Assessing Nutritional Status in Gastric Cancer Patients after Total versus Subtotal Gastrectomy: Cross-Sectional Study.

Gastric cancer (GC) remains a significant global health concern, ranking as the third leading cause of cancer-related deaths. Malnutrition is common in GC patients and can negatively impact prognosis and quality of life. Understanding nutritional issues and their management is crucial for improving patient outcomes. This cross-sectional study included 51 GC patients who underwent curative surgery, either total or subtotal gastrectomy. Various nutritional assessments were conducted, including anthropometric measurements, laboratory tests, and scoring systems such as Eastern Cooperative Oncology Group/World Health Organization Performance Status (ECOG/WHO PS), Observer-Reported Dysphagia (ORD), Nutritional Risk Screening-2002 (NRS-2002), Patient-Generated Subjective Global Assessment (PG-SGA), and Simplified Nutritional Appetite Questionnaire (SNAQ). Serum carcinoembryonic antigen (CEA) levels were significantly higher in the subtotal gastrectomy group. Nutritional assessments indicated a higher risk of malnutrition in patients who underwent total gastrectomy, as evidenced by higher scores on ORD, NRS-2002, and PG-SGA. While total gastrectomy was associated with a higher risk of malnutrition, no single nutritional parameter emerged as a strong predictor of surgical approach. PG-SGA predominantly identified malnutrition, with its occurrence linked to demographic factors such as female gender and age exceeding 65 years.

Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation.

Mesenchymal stromal cells (MSCs) hold great promise for tissue regeneration in debilitating disorders. Despite reported improvements, the short-term outcomes of MSC transplantation, which is possibly linked to poor cell survival, demand extensive investigation. Disease-associated stress microenvironments further complicate outcomes. This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations. Additionally, questions arise about how to predict, track, and comprehend cell fate post-transplantation. In vivo cellular imaging has emerged as a critical requirement for both short- and long-term safety and efficacy studies. However, translating preclinical imaging methods to clinical settings remains challenging. The fate and function of transplanted cells within the host environment present intricate challenges, including MSC engraftment, variability, and inconsistencies between preclinical and clinical data. The study explored the impact of high glucose concentrations on MSC survival in diabetic environments, emphasizing mitochondrial factors. Preserving these factors may enhance MSC survival, suggesting potential strategies involving genetic modification, biomaterials, and nanoparticles. Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies. These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data, computational disease modeling, and possibly artificial intelligence to enable deterministic insights.

Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer.

Individualized gastric cancer (GC) treatment aims at providing targeted therapies that translate the latest research into improved management strategies. Extracellular vesicle microRNAs have been proposed as biomarkers for GC prognosis. Helicobacter pylori infection influences the therapeutic response to and the drivers of malignant changes in chronic gastritis. The successful use of transplanted mesenchymal stem cells (MSCs) for gastric ulcer healing has raised interest in studying their effects on tumor neovascularization and in potential antiangiogenic therapies that could use mesenchymal stem cell secretion into extracellular vesicles-such as exosomes-in GC cells. The use of MSCs isolated from bone marrow in order to achieve angiogenic modulation in the tumor microenvironment could exploit the inherent migration of MSCs into GC tissues. Bone marrow-derived MSCs naturally present in the stomach have been reported to carry a malignancy risk, but their effect in GC is still being researched. The pro- and antiangiogenic effects of MSCs derived from various sources complement their role in immune regulation and tissue regeneration and provide further understanding into the heterogeneous biology of GC, the aberrant morphology of tumor vasculature and the mechanisms of resistance to antiangiogenic drugs.

The mesocolic apical fragment in complete mesocolic excision colectomies: Should it be analysed separately? A proof-of-concept study.

