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Advancements in pathology have given rise to software applications intended to minimize human error and improve efficacy of image analysis. Still, the subjectivity of image quantification performed manually and the limitations of the most ubiquitous tissue stain analysis software requiring parameters tuned by the observer, reveal the need for a highly accurate, automated nuclear quantification software specific to immunohistochemistry, with improved precision and efficiency compared with the methods currently in use. We present a method for the quantification of immunohistochemical biomarkers in keratinocyte nuclei proposed to overcome these limitations, contributing sensitive shape-focused segmentation, accurate nuclear detection, and automated device-independent color assessment, without observer-dependent analysis parameters.

Summary: The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rendering the mouse SC a popular model to study establishment of neural connectivity. Here we perform single-nucleus RNA-sequencing analysis of the mouse SC isolated at various developmental time points. Our study provides a transcriptomic landscape of the cell types that comprise the SC across murine development with particular emphasis on neuronal heterogeneity. We report a repertoire of genes differentially expressed across the different postnatal ages, many of which are known to regulate axon guidance and synapse formation. Using these data, we find that Pax7 expression is restricted to a subset of GABAergic neurons. Our data provide a valuable resource for interrogating the mechanisms of circuit development and identifying markers for manipulating specific SC neuronal populations and circuits.

Abstract Background Decisions in healthcare usually rely on the goodness and completeness of data that could be coupled with heuristics to improve the decision process itself. However, this is often an incomplete process. Structured interviews denominated Delphi surveys investigate experts' opinions and solve by consensus complex matters like those underlying surgical decision-making. Natural Language Processing (NLP) is a field of study that combines computer science, artificial intelligence, and linguistics. NLP can then be used as a valuable help in building a correct context in surgical data, contributing to the amelioration of surgical decision-making. Results We applied NLP coupled with machine learning approaches to predict the context (words) owning high accuracy from the words nearest to Delphi surveys, used as input. Conclusions The proposed methodology has increased the usefulness of Delphi surveys favoring the extraction of keywords that can represent a specific clinical context. It permits the characterization of the clinical context suggesting words for the evaluation process of the data.

Background: Measurements of breast morphology are a determinant of the assessment of any surgical procedure, either reconstructive or cosmetic. This study aims to investigate the association between easy anthropometric measurements and values of quality of life assessed in a sample of asymptomatic women. Methodology: Healthy asymptomatic women were admitted for this study. The following measurements were assessed: height, weight, nipple to sternal notch distance, areola to infra-mammary fold distance (right vs. left), right–left nipple distance. The Breast Q questionnaire (Italian translation V.1, pre-op breast conservation surgery) in the following domains: satisfaction with breasts; psycho-social satisfaction; physical satisfaction; sexual satisfaction, which was used to assess breast-related quality of life. Results: One hundred and forty-five women responded to the breast Q questionnaire. The mean age of the sample was 44.3 years; the medium BMI was 24.1; Spearman correlation coefficients revealed that all the investigated values were negatively correlated to the “satisfaction with breasts” domain. Psychosexual satisfaction was associated with age; BMI; nipple to sternal notch distance. After normalization for age values, we observed that “satisfaction with breast” was, once again, highly correlated to BMI; nipple to sternal notch distance; areola to IMF distance. In all cases, the higher the values, the lower the scores. Conclusions: Distances between easy relevant anatomical landmarks are representative of patients’ breast-related quality of life in a population of asymptomatic women. These findings allow us to identify an ideal anthropometric framework that can be used as a validated surgical endpoint for cosmetic and oncological procedures.

