Inhibition of miR-96-5p alleviates intervertebral disc degeneration by regulating the peroxisome proliferator-activated receptor γ/nuclear factor-kappaB pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is the main pathogenesis of low back pain. MicroRNAs (miRNAs) have been found to exert regulatory function in IDD. This study aimed to investigate the effect and potential mechanism of miR-96-5p in IDD. METHODS: In vitro cell model of IDD was established by treating human nucleus pulposus cells (HNPCs) with interleukin-1ß (IL-1ß). The level of peroxisome proliferator-activated receptor γ (PPARγ) was examined in the IDD cell model by Western blot and quantification real-time reverse transcription-polymerase chain reaction (qRT-PCR). The expression level of miR-96-5p was detected by RT-qPCR. Effects of PPARγ or/and PPARγ agonist on inflammatory factors, extracellular matrix (ECM), apoptosis, and nuclear factor-kappaB (NF-κB) nuclear translocation were examined through enzyme-linked immunosorbent assay (ELISA), Western blot, flow cytometry assay, and immunofluorescence staining. The Starbase database and dual luciferase reporter assay were used to predict and validate the targeting relationship between miR-96-5p and PPARγ, and rescue assay was performed to gain insight into the role of miR-96-5p on IDD through PPARγ/NF-κB signaling. RESULTS: PPARγ expression reduced with concentration and time under IL-1ß stimulation, while miR-96-5p expression showed the reverse trend (P < 0.05). Upregulation or/and activation of PPARγ inhibited IL-1ß-induced the increase in inflammatory factor levels, apoptosis, degradation of the ECM, and the nuclear translocation of NF-κB (P < 0.05). MiR-96-5p was highly expressed but PPARγ was lowly expressed in IDD, while knockdown of PPARγ partially reversed remission of IDD induced by miR-96-5p downregulation (P < 0.05). MiR-96-5p promoted NF-κB entry into the nucleus but PPARγ inhibited this process. CONCLUSION: Inhibition of miR-96-5p suppressed IDD progression by regulating the PPARγ/NF-κB pathway. MiR-96-5p may be a promising target for IDD treatment clinically.

Imaging study of the effect of postural changes on the retroperitoneal oblique corridor in degenerative lumbar scoliosis.

PURPOSE: To investigate the effect of postural changes on access for the OLIF of L2 to L5 in patients with degenerative lumbar scoliosis. METHODS: Twenty-one individuals with degenerative lumbar scoliosis were chosen at random, 11 with left-sided convexity and 10 with left-sided concavity. Axial T2-weighted images were used to measure the following variables: (1) the distance between the left psoas major muscle and the abdominal aorta; (2) the angle of the surgical access; (3) the distance between the psoas major muscle attachment point and the vertebral body's transverse axis; (4) the region of the psoas major muscle above the vertebrae; and (5) the width-to-thickness ratio. A statistical analysis of the measured parameters was done. RESULTS: The L2-5 segment in the supine position had a significantly longer window distance in the left convex and left concave groups than in the right lateral recumbent posture (P < 0.05). In all segments, the left concave group outperformed the left convex group, which was substantially higher in the right lateral recumbent posture than in the supine position (P < 0.05). After the position change, the spanning area was significantly higher compared to the same segment in the supine position. The psoas major muscle's morphology was stretched. CONCLUSIONS: The right lateral recumbent position limits access to OLIF for degenerative lumbar scoliosis, and the "safety window" for OLIF operation in the parietal region is smaller in the left convex group compared to the left concave group, posing a higher risk of intraoperative vascular and neurological injury.

Mmu-miR-25-3p promotes macrophage autophagy by targeting DUSP10 to reduce mycobacteria survival.

