Signal peptide replacement of Ag43 enables an efficient bacterial cell surface display of receptor-binding domain of coronavirus.

To enable an efficient bacterial cell surface display with effective protein expression and cell surface loading ability via autotransporter for potential vaccine development applications, the inner membrane protein translocation efficiency was investigated via a trial-and-error strategy by replacing the original unusual long signal peptide of E. coli Ag43 with 11 different signal peptides. The receptor-binding domain (RBD) of coronavirus was used as a neutral display substrate to optimize the expression conditions, and the results showed that signal peptides from PelB, OmpC, OmpF, and PhoA protein enhance the bacterial cell surface display efficiency of RBD. In addition, the temperature has also a significant effect on the autodisplay efficiency of RBD. Our data provide further technical basis for the biotechnological application of Ag43 as a bacterial surface display carrier system and further potential application in vaccine development.

A minimum functional form of the Escherichia coli BAM complex constituted by BamADE assembles outer membrane proteins in vitro.

The biogenesis of outer membrane proteins is mediated by the ß-barrel assembly machinery (BAM), which is a heteropentomeric complex composed of five proteins named BamA-E in Escherichia coli. Despite great progress in the BAM structural analysis, the molecular details of BAM-mediated processes as well as the exact function of each BAM component during OMP assembly are still not fully understood. To enable a distinguishment of the function of each BAM component, it is the aim of the present work to examine and identify the effective minimum form of the E. coli BAM complex by use of a well-defined reconstitution strategy based on a previously developed versatile assay. Our data demonstrate that BamADE is the core BAM component and constitutes a minimum functional form for OMP assembly in E. coli, which can be stimulated by BamB and BamC. While BamB and BamC have a redundant function based on the minimum form, both together seem to cooperate with each other to substitute for the function of the missing BamD or BamE. Moreover, the BamAE470K mutant also requires the function of BamD and BamE to assemble OMPs in vitro, which vice verse suggests that BamADE are the effective minimum functional form of the E. coli BAM complex.

The Lnc-ENST00000602558/IGF1 axis as a predictor of response to treatment with tripterygium glycosides in rheumatoid arthritis patients.

AIMS: Growing clinical evidence suggests that not all patients with rheumatoid arthritis (RA) benefit to the same extent by treatment with tripterygium glycoside (TG), which highlights the need to identify RA-related genes that can be used to predict drug responses. In addition, single genes as markers of RA are not sufficiently accurate for use as predictors. Therefore, there is a need to identify paired expression genes that can serve as biomarkers for predicting the therapeutic effects of TG tablets in RA. METHODS: A total of 17 pairs of co-expressed genes were identified as candidates for predicting an RA patient's response to TG therapy, and genes involved in the Lnc-ENST00000602558/GF1 axis were selected for that purpose. A partial-least-squares (PLS)-based model was constructed based on the expression levels of Lnc-ENST00000602558/IGF1 in peripheral blood. The model showed high efficiency for predicting an RA patient's response to TG tablets. RESULTS: Our data confirmed that genes co-expressed in the Lnc-ENST00000602558/IGF1 axis mediate the efficacy of TG in RA treatment, reduce tumor necrosis factor-α induced IGF1 expression, and decrease the inflammatory response of MH7a cells. CONCLUSION: We found that genes expressed in the Lnc-ENST00000602558/IGF1 axis may be useful for identifying RA patients who will not respond to TG treatment. Our findings provide a rationale for the individualized treatment of RA in clinical settings.

Next-generation sequencing in the diagnosis of neurobrucellosis: a case series of eight consecutive patients.

BACKGROUND: Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. METHODS: Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. RESULTS: Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1-4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. CONCLUSION: NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.

Real-Time Decoding of Snapshot Compressive Imaging Using Tensor FISTA-Net.