Aim: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR

Background:. Acellular dermal matrices (ADMs) entered the market in the early 2000s and their use has increased thereafter. Several retrospective cohort studies and single surgeon series reported benefits with the use of ADMs. However, robust evidence supporting these advantages is lacking. There is the need to define the role for ADMs in implant-based breast reconstruction (IBBR) after mastectomy. Methods:. A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints, and establish recommendation for the use of ADMs for subpectoral one-/two-stage IBBR (compared with no ADM use) for adult women undergoing mastectomy for breast cancer treatment or risk reduction using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results:. Based on the voting outcome, the following recommendation emerged as a consensus statement: the panel members suggest subpectoral one- or two-stage IBBR either with ADMs or without ADMs for adult women undergoing mastectomy for breast cancer treatment or risk reduction (with very low certainty of evidence). Conclusions:. The systematic review has revealed a very low certainty of evidence for most of the important outcomes in ADM-assisted IBBR and the absence of standard tools for evaluating clinical outcomes. Forty-five percent of panel members expressed a conditional recommendation either in favor of or against the use of ADMs in subpectoral one- or two-stages IBBR for adult women undergoing mastectomy for breast cancer treatment or risk reduction. Future subgroup analyses could help identify relevant clinical and pathological factors to select patients for whom one technique could be preferable to another.

Background: MicroRNAs (miRNA) and other components contained in extracellular vesicles may reflect the presence of a disease. Lung tissue, sputum, and sera of individuals with idiopathic pulmonary fibrosis (IPF) show alterations in miRNA expression. We designed this study to test whether urine and/or tissue derived exosomal miRNAs from individuals with IPF carry cargo that can promote fibrosis. Methods: Exosomes were isolated from urine (U-IPFexo), lung tissue myofibroblasts (MF-IPFexo), serum from individuals with IPF (n=16) and age/sex-matched controls without lung disease (n=10). We analyzed microRNA expression of isolated exosomes and their in vivo bio-distribution. We investigated the effect on ex vivo skin wound healing and in in vivo mouse lung models. Results: U-IPFexo or MF-IPFexo expressed miR-let-7d, miR-29a-5p, miR-181b-3p and miR-199a-3p consistent with previous reports of miRNA expression obtained from lung tissue/sera from patients with IPF. In vivo bio-distribution experiments detected bioluminescent exosomes in the lung of normal C57Bl6 mice within 5 min after intravenous infusion, followed by distribution to other organs irrespective of exosome source. Exosomes labeled with gold nanoparticles and imaged by transmission electron microscopy were visualized in alveolar epithelial type I and type II cells. Treatment of human and mouse lung punches obtained from control, non-fibrotic lungs with either U-IPFexo or MF-IPFexo produced a fibrotic phenotype. A fibrotic phenotype was also induced in a human ex vivo skin model and in in vivo lung models. Conclusions: Our results provide evidence of a systemic feature of IPF whereby exosomes contain pro-fibrotic miRNAs when obtained from a fibrotic source and interfere with response to tissue injury as measured in skin and lung models. Funding: This work was supported in part by Lester and Sue Smith Foundation and The Samrick Family Foundation and NIH grants R21 AG060338 (SE and MKG), U01 DK119085 (IP, RS, MTC).

Introduction: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. Results: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). Discussion: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values.Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.

The evolution of breast reconstructive surgery keeps pace with the evolution of breast oncologic surgery. The reconstructive choice should always balance the optimal local control of disease and the best cosmetic result, reflecting an informed decision that is shared with the patient, who is always at the center of the decision-making process. Implant-based breast reconstruction following mastectomy represents a complex choice. In order to obtain optimal results, the following considerations are mandatory: thorough preoperative planning, a complete knowledge of the devices that are used, accurately performed surgery, and appropriate follow-up.

