1.Is the myonuclear domain ceiling hypothesis dead?
Ferdos AMAN ; Eman EL KHATIB ; Alanood ALNEAIMI ; Ahmed MOHAMED ; Alya Sultan ALMULLA ; Amna ZAIDAN ; Jana ALSHAFEI ; Omar HABBAL ; Salma ELDESOUKI ; Rizwan QAISAR
Singapore medical journal 2023;64(7):415-422
Muscle fibres are multinuclear cells, and the cytoplasmic territory where a single myonucleus controls transcriptional activity is called the myonuclear domain (MND). MND size shows flexibility during muscle hypertrophy. The MND ceiling hypothesis states that hypertrophy results in the expansion of MND size to an upper limit or MND ceiling, beyond which additional myonuclei via activation of satellite cells are required to support further growth. However, the debate about the MND ceiling hypothesis is far from settled, and various studies show conflicting results about the existence or otherwise of MND ceiling in hypertrophy. The aim of this review is to summarise the literature about the MND ceiling in various settings of hypertrophy and discuss the possible factors contributing to a discrepancy in the literature. We conclude by describing the physiological and clinical significance of the MND ceiling limit in the muscle adaptation process in various physiological and pathological conditions.
Humans
;
Muscle Fibers, Skeletal/physiology*
;
Hypertrophy/pathology*
;
Muscle, Skeletal
2.Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats.
Xiao-Li DING ; Qing-Qing YUAN ; Ding-Jia XUE ; Fu-Ming YANG ; Yi-Zhun ZHU ; Hai-Bing QIAN
China Journal of Chinese Materia Medica 2022;47(2):461-468
To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.
Angiotensin II/metabolism*
;
Animals
;
Cardiomegaly/genetics*
;
Gallic Acid/analogs & derivatives*
;
Hypertrophy, Left Ventricular/pathology*
;
Myocardium/pathology*
;
Rats
3.Automatic Identification and Classification Diagnosis of Atrial Ventricular Hypertrophy Electrocardiogram Based on Convolutional Neural Network.
Yanni TONG ; Ruiqing ZHANG ; Yang SHEN ; Hua JIANG ; Shijie CHANG ; Xianzheng SHA
Chinese Journal of Medical Instrumentation 2020;44(1):20-23
OBJECTIVE:
Identifying Atrial Ventricular Hypertrophy Electrocardiogram (AVH ECG)and diagnosing the classification of theirs automatically.
METHODS:
The ECG data used in this experiment was collected from the First Affiliated Hospital of China Medical University. CNN are combined with conventional methods and a 10 layers of one dimensional CNN are created in this experiment to extract the features of ECG signals automatically and achieve the function of classifying. ROC, sensitivity and F1-score are used here to evaluate the effects of the model.
RESULTS:
In the experiment of identifying AVH ECG, the AUC of test dataset is 0.991, while in the experiment of classifying AVH ECG, the maximal F1-score can reach 0.992.
CONCLUSIONS
The CNN model created in this experiment can achieve the auxiliary diagnosis of AVH ECG.
China
;
Electrocardiography
;
Heart Atria/pathology*
;
Humans
;
Hypertrophy
;
Neural Networks, Computer
4.A Case Report of Juvenile Hypertrophy of the Breast in a 15-Year-Old Girl: Presented with Asymmetric Breast Enlargement and a Focal Mass-like Lesion
Jae Yeon PARK ; Sung Hun KIM ; Na Young JUNG ; Bong Joo KANG ; Ah Won LEE ; Min Sun JIN
Investigative Magnetic Resonance Imaging 2019;23(2):175-178
Juvenile hypertrophy of the breast is a rare condition, leading to hyperplastic breast anomalies in adolescents. Here, we report a case involving a 15-year-old girl, presented with asymmetric enlargement of the left breast. Pronounced parenchymal thickening was found on initial ultrasonography (US). MRI and second-look US revealed a focal mass-like lesion on the left mid-lateral breast, confirmed as juvenile hypertrophy of the breast on pathology.
Adolescent
;
Breast
;
Female
;
Humans
;
Hypertrophy
;
Magnetic Resonance Imaging
;
Pathology
;
Ultrasonography
5.Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy.
Na HE ; Qi-Hai GONG ; Feng ZHANG ; Jing-Yi ZHANG ; Shu-Xian LIN ; Hua-Hua HOU ; Qin WU ; An-Sheng SUN
Chinese journal of integrative medicine 2018;24(5):359-365
OBJECTIVETo investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms.
METHODSCardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca]) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively. The mRNA expressions of atrial natriuretic factor (ANF), calcineurin (CaN), extracellular signal-regulated kinase-2 (ERK-2), and endothelial nitric oxide synthase (eNOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit (CnA) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by Western blot analysis.
RESULTSCompared with the control group, Ang II induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF mRNA expression; increased intracellular free calcium ([Ca]) concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but decreased MKP-1 protein expression (P<0.05 or P<0.01). Compared with Ang II, Evo (0.3, 3 μmol/L) significantly attenuated Ang II-induced cardiomyocyte hypertrophy, decreased the [Ca] concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but increased MKP-1 protein expression (P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the eNOS mRNA expression (P<0.05).
CONCLUSIONEvo signifificantly attenuated Ang II-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.
Angiotensin II ; Animals ; Atrial Natriuretic Factor ; metabolism ; Calcineurin ; genetics ; metabolism ; Calcium ; metabolism ; Dual Specificity Phosphatase 1 ; genetics ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Hypertrophy ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Quinazolines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley
6.Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy.
