Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.
The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = −0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.
Lung transplantation can improve the survival of patients with severe chronic pulmonary disorders. However, the short- and long-term risk of infections can increase morbidity and mortality rates. A non-systematic review was performed to provide the most updated information on pathogen, host, and environment-related factors associated with the occurrence of bacterial, fungal, and viral infections as well as the most appropriate therapeutic options. Bacterial infections account for about 50% of all infectious diseases in lung transplanted patients, while viruses represent the second cause of infection accounting for one third of all infections. Almost 10% of patients develop invasive fungal infections during the first year after lung transplant. Pre-transplantation comorbidities, disruption of physical barriers during the surgery, and exposure to nosocomial pathogens during the hospital stay are directly associated with the occurrence of life-threatening infections. Empiric antimicrobial treatment after the assessment of individual risk factors, local epidemiology of drug-resistant pathogens and possible drug-drug interactions can improve the clinical outcomes.
9 September 2017 in Multidisciplinary Respiratory Medicine
Desmoplastic small round cell tumor of the pleura is a rare malignancy, with only a few cases reported in the scientific literature. The aim of the present review is to discuss the demographic, pathological, clinical, and therapeutic features of this rare tumor. English-language articles published since 1989, when the first case of desmoplastic small round cell tumor of the pleura was described, were retrieved, and fifteen cases included in fourteen articles were revised. The mean age of the patients was 25.5 years, out of them 60% were males. Chest pain, pleural effusion, and dyspnea were the most common clinical manifestations, while chest roentgenogram and computed tomography were the imaging techniques most commonly used. Surgical biopsy was employed in 80% of the cases for diagnosis. A multidisciplinary approach consisting in a combination of surgery with chemotherapy and radiation therapy was adopted in most cases. Only two patients (13.3%) were alive at 3 years from diagnosis, reflecting the aggressiveness of the disease, and the poor outcomes of the treatments currently available. Desmoplastic small round cell tumors of the pleura are extremely aggressive and challenging to diagnose, because of their rarity and unspecific demographic, clinical, and radiological features. An in-depth knowledge of such features is necessary for the optimal management of patients with this rare malignancy.
Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.
Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.