Background: The present study aimed to investigate the regulation of miR-25-3p on macrophage autophagy and its effect on macrophage clearance of intracellular Mycobacterium bovis Bacillus Calmette-Guerin (BCG) retention based on the previous findings on the differential expression of exosomal miRNA in macrophages infected with BCG. Methods: Through enrichment analysis and Hub gene analysis, key differentially expressed miRNA and its target genes were selected. The targeted binding ability of the screened mmu-miR-25-3p and its predicted target gene DUSP10 was determined through the TargetScan database, and this was further verified by dual luciferase reporter gene assay. mmu-miR-25-3p mimics, mmu-miR-25-3p inhibitor, si-DUSP10, miR-NC,si-NC and PD98059 (ERK Inhibitor) were used to intervene macrophages Raw264.7. Rt-qPCR was used to detect the expression levels of mmu-miR-25-3p and DUSP10 mRNA. Western blot was used to detect the expression levels of DUSP10, LC3-II, p-ERK1/2, beclin1, Atg5 and Atg7. The autophagy flux of macrophage Raw264.7 in each group was observed by confocal laser microscopy, and the expression distribution of DUSP10 and the structure of autophagosomes were observed by transmission electron microscopy. Finally, the intracellular BCG load of macrophage Raw264.7 was evaluated by colony-forming unit (CFU) assay. Results: Bioinformatics analysis filtered and identified the differentially expressed exosomal miRNAs. As a result, mmu-miR-25-3p expression was significantly increased, and dual specificity phosphatase 10 (DUSP10) was predicted as its target gene that was predominantly involved in autophagy regulation. The dual luciferase reporter gene activity assay showed that mmu-miR-25-3p was targeted to the 3'-untranslated region (UTR) of DUSP10. The infection of BCG induced the upregulation of mmu-miR-25-3p and downregulation of DUSP10 in RAW264.7 cells, which further increased the expression of LC3-II and promoted autophagy. Upregulated mmu-miR-25-3p expression decreased the level of DUSP10 and enhanced the phosphorylation of ERK1/2, which in turn upregulated the expression of LC3-II, Atg5, Atg7, and Beclin1. Immuno-electron microscopy, transmission electron microscopy, and autophagic flux analysis further confirmed that the upregulation of mmu-miR-25-3p promotes the autophagy of macrophages after BCG infection. The CFU number indicated that upregulated mmu-miR-25-3p expression decreased the mycobacterial load and accelerated residual mycobacteria clearance. Conclusion: mmu-miR-25-3p promotes the phosphorylation of ERK1/2 by inhibiting the expression of DUSP10, thus enhancing the BCG-induced autophagy of macrophages. These phenomena reduce the bacterial load of intracellular Mycobacterium and facilitate the clearance of residual mycobacteria. mmu-miR-25-3p has great potential as a target for anti-tuberculosis immunotherapy and can be the optimal miRNA loaded into exosomal drug delivery system in future studies.

Inhibition of miR-221-3p promotes axonal regeneration and repair of primary sensory neurons via regulating p27 expression.

This study aimed to explore the key microRNA (miRNA) playing a vital role in axonal regeneration with a hostile microenvironment after spinal cord injury. Based on the theory that sciatic nerve conditioning injury (SNCI) could promote the repair of the injured dorsal column. Differentially expressed miRNAs were screened according to the microarray, revealing that 47 known miRNAs were differentially expressed after injury and perhaps involved in nerve regeneration. Among the 47 miRNAs, the expression of miR-221-3p decreased sharply in the SNCI group compared with the simple dorsal column lesion (SDCL) group. Subsequently, it was confirmed that p27 was the target gene of miR-221-3p from luciferase reporter assay. Further, we found that inhibition of miR-221-3p expression could specifically target p27 to upregulate the expression of growth-associated protein 43 (GAP-43), α-tubulin acetyltransferase (α-TAT1) together with α-tubulin, and advance the regeneration of dorsal root ganglion (DRG) neuronal axons. Chondroitin sulfate proteoglycans (CSPGs) are the main components of glial scar, which can hinder the extension and growth of damaged neuronal axons. After CSPGs were used in this study, the results demonstrated that restrained miR-221-3p expression also via p27 promoted the upregulation of GAP-43, α-TAT1, and α-tubulin and enhanced the axonal growth of DRG neurons. Hence, miR-221-3p could contribute significantly to the regeneration of DRG neurons by specifically regulating p27 in the p27/CDK2/GAP-43 and p27/α-TAT1/α-tubulin pathways even in the inhibitory environment with CSPGs.

Small RNA sequencing and bioinformatics analysis of RAW264.7-derived exosomes after Mycobacterium Bovis Bacillus Calmette-Guérin infection.

