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BioRxiv : the Preprint Server For... Jun 2024The "bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during the development of the mouse brain, facilitating the activation of long-chain...
The "bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during the development of the mouse brain, facilitating the activation of long-chain fatty acids (LCFAs) and their integration into essential lipid species crucial for brain function. Through its enzymatic activity, ACSBG1 converts LCFAs into acyl-CoA derivatives, supporting vital processes like membrane formation, myelination, and energy production. Its regulatory role significantly influences neuronal growth, synaptic plasticity, and overall brain development, highlighting its importance in maintaining lipid homeostasis and proper brain function. Originally discovered in the fruit fly brain, ACSBG1 attracted attention for its potential implication in X-linked adrenoleukodystrophy (XALD) pathogenesis. Studies using Drosophila melanogaster lacking the ACSBG1 homolog, bubblegum, revealed adult neurodegeneration with elevated levels of very long-chain fatty acids (VLCFA). To explore ACSBG1's role in fatty acid (FA) metabolism and its relevance to XALD, we created an ACSBG1 knockout (Acsbg1 ) mouse model and examined its impact on lipid metabolism during mouse brain development. Phenotypically, Acsbg1 mice resembled wild type (w.t.) mice. Despite its primary expression in tissues affected by XALD, brain, adrenal gland and testis, ACSBG1 depletion did not significantly reduce total ACS enzyme activity in these tissues when using LCFA or VLCFA as substrates. However, analysis unveiled intriguing developmental and compositional changes in FA levels associated with ACSBG1 deficiency. In the adult mouse brain, ACSBG1 expression peaked in the cerebellum, with lower levels observed in other brain regions. Developmentally, ACSBG1 expression in the cerebellum was initially low during the first week of life but increased dramatically thereafter. Cerebellar FA levels were assessed in both w.t. and Acsbg1 mouse brains throughout development, revealing notable differences. While saturated VLCFA levels were typically high in XALD tissues and in fruit flies lacking ACSBG1, cerebella from Acsbg1 mice displayed lower saturated VLCFA levels, especially after about 8 days of age. Additionally, monounsaturated ω9 FA levels exhibited a similar trend as saturated VLCFA, ω3 polyunsaturated FA levels werewhile elevated in Acsbg1 mice. Further analysis of specific FA levels provided additional insights into potential roles for ACSBG1. Notably, the decreased VLCFA levels in Acsbg1 mice primarily stemmed from changes in C24:0 and C26:0, while reduced ω9 FA levels were mainly observed in C18:1 and C24:1. ACSBG1 depletion had minimal effects on saturated long-chain FA or ω6 polyunsaturated FA levels but led to significant increases in specific ω3 FA, such as C20:5 and C22:5. Moreover, the impact of ACSBG1 deficiency on the developmental expression of several cerebellar FA metabolism enzymes, including those required for synthesis of ω3 polyunsaturated FA, was assessed; these FA can potentially be converted into bioactive signaling molecules like eicosanoids and docosanoids. In conclusion, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and/or docosanoids should be further investigated.
PubMed: 38948805
DOI: 10.1101/2024.06.19.599741 -
Urology Case Reports Jul 2024Inflammatory Myofibroblastic Tumor (IMT) occurring in the adrenal gland is extremely rare, and pathologic examination is the gold standard for confirming the diagnosis....
Inflammatory Myofibroblastic Tumor (IMT) occurring in the adrenal gland is extremely rare, and pathologic examination is the gold standard for confirming the diagnosis. We report a case of IMT of adrenal origin in a patient whose diagnosis was confirmed by pathological examination after surgical resection of the tumor. Although previous studies have reported an overall favorable prognosis for IMT, regular and long-term follow-up is necessary.
PubMed: 38948679
DOI: 10.1016/j.eucr.2024.102763 -
Frontiers in Endocrinology 2024Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10%...
Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.