Snapshot compressive imaging (SCI) cameras compress high-speed videos or hyperspectral images into measurement frames. However, decoding the data frames from measurement frames is compute-intensive. Existing state-of-the-art decoding algorithms suffer from low decoding quality or heavy running time or both, which are not practical for real-time applications. In this article, we exploit the powerful learning ability of deep neural networks (DNN) and propose a novel tensor fast iterative shrinkage-thresholding algorithm net (Tensor FISTA-Net) as a real-time decoder for SCI cameras. Since SCI cameras have an accurate physical model, we can trade training time for the decoding time by generating abundant synthetic data and training a decoder on the cloud. Tensor FISTA-Net not only learns a sparse representation of the frames through convolution layers but also reduces the decoding time and memory consumption significantly through tensor operations, which makes Tensor FISTA-Net an appropriate approach for a real-time decoder. Our proposed Tensor FISTA-Net obtains an average PSNR improvement of 0.79-2.84 dB (video images) and 2.61-4.43 dB (hyperspectral images) over the state-of-the-art algorithms, along with more clear and detailed visual results on real SCI datasets, Hammer and Wheel, respectively. Our Tensor FISTA-Net reaches 45 frames per second in video datasets and 70 frames per second in hyperspectral datasets, meeting the real-time requirement. Besides, the trained model occupies only a 12 -MB memory footprint, making it applicable to real-time Internet of Things (IoT) applications.

Hydrogen exerts neuroprotective effects by inhibiting oxidative stress in experimental diabetic peripheral neuropathy rats.

Diabetic peripheral neuropathy (DPN) is a complex disorder caused by long-standing diabetes. Oxidative stress was considered the critical creed in this DPN pathophysiology. Hydrogen has antioxidative effects on diabetes mellitus and related complications. However, there is still no concern on the beneficial effects of hydrogen in DPN. This paper aimed to evaluate the effects of exogenous hydrogen to reduce the severity of DPN in streptozotocin-induced diabetic rats. Compared with hydrogen-rich saline treatment, hydrogen inhalation significantly reduced blood glucose levels in diabetic rats in the 4th and 8th weeks. With regard to nerve function, hydrogen administration significantly attenuated the decrease in the velocity of motor nerve conduction in diabetic animals. In addition, hydrogen significantly attenuated oxidative stress by reducing the level of malondialdehyde, reactive oxygen species, and 8-hydroxy-2-deoxyguanosine and meaningfully enhanced the antioxidant capability by partially restoring the activities of superoxide dismutase. Further studies showed that hydrogen significantly upregulated the expression of nuclear factor erythroid-2-related factor 2 and downstream proteins such as catalase and hemeoxygenase-1 in the nerves of diabetic animals. Our paper showed that hydrogen exerts significant protective effects in DPN by downregulating oxidative stress via the pathway of nuclear factor erythroid-2-related factor 2, which suggests its potential value in clinical applications.

A 5-year follow-up study on the efficacy and safety of ultrasound-guided laser ablation in elderly patients with papillary thyroid microcarcinoma: A retrospective, single-center study from China.

Objective: The aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC). Methods: From September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients' symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions. Result: The ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60-78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P < 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected. Conclusion: Ultrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.

Clinical heterogeneity in a family with flail arm syndrome and review of hnRNPA1-related spectrum.

OBJECTIVE: Flail arm syndrome (FAS) is one of the atypical subtypes of amyotrophic lateral sclerosis (ALS). Mutations in hnRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare genetic cause of ALS. Herein, marked clinical heterogeneity of FAS in a pedigree with a known hnRNPA1 variant was described to raise early awareness of the ALS variant. Furtherly, a literature review of the hnRNPA1-related spectrum was made to summarize the clinical and genetic characteristics. METHODS: Detailed clinical evaluation, muscle pathology, and whole-exome sequencing were performed. The sequence and co-segregation of the mutation among the family members were confirmed by Sanger sequencing. RESULTS: The great clinical variability was found in a FAS pedigree. Muscle pathology revealed a cluster distribution of angulated or rounded atrophic fibers, accompanied by significant multi-nucleus aggregation. Immunohistochemical staining showed that mutant hnRNPA1 proteins accumulated in muscle fiber cytoplasm. Exome sequencing identified a documented variant in hnRNPA1 gene c.1018C > T (p.P340S), which co-segregated with disease in the family. Besides, highly phenotypic heterogeneity was also found in other hnRNPA1-related diseases. INTERPRETATION: We described a Chinese pedigree with hnRNPA1-related FAS, which showed significant clinical variability among the intrafamilial members. FAS is a relatively milder variant of ALS, due to the highly heterogeneous clinical spectrum, early observation is of paramount importance. In addition, the highly phenotypic heterogeneity and molecular genetic mechanism of the hnRNPA1-related spectrum are still beyond fully understood. Further, the detailed molecular mechanism underlying the clinical diversity is warranted to be explored.

Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease.

