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Current Molecular Medicine Mar 2024Inflammatory bowel disease (IBD), a chronic inflammatory condition of the human intestine, comprises Crohn's Disease (CD) and Ulcerative Colitis (UC). IBD causes severe...
Inflammatory bowel disease (IBD), a chronic inflammatory condition of the human intestine, comprises Crohn's Disease (CD) and Ulcerative Colitis (UC). IBD causes severe gastrointestinal symptoms and increases the risk of developing colorectal carcinoma. Although the etiology of IBD remains ambiguous, complex interactions between genetic predisposition, microbiota, epithelial barrier, and immune factors have been implicated. The disruption of intestinal homeostasis is a cardinal characteristic of IBD. Patients with IBD exhibit intestinal microbiota dysbiosis, impaired epithelial tight junctions, and immune dysregulation; however, the relationship between them is not completely understood. As the largest body surface is exposed to the external environment, the gastrointestinal tract epithelium is continuously subjected to environmental and endogenous stressors that can disrupt cellular homeostasis and survival. Heat shock proteins (HSPs) are endogenous factors that play crucial roles in various physiological processes, such as maintaining intestinal homeostasis and influencing IBD progression. Specifically, HSPs share an intricate association with microbes, intestinal epithelium, and the immune system. In this review, we aim to elucidate the impact of HSPs on IBD development by examining their involvement in the interactions between the intestinal microbiota, epithelial barrier, and immune system. The recent clinical and animal models and cellular research delineating the relationship between HSPs and IBD are summarized. Additionally, new perspectives on IBD treatment approaches have been proposed.
PubMed: 38465431
DOI: 10.2174/0115665240286793240306053111 -
Scientific Reports Mar 2024Detecting breast tissue alterations is essential for cancer diagnosis. However, inherent bidimensionality limits histological procedures' effectiveness in identifying...
Detecting breast tissue alterations is essential for cancer diagnosis. However, inherent bidimensionality limits histological procedures' effectiveness in identifying these changes. Our study applies a 3D virtual histology method based on X-ray phase-contrast microtomography (PhC CT), performed at a synchrotron facility, to investigate breast tissue samples including different types of lesions, namely intraductal papilloma, micropapillary intracystic carcinoma, and invasive lobular carcinoma. One-to-one comparisons of X-ray and histological images explore the clinical potential of 3D X-ray virtual histology. Results show that PhC CT technique provides high spatial resolution and soft tissue sensitivity, while being non-destructive, not requiring a dedicated sample processing and being compatible with conventional histology. PhC CT can enhance the visualization of morphological characteristics such as stromal tissue, fibrovascular core, terminal duct lobular unit, stromal/epithelium interface, basement membrane, and adipocytes. Despite not reaching the (sub) cellular level, the three-dimensionality of PhC CT images allows to depict in-depth alterations of the breast tissues, potentially revealing pathologically relevant details missed by a single histological section. Compared to serial sectioning, PhC CT allows the virtual investigation of the sample volume along any orientation, possibly guiding the pathologist in the choice of the most suitable cutting plane. Overall, PhC CT virtual histology holds great promise as a tool adding to conventional histology for improving efficiency, accessibility, and diagnostic accuracy of pathological evaluation.
Topics: Humans; Female; X-Rays; Breast Neoplasms; X-Ray Microtomography; Microscopy, Phase-Contrast; Histological Techniques; Imaging, Three-Dimensional
PubMed: 38461221
DOI: 10.1038/s41598-024-56341-6 -
BMJ Case Reports Mar 2024We present a case of a transwoman taking hormonal feminisation therapy for over 20 years, who underwent surgical excision of a benign phyllodes tumour of the breast....
We present a case of a transwoman taking hormonal feminisation therapy for over 20 years, who underwent surgical excision of a benign phyllodes tumour of the breast. Hormones progesterone and oestrogen act on breast epithelium to increase proliferation. For ciswomen, endogenous and exogenous oestrogen exposure over a lifetime is associated with increased risk for certain benign and malignant breast pathologies. Transwomen taking hormonal therapy may also be at an increased risk of breast disease.
Topics: Female; Humans; Breast; Breast Neoplasms; Estrogens; Phyllodes Tumor; Transgender Persons; Male
PubMed: 38453219
DOI: 10.1136/bcr-2023-258616 -
Journal of the West African College of... 2023Breast cancer is the most common female cancer worldwide, affecting 13.5-30 per 100,000 women in sub-Saharan Africa. The most common histopathologic variants of breast...
