TR, Rosengart MR, Tsung A. Calcium/ calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy.

BackgroundRheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) actively drive joint inflammation and degradation by producing inflammatory cytokines and matrix-degrading molecules, making them key factors in the pathogenesis of RA. Cylindromatosis (CYLD) is a tumor suppressor that downregulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation by deubiquitinating NF-κB essential modulator and tumor necrosis factor receptor-associated factors 2 and 6. In this study, we aimed to determine CYLD expression in the synovium of patients with RA, analyze its correlation with NF-κB activation and clinical disease activity, further investigate CYLD expression in RA-FLSs, and explore CYLD’s roles and mechanisms in the pro-inflammatory effects, proliferation, apoptosis, and cell cycles of RA-FLSs.MethodsWe obtained synovia from 50 patients with active RA and 20 with osteoarthritis (OA) and then cultured FLSs from the samples. We determined CYLD expression in the synovia of RA patients and in FLSs via reverse transcription polymerase chain reaction (RT-PCR). CYLD was depleted by lentiviral CYLD short hairpin ribonucleic acid. We used RT-PCR and enzyme-linked immunosorbent assay to analyze the expression of pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and receptor activator of nuclear factor kappa-B ligand (RANKL). We detected cell proliferation using Cell Counting Kit-8 and examined cell apoptosis and cell cycle using flow cytometry.ResultsWe obtained the following results:In synovia from patients with RA, CYLD expression was significantly downregulated while NF-κB expression was distinctly upregulated, compared with synovia from patients with OA. Thus, there is a significant inverse correlation between CYLD and NF-κB in synovia affected by RA.CYLD expression significantly decreased in RA-FLSs compared with OA-FLSs.CYLD suppression enhanced the production of pro-inflammatory cytokines, MMPs, and RANKL by activating NF-κB in RA-FLSs.CYLD suppression enhanced proliferation, reduced apoptosis, and increased cell division of RA-FLSs and aggravated the activity of NF-κB in RA-FLSs.ConclusionsVia its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy.

BackgroundDue to the lack of specific clinical manifestations and imaging features, the diagnosis of pulmonary mycosis is difficult. This study aimed to investigate the pathogens, clinical manifestations, imaging features, diagnosis and management of pulmonary mycosis.MethodsData on 68 patients diagnosed as pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were collected and their clinical manifestations, radiographic characterization, diagnostic methods and management were analyzed.ResultsAll patients were diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and computerized tomography (CT) guided percutaneous needle biopsy in 11 (16.2%). Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38 (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%) were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52 cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before pathological examination occurred. Surgical resection was performed in 38 patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was administered, and 20 patients (29.4%) experienced complete responses or partial responses.ConclusionThe main pathogens of pulmonary mycosis are Aspergillus, followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends on pathological examination. The clinical manifestations, imaging features, diagnostic methods and management differ depending on the pathogens. Satisfactory therapy can be obtained by both antifungal and surgical treatment.

Background: Due to the lack of specific clinical manifestations and imaging features, the diagnosis of pulmonary mycosis is difficult. This study aimed to investigate the pathogens, clinical manifestations, imaging features, diagnosis and management of pulmonary mycosis. Methods: Data on 68 patients diagnosed as pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were collected and their clinical manifestations, radiographic characterization, diagnostic methods and management were analyzed. Results: All patients were diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and computerized tomography (CT)-guided percutaneous needle biopsy in 11 (16.2%). Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38 (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%) were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52 cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before pathological examination occurred. Surgical resection was performed in 38 patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was administered, and 20 patients (29.4%) experienced complete responses or partial responses. Conclusion: The main pathogens of pulmonary mycosis are Aspergillus, followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends on pathological examination. The clinical manifestations, imaging features, diagnostic methods and management differ depending on the pathogens. Satisfactory therapy can be obtained by both antifungal and surgical treatment.