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Current Medical Science Jun 2024Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain...
OBJECTIVE
Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model.
METHODS
A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated β-galactosidase (SA-β-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry.
RESULTS
D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-β-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine).
CONCLUSION
ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.
PubMed: 38900385
DOI: 10.1007/s11596-024-2892-0 -
Endocrinologia, Diabetes Y Nutricion May 2024
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Pancreatitis; Acute Disease; Male; Female; Adrenalectomy; Middle Aged
PubMed: 38897706
DOI: 10.1016/j.endien.2024.02.008 -
Journal of Cerebrovascular and... Jun 2024This is a unique case of metastatic pheochromocytoma of the cervical spine treated with preoperative embolization and subsequent en bloc resection. A 65-year-old man...
This is a unique case of metastatic pheochromocytoma of the cervical spine treated with preoperative embolization and subsequent en bloc resection. A 65-year-old man with metastatic pheochromocytoma presented with two weeks of worsening neck pain, left arm and leg weakness and paresthesia, and urinary incontinence. Magnetic resonance imaging showed a metastatic osseous lesion at C6 with severe stenosis and spinal cord compression. The patient underwent successful preoperative angiographic embolization with a liquid embolic agent followed by C5-C7 laminectomy, en bloc tumor resection, and C3-T2 posterior spinal fusion. Six weeks postoperatively, the patient reported improving strength and resolving neck pain and paresthesias. While there is no standard paradigm for the treatment of metastatic pheochromocytomas of the cervical spine, preoperative embolization may minimize intraoperative blood loss and hemodynamic instability during subsequent surgical resection.
PubMed: 38897596
DOI: 10.7461/jcen.2024.E2023.04.005 -
Handbook of Experimental Pharmacology Jun 2024Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage....
Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α- and ß-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α blockers, α agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.
PubMed: 38890192
DOI: 10.1007/164_2024_719 -
Advanced Science (Weinheim,... Jun 2024Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve...
Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4-ethylenedioxythiophene) (PEDOT)-integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre-coating with polydopamine. The obtained PEDOT/IKVAV-integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV-integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV-integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB-derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long-segment neural defects.
PubMed: 38881504
DOI: 10.1002/advs.202400827 -
Scientific Reports Jun 2024This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled... (Comparative Study)
Comparative Study
This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and I-mIBG as a pretreatment screening for I-mIBG therapy. Two expert reviewers evaluated WB-MRI, I-mIBG images, and post-therapy I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.
Topics: Humans; Pheochromocytoma; 3-Iodobenzylguanidine; Paraganglioma; Female; Male; Magnetic Resonance Imaging; Middle Aged; Adult; Whole Body Imaging; Adrenal Gland Neoplasms; Retrospective Studies; Iodine Radioisotopes; Aged; Neoplasm Metastasis; Radiopharmaceuticals; Sensitivity and Specificity; Young Adult
PubMed: 38879654
DOI: 10.1038/s41598-024-64607-2 -
Medicine Jun 2024Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor...
INTRODUCTION
Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis.
CASE REPORT
This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma.
CONCLUSION
This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.
Topics: Humans; Female; Lymphoma, Large B-Cell, Diffuse; Adrenal Gland Neoplasms; Adult; Tomography, X-Ray Computed; Adrenal Glands
PubMed: 38875421
DOI: 10.1097/MD.0000000000038298 -
Cancer Jun 2024Pheochromocytomas and paragangliomas (PPGLs) typically secrete catecholamines and their metabolites (metanephrines [MN] and normetanephrine [NMN]). Catecholamines are...
INTRODUCTION
Pheochromocytomas and paragangliomas (PPGLs) typically secrete catecholamines and their metabolites (metanephrines [MN] and normetanephrine [NMN]). Catecholamines are synthesized by several enzymes: phenylalanine hydroxylase (encoded by PAH), tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (DDC), dopamine β-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT). MN/NMN secretion varies between anatomical and molecular subgroups. The aim of this study was to assess the correlation between DNA methylation of catecholamine synthesis genes and MN/NMN secretion.
METHODS
Gene promoter methylation of PAH, TH, AADC, DBH, and PNMT were extracted and calculated based on publicly available data. Comparisons and correlation analysis were performed between MN ± NMN (MN/NMN), NMN only, and neither/unknown secretion patterns. Methylation levels and MN/NMN patterns were compared by three genetic alteration subgroups: pseudohypoxia (PH), kinase signaling (KS), and others.