BACKGROUND: The mechanisms through which Mycobacterium tuberculosis evades immune surveillance during tuberculosis (TB) infection remain complex. Previous studies have found that Mycobacteria can manipulate the miRNAs of host cells to promote their survival during host-pathogen interactions, and most of these effects occur at the cellular miRNA level. We attempted to investigate the possible related mechanisms at the exosomal miRNA level. RESULTS: High-throughput sequencing revealed that Bacillus Calmette-Guérin (BCG) infection could alter the composition of the macrophage exosome content, and the expression levels of miRNAs in exosomes derived from the cell culture media of macrophages showed significant differences between the BCG-infected and non-infected groups. Compared with the non-infected group, 20 exosomal miRNAs were up-regulated and 7 exosomal miRNAs were down-regulated in the infection group (p < 0.05), of which mmu-miR-27b-3p, mmu-miR-93-5p, mmu-miR-25-3p, mmu-miR-1198-5p, mmu-let-7c-5p and let-7a-5p were significantly up-regulated. A bioinformatic analysis indicated that these differentially expressed exosomal miRNAs were involved in multiple biological processes and pathways. The target genes of top six miRNAs in up-regulated groups were positively correlated with the regulation of apoptosis. CONCLUSIONS: The expression profile of miRNA in exosomes derived from macrophage were altered after Mycobacterium Bovis Bacillus Calmette-Guérin infection, and the differentially expressed miRNAs were involved in multiple biological processes and signalling pathways. The top six up-regulated miRNAs and their targeted genes were predominantly correlated with the regulation of apoptosis.

Granular indigenous microalgal-bacterial consortium for wastewater treatment: Establishment strategy, functional microorganism, nutrient removal, and influencing factor.

Granular indigenous microalgal-bacterial consortium (G-IMBC) system integrates the advantages of the MBC and granular activated sludge technologies, also with superior microalgal wastewater adaptation capacity. In this review, the concept of IMBC was firstly described, followed by its establishment and acclimation strategies. Characteristics and advantages of G-IMBC system compared to other IMBC systems (i.e., attached and floc IMBC systems) were then introduced. Moreover, the involved functional microorganisms and their interactions, as well as nutrient removal mechanisms were systematically and critically reviewed. Finally, the influencing factors including wastewater characteristics and operation factors were discussed. This study aims to provide a comprehensive up-to-date summary of the G-IMBC system for sustainable wastewater treatment.

Evaluation of a rabbit model of adjacent intervertebral disc degeneration after fixation and fusion and maintenance in an upright feeding cage.

Purpose: To establish an animal model of adjacent intervertebral disc degeneration by performing spinal fixation and fusion after percutaneous needle puncture and removal of the intervertebral disc or percutaneous needling of the vertebral body without removal of the intervertebral disc. Methods: We established a model of adjacent intervertebral disc degeneration after spinal fixation and fusion of rabbits maintained in upright feeding cages. Twenty-five healthy New Zealand rabbits were used. In the experimental group, the L3-4 intervertebral disc was percutaneously punctured with an 18-G needle under fluoroscopic guidance. Once degeneration occurred, the L3-4 disc was excised, and interbody fusion was performed. The changes in the adjacent intervertebral discs were observed periodically via X-ray and MRI. In the control group, the L3 vertebral body was percutaneously needled with an 18-G needle under fluoroscopic guidance. The changes in the adjacent intervertebral discs were observed on X-ray and MRI at 4, 8, and 12 weeks after puncture in both groups. At 12 weeks postoperatively, the animals were euthanized, and the histopathologic changes of the adjacent intervertebral discs were assessed using hematoxylin-eosin and TdT-mediated dUTP nick end labeling (TUNEL) staining. The mRNA and protein expressions of aggrecanase-1 were measured by real-time quantitative PCR and Western blot analysis. The product of aggrecan degradation, Aggrecan ARGxx, was measured by Western blot analysis. Results: The degeneration of the intervertebral discs in the adjacent segments in the experimental group increased over time. The mRNA and protein expressions of aggrecanase-1 and the expression of Aggrecan ARGxx in the experimental group were significantly increased after puncture, fixation, and fusion (P<0.05). The adjacent intervertebral disc sections had a significantly lower cell density and significantly higher TUNEL-positive cell rate in the experimental group than the control group (P<0.05). Conclusion: The results suggest that the occurrence of intervertebral disc degeneration in adjacent segments may begin with the degeneration of the punctured intervertebral disc.

Sorafenib promotes sensory conduction function recovery via miR-142-3p/AC9/cAMP axis post dorsal column injury.

