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BioMed Research International 2024The loss of RAB25 expression-RAS superfamily of GTPase characteristic of numerous breast cancers-corresponds with H-RAS point mutations, particularly in triple-negative...
The loss of RAB25 expression-RAS superfamily of GTPase characteristic of numerous breast cancers-corresponds with H-RAS point mutations, particularly in triple-negative breast cancers (TNBC), a subtype associated with a poor prognosis. To address the poorly understood factors dictating the progression of TNBC tumors, we examine the cooperative effects that loss of RAB25 expression in human mammary epithelial cell (HMEC) lines with H-RAS mutations confers in tumorigenesis. HMECs were immortalized by transduction with LXSN CDK4 R24C, a mutant form of cyclin-dependent kinase, followed by transduction with hTERT, a catalytic subunit of the telomerase enzyme. We found that with the loss of RAB25 and overexpression of mutant H-RAS61L, immortal HMECs transformed toward anchorage-independent growth and acquired an increased ability to migrate. Furthermore, cells express low CD24, high CD44, and low claudin levels, indicating stem-like properties upon transformation. Besides, loss of RAB25 and overexpression of H-RAS61L resulted in increased expression of transcription factors Snail and Slug that drive these cells to lose E-cadherin and undergo epithelial-mesenchymal transition (EMT). This study confirms that loss of RAB25 and overexpression of mutant H-RAS can drive HMECs toward a mesenchymal stem-like state. Our findings reveal that RAB25 functions as a tumor suppressor gene, and loss of RAB25 could serve as a novel biomarker of the claudin-low type of TNBC.
Topics: Humans; rab GTP-Binding Proteins; Cell Transformation, Neoplastic; Epithelial Cells; Epithelial-Mesenchymal Transition; Claudins; Female; Mammary Glands, Human; Triple Negative Breast Neoplasms; Gene Expression Regulation, Neoplastic; Oncogenes; Snail Family Transcription Factors; Mutation
PubMed: 38803515
DOI: 10.1155/2024/8544837 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2024Mastitis affects almost all mammals including humans and dairy cows. In the dairy industry, bovine mastitis is a disease with a persistently high incidence, causing... (Review)
Review
Mastitis affects almost all mammals including humans and dairy cows. In the dairy industry, bovine mastitis is a disease with a persistently high incidence, causing serious losses to the health of cows, the quality of dairy products, and the economy of dairy farms. Although local udder infection caused by the invasion of exogenous pathogens into the mammary gland was considered the main cause of mastitis, evidence has been established and continues to grow, showing that nutrition factors and gastrointestinal microbiome (GM) as well as their metabolites are also involved in the development of mammary inflammatory response. Suboptimal nutrition is recognized as a risk factor for increased susceptibility to mastitis in cattle, in particular the negative energy balance. The majority of data regarding nutrition and bovine mastitis involves micronutrients. In addition, the dysbiotic GM can directly trigger or aggravate mastitis through entero-mammary gland pathway. The decreased beneficial commensal bacteria, lowered bacterial diversity, and increased pathogens as well as proinflammatory metabolites are found in both the milk and gastrointestinal tract of mastitic dairy cows. This review discussed the relationship between the nutrition (energy and micronutrient levels) and mastitis, summarized the role of GM and metabolites in regulating mastitis. Meanwhile, several non-antibiotics strategies were provided for the prevention and alleviation of mastitis, including micronutrients, probiotics, short-chain fatty acids, high-fiber diet, inulin, and aryl hydrocarbon receptor.
PubMed: 38800734
DOI: 10.1016/j.aninu.2024.01.010 -
Frontiers in Cell and Developmental... 2024Neurofibromin, coded by the tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with...
BACKGROUND
Neurofibromin, coded by the tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which mutations lead to breast cancer tumorigenesis is not well understood. Therefore, the objective of this work was to identify stromal alterations before tumor formation that result in the increased risk and poorer outcome seen among NF1 patients with breast cancer.
APPROACH
To accurately model the germline monoallelic mutations in NF1 patients, we utilized an deficient rat model with accelerated mammary development before presenting with highly penetrant breast cancer.
RESULTS
We identified increased collagen content in -deficient rat mammary glands before tumor formation that correlated with age of tumor onset. Additionally, gene expression analysis revealed that -deficient mature adipocytes in the rat mammary gland have increased collagen expression and shifted to a fibroblast and preadipocyte expression profile. This alteration in lineage commitment was also observed with differentiation, however, flow cytometry analysis did not show a change in mammary adipose-derived mesenchymal stem cell abundance.