BACKGROUND: GGC repeat expansion in NOTCH2NLC has been recently linked to neuronal intranuclear inclusion disease (NIID) via unknown disease mechanisms. Herein, we explore the genetic origin of the sporadic cases and toxic RNA gain-of-function mechanism in NIID. METHODS: Multiple genetic screenings were performed on NIID individuals and their available family members. Methylation status of blood DNA, NOTCH2NLC mRNA level from muscle biopsies and RNA foci from skin biopsies of NIID individuals or asymptomatic carriers were evaluated and compared. RESULTS: In two sporadic NIID families, we identified two clinically and pathologically asymptomatic fathers carrying large GGC repeat expansion, above 300 repeats, with offspring repeat numbers of 172 and 148, respectively. Further evaluation revealed that the GGC repeat numbers in the sperm from two asymptomatic fathers were only 63 and 98, respectively. The CpG island in NOTCH2NLC of the asymptomatic carriers was hypermethylated, and accordingly, the NOTCH2NLC mRNA levels were decreased in the asymptomatic fathers. GGC repeat expansion RNA formed RNA foci and sequestered RNA binding proteins into p62 positive intranuclear inclusions in NIID individuals but not in the control or asymptomatic carrier. CONCLUSION: Our study suggested the GGC repeat expansion in NOTCH2NLC might have a disease-causing number ranging from ~41 to ~300 repeats. The contraction of GGC repeat expansion in sperm could be a possible mechanism for the paternal-biased origin in some sporadic or recessive inherited NIID individuals. The toxic RNA gain-of-function mechanism was identified to be involved in the pathogenicity of this disease.

Functional Significance and Therapeutic Potential of miRNA-20b-5p in Esophageal Squamous Cell Carcinoma.

Novel therapies tailored to the molecular composition mechanism of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. miR-20b-5p expression was significantly upregulated in cancerous tissues and associated with lymph node metastasis, clinical stage, and overall survival (OS). An analysis of the methylation status of the miR-20b-5p gene indicated that the hypomethylation of the CpG sites located upstream of the miR-20b-5p gene in the ESCC tissues was more frequent than in the adjacent normal tissues, and the methylation status of miR-20b-5p correlated inversely with its expression levels. Notably, a series of gain- and loss-of-function assays elucidated that miR-20b-5p promoted ESCC cell proliferation, migration, and invasion both in vitro and in vivo. Luciferase reporter assays, western blot, and qRT-PCR revealed that RB1 and TP53INP1 were the direct targets of miR-20b-5p. Moreover, the effects of ectopic miR-20b-5p expression were abrogated by RB1 and TP53INP1 overexpression. In contrast, the effects of miR-20b-5p depletion were impaired by RB1 and TP53INP1 knockdown. Treatment with a miR-20b-5p antagomir dramatically increased tumor growth and inhibited RB1 and TP53INP1 protein expression in nude mice. This work provided novel insights on the molecular mechanism of ESCC and further provided suggestions for therapy development.

[Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis].

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.

OBJECTIVE: Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells. MATERIALS AND METHODS: GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 µg/mL GO-PEG, 1 µg/mL DOX, or 40 µg/mL +1 µg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points. RESULTS: GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05). CONCLUSION: GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.

Night Sleep Duration and Risk of Incident Anemia in a Chinese Population: A Prospective Cohort Study.

The purpose was to study the association between sleep duration and the prevalence of anemia in Chinese people. There were 84,791 participants (men: 79.1%; women: 20.9%) aged 18-98 years in the prospective study. We divided the participants into five categories based on the individual sleep duration: ≤5 h, 6 h, 7 h(reference), 8 h, and ≥9 h. Anemia was defined based on hemoglobin <12 g/dL for men and <11 g/dL for women. The Cox proportional hazards model was used to assess the association between sleep duration and anemia. During median follow-up of 7.9 years, 2698 cases of anemia had occurred. The HRand (95% CI) of anemia (7 h as the reference group) for individuals reporting ≤5 h, 6 h, 8 h, and ≥9 h were 1.23(1.04-1.45), 1.26(1.11-1.44), 1.04(0.92-1.16) and 1.42(1.08-1.86), respectively. It showed that there was a significant interaction on the risk of anemia between sleep duration and sex in the secondary analysis (p < 0.001).The significant association between long sleepduration and anemia was found in women (HR, 2.29; 95% CI, 1.56-3.37), not in men(HR, 0.90; 95% CI, 0.60-1.34). Both short and long night sleep duration were associated with increased risk of anemia.

Visit-to-Visit Variability of Fasting Plasma Glucose and the Risk of Cardiovascular Disease and All-Cause Mortality in the General Population.