INTRODUCTION
Breast cancer is the most common female cancer worldwide, affecting 13.5-30 per 100,000 women in sub-Saharan Africa. The most common histopathologic variants of breast cancer are those that originate from the glandular epithelium of the breast. Primary breast lymphomas are uncommon, and they represent only 0.04%-0.5% of all breast cancers. Burkitt lymphoma is the least of this rare group. The report intends to present Burkitt's lymphoma, a rare histopathological diagnosis of primary breast tumour in an HIV+ patient. Description of a case of bilateral breast disease and the histopathologic diagnosis. Our case was a 28-year-old HIV+ woman who presented with multiple bilateral breast lumps for 2 months duration, associated with bilateral axillary lumps, weight loss, night sweat, and malaise. Lumps range from 2 to 8 cm in size with multiple axillary lymph nodes. Core tissue biopsy showed a monotonous population of intermediate-sized lymphoid cells with round nuclei, clumped chromatin, and several nucleoli interspersed by numerous tangible body macrophages, presenting a starry-sky appearance. Diagnosis of bilateral primary breast Burkitt's lymphoma was performed, and the patient was referred to oncology. She was placed on antiretroviral therapy and chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristine sulphate, and prednisone) and clinically responded to therapy.
CONCLUSIONS
Breast lumpiness in immunocompromised patients calls for the suspicion of lymphoma.
PubMed: 38449543
DOI: 10.4103/jwas.jwas_43_23 -
ELife Mar 2024The mammary gland is a unique organ that undergoes dynamic alterations throughout a female's reproductive life, making it an ideal model for developmental, stem cell and...
The mammary gland is a unique organ that undergoes dynamic alterations throughout a female's reproductive life, making it an ideal model for developmental, stem cell and cancer biology research. Mammary gland development begins in utero and proceeds via a quiescent bud stage before the initial outgrowth and subsequent branching morphogenesis. How mammary epithelial cells transit from quiescence to an actively proliferating and branching tissue during embryogenesis and, importantly, how the branch pattern is determined remain largely unknown. Here, we provide evidence indicating that epithelial cell proliferation and onset of branching are independent processes, yet partially coordinated by the Eda signaling pathway. Through heterotypic and heterochronic epithelial-mesenchymal recombination experiments between mouse mammary and salivary gland tissues and ex vivo live imaging, we demonstrate that unlike previously concluded, the mode of branching is an intrinsic property of the mammary epithelium whereas the pace of growth and the density of ductal tree are determined by the mesenchyme. Transcriptomic profiling and ex vivo and in vivo functional studies in mice disclose that mesenchymal Wnt/ß-catenin signaling, and in particular IGF-1 downstream of it critically regulate mammary gland growth. These results underscore the general need to carefully deconstruct the different developmental processes producing branched organs.
Topics: Mice; Animals; Epithelium; Epithelial Cells; Cell Proliferation; Morphogenesis; Wnt Signaling Pathway; Mesoderm; Mammary Glands, Animal
PubMed: 38441552
DOI: 10.7554/eLife.93326 -
Endocrinology Feb 2024Macromastia is an excessive, rapid, or slow growth of breast tissue in 1 or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder,...
Macromastia is an excessive, rapid, or slow growth of breast tissue in 1 or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder, back, and neck pain, poor posture, infections, and loss of nipple sensation. The pathogenesis of macromastia or hypertrophy of mammary tissue remains poorly understood. The purpose of this study is to investigate the immunohistochemical expression of several hormone receptors that may potentially influence the growth of breast tissue in women with macromastia. Immunohistochemical studies performed on representative sections of breast tissue from 63 patients diagnosed with macromastia included estrogen receptor, progesterone receptor, androgen receptor (AR), prolactin receptor, growth hormone receptor, and vascular endothelial growth factor. The expression of each stain was evaluated separately in the glandular epithelium and adipose tissue and calculated as an H-score. We observed that AR expression in breast glandular and adipose tissue in women with macromastia was significantly lower than benign, nonhypertrophic breast tissue of a control group. Although the analyses were controlled for the age, the fact the mean age and hormonal status differed between the patients and the controls could have affected the results. Additional large studies will be required to further verify this finding and increase the knowledge about the etiology of this condition and then guide pharmacological treatment of juvenile and/or idiopathic gigantomastia.
