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The cellular biology of megakaryocytes.

Megakaryocytes show a pattern of cellular proliferation and maturation which is unique in mammalian biology. Cells mature to the point of cytoplasmic fragmentation in three major ploidy classes, 8n, 16n, and 32n and the three are fed from a precursor committed stem cell. Two-thirds of the cells belong in the 16n class, and approximately one-sixth in the 8n and 32n classes. The cytoplasm of cells in each ploidy class has a characteristic concentration of granules and demarcation membrane system which appears to be translated into the characteristic features of the platelet progeny from each class. These differ from normal young platelets. Megakaryocytes release fragments of cytoplasm into marrow sinusoids and these differ from platelets in that they do not have the peripheral microtubular bundle or sub-marginal dense tubular system. Transition from fragment to circulating platelet presumably takes place elsewhere in the circulation. With stimulation of platelet production, "stress" platelets are produced, from megakaryocytes which show changes with respect to content of polyribosomes, glycogen and membrane.

Animals

Serum and cellular biologic tumor markers in patients with urologic cancer.

During the past several years the development of radioimmunoassay and immunocytochemical techniques to detect small amounts of marker in the sera and cancer cells of cancer patients has made a significant impact on the diagnosis and management of certain cancers. Among these markers alpha-fetoprotein, human chorionic gonadotropin, and pregnancy specific beta-1 glycoprotein have been useful in the staging, detection of recurrence, prognosis, and management of testicular cancer. In this article the recent developments and future perspectives concerning these and other newer markers are discussed.

Acid Phosphatase

Organization and cellular biology of the perichondrial ossification groove of ranvier: a morphological study in rabbits.

The perichondrial ossification groove of Ranvier, a circumferential groove in the periphery of the epiphyseal cartilage, was studied in rabbits whose ages ranged from one week to eight months using light and electron microscopy, autoradiography after labeling with 3H-thymidine, 3H-proline, and 3H-glucosamine, and histochemical staining for proteoglycans and alkaline phosphatase. By these methods, three groups of cells were identified within the groove: 1. A group of densely packed cells deep in the groove, which are the progenitor cells for the osteoblasts that form the bone bark, a cuff of bone surrounding the epiphyseal growth-plate region and the adjacent part of the metaphysis. 2. A group of more widely dispersed, relatively undifferentiated mesenchymal cells and fibroblasts, some of which are chondroblast precursors that probably contribute to appositional chondrogenesis and growth in width of the epiphyseal cartilage. 3. Fibroblasts and fibrocytes among sheets of highly oriented and organized collagen fibers which form a fibrous layer that is continuous with the outer fibrous layer of the periosteum and with the perichondrium. This layer also sends fibers into the epiphyseal cartilage and anchors the periosteum firmly to the epiphyses as bone growth proceeds.

Animals

miR-335-3p acts as a tumor suppressor in esophageal squamous cell carcinoma and predicts favorable prognosis.

BACKGROUND: Esophageal cancer is a highly invasive malignancy that severely impairs normal digestive function and poses a substantial threat to patient survival. The pathogenesis of miRNA-mediated tumors has been widely documented. AIM: Verifying the involvement of miR-335-3p in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: The study enrolled 90 ESCC patients, from whom clinical data and pathological tissue samples were acquired. The prognostic potential of dysregulated miR-335-3p in ESCC was assessed using the Kaplan-Meier method. miR-335-3p and GFPT1 expression in the specimens were measured by RT-qPCR. Cellular biological functions were verified through transfection, CCK-8, Transwell, and kit-based assays. The targeting relationship was ascertained by luciferase activity assays. RESULTS: miR-335-3p was downregulated in ESCC, which is indicative of poorer prognostic outcomes. GFPT1 was up-regulated and was regarded as a target of miR-335-3p. Increased miR-335-3p levels markedly impaired cellular biological functions. Conversely, simultaneous overexpression of GFPT1 alleviated the negative effects induced by miR-335-3p mimic, which was associated with the partial restoration of cell activity and antioxidant capacity. CONCLUSION: miR-335-3p represents a potential independent prognostic marker in ESCC. The anti-tumor activity induced by miR-335-3p overexpression may be associated with its regulation of GFPT1.

Humans

The illusion of simplicity: the medical model revisited.

