Animals ; Endothelins ; physiology ; Humans ; Mice ; Pulmonary Fibrosis ; etiology ; Rats

OBJECTIVEOvarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis.

DATA SOURCESWe searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms.

STUDY SELECTIONArticles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases.

RESULTSMany cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide.

CONCLUSIONSPatients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

Animals ; Cytokines ; metabolism ; Female ; Fibrosis ; complications ; diagnosis ; etiology ; metabolism ; Humans ; Infertility, Female ; etiology ; Ovary ; pathology

OBJECTIVE: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. DATA SOURCES: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases." STUDY SELECTION: Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English. RESULTS: SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome. CONCLUSIONS Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.
Acute Kidney Injury ; etiology ; Carcinoma, Renal Cell ; etiology ; Diabetic Nephropathies ; etiology ; Fibrosis ; Humans ; Kidney ; pathology ; Kidney Diseases ; etiology ; metabolism ; Kidney Neoplasms ; etiology ; SUMO-1 Protein ; physiology ; Sumoylation

BACKGROUNDCystic fibrosis (CF) is rare in Chinese. We investigated the mutations in the gene of cystic fibrosis transmembrane conductance regulator (CFTR) in a Chinese CF patient and reviewed the clinical features, gene mutations in Chinese CF cases.

METHODSBlood samples were collected from a previously reported CF girl and her parents. The 24 coding exons of CFTR of the proband were amplified and sequenced.

RESULTSA Chinese girl of 16 years old was diagnosed as CF at the age of 14. She had recurrent productive cough with bronchiectasis in bilateral upper lobes, parasinusitis and otitis media, but without pancreatic involvement. Her sweat chloride was (108.9 +/- 3.3) mmol/L. A heterozygous novel missense mutation of 699 C --> A which results in the amino acid change of N189K was identified in exon 5. In addition, a heterozygous 3821 - 3823 delT mutation in exon 19 was found in CFTR. The mutation 699C --> A was inherited from her father, and the 3821 - 3823 delT mutation was from her mother. Twenty patients with CF in Chinese reported from 1974 to 2004 were also reviewed. DelF508 mutation was not found in the nine cases whose CFTR mutations were analyzed.

CONCLUSIONSThe CF proband carries two heterozygous mutations (699C --> A and 3821 - 3823 delT) in CFTR. 699C --> A mutation is a novel mutation which is not reported previously. Review of reported Chinese cases suggests that the genotype of Chinese CF may be different from those of white cases. More studies are needed to understand the spectra of CFTR and clinical CF features in Chinese.

Adolescent ; Cystic Fibrosis ; complications ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; Exocrine Pancreatic Insufficiency ; etiology ; Female ; Humans ; Mutation, Missense ; Respiratory Tract Diseases ; etiology

miRNAs are important post-transcriptional regulators. The aberrant expression of miRNAs is strongly associated with the initiation and progression of pathophysiologic processes in a wide range of human diseases. Scleroderma (systemic sclerosis; SSc) is a highly heterogeneous autoimmune disease that includes the progressive fibrotic replacement of normal tissue architecture in multiple organs. Our previous studies have suggested that SSc skin tissues display a different miRNA expression signature than that found in normal controls. miRNAs with pro- or antifibrotic properties are found to be dysregulated in SSc skin fibrosis. Serum miRNA levels are associated with SSc activity and severity. miRNAs have the potential to be therapeutic targets and serve as biomarkers for SSc diagnosis and assessment of disease state and severity. This review summarizes the SSc miRNA expression signature and the roles of dysregulation of miRNAs in SSc tissues and serum and examines the future therapeutic potential of targeting miRNAs in the management of SSc patients.
Animals ; Biological Markers/metabolism ; Fibrosis/etiology/metabolism ; Humans ; MicroRNAs/*genetics/metabolism ; Scleroderma, Systemic/diagnosis/etiology/genetics/*metabolism