Topics: Female; Humans; Vascular Endothelial Growth Factor A; Mammaplasty; Breast; Hypertrophy
PubMed: 38437158
DOI: 10.1210/endocr/bqae026 -
Journal of Bioenergetics and... Jun 2024Diabetic retinopathy is one of the complications of diabetes mellitus. The aim of this study was to explore the effects of ubiquitin-specific protease 48 (USP48) and its...
USP48 deubiquitination stabilizes SLC1A5 to inhibit retinal pigment epithelium cell inflammation, oxidative stress and ferroptosis in the progression of diabetic retinopathy.
BACKGROUND
Diabetic retinopathy is one of the complications of diabetes mellitus. The aim of this study was to explore the effects of ubiquitin-specific protease 48 (USP48) and its underlying mechanisms in the development of diabetic retinopathy.
METHODS
CCK-8 assay, EdU assay, and flow cytometry were used to measure the proliferative ability and the apoptotic rate of ARPE-19 cells, respectively. ELISA kits were utilized to assess the levels of inflammatory cytokines. The levels of Fe, ROS and MDA were detected using the corresponding biochemical kits. The protein expression of USP48 and SLC1A5 was examined through western blot. The mRNA level of SLC1A5 was determined using RT-qPCR. The interaction relationship between USP48 and SLC1A5 was evaluated using Co-IP assay.
RESULTS
High glucose (HG) treatment significantly inhibited cell proliferation and elevated cell apoptosis, inflammation, ferroptosis and oxidative stress in ARPE-19 cells. HG treatment-caused cell damage was hindered by USP48 or SLC1A5 overexpression in ARPE-19 cells. Fer-1 treatment improved HG-caused cell damage in ARPE-19 cells, which was blocked by USP48 knockdown. Moreover, USP48 knockdown decreased SLC1A5 expression. SLC1A5 downregulation reversed the improvement effects of USP48 upregulation on cell damage in HG-treated ARPE-19 cells.
CONCLUSION
USP48 overexpression deubiquitinated SLC1A5 to elevate cell proliferation and suppress cell apoptosis, inflammation, ferroptosis and oxidative stress in HG-triggered ARPE-19 cells, thereby inhibiting the progression of diabetic retinopathy.
Topics: Humans; Diabetic Retinopathy; Retinal Pigment Epithelium; Oxidative Stress; Ferroptosis; Inflammation; Ubiquitination; Minor Histocompatibility Antigens; Ubiquitin-Specific Proteases; Cell Line; Amino Acid Transport System ASC
PubMed: 38427128
DOI: 10.1007/s10863-024-10008-z -
Frontiers in Bioengineering and... 2023Nipple-areolar complex (NAC) reconstruction after breast cancer surgery is challenging and does not always provide optimal long-term esthetic results. Therefore,...
Nipple-areolar complex (NAC) reconstruction after breast cancer surgery is challenging and does not always provide optimal long-term esthetic results. Therefore, generating a NAC using tissue engineering techniques, such as a decellularization-recellularization process, is an alternative option to recreate a specific 3D NAC morphological unit, which is then covered with an regenerated epidermis and, thereafter, skin-grafted on the reconstructed breast. Human NACs were harvested from cadaveric donors and decellularized using sequential detergent baths. Cellular clearance and extracellular matrix (ECM) preservation were analyzed by histology, as well as by DNA, ECM proteins, growth factors, and residual sodium dodecyl sulfate (SDS) quantification. biocompatibility was evaluated 30 days after the subcutaneous implantation of native and decellularized human NACs in rats. scaffold cytocompatibility was assessed by static seeding of human fibroblasts on their hypodermal side for 7 days, while human keratinocytes were seeded on the scaffold epidermal side for 10 days by using the reconstructed human epidermis (RHE) technique to investigate the regeneration of a new epidermis. The decellularized NAC showed a preserved 3D morphology and appeared white. After decellularization, a DNA reduction of 98.3% and the absence of nuclear and HLA staining in histological sections confirmed complete cellular clearance. The ECM architecture and main ECM proteins were preserved, associated with the detection and decrease in growth factors, while a very low amount of residual SDS was detected after decellularization. The decellularized scaffolds were biocompatible, fully revascularized, and did not induce the production of rat anti-human antibodies after 30 days of subcutaneous implantation. Scaffold cytocompatibility was confirmed by the increasing proliferation of seeded human fibroblasts during 7 days of culture, associated with a high number of living cells and a similar viability compared to the control cells after 7 days of static culture. Moreover, the RHE technique allowed us to recreate a keratinized pluristratified epithelium after 10 days of culture. Tissue engineering allowed us to create an acellular and biocompatible NAC with a preserved morphology, microarchitecture, and matrix proteins while maintaining their cell growth potential and ability to regenerate the skin epidermis. Thus, tissue engineering could provide a novel alternative to personalized and natural NAC reconstruction.