Traditional medical models have been found to be linear, restrictive, and oversimplified. Only a truly biological model, encompassing evolutionary as well as molecular and cellular biology, can account for the complex origins, forms, and effects of disease, which are illustrated by a discussion of hepatitis B and slow virus disease. An updated biological model of disease takes into account predisposition to disease, the timing and route of infection, multiple disease forms, variable adaptive response, and the role of social and cultural factors and views disease as a failure of adaptation in one or more systems. Its application to psychiatry is shown in a discussion of stress, bereavement, and separation.

Adaptation, Physiological

Aberrant TERT expression: linking chronic inflammation to hepatocellular carcinoma†.

Telomerase reverse transcriptase (TERT), the catalytic enzyme component of telomerase, plays multiple roles in cellular biology. Its canonical function is primarily associated with telomere maintenance and genomic stability. In addition, several studies revealed critical non-canonical extra-telomeric functions of TERT in various cellular processes, including cell proliferation and survival, DNA damage response, transcription, signal transduction, and metabolic regulation, both in normal and in cancer cells. Notably, TERT is aberrantly upregulated in more than 80% of hepatocellular carcinoma (HCC) cases, making it an important target in liver cancer research. However, due to the diversity and complexity of TERT's functions in vivo, the precise mechanisms by which TERT contributes to the initiation and progression of HCC remain unclear. A recent study published in The Journal of Pathology using the Alb-Cre;TertTg mouse model and clinical HCC samples addresses the role of TERT in hepatocarcinogenesis. The study demonstrates that TERT promotes cell cycle progression and hepatocarcinogenesis by enhancing NF-κB promoter activity and facilitating the ubiquitination of p21. Notably, absence of functional p53 accelerates liver tumor development in TERT transgenic mice. These findings further underscore the critical role of TERT in inflammation-driven hepatocarcinogenesis and provide new insights into its underlying mechanisms. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Telomerase

5-(125I)-iododeoxyuridine and the Auger effect: biological consequences and implications for therapy.

If the full potential for the use of radionuclides in the treatment of cancer is to be realized, the problem of locating internal emitters with a short range of action in the sensitive targets of the cell must be solved. It is already clear that only two types of radioactivity will satisfy these requirements: alpha decay and, as this review has attempted to demonstrate, electron capture with subsequent Auger cascade. Although mechanisms have yet to be clarified, it is clear that an Auger emitter located within the genetic apparatus is extremely radiotoxic with as little as a single disintegration being lethal in some organisms. Moreover, the available experimental evidence suggests that the extreme lethality is confined to a very small volume, probably that of molecular dimensions. These facts highlight the advantages as well as the limitations of using the Auger effect for cancer therapy. A favorable feature is that extreme damage is confined only to the cell in which radioactive decay takes place; a disadvantage is that the biochemical specificities are very great. Not only must the radioactivity be directed specifically to malignant calls, but it must also be very closely approximated to their genetic structures as well. This circumstance has its counterpart in considering the use of electron capture emitters for diagnostic purposes since their potential hazard depends in large measure on their cellular localization. These microscopic considerations have largely been neglected in traditional radionuclide dosimetry but, considering the magnitude of the effect and the widespread use of such radionuclides as chromium-51, gallium-67, selenium-75, iodine-123, and thallium-201, they should be reexamined. In some cases, such as with 67Ga, we may find that standard dosimetric calculations have overestimated the hazard. In others, the opposite may be true. Whichever the result, it should serve as an impetus to obtain data on the cellular localization of commonly employed radionuclides and on the microscopic distribution of dose. Lastly, it is clear that Auger emitters can be used as ultramicroscopic probes to define the radiosensitive targets of the cell and to destroy regions of subcellular dimensions. This potential use in radiation and cellular biology has only now begun to be exploited.

Animals

The use of cytochalasins to probe the immunobiolgoy of lymphocytes.

No attempt will be made to summarize in any formal way the "pot-pourri" of experiments we have considered in this chapter. It may occur to some that immunologists as a group have been somewhat removed from the advances made in cellular biology during the last decade. Specifically, they may appear to lack an appreciation of the many ways in which durgs like the cytochalasins can affect cell function. Perhaps because of this naivety however, the immunologists have used the cytochalasins to probe systems so complex that they would never have been comtemplated by more conservative investigaors. In doing so they have revealed insight into many systems that will hopefully be of broad biolgical interest. To date the insights have been mostly of a rather superficial nature and clearly demand more thorough investigation. If they are to be done, such studies will have to be performed by non-immunologists bringing new tools and new perspectives to bear on the immunologists' problems.

