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Lactotrehalose, an Analog of Trehalose, Increases Energy Metabolism Without Promoting Clostridioides difficile Infection in Mice.

BACKGROUND & AIMS: Trehalose is a disaccharide that might be used in the treatment of cardiometabolic diseases. However, trehalose consumpti … performed studies with HEK293 and Caco2 cells, primary hepatocytes from mice, and human intestinal organoids. Glucose transporters were overexpressed in HEK293 cells, and glucose tra2nsport was quantified. Primary hepatocytes were cultured with or without trehalose or lactotrehalose, and gene expression patterns were analyzed. C57B6/J mice were given oral …

Animal and translational models of SARS-CoV-2 infection and COVID-19.

COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using

Aberrant endocytosis leads to the loss of normal mitotic spindle orientation during epithelial glandular morphogenesis.

Epithelial cells form tissues with many functions, including secretion and environmental separation and protection. Glandular epithelial tissues comprise cysts and tubules that are formed from a polarized, single-epithelial cell layer surrounding a central, fluid-filled lumen. The pathways regulating key processes in epithelial tissue morphogenesis such as mitotic spindle formation are incompletely understood, but are important to investigate, as their dysregulation is a signature of epithelial tumors. Here, we describe a signaling axis that manifests in a defect in mitotic spindle orientation

Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.

BACKGROUND: Understanding the mechanisms that promote or hinder healthy placental development and functionality is fundamental to advancing … cytiotrophoblast models,' 'syncytiotrophoblast development,' 'trophoblast stem cells,' 'trophoblast organoids,' and 'trophoblast cell models.' The literature search was limited to English-language publications available up to August 2025. OUTCOMES: We provide a narrative which explores the features, potential applications, and limitations of various STB mo …

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

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… IFN-γ and IL-10, and decreased levels of IL-6 | [ 58 ] ↑ tumor growth and metastasis MCF10A, PY8119 cells in mice with MDA-MB-231-, MDA-MB-453-, MDA-MB-468-, MCF10A-, and PY8119-induced tumors | [ 61 , 65 ] ↑ tumor growth and metastasis in mice with 4T1-induced tumors, PDX models, and human and mice organoids … in mice through an increase in NGF expression and TrkA signaling, which is induced by acetylcholine-M3R signaling | [ 34 ] ↑ cancer development and progression in INS-GAS mice through activation of Wnt signaling by M3R acetylcholine receptors | [ 13 ] ↑ cancer progression in mouse and human gastric organoids …

Beyond the loss of beta cells: a quantitative analysis of islet architecture in adults with and without type 1 diabetes.

AIMS/HYPOTHESIS: The organisation and cellular architecture of islets of Langerhans are critical to the physiological regulation of hormone secretion but it is debated whether human islets adhere to the characteristic mantle-core (M-C) structure seen in rodents. It is also unclear whether inherent architectural changes contribute to islet dysfunction in type 1 diabetes, aside from the loss of beta cells. Therefore, we have exploited advances in immunostaining, spatial biology and machine learning to undertake a detailed, systematic analysis of adult human islet architecture in health and type

Epigenetic insights to pediatric uropathology: Celebrating the fundamental biology vision of Tony Khoury.

INTRODUCTION: Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically. In this commentary, we highlight work on the criti

Atypical carcinoid of the uterine cervix accompanying adenocarcinoma in situ.

CLINICAL QUESTION: A 45-year-old woman presented with painless vaginal bleeding for 2 months. A biopsy was taken from the uterine cervix, and poorly differentiated adenocarcinoma was suspected. After three cycles of neoadjuvant chemotherapy treatment, the patient underwent radical hysterectomy with bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy.Review the high quality, interactive digital Aperio slide at http://virtualacp.com/JCPCases/jclinpath-2018-205081-1/ and consider your diagnosis. WHAT IS YOUR DIAGNOSIS?: Typical carcinoid.Poorly differentiated adenocarcinom

Basaloid neoplasms in nevus sebaceus.

BACKGROUND: Nevus sebaceus (NS) (organoider nevus) may frequently be associated with the development of a number of benign and malignant neoplasms among which basaloid neoplasms are the most common. Histopathologic criteria for diagnosis and classification of basaloid proliferations arising in NS are still debated. Most previous investigators have considered them to represent mainly basal cell carcinomas (BCCs). On the contrary, a number of recent authors have proposed that most basaloid neoplasms in NS exhibit predominantly morphologic features implying benignancy, thus representing trichobla

Ectopic sphenoid sinus pituitary adenoma (ESSPA) with normal anterior pituitary gland: a clinicopathologic and immunophenotypic study of 32 cases with a comprehensive review of the english literature.