Spinal cord injury results in sensation dysfunction. This study explored miR-142-3p, which acts a critical role in sciatic nerve conditioning injury (SNCI) promoting the repair of the dorsal column injury and validated its function on primary sensory neuron(DRG). miR-142-3p expression increased greatly in the spinal cord dorsal column lesion (SDCL) group and increased slightly in the SNCI group. Subsequently, the expression of adenylate cyclase 9 (AC9), the target gene of miR-142-3p, declined sharply in the SDCL group and declined limitedly in the SNCI group. The expression trend of cAMP was opposite to that of miR-142-3p. MiR-142-3p inhibitor improved the axon length, upregulated the expression of AC9, cAMP, p-CREB, IL-6, and GAP43, and downregulated the expression of GTP-RhoA. miR-142-3p inhibitor combined with AC9 siRNA showed shorter axon length, the expression of AC9, cAMP, p-CREB, IL-6, and GAP43 was decreased, and the expression of GTP-RhoA was increased. H89 and AG490, inhibitors of cAMP/PKA pathway and IL6/STAT3/GAP43 axis, respectively, declined the enhanced axonal growth by miR-142-3p inhibitor and altered the expression level of the corresponding proteins. Thus, a substitution therapy using Sorafenib that downregulates the miR-142-3p expression for SNCI was investigated. The results showed the effect of Sorafenib was similar to that of miR-142-3p inhibitor and SNCI on both axon growth in vitro and sensory conduction function recovery in vivo. In conclusion, miR-142-3p acts a pivotal role in SNCI promoting the repair of dorsal column injury. Sorafenib mimics the treatment effect of SNCI via downregulation of miR-142-3p, subsequently, promoting sensory conduction function recovery post dorsal column injury.

PEITC promotes neurite growth in primary sensory neurons via the miR-17-5p/STAT3/GAP-43 axis.

The present study explored a key miRNA that plays a vital role in sciatic nerve conditioning injury promoting repair of injured dorsal column, and validated its function. Microarray analysis revealed miR-17-5p expression decreased sharply at 3, 7 and 14 days in the sciatic nerve conditioning injury group compared with the simple dorsal column lesion group. After miR-17-5p inhibition in DRG neurons, GAP-43 expression was upregulated and neurite growth was increased. STAT3 together with p-STAT3 showed opposite trends with miR-17-5p. MiR-17-5p inhibition extended neurite and upregulated STAT3, p-STAT3 and GAP-43. To further determine a substitution therapy for sciatic nerve conditioning injury, beta-phenethyl isothiocyanate (PEITC), which downregulates miR-17-5p, was assessed. The results showed that treatment with 10 µM PEITC resulted in longest neurite length. Further experiments demonstrated PEITC induced neurite growth by inhibiting miR-17-5p and further upregulating STAT3, p-STAT3 and GAP-43. The somatosensory evoked potential test confirmed similar treatment effects for PEITC, Ad-miRNA-17-5p inhibitor, and sciatic nerve conditioning injury on the dorsal column lesion. In conclusion, the miR-17-5p/STAT3/GAP-43 axis is an indispensable component of sciatic nerve conditioning injury promoting repair of injured dorsal column. PEITC could promote repair of injured dorsal column via the miR-17-5p/STAT3/GAP-43 axis, and could mimic the treatment effect of sciatic nerve conditioning injury.

miR-142-3p is a Potential Therapeutic Target for Sensory Function Recovery of Spinal Cord Injury.

Spinal cord injury (SCI), which is a leading cause of disability in modern society, commonly results from trauma. It has been reported that application of sciatic nerve conditioning injury plays a positive role in repairing the injury of the ascending spinal sensory pathway in laboratory animals. Because of the complexity of SCI and related ethics challenges, sciatic nerve conditioning injury cannot be applied in clinical therapy. Accordingly, it is extremely important to study its mechanism and develop replacement therapy. Based on empirical study and clinical trials, this article suggests that miR-142-3p is the key therapeutic target for repairing sensory function, based on the following evidence. Firstly, studies have reported that endogenous cAMP is the upstream regulator of 3 signal pathways that are partially involved in the mechanisms of sciatic nerve conditioning injury, promoting neurite growth. The regulated miR-142-3p can induce cAMP elevation via adenylyl cyclase 9 (AC9), which is abundant in dorsal root ganglia (DRG). Secondly, compared with gene expression regulation in the injured spinal cord, inhibition of microRNA (miRNA) in DRG is less likely to cause trauma and infection. Thirdly, evidence of miRNAs as biomarkers and therapeutic targets in many diseases has been reported. In this article we suggest, for the first time, imitating sciatic nerve conditioning injury, thereby enhancing central regeneration of primary sensory neurons via interfering with the congenerous upstream regulator AC9 of the 3 above-mentioned signal pathways. We hope to provide a new clinical treatment strategy for the recovery of sensory function in SCI patients.