BACKGROUND: The association of short-term variability of fasting plasma glucose (FPG) and mortality has been well investigated. However, the relationships between visit-to-visit variability of FPG over longer periods of follow-up and cardiovascular disease (CVD) and all-cause mortality are unclear. This study aimed to investigate these relationships. METHODS AND RESULTS: The current analysis included 53 607 Chinese participants (mean age, 49.10 years) who were free of CVD in the Kailuan study. Participants were divided into 4 categories by quartiles of visit-to-visit variability of FPG. Visit-to-visit variability of FPG was defined as the coefficient of variation of 3 values of FPG that were measured from the examination periods of 2006 to 2007, 2008 to 2009, and 2010 to 2011. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for CVD and all-cause mortality. After a mean follow-up of 4.93 years, 4261 individuals developed CVD and 1545 individuals died. The incidence of CVD and all-cause mortality was 5.04 and 5.85 per 1000 person-years, respectively. After adjusting for mean FPG and other potential confounders, individuals in the highest quartile of variability of FPG compared with participants in the lowest quartile showed a 26% greater risk of developing CVD (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47) and a 46% greater risk for all-cause mortality (hazard ratio, 1.46; 95% confidence interval, 1.25-1.70). CONCLUSIONS: Independent of mean FPG and other baseline parameters, elevated visit-to-visit variability of FPG significantly increases the risk of CVD and all-cause mortality in the general population. Measuring long-term visit-to-visit variability of FPG is helpful for predicting the risk for CVD and all-cause mortality.

Trichostatin A inhibits radiation-induced epithelial-to-mesenchymal transition in the alveolar epithelial cells.

Radiation-induced pneumonitis and fibrosis are major complications following thoracic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue injury leading to organ fibrosis, including lung. Our previous studies have reported that radiation can induce EMT in the type II alveolar epithelial cells in both in vitro and in vivo. HDAC inhibitors are a new family of anti-cancer agents currently being used in several clinical trials. In addition to their intrinsic anti-tumor properties, HDAC inhibition is also important in other human diseases, including fibrosis and radiation-induced damage. In this study, we evaluated the effect of Trichostatin A (TSA), a HDAC inhibitor, on radiation-induced EMT in type II alveolar epithelial cells (RLE-6TN). Pre-treatment of RLE-6TN cells with TSA inhibited radiation-induced EMT-like morphological alterations including elevated protein level of α-SMA and Snail, reduction of E-cadherin expression, enhanced phosphorylation of GSK3ß and ERK1/2, increased generation of ROS. Radiation enhanced the protein level of TGF-ß1, which was blocked by N-acetylcysteine, an antioxidant. Treating cells with SB-431542, TGF-ß1 type I receptor inhibitor, diminished radiation-induced alterations in the protein levels of p-GSK-3ß, Snail-1 and α-SMA, suggesting a regulatory role of TGF-ß1 in EMT. Pre-incubation of cells with TSA showed significant decrease in the level of TGF-ß1 compared to radiation control. Collectively, these results demonstrate that i] radiation-induced EMT in RLE-6TN cells is mediated by ROS/MEK/ERK and ROS/TGF-ß1 signaling pathways and ii] the inhibitory role of TSA in radiation-induced EMT appears to be due, at least in part, to its action of blocking ROS and TGF-ß1 signaling.

Chaperonin containing TCP1 subunit 5 is a tumor associated antigen of non-small cell lung cancer.

Novel tumor antigens and their related autoantibodies have tremendous potential for early diagnosis of non-small cell lung cancer (NSCLC). In this study, we identify antigens from NSCLC tissue and autoantibodies in sera of patients with NSCLC using a modified proteomics-based approach. We seperated and identified four NSCLC-associated proteins extracted from the cytosol in tumor tissues by mini-two-dimensional gel electrophoresis, followed by Western blot and hybridization with individual sera for confirmation of antibody binding. Of the proteins we identified, we selected 58 kDa chaperonin containing TCP1(T-Complex Protein 1) subunit 5 (CCT5) for validation. Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were measured in all serum samples with an immunoluminometric assay and a receiver operating characteristic (ROC) curve was analyzed for autoantibodies against CCT5, CEA and CYFRA 21-1. The results show that CCT5 can induce an autoantibody response in NSCLC sera and show higher expression in NSCLC tissues by immunohistochemistry and Western blot. Anti-CCT5 autoantibody was found in 51% (23/45) of patients with NSCLC, but only 2.5% (1/40) in non-tumor individual controls. A receiver operating characteristic curve constructed with a panel of autoantibodies against CCT5 (AUC=0.749), CEA (AUC=0.6758), and CYFRA 21-1(AUC=0.760) show a sensitivity of 51.1% and 97.5% specificity in discriminating NSCLC from matched controls. These results indicate the potential utility of screening autoantibodies in sera, show that CCT5 could be used as a biomarker in cancer diagnosis.