Background:. Autologous fat grafting has broad applications in reconstructive and aesthetic breast surgery as a natural filler and for its regenerative purposes. Despite the widespread use of fat grafting, there remains no shared consensus on what constitutes the optimal fat grafting technique and its oncological safety. For this reason, the authors of this study have organized a Survey and an International Consensus Conference that was held at the Aesthetic Breast Meeting in Milan (December 15, 2018). Methods:. All studies on fat grafting, both for breast aesthetic and reconstructive purposes, were electronically screened. The literature review led to 17 “key questions” that were used for the Survey. The authors prepared a set of 10 “key statements” that have been discussed in a dedicated face-to-face session during the meeting. Results:. The 10 key statements addressed all the most debated topics on fat grafting of the breast. Levels of evidence for the key statements ranged from III to IV with 2 statements (20%) supported by a level of evidence III and 6 statements (60%) by level of evidence IV. Overall consensus was reached for 2 statements (20%) with >75% agreement reached for 7 statements. Conclusions:. The survey demonstrated a diversity of opinion and attitude among the panelists with regard to technique. Clear recommendations for evidence-based clinical practice for fat grafting use both in aesthetic and reconstructive breast surgery could not be defined due to the scarcity of level 1 or 2 studies.

Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. Twenty-seven experts were invited to partake into a Delphi Survey. At the first round they have been asked to provide a list of features involved in the decision making process (patient's characteristics; disease characteristics; surgical techniques, outcomes) and comment on it. Using text-mining techniques we extracted a list of mono-bi-trigrams potentially representative of decision drivers. A technique of "natural language processing" called Word2vec was used to validate changes to texts using synonyms and plesionyms. Word2Vec was also used to test the semantic relevance of n-grams within a corpus of knowledge made up of books edited by panel members. The final list of variables extracted was submitted to the judgement of the panel for final validation at the second round of the Delphi using closed ended questions. 52 features out of 59 have been approved by the panel. The overall consensus was 87.1% Text mining and natural language processing allowed the extraction of a number of decision drivers and outcomes as part of the decision making process in surgical oncology on the breast. This result was obtained transforming narrative texts into structured data. The high level of consensus among experts provided validation to this process. [ABSTRACT FROM AUTHOR]

The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs. [ABSTRACT FROM AUTHOR]

Breast lesions of uncertain malignant potential (B3) include atypical ductal and lobular hyperplasias, lobular carcinoma in situ, flat epithelial atypia, papillary lesions, radial scars and fibroepithelial lesions as well as other rare miscellaneous lesions. They are challenging to categorise histologically, requiring specialist training and multidisciplinary input. They may coexist with in situ or invasive breast cancer (BC) and increase the risk of subsequent BC development. Management should focus on adequate classification and management whilst avoiding overtreatment. The aim of these guidelines is to provide updated information regarding the diagnosis and management of B3 lesions, according to updated literature review evidence. These guidelines provide practical recommendations which can be applied in clinical practice which include recommendation grade and level of evidence. All sections were written according to an updated literature review and discussed at a consensus meeting. Critical appraisal by the expert writing committee adhered to the 23 items in the international Appraisal of Guidelines, Research and Evaluation (AGREE) tool. Recommendations for further management after core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB) diagnosis of a B3 lesion reported in this guideline, vary depending on the presence of atypia, size of lesion, sampling size, and patient preferences. After CNB or VAB, the option of vacuum-assisted excision or surgical excision should be evaluated by a multidisciplinary team and shared decision-making with the patient is crucial for personalizing further treatment. De-escalation of surgical intervention for B3 breast lesions is ongoing, and the inclusion of vacuum-assisted excision (VAE) will decrease the need for surgical intervention in further approaches. Communication with patients may be different according to histological diagnosis, presence or absence of atypia, or risk of upgrade due to discordant imaging. Written information resources to help patients understand these issues alongside with verbal communication is recommended. Lifestyle interventions have a significant im pact on BC incidence so lifestyle interventions need to be suggested to women at increased BC risk as a result of a diagnosis of a B3 lesion. These guidelines provide a state-of-the-art overview of the diagnosis, management and prognosis of B3 lesions in modern multidisciplinary breast practice. [ABSTRACT FROM AUTHOR]