AIM: The aim of this work is to describe a protocol and assess the feasibility of harvesting and analysing the mesocolic apical fragment (MAF) for the presence of central lymph node (LN) metastasis and extra lymphatic free tumour cells in a random subgroup extracted from a cohort of complete mesocolic excision colectomies with central vascular ligation. METHOD: Forty-seven patients diagnosed with colorectal cancer were included. A 2/2 cm pyramid of tissue was cut around the central tie and sent for pathological examination. The MAF was sectioned into 16 slices. High-definition images were taken from the slices which were merged into a panoramic three-dimensional image of the MAF. The distribution of LNs in the MAF was quantified. Immunohistochemistry staining for cytokeratin 14 was used to identify isolated tumour cells and micrometastases in the extranodal tissue. RESULTS: No tumoural cells migrating through the apical zone, outside of the LNs, were identified. Margins of resection, mesocolic tissue and LNs were all negative in the subgroup of ultrastaged MAFs. The number of examined central LNs varied between 0 and 24, with positive MAF LNs being identified only in pN2 stages. The rate of positive apical LNs in our cohort was 4.2% (n = 2). CONCLUSIONS: The MAF can be easily extracted from standard specimens, allowing for accurate analysis of lymphatic and extra-nodal tumour cells on the central resection margins, in central LNs and in the apical mesocolic tissue. Future research on larger cohorts is required to establish if analysing the MAF has an impact on patient staging, prognosis and management.

NHF-derived carbon dots: prevalidation approach in breast cancer treatment.

Metastatic breast cancer dominates the female cancer-related mortality. Tumour-associated molecules represents a crucial for early disease detection and identification of novel therapeutic targets. Nanomaterial technologies provide promising novel approaches to disease diagnostics and therapeutics. In the present study we extend the investigations of antitumoral properties of Carbon Dots prepared from N-hydroxyphthalimide (CD-NHF) precursor. We evaluate the effect of CD-NHF on tumour cell migration and invasion in vitro and their impact on tumour progression using an in vivo model. Furthermore, we investigate the molecular mechanisms involved in CD-NHF antitumour effects. In vivo mammary tumours were induced in Balb/c female mice by injecting 4T1 cells into the mammary fat pad. Conditional treatment with CD-NHF significantly impair both migration and invasion of metastatic breast cancer cells. The presence of CD-NHF within the 3D cell cultures strongly inhibited the malignant phenotype of MDA-MB-231, 4T1 and MCF-7 cells in 3D culture, resulting in culture colonies lacking invasive projections and reduction of mammospheres formation. Importantly, breast tumour growth and metastasis dissemination was significantly reduced upon CD-NHF treatments in a syngeneic mouse model and is associated with down-regulation of Ki67 and HSP90 expression. CD-NHF nanostructures provide exciting perspective for improving treatment outcome in breast cancer.

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression-Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study.

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1α, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.

Association of intracellular lipid accumulation in subcutaneous adipocyte precursors and plasma adipokines in bariatric surgery candidates.

BACKGROUND: The adipocyte expansion is a critical process with implications in the pathogenesis of obesity associated metabolic syndrome. Impaired adipogenesis leads to dysfunctional, hypertrophic adipocytes, local inflammation and peripheric insulin resistance. METHODS: We assessed the relationship between the adipogenic differentiation capacity of the subcutaneous adipose derived stem cells (ASCs), evaluated by total lipid accumulation, and the metabolic and hormonal profile in a group of obese female patients proposed for bariatric surgery (N = 20) versus normal weight female controls (N = 7). RESULTS: The lipid accumulation (measured as optical density at 492 nm) of ASCs during their differentiation to adipocytes was significantly lower in ASCs isolated from obese patients as compared to ASCs isolated from normal weight patients (0.49 ± 0.1 vs. 0.71 ± 0.1, p < 0.001). Significant negative correlations between lipid accumulation in adipogenic differentiated ASCs and plasma concentrations of triglycerides (p < 0.01), insulin (p < 0.001), HOMA-IR (p < 0.01), adiponectin (p < 0.05) and leptin/adiponectin ratio (p < 0.05) were found in obese group. CONCLUSIONS: In severely obese female patients, the abnormal adipogenesis is related to insulin resistance and leptin/adiponectin ratio. The abnormal lipid accumulation in the mature adipocyte derived from obese ASCs could possible predict the further development of type 2 diabetes mellitus in severely obese patients and influence the selection of patients for bariatric surgery.