Identification of microRNAome in rat bladder reveals miR-1949 as a potential inducer of bladder cancer following spinal cord injury.

The costs of spinal cord injury and its complications are high in personal, social and financial terms. Complications include bladder cancer, for which the risk is 16-28 times higher than that of the general population, There is currently little consensus regarding the cause of this discrepancy. As microRNAs are stable biomarkers and potential therapeutic targets of cancer, the present study aimed to explore the underlying mechanisms of this phenomenon by examining changes in the microRNAome. Rats were used to produce models of spinal cord injury. Microarrays and bioinformatics were used to investigate the cancer-associated microRNAs that are upregulated in rat bladders following spinal cord injury. In order to validate the results, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were performed. The expression of miR-1949 was found to be deregulated and abundant in the rat bladder following spinal cord injury. Bioinformatics demonstrated that retinoblastoma 1, which is involved in tumorigenesis, is a target gene of miR-1949. qRT-PCR, western blotting and immunohistochemistry confirmed the results of the microarray analysis. In addition, it was shown that miR-1949 expression was not influenced by aging. Furthermore, the expression of miR-1949 was stable until the third month following spinal cord injury, after which it significantly increased. If this increase was prolonged, the expression of retinoblastoma 1 may decline to a carcinogenic level. The present study suggests a role for miR-1949 in the translational regulation of retinoblastoma 1 and in subsequent bladder tumorigenesis following spinal cord injury.

The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury.

Patients with spinal cord injuries can develop severe neurological damage and dysfunction, which is not only induced by primary but also by secondary injuries. As an evolutionarily conserved pathway of eukaryotes, the JAK-STAT pathway is associated with cell growth, survival, development and differentiation; activation of the JAK-STAT pathway has been previously reported in central nervous system injury. The JAK-STAT pathway is directly associated with neurogenesis and glia scar formation in the injury region. Following injury of the axon, the overexpression and activation of STAT3 is exhibited specifically in protecting neurons. To investigate the role of the JAK-STAT pathway in neuroprotection, we summarized the effect of JAK-STAT pathway in the following three sections: Firstly, the modulation of JAK-STAT pathway in proliferation and differentiation of neural stem cells and neural progenitor cells is discussed; secondly, the time-dependent effect of JAK-STAT pathway in reactive astrocytes to reveal their capability of neuroprotection is revealed and lastly, we focus on how the astrocyte-secretory polypeptides (astrocyte-derived cytokines and trophic factors) accomplish neuroprotection via the JAK-STAT pathway.

Gene expression profiles of phaeochromocytomas with ERBB2 overexpression reveal a new molecular mechanism tumourigenicity.

OBJECTIVE: Phaeochromocytomas (PHEO) and functional paragangliomas (PGLs) are catecholamine-secreting neuroendocrine tumours. Although most PHEO/PGLs are benign, 10-35% present as (or develop into) malignant tumours with a poor prognosis. Overexpression of ERBB2 (v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2) has been reported to be associated with malignant PHEO. We used gene expression profiling of PHEO/PGLs to gain a better understanding of the tumourigenic pathways associated with ERBB2. METHODS: We used the Affymetrix Gene Chip U133 Plus 2·0 genome-wide gene expression cDNA microarray of 18 PHEO/PGLs (12 benign and six malignant, divided into two groups depending on ERBB2 expression levels) to analyse the gene expression patterns. RESULTS: Unsupervised hierarchical cluster analysis of transcription profiles of 18 samples identified two dominant expression clusters corresponding to samples belonging to the ERBB2+ and ERBB2- groups. According to the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases, the differentially expressed genes were classified into diverse functional categories and signalling pathways. In particular, the focal adhesion signalling pathway showed significant differences between the groups; specifically, the FAK-Src-MAPK pathway was prominently activated in the ERBB2+ group. CONCLUSIONS: In summary, ERBB2+ PHEO/PGLs have a distinct expression pattern compared with the ERBB2- group. The focal adhesion signalling pathway may participate in ERBB2-induced tumourigenesis in PHEO/PGLs.