Animals

The oxyphil and C cells of the human thyroid gland. A cytochemical and histopathologic review.

The C and oxyphil cells of the human thyroid are analyzed in the light of recent advances in cellular biology, cytochemistry, and histopathology. The C cell is present in the normal human thyroid, where its identification is cardinally by means of argyrophilic cytoplasmic granules. The morphology, topography and argyrophilia of C cells are discussed with reference to tumor, cyst, and teratoma formation in the thyroid gland. Oxyphil cells of the thyroid are cytochemically akin to C cells but arise from follicular cells. They occur in the thyroid and other protein-producing organs, but are themselves inefficient producers of proteins and glycoproteins. Speculation is made on their morphological characteristics, and consideration is given to DNA-RNA involvement in the functional and morphological alterations of this follicular cell type.

Adenoma

The caudal neurosecretory system. A critical evaluation of the two-hormone hypothesis.

Recent information on the caudal neurosecretory system (urophysis) is collated, with special reference to cellular biology including neural relations, activity and chemistry 8 the biological principles associated with the urophysis, pharmacological analysis of the receptors for these principles, and their possible functions in a physiological sense. The existence of at least two principles, urotensins I and II, is well established. They differ pharmacologically and chemically and may arise from different cell types. At present, osmoregulation, cardiovascular regulation and reproduction are the most likely aspects of organismal physiology wherein these principles may be involved.

Animals

Toward large-scale mass spectrometry-based omics for clinical applications.

INTRODUCTION: As healthcare advances toward personalized medicine, mass spectrometry-based research is advancing our understanding of cellular biology and disease states, and translating these findings into clinical applications. This review highlights recent advances in methodology and technology that demonstrate the capabilities of mass spectrometry-based proteomics, lipidomics, and metabolomics in clinical practice. AREAS COVERED: The ability to directly analyze functional molecules with mass spectrometry uncovers crucial clinical information. Each data modality (proteins, lipids, and metabolites) provides essential insight into healthy and disease states. As technology advances, integrating data from different modalities unlocks new possibilities for clinical research. To gain the most from this multi-omic data, unsupervised integration methods can provide detailed insights into complex biological processes. As the field applies this knowledge, healthcare could experience significant leaps in the near future. This review examines recent advancements in mass spectrometry-based proteomics, lipidomics, and metabolomics, focusing on how improvements in sample preparation, automation, and multi-omics data integration are making large-scale clinical studies more accessible. EXPERT OPINION: Recent technical and methodological advancements in mass spectrometry analysis have propelled healthcare toward a tipping point, shifting from traditional RNA- and DNA-based research to downstream analysis of protein, lipid, and metabolite effectors.

Humans

Computational mass spectrometry and genome mining guided discovery of metallophores produced by Microbulbifer.

Iron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is a chemically underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals, and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language code to determine siderophore production by Microbulbifer spp. in mono- and mixed cultures. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing an unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.

MassQL

Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.

Uncovering the role of upstream open reading frames (uORFs) challenges conventional views of one protein per messenger RNA and reveals the capacity of some uORFs to encode microproteins that contribute to cellular biology and physiology. This study explores the functional role of a recently identified mitochondrial microprotein, SLC35A4-MP, in the brown adipose tissue of mice. Our findings reveal dynamic regulation of SLC35A4-MP expression during primary brown adipocyte differentiation in vitro and during cold exposure or high-fat diet (HFD)-induced obesity in mice. Using a knockout mouse model, we show that loss of SLC35A4-MP disrupts mitochondrial lipid composition, decreasing cardiolipins and phosphatidylethanolamine in brown adipose tissue from HFD-fed mice. SLC35A4-MP deficiency also impairs mitochondrial activity, alters mitochondrial number and morphology, and promotes inflammation. Knockout mice accumulate acylcarnitines during cold exposure, indicating defective fatty acid oxidation. These findings reveal SLC35A4-MP as a previously unrecognized microprotein in regulating mitochondrial function and tissue lipid metabolism, adding to the growing list of functional endogenous microproteins.

Animals