Shun-Jin HU ; Bing SHU ; Hua JIN ; Xiao-Feng LI ; Jia-Rong MAO ; Ke-Jun REN ; Lei GAO ; Li YANG ; You-Wan WU ; Yong-Jun WANG
Chinese journal of integrative medicine 2018;24(8):600-605
OBJECTIVETo evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN).
METHODSForty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.
RESULTSCompared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).
CONCLUSIONSTangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.
Albuminuria ; complications ; Animals ; Basement Membrane ; drug effects ; metabolism ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; urine ; Diabetic Nephropathies ; blood ; drug therapy ; physiopathology ; urine ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; Kidney Function Tests ; Kidney Glomerulus ; drug effects ; pathology ; physiopathology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Male ; Rats, Sprague-Dawley
7.Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension
Dong Seok LEE ; Yong Wook JUNG
Korean Circulation Journal 2018;48(12):1135-1144
BACKGROUND AND OBJECTIVES: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). METHODS: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. RESULTS: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. CONCLUSIONS: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
;
Adenine Nucleotide Translocator 1
;
Arterioles
;
Blotting, Western
;
Caspase 3
;
Cell Death
;
Cyclophilins
;
Cyclosporine
;
Heart Failure
;
Heart Ventricles
;
Hypertension
;
Hypertension, Pulmonary
;
Hypertrophy, Right Ventricular
;
Microscopy, Electron
;
Mitochondria
;
Monocrotaline
;
Pathology
;
Permeability
;
Polymerase Chain Reaction
;
Pulmonary Circulation
;
Rats, Sprague-Dawley
;
Reverse Transcription
8.Histopathological Analysis of Ligamentum Flavum in Lumbar Spinal Stenosis and Disc Herniation.
Idiris ALTUN ; Kasım Zafer YÜKSEL
Asian Spine Journal 2017;11(1):71-74
STUDY DESIGN: Histopathological analyses were performed in ligamentum flavum (LF) hypertrophy patients with lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). PURPOSE: The aim of the present study was to evaluate histopathological changes in LF patients with LSS and LDH. OVERVIEW OF LITERATURE: LSS is the most common spinal disorder in elderly patients. This condition causes lower back and leg pain and paresis, and occurs as a result of degenerative changes in the lumbar spine, including bulging of the intervertebral discs, bony proliferation of the facet joints, and LF thickening; among these, LF thickening is considered a major contributor to the development of LSS. METHODS: A total of 71 patients operated with the surgical indications of LSS and LDH were included. LF samples were obtained from 31 patients who underwent decompressive laminectomy for symptomatic degenerative LSS (stenotic group) and from 40 patients who underwent lumbar discectomy for LDH (discectomy group). LF materials were examined histopathologically, and other specimens were examined for collagen content, elastic fiber number and array, and presence of calcification. RESULTS: The stenotic and discectomy groups did not differ with regard to mean collagen concentration or mean elastic fiber number (p=0.430 and p=0.457, respectively). Mean elastic fiber alignment was 2.36±0.99 in the stenotic group and 1.38±0.54 in the discectomy group (p<0.001). Mean calcification was 0.39±0.50 in the stenotic group, whereas calcification was not detected (0.00±0.00) in the discectomy group; a statistically significant difference was detected (p<0.001) between groups. CONCLUSIONS: LF hypertrophy in spinal stenosis may occur as a result of elastic fiber misalignment along with the development of calcification over time. Further studies determining the pathogenesis of LSS are needed.
Aged
;
Collagen
;
Diskectomy
;
Elastic Tissue
;
Humans
;
Hypertrophy
;
Intervertebral Disc
;
Laminectomy
;
Leg
;
Ligamentum Flavum*
;
Paresis
;
Pathology
;
Spinal Stenosis*
;
Spine
;
Zygapophyseal Joint
9.Xuezhikang () reduced renal cell apoptosis in streptozocin-induced diabetic rats through regulation of Bcl-2 family.
Wei-Na LU ; Fen-Ping ZHENG ; Dong-Wu LAI ; Hong LI
Chinese journal of integrative medicine 2016;22(8):611-618
OBJECTIVETo investigate the effect of Xuezhikang (, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism.
METHODSSixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion (UAE) measurement. Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by Western blot.
RESULTSCompared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent.
CONCLUSIONSRenal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.
Albuminuria ; blood ; complications ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; In Situ Nick-End Labeling ; Kidney ; drug effects ; pathology ; Kidney Glomerulus ; pathology ; Lipids ; blood ; Male ; Mesangial Cells ; drug effects ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats, Sprague-Dawley ; Streptozocin ; bcl-2-Associated X Protein ; metabolism
10.Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects.
Yong QI ; Hong-Tao SUN ; Yue-Guang FAN ; Fei-Meng LI ; Zhou-Sheng LIN
Chinese Journal of Traumatology 2016;19(3):179-181
The presence of large segmental defects of the diaphyseal bone is challenging for orthopedic surgeons. Free vascularized fibular grafting (FVFG) is considered to be a reliable reconstructive procedure. Stress fractures are a common complication following this surgery, and hypertrophy is the main physiological change of the grafted fibula. The exact mechanism of hypertrophy is not completely known. To the best of our knowledge, no studies have examined the possible relationship between stress fractures and hypertrophy. We herein report three cases of patients underwent FVFG. Two of them developed stress fractures and significant hypertrophy, while the remaining patient developed neither stress fractures nor significant hypertrophy. This phenomenon indicates that a relationship may exist between stress fractures and hypertrophy of the grafted fibula, specifically, that the presence of a stress fracture may initiate the process of hypertrophy.
Adult
;
Female
;
Fibula
;
pathology
;
transplantation
;
Fractures, Stress
;
pathology
;
Humans
;
Hypertrophy
;
Male
;
Middle Aged
;
Tibia
;
surgery
;
Tibial Fractures
;
surgery

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