Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis.

AIM: Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. MATERIALS AND METHODS: We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co-invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. RESULTS: A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+ ). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6-month follow-up. CONCLUSION: Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats.

INTRODUCTION: Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. METHODS: Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor ß (TGF-ß) in kidney tissue were detected by Western blot. RESULTS: DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-ß1. CONCLUSION: Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

A prospective study of dual-energy computed tomography for differentiating metastatic and non-metastatic lymph nodes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy worldwide, and lymph node metastasis is considered to be a risk factor for local recurrence and a poor prognosis in colorectal cancer. However, there remains a lack of reliable and non-invasive biomarkers to identify the lymph node status of CRC patients preoperatively. The purpose of this study was to explore the ability of dual-energy computed tomography (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer. METHODS: Seventy-one patients with primary colorectal cancer underwent contrast-enhanced dual-energy computed tomography imaging preoperatively. The colorectal specimen was scanned postoperatively, and lymph nodes were matched to the pathology report. The following dual-energy computed tomography quantitative parameters were analyzed: dual-energy curve slope value (λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), and effective atom-number (nZ), based on metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed using receiver operating characteristic curves. RESULTS: In all patients, one hundred and fifty lymph nodes, including 66 non-metastatic and 84 metastatic lymph nodes, were matched using the radiological-pathological correlation. Metastatic nodes had significantly greater λHU, n△HU, and nIWR values than non-metastatic nodes in both the arterial and venous phases (P<0.01). The area under curve (AUC), sensitivity, and specificity were 0.80, 80%, and 66% for λHU; 0.86, 70%, and 95% for n△HU; and 0.88, 71%, and 95% for nIWR in the arterial phase. There was no significant difference in electron density and effective Z values between metastatic and non-metastatic lymph nodes. CONCLUSIONS: DECT quantitative parameters may help differentiate between metastatic and normal lymph nodes in patients with CRC.

Epithelioid hemangioendothelioma of spine: A case report with review of literatures.

Primary epithelioid hemangioendothelioma of the spine is the extremely rare malignant vascular neoplasm with an unpredictable outcome. A case of epithelioid hemangioendothelioma with multiple lytic lesions of thoracolumbar spine and other bones in a 29-year-old male patient is reported. A review of the published data regarding this rare neoplasm is also presented. The features of epithelioid hemangioendothelioma include the occurrence in the young male patient, multiple osteolytic lesions with thin sclerotic rim and hypermetabolic activities. However, its imaging features are not specific. Positron emission tomography/computed tomography is essential for identification of the lesions and subsequent follow-up for treatment.

High-grade B-Cell Lymphoma With MYC, BCL2, and/or BCL6 Translocations/Rearrangements: Clinicopathologic Features of 51 Cases in a Single Institution of South China.

Double-hit/triple-hit lymphomas (DH/THLs) are high-grade B-cell lymphomas with MYC and BCL2 rearrangements and/or BCL6 rearrangements, which have poor outcomes after standard chemoimmunotherapy. This retrospective study analyzed 51 patients (range, 19 to 82 y) diagnosed from 2016 to 2019 and treated for DH/THL (n=34 MYC/BCL6 DHL, n=14 MYC/BCL2 DHL, n=3 THL) at one institution in South China. Extranodal lesions occurred in 32 patients (62.7%), more frequently in MYC/BCL6 DHL (22/34, 64.7%) than in MYC/BCL2 DHL (7/14, 50%). The most common extranodal sites were the stomach (8/32, 25.0%) and intestine (5/32, 15.6%). Most patients (33/45, 73.3%) presented with Ann Arbor stage III/IV. Interestingly, 14.3% (4/28) of MYC/BCL6 DHL tumors showed diffuse, medium-intensity CD30 expression. Epstein-Barr virus-encoded RNA was positive in 3 cases, all MYC/BCL6 DHL. Among 48 patients (94.1%) with follow-up data, 18 (37.5%) died owing to the disease, and the median survival was 5.5 months. Germinal center B cells were observed more frequently in MYC/BCL2 DHL (14/14, 100.0%) than in MYC/BCL6 DHL (15/34, 44.1%; P<0.001). Bone marrow involvement tended to lower overall survival (OS) (P=0.033). No association was observed between stage, B symptoms, lactate dehydrogenase levels, and central nervous system involvement and OS. A total of 25 patients (25/47, 53.2%) with previous hepatitis B virus (HBV) infections had significantly poorer OS (P=0.014). Chronic HBV infection was positively correlated with MYC/BCL6 DHL (r=0.317, P=0.030). Compared with DH/THL in western countries, the disease in South China has distinct characteristics with a higher prevalence of MYC/BCL6 DHL. We speculate that HBV is important in DH/THL tumorigenesis. These findings might provide clues for novel treatment strategies.

MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway.

BACKGROUND: MicroRNAs have been involved in regulating crucial biological function in some tumors. However, the clinical role and functional effects of miR-591 in breast cancer remain unknown. METHODS: The expression of miR-591 was detected in breast cancer tissues and their paired normal tissues by qRT-PCR. Functional assays were performed to confirm the effects of miR-591 on the proliferation and invasion of breast cancer. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that TCF4 was a target gene of miR-591. Western blot analysis was carried out to analyze the relationship between miR-591 expression and YAP1 expression in breast cancer. RESULTS: We found that miR-591 expression levels were significantly downregulated in breast cancer tissues compared to adjacent normal tumor tissues. Lower miR-591 expression notably related to lymph node metastasis and advanced TNM stage in patients with breast cancer. In vitro, cell proliferation and invasion were inhibited by transfection of miR-591 mimic in breast cancer cells, but were promoted by transfection of miR-591 inhibitor, compared to the controls. In vivo, we also found that miR-591 mimic significantly inhibited cell proliferation ability. Moreover, we identified that TCF4 was a direct target of miR-591 in breast cancer. TCF4 mediated the inhibiting effects of miR-591 on cell proliferation and invasion in breast cancer cells. In additional, we revealed that miR-591 overexpression significantly inhibited the Hippo-YAP/TAZ signaling pathway in breast cells by downregulated YAP1 expression in breast cells. CONCLUSION: Together, these results indicated that miR-591 is downregulated in breast cancer and could act as a potential target of breast cancer treatment.

Mesenchymal stem cells attenuate sepsis-induced liver injury via inhibiting M1 polarization of Kupffer cells.

Sepsis is a leading cause of death in intensive care units that can result in acute hepatic damage. Animal experiments and clinical trials have shown that mesenchymal stem cell (MSC) therapy has some beneficial in several liver diseases. However, the protective effects of MSC therapy on sepsis-induced hepatic damage and associated mechanisms are not completely understood. The aim of the present study was to investigate the effects of MSCs on sepsis-induced liver injury and underlying mechanisms. A rat model of sepsis-induced liver injury was established by cecal ligation and puncture, and serum alanine aminotransferase and aspartate transaminase activities as well as liver histological changes were measured. Inflammatory cytokines, Kupffer cell M1 phenotype markers, and associated signal molecules were also determined in septic rats and in lipopolysaccharide (LPS)-treated Kupffer cells. Our results showed that injection of MSCs attenuated sepsis-induced liver injury. Treatment with MSCs inhibited activation of Kupffer cells towards M1 phenotype, attenuated TNF-α and IL-6 expression, and promoted IL-4 and IL-10 expression in septic rats and LPS-treated Kupffer cells. Furthermore, MSCs also inhibited the nuclear translocation of nuclear factor-kappa B in LPS-challenged Kupffer cells and the liver of septic rats. These results indicated that MSCs attenuated sepsis-induced liver injury through suppressing M1 polarization of Kupffer cells.

Hybrid Structure of 2D Layered GaTe with Au Nanoparticles for Ultrasensitive Detection of Aromatic Molecules.

