Mechanism of Jinrong granule in inhibiting the invasion of breast cancer cells by the CXCL-1-CXCR2/CCL20 pathway.

The purpose of this study was to explore the effect of the Jinrong granule on CXCL-1 and the mechanism of the Jinrong granule on the metastasis and apoptosis of breast cancer cell lines. MDA-MB-231 human breast cancer cell line was divided into a control group, Jinrong extract group, CXCL-1 group and Jinrong extract + CXCL-1 group. The proliferation, apoptosis and permeability of the cells in the experimental group were studied. The protein expression of CXCL-1 was detected by Western blot. On this basis, a bioinformatics method was used to analyze the mechanism of CXCL-1. The results of the CCK8 experiment showed that compared with the control group, the cell proliferation activity of the CXCL-1 treatment group was enhanced while that of the Jinrong granule group was decreased. Compared with that of the CXCL-1 treatment group, the cell proliferation rate of the CXCL-1 + Jinrong granule group was significantly lower. The results showed that CXCL-1 could inhibit apoptosis of breast cancer cells, while the Jinrong granule could reverse the inhibition of apoptosis induced by CXCL-1. The results showed that the Jinrong granule could inhibit the ability of CXCL-1 to promote the migration and proliferation of breast cancer cells. The Jinrong granule could reverse the promoting effect of CXCL-1 on breast cancer through the CXCL-1- CLCR2/CCL20 pathway. In conclusion, the Jinrong granule can inhibit the invasion of breast cancer cells through the CXCL-1-CLCR2/CCL20 pathway.

Lipoxin A4 alleviates lung injury in sepsis rats through p38/MAPK signaling pathway.

The aim of the study was to explore the effect of lipoxin A4 (LXA4) on lung injury in sepsis rats through the p38/mitogen-activated protein kinase (MAPK) signaling pathway. Sprague-Dawley rats were used for the study. The rat model of sepsis-induced acute lung injury was established via cecal ligation (Sepsis group, n=20). LXA4 (0.1 mg/kg) was injected at 6 h after modeling (Treatment group, n=20), and a The Control group (n=20) was also set up. The 7-day survival rate was 100% in The Control group, and LXA4 raised the survival rate of rats in the Sepsis group from 40% to 60% (P<0.01). Alveolar fluid clearance (AFC) significantly declined and the wet/dry weight (W/D) ratio of lung tissues rose remarkably in the Sepsis group compared with those in the Control group, while LXA4 restored AFC and reduced the W/D ratio of lung tissues (P<0.05), suggesting that LXA4 treatment reduces lung fluids and partially enhances AFC, thus lowering the W/D ratio of lung. The total cell count, polymorphonuclear neutrophils (PMN) percentage and concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were obviously increased in the Sepsis group compared with those in the Control group, while they were markedly decreased in the Treatment group (P<0.05). The activity of myeloperoxidase (MPO) in lung tissue homogenate was evidently higher in the Sepsis group than that in The Control group, while it was notably lower in the Treatment group than that in the Sepsis group after LXA4 treatment (P<0.05). Moreover, it was observed microscopically that the morphology of lung tissues was intact in the Control group. Finally, the results of Western blotting manifested that the p-p38/ MAPK protein expression was remarkably increased in the Sepsis group, indicating the activation of the p38/MAPK pathway, while it was remarkably decreased in the Treatment group, indicating the inhibited activity of the pathway (P<0.05). LXA4 has an anti-inflammatory effect on sepsis rats with lung injury, and such effect is related to the p38/MAPK signaling pathway.

Self-driving laboratory for accelerated discovery of thin-film materials.

Discovering and optimizing commercially viable materials for clean energy applications typically takes more than a decade. Self-driving laboratories that iteratively design, execute, and learn from materials science experiments in a fully autonomous loop present an opportunity to accelerate this research process. We report here a modular robotic platform driven by a model-based optimization algorithm capable of autonomously optimizing the optical and electronic properties of thin-film materials by modifying the film composition and processing conditions. We demonstrate the power of this platform by using it to maximize the hole mobility of organic hole transport materials commonly used in perovskite solar cells and consumer electronics. This demonstration highlights the possibilities of using autonomous laboratories to discover organic and inorganic materials relevant to materials sciences and clean energy technologies.

[Application of image-guided system in endoscopic sinus and skull base surgery].