CONCLUSION
Collectively, this study uncovered the previously undescribed role of in mammary collagen deposition and regulating adipocyte differentiation. In addition to unraveling the mechanism of tumor formation, further investigation of adipocytes and collagen modifications in preneoplastic mammary glands will create a foundation for developing early detection strategies of breast cancer among NF1 patients.
PubMed: 38799507
DOI: 10.3389/fcell.2024.1375441 -
Developmental and Comparative Immunology Sep 2024Defensins are antimicrobial peptides involved in innate immunity, and gene number differs amongst eutherian mammals. Few studies have investigated defensins in...
Defensins are antimicrobial peptides involved in innate immunity, and gene number differs amongst eutherian mammals. Few studies have investigated defensins in marsupials, despite their potential involvement in immunological protection of altricial young. Here we use recently sequenced marsupial genomes and transcriptomes to annotate defensins in nine species across the marsupial family tree. We characterised 35 alpha and 286 beta defensins; gene number differed between species, although Dasyuromorphs had the largest repertoire. Defensins were encoded in three gene clusters within the genome, syntenic to eutherians, and were expressed in the pouch and mammary gland. Marsupial beta defensins were closely related to eutherians, however marsupial alpha defensins were more divergent. We identified marsupial orthologs of human DEFB3 and 6, and several marsupial-specific beta defensin lineages which may have novel functions. Marsupial predicted mature peptides were highly variable in length and sequence composition. We propose candidate peptides for future testing to elucidate the function of marsupial defensins.
Topics: Animals; Marsupialia; Phylogeny; beta-Defensins; Humans; Multigene Family; Immunity, Innate; Defensins; Transcriptome; Genome; alpha-Defensins; Amino Acid Sequence; Evolution, Molecular
PubMed: 38797458
DOI: 10.1016/j.dci.2024.105207 -
Microorganisms May 2024The existence of the human milk microbiome has been widely recognized for almost two decades, with many studies examining its composition and relationship to maternal... (Review)
Review
The existence of the human milk microbiome has been widely recognized for almost two decades, with many studies examining its composition and relationship to maternal and infant health. However, the richness and viability of the human milk microbiota is surprisingly low. Given that the lactating mammary gland houses a warm and nutrient-rich environment and is in contact with the external environment, it may be expected that the lactating mammary gland would contain a high biomass microbiome. This discrepancy raises the question of whether the bacteria in milk come from true microbial colonization in the mammary gland ("residents") or are merely the result of constant influx from other bacterial sources ("tourists"). By drawing together data from animal, in vitro, and human studies, this review will examine the question of whether the lactating mammary gland is colonized by a residential microbiome.
PubMed: 38792838
DOI: 10.3390/microorganisms12051009 -
Animals : An Open Access Journal From... May 2024Additional Affiliation(s) [...].
Correction: Geldsetzer-Mendoza, C.; Riveros, J.L. Morphophysiological Responses of the Goat Mammary Gland to Water Scarcity in Arid and Semi-Arid Environments: Are They Enough to Generate Adaptation to New Climatic Challenges? 2023, , 3825.
Additional Affiliation(s) [...].
PubMed: 38791731
DOI: 10.3390/ani14101445 -
Animals : An Open Access Journal From... May 2024Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary...
Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.
PubMed: 38791685
DOI: 10.3390/ani14101469 -
Journal of Dairy Science May 2024The presence of an autocrine factor in milk that can trigger mammary gland involution was proposed more than 50 years ago. To provide evidences that one or more...