Lower expression of ATM and gene deletion is more frequent in adrenocortical carcinomas than adrenocortical adenomas.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for approximately 0.02-0.2% of all cancer deaths. The molecular pathogenesis of ACC has been the hot topic of recent reviews but it is still poorly understood. It is imperative to have a better understanding on the pathophysiology of ACC so as to establish precise diagnosis and effective treatment. This study aims to identify the molecular markers between ACCs and adrenocortical adenomas (ACAs). With MLPA, we checked on 10 ACA and 9 ACC tissue samples. The MLPA results showed deletion on chromosomes 18q, 11q, 11p, and 13q and duplication on chromosomes 3q, 4q, 6p, and 19p. There was a significant difference in the number of aberration copies of the ataxia telangiectasia-mutated (ATM) gene located on chromosome 11q22-q23 between ACCs and ACAs. Five out of 9 (56%) ACC specimens had deletion of ATM (P = 0.011). RT-PCR result then demonstrated that ATM mRNA level is lower in ACCs than in ACAs (P < 0.001). In addition, immunohistochemistry (IHC) study of the 19 ACA and 18 ACC samples confirmed lower expression of ATM protein in ACCs than in ACAs (P < 0.001). The study demonstrated that ATM expression was diminished in ACC than in ACA, suggesting an important role of ATM in the tumorigenesis of ACC.

Overexpression of ERBB-2 was more frequently detected in malignant than benign pheochromocytomas by multiplex ligation-dependent probe amplification and immunohistochemistry.

To analyze the genetic alterations of pheochromocytomas and evaluate the difference among malignant, extra-adrenal, and benign pheochromocytomas. Forty-three tumor samples were tested for genetic changes using multiplex ligation-dependent probe amplification. Among them, 39 samples were available for protein expression analysis by immunohistochemistry (IHC). All 43 patients (24 women and 19 men; mean age 44.6+/-13.6 years; range 18-75 years; 9 with malignant, 7 extra-adrenal, and 27 benign) showed multiple copy number losses or gains. The average copy number change was 13.10 in malignant, 13.93 in benign, and 13.47 in paraganglioma patients. There is no significant difference among the three groups of pheochromocytomas. However, we discovered that in the malignant pheochromocytomas, 6 of the 9 patients (67%) showed erythroblastic leukemia viral oncogene homolog 2 (ERBB-2) oncogene gain, whereas only 12 of the 34 (35%) identified change in the benign and extra-adrenal pheochromocytomas. Further, IHC confirmed that ERBB-2-positive staining was more frequent and stronger in malignant pheochromocytomas than in benign and extra-adrenal pheochromocytomas. Our study illustrates the chromosomal changes of the whole genome of Chinese pheochromocytoma patients. The results suggest that there may be certain progression of genetic events that involves chromosomes 1p, 3p, 6p, 11q, 12q, 17q, and 19q in the development of pheochromocytomas, and the activation of ERBB-2 located on chromosome 17q is an important and early event in the malignancy development of these tumor types. The overexpression of ERBB-2 identified by IHC suggested that this oncogene could be associated with the malignancy of pheochromocytomas and paragangliomas.

A primary right atrium paraganglioma in a 15-year-old patient.

Thoracic pheochromocytomas account for less than 2% of reported cases, while primary cardiac paragangliomas are even rare. The following case illustrates a 15-year-old patient with primary right atrium paraganglioma. This patient was referred for paroxysmal hypertension and excessive perspiration. Pheochromocytoma was suspected and then confirmed by very high serum nor-metanephrine which increased more than 30-fold above the upper limit of normal. 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed high uptake only in the middle mediastinum, but not in the adrenal glands or elsewhere. Both contrast CT and gated MRI of the chest disclosed a 5.0 x 4.0 cm2 mass in the right atrium. Coronary angiography demonstrated the mass with feeding vessels from the right coronary artery. When the patient's blood pressure was well controlled with doxazosin and metoprolol, surgery was then performed. A 6.0 x 4.9 x 4.0 cm3 round solid right atrium paraganglioma weighing 41.7 g was resected. The second day after surgery, serum nor-metanephrine and urinary noradrenaline levels dropped rapidly to normal range, and the patient was free of clinical symptoms with normal BP. Postoperative cardiac function, as measured by echocardiogram, was normal. Although cardiac paraganglioma may be difficult to resect, it can be cured.