Topics: Humans; Female; Adult; Thymus Neoplasms; Cushing Syndrome; Carcinoma, Neuroendocrine; Adrenal Gland Neoplasms; ACTH Syndrome, Ectopic; Adrenalectomy; Neoplasms, Multiple Primary
PubMed: 38948516
DOI: 10.3389/fendo.2024.1399930 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024As a member of the tumor necrosis factor receptor family, osteoprotegerin (OPG) is highly expressed in adults in the lung, heart, kidney, liver, spleen, thymus,... (Review)
Review
As a member of the tumor necrosis factor receptor family, osteoprotegerin (OPG) is highly expressed in adults in the lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestines, thyroid gland, lymph nodes, trachea, adrenal gland, the testis, and bone marrow. Together with the receptor activator of nuclear factor-κB (RANK) and the receptor activator of nuclear factor-κB ligand (RANKL), it forms the RANK/RANKL/OPG pathway, which plays an important role in the molecular mechanism of the development of various diseases. MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs performing regulatory functions in eukaryotes, with a size of about 20-25 nucleotides. miRNA genes are transcribed into primary transcripts by RNA polymerase, bind to RNA-induced silencing complexes, identify target mRNAs through complementary base pairing, with a single miRNA being capable of targeting hundreds of mRNAs, and influence the expression of many genes through pathways involved in functional interactions. In recent years, a large number of studies have been done to explore the mechanism of action of miRNA in diseases through miRNA isolation, miRNA quantification, miRNA spectrum analysis, miRNA target detection, and regulation of miRNA levels, and other technologies. It was found that miRNA can play a key role in the pathogenesis of osteoporosis, rheumatoid arthritis, and other diseases by targeting OPG. The purpose of this review is to explore the interaction between miRNA and OPG in various diseases, and to propose new ideas for studying the mechanism of action of OPG in diseases.
Topics: Osteoprotegerin; Humans; MicroRNAs; Receptor Activator of Nuclear Factor-kappa B; RANK Ligand; Neoplasms; Animals; Signal Transduction; Arthritis, Rheumatoid
PubMed: 38948285
DOI: 10.12182/20240560607 -
Cureus May 2024Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology...
Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology and the loss of the Brahma-related gene 1 (BRG1) protein. Its pathogenesis involves mutational loss of SMARCA4 gene expression, which encodes the BRG1 protein that serves as one of the catalytic subunits of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. This malignancy of the thorax predominantly affects middle-aged male smokers and commonly metastasizes to lymph nodes, bones, adrenal glands, liver, gastrointestinal tract, central nervous system, and kidney. Cases of brain metastasis have been reported but are less common. We report a case of this tumor initially presenting with diffuse brain metastasis in a 55-year-old male with a significant smoking history. We reviewed the current literature on the diagnostic and therapeutic challenges posed by this highly aggressive thoracic tumor.
PubMed: 38947666
DOI: 10.7759/cureus.61367 -
Cureus May 2024Adrenal haemorrhage, although a rare entity in the neonatal period, is a known complication of birth asphyxia. Adrenal haemorrhage progresses differently depending on...
Adrenal haemorrhage, although a rare entity in the neonatal period, is a known complication of birth asphyxia. Adrenal haemorrhage progresses differently depending on the type and extent of the glands involved. Adrenal haemorrhage can cause persistent jaundice, fever, dehydration, scrotal swelling, abdominal wall discolouration, septicemia, and a shock-like state. Here, we report the case of a four-day-old male infant who presented with jaundice, poor feeding, and hypernatremic dehydration. The patient developed acute kidney injury and, eventually, renal failure due to adrenal haemorrhage. He had an abdominal lump with deranged renal parameters along with hyperbilirubinemia. Abdominal ultrasonography and contrast computed tomography scan showed left suprarenal enlargement with evidence of adrenal haemorrhage. The patient was managed well with ventilatory support and peritoneal dialysis and discharged successfully. A subsequent follow-up showed complete resolution of the adrenal haemorrhage. Single ultrasonography is a good modality for diagnosis but not sufficient, so serial ultrasonography at subsequent follow-up is a must.