PubMed: 38425730
DOI: 10.3389/fbioe.2023.1295075 -
Materials Today. Bio Apr 2024Extracellular matrix (ECM) stiffening is a common occurrence during the progression of many diseases, such as breast cancer. To accurately mimic the pathophysiological...
Extracellular matrix (ECM) stiffening is a common occurrence during the progression of many diseases, such as breast cancer. To accurately mimic the pathophysiological context of disease within 3D models, there is high demand for smart biomaterials which replicate the dynamic and temporal mechanical cues of diseased states. This study describes a preclinical disease model, using breast cancer as an example, which replicates the dynamic plasticity of the tumour microenvironment by incorporating temporal (3-week progression) biomechanical cues within a tissue-specific hydrogel microenvironment. The composite hydrogel formulation, integrating adipose-derived decellularised ECM (AdECM) and silk fibroin, was initially crosslinked using a visible light-mediated system, and then progressively stiffened through spontaneous secondary structure interactions inherent between the polymer chains (∼10-15 kPa increase, with a final stiffness of 25 kPa). When encapsulated and cultured , MCF-7 breast cancer cells initially formed numerous, large spheroids (>1000 μm in area), however, with progressive temporal stiffening, cells demonstrated growth arrest and underwent phenotypic changes resulting in intratumoral heterogeneity. Unlike widely-investigated static mechanical models, this stiffening hydrogel allowed for progressive phenotypic changes to be observed, and fostered the development of mature organoid-like spheroids, which mimicked both the organisation and acinar-structures of mature breast epithelium. The spheroids contained a central population of cells which expressed aggressive cellular programs, evidenced by increased fibronectin expression and reduction of E-cadherin. The phenotypic heterogeneity observed using this model is more reflective of physiological tumours, demonstrating the importance of establishing temporal cues within preclinical models in future work. Overall, the developed model demonstrated a novel strategy to uncouple ECM biomechanical properties from the cellular complexities of the disease microenvironment and offers the potential for wide applicability in other 3D disease models through addition of tissue-specific dECM materials.
PubMed: 38420142
DOI: 10.1016/j.mtbio.2024.101004 -
Frontiers in Nutrition 2024The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The...
OBJECTIVE
The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation within a sample of US mothers.
METHODS
Participants were drawn from a previous study of human milk cytokines. The present analysis includes 162 participants (98 Black, 64 White) with infants ranging from 1 to 18 months of age. Levels of cytokines were determined previously. Here we measure milk sodium (Na) and potassium (K) levels with ion-selective probes. Two approaches were used to define : Na levels ≥10 mmol/L and Na/K ratios greater than 0.6. Associations between maternal-infant characteristics, elevated MEP, and twelve analytes (IL-6, IL-8, TNFα, IL-1β, FASL, VEGFD, FLT1, bFGF, PLGF, EGF, leptin, adiponectin) were examined using bivariate associations, principal components analysis, and multivariable logistic regression models.
RESULTS
Elevated MEP was observed in 12 and 15% of milk samples as defined by Na and Na/K cutoffs, respectively. The odds of experiencing elevated MEP (defined by Na ≥ 10 mmol/L) were higher among Black participants and declined with older infant age. All cytokines, except leptin, were positively correlated with either Na or the Na/K ratio. A pro-inflammatory factor (IL-6, IL-8, TNFα, IL-1β, EGF) and a tissue remodeling factor (FASL, VEGFD, FLT1, bFGF, PLGF, adiponectin) each contributed uniquely to raising the odds of elevated MEP as defined by either Na or the Na/K ratio.
CONCLUSION
This exploratory analysis of MEP and cytokine levels during established lactation indicates that elevated MEP may be more common in US populations than previously appreciated and that individuals identifying as Black may have increased odds of experiencing elevated MEP based on current definitions. Research aimed at understanding the role of MEP in mammary gland health or infant growth and development should be prioritized.
PubMed: 38419845
DOI: 10.3389/fnut.2024.1258905