrina/uso terapéutico , Complejo de Antígeno L1 de Leucocito/uso terapéutico , Muramidasa/uso terapéutico , Péptidos/uso terapéutico , Ribonucleasas/uso terapéutico , Inhibidor Secretorio de Peptidasas Leucocitarias/uso terapéutico , Factores de Virulencia/antagonistas & inhibidores , Catelicidinas
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