Objective:To evaluate the applicative value of image-guided system in endoscopic sinus and skull base surgeries. Method:A total of 103 endoscopic surgical procedures were performed.All these procedures were conducted with the utilization of image-guided system, among which there were 92 cases of sinonasal-skull base surgery(including nasal sinuses resection of benign and malignant tumors involving skull base lesions, the cumulative orbital lesion resection of nasal sinus lesions, etc. ), 6 repair of cerebrospinal fluid leak, 3 pituitary adenoma resection, 2 traumatic neuropathy optic nerve decompression. Result:With the utilization of image-guided system, all patients had successful surgery without major and minor complications. The image-guided system provided high precision with short registration time. Conclusion:Image-guided system can help the surgeon to identify accurately the vital anatomic landmarks of sinus and skull base, improving surgical accuracy and safety as well as reducing or avoiding the intraoperative and postoperative complications.

Divergent solid-phase synthesis and candidacidal activity of MUC7 D1, a 51-residue histidine-rich N-terminal domain of human salivary mucin MUC7.

Domain 1 of the low-molecular-weight human salivary mucin, designated MUC7 D1, spans the 51 N-terminal amino acid residues. This domain contains a 15-residue basic histidine-rich subdomain (R3-Q17) which has 53% sequence similarity to histatin 5 (Hsn-5), a salivary molecule known to exert potent in vitro cidal activity against Candida albicans and many other medically important fungi. The MUC7 D1-15mer and its derivatives have previously been synthesized in our laboratory and their candidacidal activities have been found to be inferior to that of Hsn-5. We were therefore intrigued to explore the candidacidal potency of the full-length MUC7 D1 (51-mer). Linear solid-phase synthesis of this domain has been accomplished following standard Fmoc chemistry. The problems of partial coupling, owing to the peptide chain length, at several stages of the solid-phase step-by-step synthesis were circumvented either by double-coupling techniques or efficient coupling procedures. The MUC7 D1 peptide was purified to homogeneity by conventional reverse-phase HPLC using two columns connected in series. Secondary structure of the purified peptide was assessed by circular dichroism (CD) spectroscopy in phosphate buffer and trifluoroethanol and compared to that of MUC7 D1-15mer and Hsn-5. The MUC7 D1 candidacidal activity was assessed against azole-sensitive and azole-resistant C. albicans strains and was found, unlike that of the MUC7 D1-15mer, to be comparable with that of Hsn-5, indicating that in addition to Hsn-5, MUC7 D1 could provide an attractive alternative to the classical antifungal agents. The candidacidal potency of MUC7 D1, like that of MUC7 D1-15mer, and of Hsn-5, appears to be largely dependent on peptide charge, irrespective of alpha-helical structure.

Role of alpha-helical conformation of histatin-5 in candidacidal activity examined by proline variants.

Human salivary histatin-5 (Hsn-5) is a potent in vitro anticandidal agent. The aim of this study was to investigate the importance of alpha-helical structure of Hsn-5 for its candidacidal activity. The following three Hsn-5 variants, where one or more functionally nonessential residues were replaced with proline (potent alpha-helix breaker), were produced by Escherichia coli expression system: H21P (1P), H19P/H21P (2P), and E16P/H19P/H21P (3P). The activities of purified proteins were determined by candidacidal assays, and the secondary structures by circular dichroism (CD) spectroscopy in trifluoroethanol (TFE) that is considered the helix-promoting solvent, and lysophosphatidyl-glycerol (LPG) micelles, the environment that more closely resembles the biological membranes. Our results indicated that 3P variant displayed a candidacidal activity which was similar to that of unaltered Hsn-5 (0P), while 1P and 2P variants showed lower cidal activity. The CD spectra in TFE indicated that 3P variant has less helical characteristics than the 0P, 1P and 2P. These results suggested that the alpha-helical content of Hsn-5 proline variants does not correlate with the candidacidal activity. Further, the CD spectral analysis of peptides in LPG micelles indicated the formation of beta-turn structures in 0P and 3P variants. In conclusion, 3P variant which exhibited comparable candidacidal activity to 0P contains lower percentage of alpha-helical structure than 1P and 2P variants, which exhibited lower candidacidal activity. This suggests alpha-helix may not be important for anticandidal activity of Hsn-5.

In vitro assessment of antifungal therapeutic potential of salivary histatin-5, two variants of histatin-5, and salivary mucin (MUC7) domain 1.