Oncoplastic breast surgery has evolved the surgical treatment of breast cancer over the past two decades. This practice still lacks validation and poses several dilemmas in terms of safety, local and systemic control, timing of adjuvant treatments and cost-effectiveness. Our case series investigates the effects of a reduced surgical complexity on cosmetic results and quality of life. We treated 76 consecutive patients affected by early stage breast cancer from January 2016 to April 2017. We employed a decision support system to assist the final shared decision making. The communication process before surgery included new specific information on recent evidence about local control of disease and outcomes after multimodality treatment. In order to estimate the oncoplastic complexity, we created a new score based on scars, bilateral procedures and type and timing of reconstructions. We compared the outcomes of this series to that of a previous one from the same institution. The medium complexity score (CS) in the current series was significantly lower compared to that of the previous series (medium CS cohort 1 = 3.1 vs medium CS cohort 2 = 1.51; p = 0.001). Complications according to Clavien-Dindo classification did not vary significantly between the two series (p = 0.7). The increased use of primary systemic treatment did not translate into a significantly lower mastectomy rate (cohort 1 = 20% vs cohort 2 = 16%; p = n.s.). There was no significant difference in breast deformities after breast conserving surgery (p = 0.2). The BCCT.Core demonstrated a 67.1% occurrence of "good" results. Quality of life in patients who underwent breast-conserving surgery measured using the Breast-Q demonstrated similar results in the pre-post-op assessment. This study hypothesizes that a proper information may impact on patient's decisions and may reduce surgical complexity. This reduction likely has no effects on the main surgical outcomes estimated using standard tools. More investigations should be performed on a larger multi-institutional scale to confirm these conclusions. • Oncoplastic breast surgery lacks evidence-based validation. • Our case series investigates the effects of a reduced surgical complexity on cometic results and quality of life. • We hypothesize that a proper information may impact on patient's decisions and may reduce surgical complexity. [ABSTRACT FROM AUTHOR]

This study reports on feasibility and applicability of totally autologous primary breast reconstructions based on TDAP flaps using a standard set of internationally approved reporting scales. We reviewed 15 cases in patients with a good donor area in the back not suitable for implant or free flaps reconstructions. Complications according to Clavien Dindo were: 1 Grade 1 (seroma in the back). The ABS-BAPRAS quality assurance indicators 10, 11, and 12 were entirely fulfilled. No pedicled flap loss occurred; no unplanned return to theatre and no unplanned readmission within 3 months. Breast-related quality of life values are reported at 3 months and one year in four domains of the BREAST Q v. 2.0 (breast reconstruction post-op questionnaire). At 1 year the mean Q-score for satisfaction with breast was 70.5, for psychosocial well-being was 72.3; for sexual well-being was 58.8; for physical well-being (chest wall) was 70.60. The TDAP based totally autologous breast reconstruction reported to be a feasible and safe alternative to implant based or free flaps reconstructions according to consolidate international outcome reporting measures. [ABSTRACT FROM AUTHOR]

Background Estrogen receptors can regulate growth in papillary thyroid cancer and may affect prognosis after menopause. This study examines changes of estrogen receptor subtype ratio expression in papillary thyroid cancer cell lines derived from pre- and postmenopausal women. Methods Cells were harvested from papillary thyroid cancer and non-papillary thyroid cancer thyroid tissue (control) from pre- (n = 9) and postmenopausal women (n = 11). Protein expression of estrogen receptor α, estrogen receptor β, and phosphorylated extracellular signal-regulated kinase and protein kinase B were analyzed. Matrix metalloproteinase-2 activity was determined as a measure of tumor invasiveness. Mitochondrial retrograde signaling was altered with ethidium bromide to determine its effect on estrogen receptor α protein expression. Results Estrogen receptor α expression was increased in postmenopausal papillary thyroid cancer cells compared with controls but was unchanged in premenopausal papillary thyroid cancer. Estrogen receptor β expression did not change in either group. Increased matrix metalloproteinase-2 activity was observed only in postmenopausal papillary thyroid cancer. Premenopausal papillary thyroid cancer cells demonstrated increased extracellular signal-regulated kinase and unchanged protein kinase B activation. Conversely, postmenopausal papillary thyroid cancer cells had decreased extracellular signal-regulated kinase and increased protein kinase B activation. Ethidium bromide treatment resulted in increased estrogen receptor α protein expression only in premenopausal papillary thyroid cancer cells. Conclusion Increased estrogen receptor α expression may be involved in papillary thyroid cancer aggressiveness after menopause. This process may be regulated by differential activation of intracellular pathways and differing sensitivities to mitochondrial signaling regulation. [ABSTRACT FROM AUTHOR]

Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease. In this study, 15-month-old female C57BL/6J mice were ovariectomized and administered either placebo (pla) or 17β-estradiol (E2, 0.025 mg) 2 weeks after ovariectomy. They were further divided into those that were exposed to CS and no-smoke controls (NSC). Mice were exposed to CS in stainless steel inhalation chambers 3 hours a day, 5 days a week for 6 months, and sacrificed after 24 weeks of CS exposure. Blood and urine were collected at sacrifice to measure estrogen and cotinine levels, a metabolite of nicotine. Uterine weight was recorded as an indicator of estrogen status. Results showed that CS in the absence of E2 induced a decrease in hydroxyproline content, macrophage number, and respiratory chain complex-1 protein. CS without E2 also resulted in an increase in matrix metalloproteinase-2 activity and apoptosis and a change in the ratio of estrogen receptor subtype. These findings were abrogated with administration of E2, suggesting that estrogen deficiency increases susceptibility to CS-induced lung disease. [ABSTRACT FROM AUTHOR]

Patients undergoing mastectomy for breast cancer have nowadays many options for breast reconstruction, that will help in re-establishing patient's self confidence in her own body image. Implant-based reconstruction remains the most common form of post-mastectomy reconstruction, but it could also present some complications, the most common being capsular contracture. Accordingly, a novel breast mound may be perfectly designed using the reverse engineering approach and additive manufacturing methods combined with autologous fat grafting. A 3D hierarchical structure with autologous adipose-derived stem cells may be used as a construct for tissue regeneration. The 3D morphologically controlled scaffold may be placed in the subcutaneous position at the level of the conservative mastectomy side. The scaffold will be colonized with autologous fat tissue in some sessions. The biodegradable customized structure will help to maintain the breast shape and the natural consistency may be obtained with the fat grafting, also considering adequate enhancement techniques (Stromal Vascular Fraction derived growth factors). The principles of regenerative medicine may be combined and integrated with those of reverse engineering (3D image capture, 3D modelling and rapid prototyping) to design custom-made and high functional hierarchical structures with tailored properties and 3D complex geometry. The current study will focus on the basic principles and strategies in designing 3D advanced and complex structures for breast repair and regeneration. [ABSTRACT FROM AUTHOR]

Background The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. Methodology We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. Results The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). Conclusion The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities. [ABSTRACT FROM AUTHOR]

The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied. Adipose-derived MSCs (ASCs) from young (4 months) and old (22 months) male mice were infused 1 day after intratracheal BLM administration. At 21-day sacrifice, aged BLM mice demonstrated lung fibrosis by Ashcroft score, collagen content, and α(v)-integrin messenger RNA (mRNA) expression. Lung tissue from aged BLM mice receiving young ASCs exhibited decreased fibrosis, matrix metalloproteinase (MMP)-2 activity, oxidative stress, and markers of apoptosis vs BLM controls. Lung mRNA expression of tumor necrosis factor-alpha was also decreased in aged BLM mice receiving young-donor ASCs vs BLM controls. In contrast, old-donor ASC treatment in aged BLM mice did not reduce fibrosis and related markers. On examination of the cells, young-donor ASCs had decreased mRNA expression of MMP-2, insulin-like growth factor (IGF) receptor, and protein kinase B (AKT) activation compared with old-donor ASCs. These results show that the BLM-induced pulmonary fibrosis in aged mice could be blocked by young-donor ASCs and that the mechanisms involve changes in collagen turnover and markers of inflammation. [ABSTRACT FROM AUTHOR]