Histology and histopathology Vol.40, nº3 (2025)
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- PublicationOpen AccessClinicopathologic and molecular characteristics of neuroendocrine carcinomas of the gallbladder(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tang, Hui; Jiang, Xiaojun; Zhu, Lili; Xu, Liming; Wang, Xiaoxi; Li, Hong; Gao, Feifei; Liu, Xinxin; Ren, Chuanli; Zhao, YanGallbladder neuroendocrine carcinomas (GB-NECs) are a rare subtype of malignant gallbladder cancer (GBC). The genetic and molecular characteristics of GB-NECs are rarely reported. This study aims to assess the frequency of microsatellite instability (MSI) in GB-NECs and characterize their clinicopathologic and molecular features in comparison with gallbladder adenocarcinomas (GB-ADCs). Data from six patients with primary GB-NECs and 13 with GB-ADCs were collected and reevaluated. MSI assay, immunohisto-chemistry for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2), comprehensive genomic profiling (CGP) via next-generation sequencing (NGS), and evaluation of tumor mutation burden (TMB) were conducted on these samples. The six GB-NEC cases were all female, with a mean age of 62.0±9.2 years. Of these, two cases were diagnosed as large cell neuroendocrine carcinomas (LCNECs), while the remaining four were small cell neuroendocrine carcinomas (SCNECs). Microsatellite states observed in both GB-NECs and GB-ADCs were consistently microsatellite stable (MSS). Notably, TP53 (100%, 6/6) and RB1 (100%, 6/6) exhibited the highest mutation frequency in GB-NECs, followed by SMAD4 (50%, 3/6), GNAS (50%, 3/6), and RICTOR (33%, 2/6), with RB1, GNAS, and RICTOR specifically present in GB-NECs. Immunohistochemical (IHC) assays of p53 and Rb in the six GB-NECs were highly consistent with genetic mutations detected by targeted NGS. Moreover, no statistical difference was observed in TMB between GB-NECs and GB-ADCs (p=0.864). Although overall survival in GB-NEC patients tended to be worse than in GB-ADC patients, this difference did not reach statistical significance (p=0.119). This study has identified the microsatellite states and molecular mutation features of GB-NECs, suggesting that co-mutations in TP53 and RB1 may signify a neuroendocrine inclination in GB-NECs. The IHC assay provides an effective complement to targeted NGS for determining the functional status of p53 and Rb in clinical practice.
- PublicationOpen AccessDiversity and dynamics of fish ovaries: Insights into reproductive strategies, hormonal regulation, and ovarian development(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Mokhtar, Doaa M.Fish ovaries exhibit a remarkable diversity in shape, size, and organization, reflecting the myriad reproductive strategies employed by different species. This review delves into the intricate biology of fish ovaries, highlighting their structural diversity and the hormonal regulation that governs ovarian development and oocyte maturation. Key hormones include pituitary gonadotropins (GTHs) and maturation-inducing hormones (MIHs), which initiate oocyte growth and maturation. GTHs stimulate ovarian production of estradiol-17β and 17α,20β-DP, which induce oocyte maturation via MPF formation. Sex steroids like estrogens and progestogens, synthesized from cholesterol, play crucial roles. Other hormones, including growth hormone, prolactin, thyroid hormones, IGFs, ACTH, and melatonin, influence ovarian activity. The review also explores the varied reproductive strategies among fish, including oviparity and viviparity, and discusses how environmental factors like water temperature and photoperiod influence ovarian histology. Understanding the complex interplay between these factors is essential for advancing fisheries management, conservation, and aquaculture practices. Additionally, the evolutionary trajectory of fish ovaries underscores their adaptation to diverse ecological niches, contributing to the survival and reproductive success of fish species. The ovarian stroma provides structural support and houses various cell types, including dendritic cells (DCs), endocrine cells, and telocytes, contributing to follicle growth and hormone production, essential for reproductive success in fish. Fish ovaries are a crucial aspect of fish biology, with their structure and function intricately regulated by hormonal, environmental, and seasonal factors.
- PublicationOpen AccessIntrinsically synthesized melatonin in mitochondria and factors controlling its production(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Reiter, Russel J.; Sharma, Ramaswamy N; Almieda Chuffa, Luiz Gustavo de; Silva, Danilo Grunig Humberto da Silva; Rosales Corral, SergioThe percentage of the total amount of melatonin produced in vertebrates that comes from the pineal is small (likely <5%) but, nevertheless, functionally highly noteworthy. The significance of pineal melatonin is that it is secreted cyclically such that it has a critical function in influencing not only the suprachiasmatic nucleus but clock genes that reside in perhaps every cell throughout the organism. Extrapineal melatonin, which may be synthesized in the mitochondria of all other cells in much larger amounts than that in the pineal gland has a different function than that derived from the pineal gland. Its synthesis is not circadian and it is not directly impacted by the photoperiodic environment. Also, melatonin from the extrapineal sites is not normally secreted into the blood stream; rather, it acts locally in its cell of synthesis or, possibly via paracrine mechanisms, on immediately adjacent cells. The functions of extrapineal melatonin include central roles in maintaining molecular and redox homeostasis and actions in resisting pathological processes due to its ability to directly or indirectly detoxify free radicals. The vast majority of organisms that exist on Earth lack a pineal gland so pineal-derived melatonin is unique to vertebrates. Evidence suggests that all invertebrates, protists and plants synthesized melatonin and they have no pineal homolog; thus, the production of melatonin by extrapineal cells in vertebrates should not be unexpected. While the factors that control pineal melatonin synthesis are well documented, the processes that regulate extrapineal melatonin production are undefined.