Human salivary histatin-5 (Hsn-5) is a 24-residue peptide that possesses potent antifungal activity in vitro. The MUC7 gene encodes human salivary low-molecular-weight mucin (MG2). The candidacidal activity of MUC7 domain 1 (MUC7 D1, the N-terminal 51 amino acid residues of MUC7) in vitro has also been demonstrated. In this study, we have investigated the antifungal therapeutic potential of Hsn-5, its two variants, R12I/K17N and R12I/H21L, and MUC7 D1. First, these peptides were tested for activities against different clinically important fungi. We found them to possess broad-spectrum antifungal activities; specifically, most exhibited excellent in vitro activity against eight clinically important fungal strains tested, including Candida albicans and Candida glabrata and their azole-resistant counterparts and Cryptococcus neoformans and its amphotericin B-resistant counterpart. These findings also suggest that the mechanism of action of both Hsn-5 and MUC7 D1 for these fungi is different from that of amphotericin B or azole antifungal agents. Second, we examined the stability of these peptides in whole human saliva and human serum. In saliva, the Hsn-5 variants R12I/K17N and R12I/H21L and MUC7 D1 degraded at a lower rate than Hsn-5. In human serum, MUC7 D1 was also more stable than Hsn-5; both peptides were more stable in serum than in saliva. Third, we examined the cytotoxicity of these peptides using human erythrocytes and two human cell lines (KB and HSG). No (or very low) hemolytic activity was observed with any of the four peptides, even at the highest protein concentration tested (200 microM), while amphotericin B caused 100% hemolysis at only 12.5 microM. The toxic effects of Hsn-5 and MUC7 D1 toward KB and HSG cells were also much lower than that of amphotericin B as measured by trypan blue exclusion. Together, these findings indicate that the investigated peptides possess high antifungal therapeutic potential, in particular for the treatment of drug-resistant fungal strains associated with immunocompromised (particularly human immunodeficiency virus-infected) patients. The same peptides could also be used as components of artificial saliva for patients with salivary dysfunction.

Construction and characterization of human salivary histatin-5 multimers.

Human salivary histatin-5 (Hsn-5), a 24-amino acid polypeptide, is a potent candidacidal molecule. In this study, we have explored the following two hypotheses: More potent Hsn molecules may be achieved by duplication of the functional domain of Hsn-5 (C16, residues 9-24 of Hsn-5), and Hsn may act like other cationic peptides which aggregate and form channels across the target membrane. A PCR-based gene splicing by overlap extension (SOE) method was used to construct the DNA fragments encoding the following fusion molecules: Hsn-5--Hsn-5, Hsn-5--C16, and C16--C16. These constructs were expressed in E. coli, the proteins produced were purified, and their anticandidal activities as well as secondary structures were determined. Contrary to our hypotheses, results showed that none of the multimers possessed increased candidacidal activity. Specifically, C16--C16 and Hsn-5--C16 displayed candidacidal activity comparable with that of Hsn-5, while Hsn-5--Hsn-5 possessed significantly decreased candidacidal activity, yet all molecules retained an alpha-helical structure in a hydrophobic environment. Additionally, the circular dichroism data showed that Hsn-5 in an alpha-helical conformation does not aggregate in a hydrophobic environment, not even at 14- to 18-fold its physiological concentration. Our results suggest that the development of enhanced Hsn-5 molecules may not be achieved by duplication of its functional domain, and that Hsns may not act like other antimicrobial cationic peptides which aggregate and form channels across the target membrane.

[Analysis of high frequency X-ray images in 43 cases of breast cancer].

OBJECTIVE: To analyse a series of breast cancer images in high frequency X-ray for more accurate diagnosis of breast cancer. METHODS: Forty three high frequency X-ray images of breast cancer surgically confirmed were comprehensively analyzed. RESULTS: Of the 43 breast cancer cases, 42 were primary breast cancers and one secondary. Tumor mass was present in 38 cases, with burrs in 26. Malignant calcification was found in 13 cases, and structural derangement in 21 cases. There were 30 cases with abnormal blood vessels, and 7 cases with thick skins. Ductal and lymph drainage features were seen in 9 cases. There were 5 cases showing ox horn sign. The high frequency X-ray diagnosis of breast cancer conformed with pathologic diagnosis in 95.6% of the cases. CONCLUSION: The advantages of high frequency X-ray are its extremely high clarity and good contrast. Pictures can be taken form various axises which help detect occult and tiny cancer.

[Clinical application of medial leg skin flap for the repair of defects of the extremities].

A total of fifteen medial leg skin flaps with the posterior tibial artery as an axial vessel have been applied successfully to reconstruct extremity defects, such as chronic ulcers, scar contracture, high-voltage electric injuries and hot crush, etc. This skin flap can be elevated as a free flap, or vascular island flap, or cross-leg vascular pedicle flap to resurface the defects on the extremities. It is especially suitable for foot repair because of its long vascular pedicle and wide rotational arc as an island skin flap. The paper describes and discusses the indications, design and operating technique of this flap.

Reconstruction of limb defects with the free posterior tibial artery fasciocutaneous flap.

There are few reports on the use of free posterior tibial artery free flaps. We present four cases of reconstruction of a limb defect with a free posterior tibial artery fasciocutaneous flap.