Congenital absence of the vas deferens (CAVD) is an important factor that contributes to obstructive azoospermia and male infertility. The etiology of CAVD is associated with the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defects in the Wolffian duct, and frequently complicated by renal agenesis and other urogenital abnormalities. Physical examination may reveal nonpalpable scrotal vas deferentia, while vasography intrinsic vasal absence. Ultrasound and computerized tomography (CT) can rule out the abnormalities of the upper urinary tracts and the seminal vesicles. Although it is difficult to cure the disease, it is now possible for CAVD patients to father children with the help of assisted reproductive technology (ART). The present review is focused on the etiology, diagnosis and treatment of CAVD.
Cystic Fibrosis ; etiology ; Humans ; Infertility, Male ; etiology ; Male ; Mesonephros ; abnormalities ; Urogenital Abnormalities ; diagnosis ; epidemiology ; therapy ; Vas Deferens ; abnormalities

Humans ; Interleukin-18 ; chemistry ; metabolism ; Pulmonary Fibrosis ; etiology ; pathology ; Silicosis ; complications ; pathology ; physiopathology

A 13-year-old girl presented with a 1-month history of progressive exertional dyspnea (NYHA class IV) and exophthalmos for 6 months. She had a history of long-standing asthma and the presence of allergy. Hypereosinophilia and increased serum IgE levels (2472 IU/mL) were observed. Chest radiography and a high resolution CT scan documented a massive interstitial pulmonary infiltration. Echocardiography confirmed mild tricuspid regurgitation, apical obliteration of the right ventricle by fibrocalcific thickening of the endocardium and echogenic material suggestive of thrombosis. Churg-Strauss syndrome with cardiac involvement (endomyocardiopathy) was diagnosed. The patient received anticoagulation and corticosteroid therapy. In view of rapidly progressive severe endomyocardiopathy and stable hematology, the patient was referred for cardiac surgery. Histopathological examination of resected specimens confirmed laminated thrombus but without any trace of eosinophils embedded.
Adolescent ; Churg-Strauss Syndrome ; complications ; Endocardium ; pathology ; Endomyocardial Fibrosis ; etiology ; Female ; Humans

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal form of interstitial lung disease. Despite extensive efforts in research during recent years, the mechanisms of the disease remain poorly understood. Evidence of an inflammatory mechanism, both supportive and contrary, is briefly reviewed in this paper. However, growing evidence has indicated that the apoptosis of alveolar epithelial cells (AECs) may be the early driving force of progression, with subsequent disrupted integrity of the alveolar-capillary basement membrane leading to an abnormal wound healing pathway. Thus, this paper will focus on outlining a process of pathogenesis of IPF from initial apoptosis of AECs to end lung remodeling.
Apoptosis ; Epithelial Cells ; pathology ; Humans ; Idiopathic Pulmonary Fibrosis ; etiology ; pathology ; Lung ; pathology

In acute injury, liver recovers completely without any scarring change or complication. However, large portion of liver is changed into fibrotic state by excessive production of extracellular matrix (ECM) under chronic injury. Excessive production of ECM results in hepatic fibrosis and repeated process of hepatic fibrosis progress into liver cirrhosis. Liver cirrhosis is an irreversible and terminal state of chronic liver disease and one of the major causes of death in Korea. To block the progression to liver cirrhosis, various studies in the field of virology and immunology have been proceeded. Recently, studies on the hepatic fibrogenesis have progressed with the development of molecular biology. Hepatic stellate cells (HSC) play a key role in the pathogenesis of hepatic fibrosis by producing ECM. The degree of hepatic fibrosis depends on the proliferation and activation of HSC and increased net production of collagen. Therefore, inhibition of HSC activation is one of the main ways to block the progression of hepatic fibrosis. Many kinds of factors such as oxidative stress, acetaldehyde, ascorbic acid, transforming growth factor-beta (TGF-beta) and carbon tetrachloride (CCl4) have been reported to activate HSC and stimulate collagen gene expression. Although there are no definite and effective antifibrogenic agents, possible candidates are antioxidants, interferon, retinoids such as beta-carotene, flavonoids, renin-angiotensin system inhibitors and peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists. We tried to evaluate the charateristics of HSC in order to develop agents that inhibit hepatic fibrogenesis.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism