Mycetoma of the forearm due to Actinomadura madurae

A case of mycetoma, with abscess-like lesions which appeared on the right forearm of a 43-year-old male, is briefly reported. A few whitish granules were detected in the oily-like discharge, the same as in the histologic examination. No bone involvement was discovered in X-ray examination. Actinomadura was identified in the culture. A daily dose of 4 g bactrin brought significant improvement to the patients continuing the treatment.     

The effects of parathyroid hormone-related peptide on cardiac angiogenesis,apoptosis, and function in mice with myocardial infarction

It is known that parathyroid hormone-related peptide (PTHrP) contains a nuclear localization sequence (NLS, 87-107), which, together with its C-terminus (107-139), has been shown to positively regulate vascular smooth muscle cell (VSMCs) proliferation and vascular neointima formation, and inhibit cellular apoptosis. The role of PTHrP in ischemic cardiac diseases remains unclear. In this study, we attempted to determine whether PTHrP 87 to 139 can play a role in promoting cardiac function via enhancing angiogenesis after myocardial infarction (MI) occurred. MI was reproduced in C57BL/6 mice using a coronary artery ligation method. In total, three groups (n = 11 per group) of animals were used, and they were received either PTHrP 87 to 139 (80 µg/kg, treatment group) or saline (MI and Sham group) subcutaneously once a day for 4 weeks after MI. To measure cardiac function, an echocardiography was generated and cardiac tissue was harvested for immunohistological studies 4 weeks after operation. Our results show that, after MI, the cardiac function of the experimental mice was significantly impaired. PTHrP 87 to 139 treatment attenuated cardiac dysfunction in MI mice. Besides, as indicated by decreased heart weight/body weight and lung weight/body weight ratio, PTHrP 87 to 139 attenuated pulmonary congestion and cardiac hypertrophy. Masson staining revealed that PTHrP 87 to 139 attenuated myocardial fibrosis after MI. Also, terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining and the expression of cleaved caspase 3 suggested that MI-induced myocytes apotosis was inhibited by PTHrP 87 to 139. In addition to the significantly increased capillary density, PTHrP 87 to 139 treatment also induced p-Akt and several angiogenic factors. In conclusion, PTHrP 87 to 139 treatment preserved cardiac function after MI, and stimulated angiogenesis via upregulating vascular endothelial growth factor and basic fibroblast growth factor (bFGF) in infarct border zone of ischemic myocardium,. These results suggest that PTHrP 87 to 139 is of therapeutic potential for MI.     

Quantitative Assessment of Polyethylene Component Position in a Mobile-Bearing Prosthetic Knee,Using a Single Radiograph

Rationale and Objectives. To reduce tibio-femoral misalignment, the polyethylene bearing-component of a new knee prosthesis was allowed limited motion on the underlying metallic component. The object of the work presented here was to develop a suitable radiographic technique for quantifying the in-vivo position of the bearing. By collecting these data at discrete flexion angles, the functional operation of the prosthesis could be determined

Methods. The known geometries between landmarks on the two components were used to produce algorithms for reconstructing their spatial positions from a single radiograph. A custom-designed computer program utilized these algorithms to determine the relative translation and rotation of the polyethylene component

Results. This technique produced typical errors of 0.54 mm translation and 0.56° rotation between the polyethylene component and the underlying metallic component

Conclusions. A practical method has been developed for assessing mobile-bearing motion, in vivo. This method can be applied to other prosthetic devices, or combinations of components, once the requirement for identifiable landmarks has been addressedClinical Relevance. Skeletal and soft-tissue changes in the pathological knee may produce abnormal rotations and translations in the transverse tibial plane. This technique is intended both to validate the design philosophy of a mobile-bearing prosthesis and to provide additional data on any pathological motions, which will have implications for future prosthetic designs.     

Myosin mediates contractile force generation by hepatic stellate cells in response to endothelin-1

Although endothelin-1-stimulated contractile force generation by stellate cells is believed to play an important role in hepatic pathophysiology, the molecular signals that mediate this process are incompletely understood. The aim of this study was to test the hypothesis that myosin mediates the contractile force generated by stellate cells in response to endothelin-1. Contractile force generation by primary and immortalized stellate cells was directly and quantitatively measured. Myosin phosphorylation and reorganization, and actin stress fiber formation were investigated in immortalized stellate cells. Endothelin-1 stimulated a rapid and robust generation of contractile force by primary and immortalized stellate cells with a similar dose dependence. Myosin phosphorylation, actin stress fiber assembly, and reorganization of myosin to stress fibers were induced by concentrations of endothelin-1 that also stimulated stellate cell contraction. BQ-123, a selective endothelin receptor antagonist, inhibited myosin phosphorylation and contractile force generation. Y-27632, which selectively inhibits rho-associated kinase, also blocked endothelin-1-stimulated myosin phosphorylation and contractile force generation with a similar dose dependence. These results suggest that endothelin-1-stimulated contractile force generation by stellate cells is mediated by myosin.     