The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints.

Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia. Hoffa fat pad (HFP) in the knee is increasingly recognized as a major player in pathological joint states such as anterior knee pain and osteoarthritis. HFP contains numerous population of mesenchymal and endothelial progenitors; however, the possible role of mature adipocytes in the maintenance of stem cell niche is unknown. We propose that AFP is an active component of the joint organ with multifunctional roles in the maintenance of joint homeostasis. Endowed with a rich network of sensitive nervous fibbers, AFPs may act as a proprioceptive organ. Adipokines and growth factors released by AFP-resident mature adipocytes could participate in the maintenance of progenitor stem cell niche as well as in local immune regulation. AFP metabolism may be locally controlled, correlated with but independent of WAT homeostasis. The identification of AFP role in normal joint turnover and its possible implication in pathological states could deliver diagnostic and therapeutic targets. Drug and/or cell therapies that restore AFP structure and function could become the next step in the design of disease modifying therapies for disabling joint conditions such as osteoarthritis and inflammatory arthritis.

Clinical and histological predictive risk factors of atrial fibrillation in patients undergoing open-heart surgery.

Postoperative atrial fibrillation (POAF) is a common complication subsequent to cardiac surgery. Various risk factors have been reported for the development of this complication; however, their precise role in POAF is unknown. In the present study, we attempted to identify clinical factors and histopathological changes in atrial tissue that may predict the development of POAF. Atrial tissue was sampled from 103 patients in sinus rhythm that had undergone open-heart surgery, including elective coronary artery bypass grafting (79.61%) and heart valve surgery (20.38%). Atrial surgical biopsies were obtained from the right atrial appendage at the site of cannulation, prior to cardiopulmonary bypass. Tissues were processed routinely for light microscopy, then stained with hematoxylin and eosin and sirius red. Microscopical exams were used to observe the atrial lesions and morphometry was conducted for quantification. In total, 37 patients (35.92%) developed POAF and atrial lesions were identified in the majority of patients in the normal postoperative sinus rhythm and POAF groups, but were most common in the POAF patients. The most common risk factors involved in developing POAF were found to be: Age of >60 years, male gender, ejection fraction of <50% and increased pulmonary hypertension. Furthermore, interstitial fibrosis and myocytolysis were the most common injuries identified. Abnormalities in atrial surgical biopsies may indicate the susceptibility of a patient to developing POAF. The present results suggest that the pre-existent alterations in the structure of the right atrium may be a major determinant in the development of POAF.

Stem cells for the treatment of musculoskeletal pain.

Musculoskeletal-related pain is one of the most disabling health conditions affecting more than one third of the adult population worldwide. Pain from various mechanisms and origins is currently underdiagnosed and undertreated. The complexity of molecular mechanisms correlating pain and the progression of musculoskeletal diseases is not yet fully understood. Molecular biomarkers for objective evaluation and treatment follow-up are needed as a step towards targeted treatment of pain as a symptom or as a disease. Stem cell therapy is already under investigation for the treatment of different types of musculoskeletal-related pain. Mesenchymal stem cell-based therapies are already being tested in various clinical trials that use musculoskeletal system-related pain as the primary or secondary endpoint. Genetically engineered stem cells, as well as induced pluripotent stem cells, offer promising novel perspectives for pain treatment. It is possible that a more focused approach and reassessment of therapeutic goals will contribute to the overall efficacy, as well as to the clinical acceptance of regenerative medicine therapies. This article briefly describes the principal types of musculoskeletal-related pain and reviews the stem cell-based therapies that have been specifically designed for its treatment.

Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer.