Ectopic sphenoid sinus pituitary adenoma (ESSPA) may arise from a remnant of Rathke's pouch. These tumors are frequently misdiagnosed as other neuroendocrine or epithelial neoplasms which may develop in this site (olfactory neuroblastoma, neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, paraganglioma, melanoma). Thirty-two patients with ESSPA identified in patients with normal pituitary glands (intact sella turcica) were retrospectively retrieved from the consultation files of the authors' institutions. Clinical records were reviewed with follow-up obtained. An immunohistochemic

Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review.

BACKGROUND: The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesio … ioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium …

SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1.

BACKGROUND: COVID-19 can cause multiple organ damages as well as metabolic abnormalities such as hyperglycemia, insulin resistance, and new … -CoV-2 compared to the control infected with mock; human pluripotent stem cell (hPSC)-derived liver organoids infected with SARS-CoV-2; adipose tissues from a mouse model of COVID-19 overexpressing human ACE2 via adeno-associated virus serotype 9 (AAV9) compared to the control GFP after SARS-CoV-2 infection; iPS-derived human pancreatic cells infected with …

TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination.

Cholesterol metabolism operates autonomously within the central nervous system (CNS), where the majority of cholesterol resides in myelin. We demonstrate that TDP-43, the pathological signature protein for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), influences cholesterol metabolism in oligodendrocytes. TDP-43 binds directly to mRNA of SREBF2, the master transcription regulator for cholesterol metabolism, and multiple mRNAs encoding proteins responsible for cholesterol biosynthesis and uptake, including HMGCR, HMGCS1, and LDLR. TDP-43 depletion leads to reduced SREBF

Human stem cell modeling in neurofibromatosis type 1 (NF1).

The future of precision medicine is heavily reliant on the use of human tissues to identify the key determinants that account for differences between individuals with the same disorder. This need is exemplified by the neurofibromatosis type 1 (NF1) neurogenetic condition. As such, individuals with NF1 are born with a germline mutation in the NF1 gene, but may develop numerous distinct neurological problems, ranging from autism and attention deficit to brain and peripheral nerve sheath tumors. Coupled with accurate preclinical mouse models, the availability of NF1 patient-derived induced plurip

Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.

Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mo

ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.

Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R), but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited, and the few remaining tumors were of low-grade dysplasia. RNA sequencing analysis demonstrated down-regulation of STAT3 and Wnt pathway components. Because EGF-R on myeloid cells, but not on intestinal epithelial cells, is required

The impact of menstrual cycle phase and BMI on mitochondrial dysfunction in PMOS endometrium.

STUDY QUESTION: Does the endometrium of oligo-ovulatory women with polyendocrine metabolic ovarian syndrome (PMOS) exhibit menstrual cycle p … in vitro experiments were conducted using cultured endometrial stromal cells (ESCs) and epithelial organoids (EEOs) derived from an additional endometrial sample cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA sequencing was performed on biopsies from 78 (oligo-)ovulatory women, age- and BMI-matched between PMOS (n = 39) and control (n = 39) groups. …

Tissue stiffness at the human maternal-fetal interface.

STUDY QUESTION: What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and place … tion of extravillous trophoblast (EVT) in three dimensions and to culture endometrial and placental organoids, was also determined (N = 5). PARTICIPANTS/MATERIALS, SETTING, METHODS: Atomic force microscopy was used to perform ex vivo direct measurements to determine the stiffness of fresh tissue samples. Decidua was stained by immunohistochemistry (IHC) fo …

Bupleurum marginatum Wall.: A comprehensive review of the traditional uses, phytochemistry, pharmacology, and quality control.

ETHNOPHARMACOLOGY RELEVANVE: Bupleurum marginatum Wall. (B. marginatum) has a long history of use as a traditional medicine among Chinese ethnic minorities. It is characterized by a pungent and bitter taste, slightly cold in nature, and is associated with the liver, gallbladder, and lung meridians. Its functions include releasing the exterior and harmonizing the interior, soothing the liver and relieving depression, as well as uplifting middle qi. AIM OF THE REVIEW: This review comprehensively reviews the traditional applications, chemical constituents, pharmacological effects, and quality co

Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study.

PURPOSE: With the conventional approach of surgery and postoperative radiotherapy for patients with Masaoka Stage III thymoma, progress has been slow for an improvement in the long-term survival rate over the past 20 years. The objective of this study was to evaluate the pattern of failure and survival after surgery and postoperative radiotherapy in Stage III thymoma and search for a new direction for better therapy outcome. METHODS AND MATERIALS: Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were determined to have Masa