PubMed: 38947616
DOI: 10.7759/cureus.61265 -
International Journal of Surgery Case... Jun 2024Adrenal Cavernous Hemangioma is an extremely rare histological type of adrenal tumors, typically asymptomatic and occasionally revealed by a symptom or complication....
INTRODUCTION AND IMPORTANCE
Adrenal Cavernous Hemangioma is an extremely rare histological type of adrenal tumors, typically asymptomatic and occasionally revealed by a symptom or complication. Here, we report an atypical symptomatic case to enrich the limited international case series.
CASE PRESENTATION
We present the case of an 80-year-old woman who underwent laparoscopic left adrenalectomy for a painful and potentially malignant left adrenal neoplasm, leading to the discovery of a five-centimeter adrenal cavernous hemangioma. The post-operative course was uneventful. The postoperative course was uneventful, and the chronic lumbar pain described initially vanished at the six-month follow-up.
CLINICAL DISCUSSION
Adrenal cavernous hemangioma is typically silent and incidentally discovered on cross-sectional imaging. Symptomatic or complicated forms are extremely rare. Clinical, biological, radiological and histology assessment are crucial for management. Therapeutic decisions depend on the malignancy probability and the functional nature of the adrenal neoplasm, considering surgery versus conservative approaches. Patient's point-of-view and background are also determining factors in the decision-making process. Mini-invasive adrenalectomy is superior to open approach, when feasible and safe.
CONCLUSION
Adrenal cavernous hemangioma is a rare benign vascular tumor often discovered on adrenalectomy specimen. This case illustrates a rare cause of chronic lumbar pain. It also underscores the importance of a multidisciplinary medical decision for this kind of tumors.
PubMed: 38945012
DOI: 10.1016/j.ijscr.2024.109936 -
Cell Reports Jun 2024Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the...
Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.
PubMed: 38941187
DOI: 10.1016/j.celrep.2024.114395 -
World Journal of Nuclear Medicine Jun 2024Phyllodes tumor is a rare fibroepithelial neoplasm of the breast. This tumor tends to spread by hematogenous route, with common metastatic sites in the lungs, bones, and...
Phyllodes tumor is a rare fibroepithelial neoplasm of the breast. This tumor tends to spread by hematogenous route, with common metastatic sites in the lungs, bones, and liver. Metastases to the pleura, stomach, pancreas, kidneys, and adrenal gland are rare. We present a case of a 52-year-old lady with malignant phyllodes tumor of breast undergone local tumor resection, followed by solitary lung metastasis with lobectomy, and subsequently diagnosed of multiple new metastatic sites in pleura, stomach, pancreas, kidneys, adrenal gland, and bone detected on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography within 2 years.
PubMed: 38933073
DOI: 10.1055/s-0044-1786519 -
World Journal of Nuclear Medicine Jun 2024Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to...
Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of I-Whole-Body Scintigraphy with Regional SPECT/CT.
Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to 60% of patients. The presence of distant metastasis impacts overall survival and prognosis. The lungs, bones, and the brain are typically involved in distant sites with less common metastatic sites that include the liver, kidney, skeletal muscle, adrenal glands, bladder, and skin. These unusual sites are rare and pose a diagnostic challenge and impact clinical decision-making to a great extent. The radioiodine I whole-body scintigraphy with single-photon emission computed tomography/computed tomography can provide a thorough investigation of unusual sites of uptake leading to diagnosis of these metastases. We present a case series of DTC showing unusual sites of metastasis and/or radioiodine uptake in urinary bladder, in the third metacarpal bone of left hand and lastly in the forearm at postoperative hypertrophic scar area.
PubMed: 38933072
DOI: 10.1055/s-0044-1779750