ABSTRACT
Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
ABSTRACT
Musashi is a family of RNA binding proteins with a conservative evolution. This protein family is selectively ex-pressed in the nervous system and comprises two members, namely, Musashi-1 and Musashi-2. Musashi-1 and Musashi-2 are transla-tional suppressors of Numb mRNA and can synergistically regulate the Notch signaling pathway;as a result, an asymmetric division of stem cells occurs. Musashi-1 is the first member of the family and was originally isolated from Drosophila. As a candidate stem gene, Musashi-1 participates in disease progression in stem cells. Musashi-1 is also an important protein that maintains the functions of stem cells, participates in tumor-related signaling pathways, and participates in cell proliferation and apoptosis. Furthermore, Musashi-1 is overexpressed in many solid tumors, such as neuroglioma, esophagus, gastric, colorectal, and breast cancers. Studies on Musashi-1 can provide new insights into genetic diagnosis and cancer treatments. In this study, the structure and function of Musashi-1 and the re-search progress of tumor mechanisms were summarized and reviewed.
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Objective To study serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and its correlation with accumulation degree of 99Tcm-MDP on bone and arthritis and to study the role of sICAM-1 in the diagnosis of patients with early RA. Methods Serum levels of sICAM-1 were measured by immunoenzymetic assay (ELISA). 99mTc-MDP scintigraphy was carried out for the same patients. The significant test between serum levels of sICAM-1 of three groups was performed with analysis of variance; Correlations between serum levels of sICAM-1 and index of semiquatitive 99Tcm-MDP were obtained using sperman's ranks correlation method. Results Compared with control group,serum levels of sICAM-1 were significantly higher in standard group (group A) (P<0.01) and non-standard group (group B) (P<0.05). No significant difference was found between group A and B(P>0.05). Serum levels of sICAM-1 were positively correlated with 99Tcm-MDP scintigraphy. Most patients of non-standard group and standard group showed visible medium-high uptake of 99Tcm-MDP. While control group had not obviously uptake of 99Tcm-MDP. Conclusion Serum levels of sICAM-1, semiquatitive 99Tcm-MDP scintigraphy, accumulation degree of radiopharmuceuutial on bone and arthritis are helpful for diagnosis of early rheumatoid arthritis and judge-ment of the clinical status and improvement of the prognosis.
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<p><b>BACKGROUND</b>To investigate the expression of cyclooxygenase-2 (COX-2) protein and inducible nitric oxide synthase (iNOS) protein during the experimental lung carcinogenesis in rats, as well as their association with microvessel density (MVD).</p><p><b>METHODS</b>Diethylinitrosamine and 3-methylcholanthrene were instilled into the left lobar bronchus to induce lung squamous cell carcinoma in 88 Wistar rats, and 10 nomal rats as controls. COX-2, iNOS expression and MVD count of the specimens obtained from the rats were examined by immunohistochemistry.</p><p><b>RESULTS</b>A total of 155 specimens of various pathological phase during the carcinogenesis were obtained: 14 hyperplasia, 25 squamous metaplasia, 33 dysplasia, 12 carcinoma in situ, 54 infiltration carcinoma, and 17 metastasis. The immunohistochemical score (IHS) of COX-2 significantly increased in dysplasia, carcinoma in situ and metastasis (P < 0.01,P < 0.05,P < 0.01). IHS of iNOS significantly increased in hyperplasia and metastasis (P < 0.05,P < 0.01 ). Remarkably increased MVD was found in carcinoma in situ, infiltration carcinoma and metastasis (P < 0.01, P < 0.01, P < 0.01). There was a positive correlation between COX-2 and iNOS (r=0.601 6,P < 0.001) expression. Expression of COX-2 or iNOS were remarkably related to MVD count (P < 0.01,P < 0.01)</p><p><b>CONCLUSIONS</b>COX-2 and iNOS may play important roles in the carcinogenesis of experimental rat lung squamous cell carcinoma as well as its progress, and it may be associated with stimulating angiogenesis.</p>
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Objective To explore the changes of urinary Trypsinogen Activation Peptide (TAP) levels in patients with acute pancreatitis (AP).Methods We observed the association between urinary TAP concentration and severity of acute pancreatitis with competitive enzyme-linked immunosorbent assay(ELISA). Urine samples were collected for TAP concentration at admission,24,48,and 72 h from 57 patients with AP who presented within 48 h of the onset of symptoms and from 11 control patients. Results The median urinary TAP at admission for severe acute pancreatitis(SAP) (98 nmol/L) was signficantly higher than the median for both mild pancreatitis (22 nmol/L,P0.05).The peak median urinary TAP in severe eroup was seen at admission.In the following days,TAP concentrations decreased graduallg.Conclusion Breakthrough activation of trypsinogen in pancreatic interstitial and blood may be the key event in the development of SAP.
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AIM: To observe the expression of HIF-1? mRNA, HIF-1?, VEGF and iNOS proteins and to investigate their relationship in h ypoxia-treated SW480 cells. METHODS: HIF-1?, VEGF and iNOS proteins were measured by immuno cytochemistry. Western-blot was used to detect HIF-1? protein. HIF-1? mRNA wa s measured by in situ hybridization. RESULTS: Under hypoxic condition, SW480 cells expressed proteins of HIF-1?, VEGF and iNOS more strongly than that under normoxia condition. How e ver, under hypoxia condition, these three proteins expressed weakly or negativel y when the cells treated with genistein, the inhibitor of HIF-1?. Expressions o f HIF-1? and VEGF proteins in cultured SW480 cells under hypoxic condition were completely or partially inhibited by the addition of SNP but the expression of iNOS was unaffected. Another NO donor NOC5, however, induced the expression of t hese three proteins. L-NAME, a non-specific inhibitor of NOS, inhibited the expr ession of HIF-1?, VEGF and iNOS. The levels of HIF-1? mRNA changed slightly i n different oxygen condition or addition of genistein, NO donor or iNOS inhibitor . CONCLUSIONS: Hypoxia induces the expression of HIF-1?, therefor e upregulates the production of VEGF and iNOS. During hypoxia, SNP inhibits but N OC5 promotes HIF-1? expression, indicating that different NO donor acts on the cells through different mechanisms.