Expression of γ-H2AX and patient prognosis in breast cancer cohort

H2AX phosphorylation is a novel marker of DNA double-stranded breaks. In the present study, we assessed the γ-H2AX expression, its association with other clinicopathologic characteristics, and the prognosis in a cohort of 97 patients with breast cancer. Ninety-seven specimens of tumor tissue and 77 adjacent normal tissues from patients with breast cancer were examined. All patients underwent modified radical mastectomy or local tumor resection without lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Patients were followed after surgery for a mean duration of 70.1 ± 18.7 months (range, 6-93 months). The γ-H2AX staining was positive in 27 (27.8%) patients. The positive rates of H2AX were 26.0% and 2.6% in tumor tissue and adjacent normal tissues, respectively. γ-H2AX positive status was negatively associated with TNM staging, with 24 positive cases (32.4%) in TNM staging I-II, while no positive cases in TNM staging III-IV (P = 0.026). Sixteen patients (16.5%) died during the follow-up. No significant association between γ-H2AX expression and patient survival was detected. The unadjusted HR (hazard ratio) for γ-H2AX positive was 0.84 (95% CI: 0.27, 2.60). In TNM staging subgroup analysis, death only occurred in γ-H2AX negative patients. Our study is the first study to demonstrate that expression of γ-H2AX is associated with TNM staging. Due to the small sample and limited follow-up time, we did not observe a significant association between γ-H2AX and patient survival. γ-H2AX expression could be a potential biomarker for cancer diagnosis and prediction, and further studies are in need.     

Identification of messenger and long noncoding RNAs associated with gallbladder cancer via gene expression profile analysis

The present study aimed to investigate the long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in the progression of gallbladder cancer and explore the potential physiopathologic mechanisms of gallbladder cancer in terms of competing endogenous RNAs (ceRNAs). The original lncRNA and mRNA expression profile data (nine gallbladder cancer tissues samples and nine normal gallbladder samples) in GSE76633 was downloaded from the Gene Expression Omnibus database. Differentially expressed mRNAs and lncRNAs between gallbladder cancer tissue and normal control were selected and the pathways in which they are involved were analyzed using bioinformatics analyses. MicroRNAs (miRNAs) were also predicted based on the differentially expressed mRNAs. Finally, the co-expression relation between lncRNA and mRNA was analyzed and the ceRNA network was constructed by combining the lncRNA-miRNA, miRNA-mRNA, and lncRNA-mRNA pairs. Overall, 373 significantly differentially expressed mRNAs and 47 lncRNAs were identified between cancer and normal tissue samples. The upregulated genes were significantly enriched in the extracellular matrix (ECM)-receptor interaction pathway, while the downregulated genes were involved in the complement and coagulation cascades. Altogether, 128 co-expression relations between lncRNA and mRNA were obtained. In addition, 196 miRNA-mRNA regulatory relations and 145 miRNA-lncRNA relation pairs were predicted. Finally, the lncRNA-miRNA-gene ceRNA network was constructed by combining the three types of relation pairs, such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6. mRNAs and lncRNAs may be involved in gallbladder cancer progression via ECM-receptor interaction pathways and the complement and coagulation cascades. Moreover, ceRNAs such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6 can also be implicated in the pathogenesis of gallbladder cancer.     

New sights on the associations between the XRCC1 gene polymorphisms and hepatocellular carcinoma susceptibility

Studies investigating the relationships between the polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene and the susceptibility of hepatocellular carcinoma (HCC) remained controversial, therefore, we assessed this associations by metaanalysis and trial sequential analysis (TSA). PubMed, Embase, Google Scholar, Chinese National Knowledge Infrastructure and Baidu Scholar were comprehensively screened to retrieve relevant studies up to May 20, 2019. A total of 32 studies was included. Significant associations were discovered in the overall and subgroup analysis in these three polymorphisms. Interestingly, the decreased risk of HCC was detected in the Indians for the rs24587 polymorphism. TSA indicated the required information size for the rs25487 polymorphism were reached, but for the rs25489 and rs1799782 polymorphisms, more well-designed trials were required. Sensitivity analysis implied our results were stable; no publication bias was observed in the rs25487 and rs1799782 polymorphisms. The bioinformatic analysis indicate that the rs1799782 polymorphism is probably damaging and has an influence on the XRCC1 protein function. Our study indicated that the XRCC1 rs25487 was a risk factor for the susceptibility of HCC, which was verified by the TSA. In addition, the rs25489 and rs1799782 polymorphisms were associated with increased risk of HCC. In the subgroup analysis, increased risks were detected in some subgroups (in accordance with Hardy-Weinberg equilibrium, Chinese groups, Mongoloid subgroup, polymerase chain reaction-restriction fragment length polymorphisms and more than 300 subgroups), moreover, decreased HCC risk of the rs25487 polymorphism was firstly observed, which required further studies to verify.     

The exploration of new therapeutic targets for HPV-negative head and neck squamous cell cancer through the construction of a ceRNA network and immune microenvironment analysis

Previous studies have shown that human papillomavirus (HPV)-negative patients with head and neck squamous cell cancer (HNSCC) suffer from an unsatisfactory prognosis. Long noncoding RNAs (lncRNAs) have been verified to participate in many biological processes, including regulating gene expression as competing endogenous RNAs (ceRNAs), while few studies focused the ceRNA network regulation mechanism in patients with HPV-negative HNSCC tumor. Meanwhile, the immune microenvironment may be critical in the development and prognosis of HPV-negative tumors. Our study aimed to further investigate the pathogenesis and potential biomarkers for the diagnosis, therapy and prognosis of HPV-negative HNSCC through a ceRNA network. Comprehensively analyzing the sequencing data of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in The Cancer Genome Atlas HNSCC dataset, we constructed a differentially expressed ceRNA network containing 131 lncRNAs, 35 miRNAs and 162 mRNAs. Then, survival analysis in the network was cited to explore the prognostic biomarkers. Eight mRNAs, nine lncRNAs, and one miRNA were identified to be associated with prognosis. Neuropilin (NRP) binding function, retinoid X receptor (RXR) binding, and the vascular endothelial growth factor (VEGF) signaling pathway were associated with the enrichment analysis, and they also related to the immune microenvironment. Combined with the analysis of the immune microenvironment differences, we obtained new targeted therapies using an RXR agonist, or a combination of the VEGF monoclonal antibody and an NRP antagonist, which may provide a promising future for HPV-negative HNSCC patients.     

Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs

Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.