Owing to a complex monocline structure and high-density of defects in monocrystalline GaTe, the performance of GaTe-based electronic devices is considerably compromised. Yet, the defects' nature in GaTe could be a merit rather than a shortcoming in other realms. In our work, the density of defects in GaTe films is utilized for a facile decoration of Au nanoparticles (NPs), which allowed us to extend its application potential to the domain of surface enhanced Raman scattering (SERS) for the first time. Two-dimensional (2D) GaTe layered structures are prepared by mechanical exfoliation, and high-density Au NPs are synthesized by immersion of 2D GaTe in HAuCl4 aqueous solution. By varying the immersion time, the sizes and coverage rate of Au NPs on GaTe can be elaborately tuned. Thanks to the defect nature of GaTe, the maximum coverage amounts to 98%. The hereby achieved Au-NPs-2D-GaTe hybrid structure demonstrates outstanding properties as a superior SERS substrate for ultrasensitive detection of R6G aromatic molecules. Remarkably, the enhancement factor reaches up to 1.6 × 104, and the minimum detectable concentration is 10-11 M, undercutting that of recently reported Au-NPs-MoS2 SERS and Au-NPs-graphene SERS substrates which have a similar structure. With superior detection capability and facile preparation, Au-NPs-GaTe SERS substrates can become a perfect choice for the detection of aromatic molecules.

Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells.

Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to "copper" cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper.

Role of quantitative intravoxel incoherent motion parameters in the preoperative diagnosis of nodal metastasis in patients with rectal carcinoma.

PURPOSE: To evaluate the diagnostic value of intravoxel incoherent motion imaging (IVIM) in differentiating metastatic and nonmetastatic lymph nodes in patients with rectal carcinoma. MATERIALS AND METHODS: In all, 68 patients with histologically proven rectal carcinoma underwent an IVIM sequence (b = 0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1000, 1200, 1500, and 2000 s/mm(2) ) on a 3.0T MRI scanner. The IVIM parameters (D, D*, f, and apparent diffusion coefficient [ADC] values) in metastatic and nonmetastatic lymph nodes were measured and calculated. Receiver-operating characteristic (ROC) analyses were conducted to determine the optimal thresholds, the sensitivities, and specificities for differentiation. RESULTS: Mean D, f, and ADC values of metastatic lymph nodes were significantly greater than those of the normal lymph nodes (P < 0.01), whereas the mean D* value of metastatic lymph node was statistically lower (P = 0.03). The AUC, sensitivity, specificity, and the cutoff value, respectively, for differentiating metastatic from nonmetastatic lymph nodes for D, D*, f, and ADC were as follows: D, 0.9460, 89.25%, 91.04%, and 1.14 × 10(-3) mm(2) /s; D*, 0.6930, 64.18%, 82.80%, and 7.02 × 10(-3) mm(2) /s; f, 0.7810, 92.47%, 55.22%, and 0.27%; ADC, 0.8970, 87.10%, 88.06%, and 0.80 × 10(-3) mm(2) /s. The ROC curves demonstrated that the area under the ROC (AUC) of the D, ADC, f, and D* values successively decreased, and D had the highest AUC, with D* values being lowest. CONCLUSION: An IVIM sequence may be helpful in diagnosing metastatic lymph nodes of rectal carcinoma. Average D and ADC values are more sensitive than f and D* values in this differentiation. J. MAGN. RESON. IMAGING 2016;44:1031-1039.

4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/Akt/mTOR-independent pathway.

Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein (4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma.

[Glucagon-like peptide-1 regulates lipometabolism by down-regulating adipose triglyceride lipase in 3T3-L1 adipocytes].

OBJECTIVE: To investigate the effect of glucagon-like peptide-1 (GLP-1) on glycolipid metabolism in 3T3-L1 adipocytes and explore the mechanism. METHODS: 3T3-L1 adipocytes were treated with GLP-1, insulin, or both for 24 h, and Western blotting was used to analyze the expression levels of adipose triglyceride lipase (ATGL), glucose transporter type 4 (GLUT4), Akt1, Akt2 and phosphorylated Akt in the cells. Immunofluorescence was used to observe lipid content in 3T3-L1 adipocytes. RESULTS: Akt1 and Akt2 were not activated by insulin stimulation in 3T3-L1 adipocytes. Akt was phosphorylated by GLP-1 stimulation, which inhibited the expression of ATGL and increased the translocation of GLUT4 from the intracellular membranes to plasma membranes. These changes were more obvious under the synergistic effect of insulin in 3T3-L1 adipocytes. CONCLUSION: GLP-1 decreases lipolysis by inhibiting the expression of ATGL and improves insulin resistance by increasing the translocation of GLUT4 in 3T3-L1 adipocytes.

[The experimental study of suppressing silicosis fibrosis].

OBJECTIVE: To compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects. METHODS: The Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method. RESULTS: On the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05). CONCLUSION: The effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.