UNLABELLED: There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer. AIM: The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC. MATERIALS AND METHODS: We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed. RESULTS: We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61). CONCLUSIONS: The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.

Novel approaches for treating musculoskeletal diseases: molecular orthopedics and systems medicine.

Molecular medicine uses knowledge about cell structure and function for disease, diagnostics, stage characterisation and treatment. The advent of genomic technologies is considerably leading to developments in the field of molecular medicine. The accumulation of detailed information about gene expression, epigenetic variability, protein transcription and functional modulation is contributing to a new era in medicine. Rapid and early diagnostic procedures, molecular characterisation of degenerative and proliferative diseases and personalized therapies are predicted to lead to advancements in health prevention and treatment of disease. Diagnostic tools and therapies based on local and /or general modulation of cellular processes for traumatic or degenerative musculoskeletal conditions are becoming available. A logical consequence of the information derived from extensive data gathering, systems biology and systemic medicine has lead to significant improvements in understanding biological structure and function in a simultaneous bottom top and integrative, holistic manner. The description of disease mechanism at an intimate, subcellular level has a dual benefit. A thorough understanding of the crosstalk involved in molecular pathways both in the normal and the diseased state are expanding scientific knowledge and simultaneously are enabling design cell-targeted and individualized therapies. This paper presents a brief overview of current molecular based treatments available to the orthopedic surgeon and introduces the concept of systemic medicine from the perspective of musculoskeletal pathology.

Stem cells derived from osteoarthritic knee mesenchymal tissues: a pilot study.

Regenerative medicine is a promising approach for addressing musculoskeletal disorders. Successful implementation of regenerative therapies is based upon existence of reliable, easy accessible cell sources. Mesenchymal tissues removed during total knee replacement (TKR) were investigated as a potential autologous stem cell source. Materials and methods Samples were collected from patients undergoing primary TKR mononuclear cells from adipose and synovial tissue; subchondral trabecular bone and osteoarthritic cartilage were isolated and assessed in terms of mesenchymal stem cells (MSC) content. Results MSCs obtained from all the investigated tissue types and from all donors showed proliferative, differentiation and surface markers characteristic of stemness. Important number of MSCs could be obtained in the first passage (P0). Mesenchymal tissues removed during TJR can qualitatively and quantitatively function as autologous MSC sources to be considered for regenerative therapies.

Isolation and phenotypic characterisation of stem cells from late stage osteoarthritic mesenchymal tissues.

INTRODUCTION: Osteoarthritis (OA) represents an increasing health issue worldwide. Regenerative medicine (RM) has raised the hope for introducing revolutionary therapies in clinical practice. Detection of autologus cell sources can improve accessibility to RM strategies. OBJECTIVES: To assess the presence and biological potential of mesehchymal stem cells in three tissues (subchondral bone, synovial layer, periarticular adipose tissue) in late stages osteoarthritic patients. MATERIAL AND METHODS: Samples were collected from subjects undergoing total knee replacement (TKR). MSCs were isolated and cultured in complete αMEM with ß FGF. Cell morphology and growth potential was assessed. Flow cytometry was used for detection of several relevant cell surface markers. Quantitative and qualitative assessment of differentiation potential towards three mesenchymal lineages (osteogenesis adipogenesis chondrogenesis) was performed. Time lapse life cell imaging of nondiferentiated cells over 24 hours period was used to determine cell kinetics. RESULTS: Mesenchymal cells derived from all donors and tissue types showed morphology, growth and surface cell markers associated with stemness. All cell types underwent differentiation toward three mesenchymal lineages with significant differences between tissues of origin, not between donors. Cell kinetics, as derived from life imaging records, was variable with tissue of origin, significant higher for adipose derived MSCS. CONCLUSION: Human late stage OA mesenchymal tissues, contain progenitors with proliferative and differentiation potential of MSCs. These populations can be used for research and autologus regenerative therapies. Further comparative studies with age matched non OA samples has the potential of contributing to deepening knowledge about disease occurrence and progression.