RESULTS
A total of 178 cases were included. Methylation of PAH CpGs negatively correlated with probability for MN/NMN secretion (p < .05 for all CpGs) and positively with NMN-only secretion. NMN-only secreting tumors had significantly higher promoter methylation of PAH, DBH, and PNMT compared with MN/NMN-secreting tumors. MN/NMN-secreting PPGLs had mainly KS alterations (52.1%), whereas NMN-only PPGLs had PH alterations (41.9%). PPGLs in the PH versus KS group had gene promoter hypermethylation of PAH (p = .002), DBH (p = .02), and PNMT (p = .003).
CONCLUSIONS
Promoter methylation of genes encoding catecholamine synthesis enzymes is strongly and inversely correlated with MN/NMN patterns in PPGLs. KS and PH-related tumors have distinct methylation patterns. These results imply that methylation is a key regulatory mechanism of catecholamine synthesis in PPGLs.
PubMed: 38872410
DOI: 10.1002/cncr.35426 -
Die Pharmazie May 2024We examined the mechanism by which 24()-ethyllophenol (MAB28) isolated from the branches of caused neurite outgrowth in rat pheochromocytoma cells (PC12). MAB28...
We examined the mechanism by which 24()-ethyllophenol (MAB28) isolated from the branches of caused neurite outgrowth in rat pheochromocytoma cells (PC12). MAB28 significantly promoted neurite outgrowth to a similar degree as the positive control, nerve growth factor (NGF). After incubation with MAB28 in PC12 cells, phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and cyclic AMP response element-binding protein was detected, but the time course of phosphorylation was different from that induced by NGF. The expression of chloride intracellular channel protein 3 (CLIC3) was significantly decreased by MAB28. 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), an outward rectifying chloride channel inhibitor, significantly promoted neurite outgrowth in PC12 cells. These data suggested that MAB28 could induce neurite outgrowth by downregulating CLIC3 expression.
Topics: Animals; PC12 Cells; Rats; Morus; Neurites; Neuronal Outgrowth; Nerve Growth Factor; Phosphorylation; p38 Mitogen-Activated Protein Kinases; Nitrobenzoates; Cyclic AMP Response Element-Binding Protein; Phenols; Blotting, Western; Extracellular Signal-Regulated MAP Kinases; Chloride Channels
PubMed: 38872272
DOI: 10.1691/ph.2024.3656 -
Innere Medizin (Heidelberg, Germany) Jul 2024Adrenal tumors are among the most common tumors in humans. They are most frequently discovered incidentally during abdominal imaging for other reasons or due to clinical...
Adrenal tumors are among the most common tumors in humans. They are most frequently discovered incidentally during abdominal imaging for other reasons or due to clinical symptoms (e.g. Conn's or Cushing's syndrome, pheochromocytoma or androgen excess). Although over 80% of adrenal tumors are benign, in cases of hormone excess, they are associated with significantly increased morbidity. In highly malignant adrenocortical carcinoma (ACC), early diagnosis is of particular prognostic relevance. Therefore, this review presents the diagnostic procedure for what are referred to as adrenal incidentalomas and provide recommendations for the management of ACC and pheochromocytomas/paragangliomas (PPGL). In primary diagnosis, sufficient hormone diagnostics is required for all adrenal tumors, as this is the only way to identify all patients with relevant hormone excess. Imaging has increasingly improved in recent years and allows a reliable assessment of the tumor's malignancy in most cases. Imaging of first choice is unenhanced computed tomography (CT), while magnetic resonance imaging (MRI) and fluorodeoxyglucose-18 positron emission tomography (FDG-PET/CT) are reserved for special situations, as published evidence on these procedures is more limited. The treatment of ACC and PPGL is complex and is carried out on an interdisciplinary basis at specialized centers. In the case of localized disease, surgery is the only curative treatment option. There are now clear recommendations for individualized adjuvant therapy for ACC. In metastatic disease, mitotane with or without platinum-containing chemotherapy is the standard. Other lines of therapy should be discussed with a reference center. Over 35% of PPGL have a germline mutation; therefore, genetic testing should be offered. In metastatic PPGL, an individual decision is required between active surveillance, radionuclide therapy, sunitinib or chemotherapy.
Topics: Humans; Adrenal Gland Neoplasms; Pheochromocytoma
PubMed: 38864873
DOI: 10.1007/s00108-024-01727-x