The presence of an autocrine factor in milk that can trigger mammary gland involution was proposed more than 50 years ago. To provide evidences that one or more autocrine factor(s) exists, 10 multiparous cows in late lactation were quarter-milked for 7 d. Following this baseline period, the right front quarter of each cow was left unmilked while the other quarters were milked for 7 d. Before the last milking of that period, milk (mammary secretions) was collected aseptically from both front quarters. After that milking, 250 mL of the collected samples was infused in the cows' respective rear quarters. No quarters were milked for the following 7 d (milk stasis period), and then quarter milking was resumed in all quarters for the last 7 d of the experiment (remilking period). Quarter milk samples were collected during the baseline period, before the milk stasis period, and during the remilking period. These samples were used for measuring milk components and the concentration of involution markers (SCC, BSA and lactoferrin). Samples of mammary secretions were collected manually from the quarters during the milk stasis period for involution marker determination. RNA was extracted from samples collected from front quarters before the last milking before the milk stasis period for microRNA (miRNA) determination. As anticipated, the longer milk stasis period implemented for the right front quarter resulted in a more advanced involution than in the left front quarter, based on the concentration of involution markers in the mammary secretions, lower milk production recovery and changes in milk composition during the remilking period. All 3 involution marker concentrations in the mammary secretions increased in both rear quarters, but were greater in the right quarter secretions than in the left quarter secretions. Resuming milking reinitiated milk production in all quarters, but milk production recovery in the right rear quarters was less robust than that in the left rear quarters (54.3 ± 1.4% vs 61.6 ± 1.4%, respectively). Milk from the quarters infused with mammary secretions (right rear) had a lower lactose content, but a higher milk protein content and higher SCC than the quarters infused with milk. We detected a total of 359 miRNAs, 76 of which were differentially expressed in milk and mammary secretions. Expression of bta-miR-221 and bta-miR-223 were upregulated in mammary secretions 34- and 40-fold, respectively. The results of the present experiment support the contention that milk stasis leads to the accumulation of one or more factors that trigger involution. The results also indicate that milk stasis leads to changes in the miRNA profile of the milk, but whether such changes are a cause or a consequence of the involution process remains to be established.
PubMed: 38788842
DOI: 10.3168/jds.2023-24603 -
Pathogens (Basel, Switzerland) May 2024Mastitis is a common mammary gland disease of dairy cattle caused by a wide range of organisms including bacteria, fungi and algae. Mastitis contributes to economic...
Mastitis is a common mammary gland disease of dairy cattle caused by a wide range of organisms including bacteria, fungi and algae. Mastitis contributes to economic losses of dairy farms due to reduced yield and poor quality of milk. Since the correct identification of pathogens responsible for the development of mastitis is crucial to the success of treatment, it is necessary to develop a quick and accurate test to distinguish the main pathogens causing this disease. In this paper, we describe the development of a test based on the multiplex polymerase chain reaction (PCR) method allowing for the identification of , , and When creating our test, we relied on the results from new generation sequencing (NGS) for accurate determination of species affiliation. The multiplex PCR test was verified on 100 strains including veterinary samples, ATCC and Polish Collection of Microorganisms (PCM) reference strains. The obtained results indicate that this test is accurate and displays high specificity. It may serve as a valuable molecular tool for the detection of major mastitis pathogens.
PubMed: 38787275
DOI: 10.3390/pathogens13050423 -
Tomography (Ann Arbor, Mich.) May 2024The aim of this study was to show for the first time that low-frequency 3D-transmitted ultrasound tomography (3D UT, volography) can differentiate breast tissue types...
The aim of this study was to show for the first time that low-frequency 3D-transmitted ultrasound tomography (3D UT, volography) can differentiate breast tissue types using tissue properties, accurately measure glandular and ductal volumes in vivo, and measure variation over time. Data were collected for 400 QT breast scans on 24 women (ages 18-71), including four (4) postmenopausal subjects, 6-10 times over 2+ months of observation. The date of onset of menopause was noted, and the cases were further subdivided into three (3) classes: pre-, post-, and peri-menopausal. The ducts and glands were segmented using breast speed of sound, attenuation, and reflectivity images and followed over several menstrual cycles. The coefficient of variation (CoV) for in premenopausal women was significantly larger than for postmenopausal women, whereas this is not true for the CoV. The glandular standard deviation (SD) is significantly larger in premenopausal women vs. postmenopausal women, whereas this is not true for ductal tissue. We conclude that ducts do not appreciably change over the menstrual cycle in either pre- or post-menopausal subjects, whereas glands change significantly over the cycle in pre-menopausal women, and 3D UT can differentiate ducts from glands in vivo.
Topics: Humans; Female; Adult; Menstrual Cycle; Middle Aged; Aged; Breast; Young Adult; Ultrasonography, Mammary; Imaging, Three-Dimensional; Adolescent; Mammary Glands, Human
PubMed: 38787020
DOI: 10.3390/tomography10050060