[Expression of BTG1 protein in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of B-cell translocation gene 1 (BTG1) and to determine the relationship between BTG1 expression and clinicopathological features, biological behaviors in laryngeal squamous cell carcinoma. METHOD: Immunohistochemistry and Western blot were used to analyze BTG1 protein expression in 70 cases of laryngeal cancer and 35 cases of adjacent corresponding laryngeal mucosal tissues to illuminate the relationship between BTG1 expression and clinical factors. RESULT: The positive rate of BTG1 protein expression was 31.43% in laryngeal carcinoma tissues, significantly lower than 91.43% in the adjacent laryngeal tissues (P < 0.05). Western blot showed the relative expression of BTG1 protein between cancer lesion and adjacent tissue were 0.217 ± 0.032 and 0.918 ± 0.081, showing the difference with statistical significance (P < 0.05). The expression of protein was significantly correlated with the tumor invasion, lymph node metastasis, clinic stage and histological grade (P < 0.05 or P < 0.01), but not with sex, age and tumor location (P > 0.05) of patients with laryngeal cancer. CONCLUSION: The expression of BTG1 protein was decreased in laryngeal squamous cell carcinoma, suggesting that BTG1 gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of BTG1 expression may be useful in diagnosis, treatment and prognosis of laryngeal carcinoma.

Increased Expression of MuRF1 Is Associated with Radiation-induced Laryngeal Muscle Atrophy.

BACKGROUND: Laryngeal muscles play an important role in breathing, sound production and trachea protection against food. Laryngeal dysfunctions during radiotherapy for head and neck cancers are common. In the present study, we aimed to investigate the early effect of radiation on the laryngeal muscles in vivo and possible mechanisms involved in this process. MATERIALS AND METHODS: Eight-week-old female C57bl/ mice received neck irradiation with a single dose of 25 Gy and bilateral thyroarytenoid (TA) muscles of mice were collected at day 3, 7 and 10 post-irradiation for evaluating muscle size, myosins, myosin heavy chain (MyHC) composition and MuRF1 protein levels. RESULTS: A significant reduction in the size of muscle fibers and myosins in the TA muscles were observed at days 3, 7, 10 after radiation (p<0.05). The loss of IIB myosin was more severe than that of IIA/X myosins at day 7 post-irradiation (75% vs. 64%). MuRF1 protein level was markedly increased at day 7 and 10 after radiation (p<0.05). CONCLUSION: Radiation induced an acute muscle fiber atrophy and myosin loss in the intrinsic laryngeal muscles. MuRF1 may play an important role in the radiation-induced protein degradation in the laryngeal muscles and warrants further investigation.

Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC).

BACKGROUND: Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic have anticancer activity. OBJECTIVE: In this study, the apoptotic effects of Garlic-derived compound S-allylmercaptocysteine (SAMC) were investigated in 8305C human anaplastic thyroid carcinoma cells. METHODS: The cell line 8305C (HPACC) were treated with SAMC and the MTT assay, flow cytometry (FCM), electron microscope method were used to test cell cycle, inhibitory rate and morphologic changes respectively. RESULTS: HPACC-8305C cells were suppressed after exposure to SAMC of 0.02 mg/ml, 0.06 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P< 0.05). SAMC could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P< 0.05). After exposure to SAMC at 0.02 mg/ml for 24 hours, HPACC-8305C cells showed typical morphologic change. CONCLUSIONS: SAMC inhibits the growth of HPACC-8305C cells by induction of apoptotic cell death and inhibit telomerase activity, which appears to account for its anti-cancer activity.

[Clinical application of mammography-guided wire localization plus ultrasound-guided core-needle biopsy for breast microcalcification].

OBJECTIVE: To evaluate the clinical usefulness of mammography-guided wire localization plus ultrasound-guided core-needle biopsy of breast microcalcification and avoid the effects of preoperative excisional biopsy for patients undergoing sentinel node biopsy. METHODS: A total of 38 patients with unpalpable lesions, ultrasonic negativity and abnormal mammography received a guide wire under mammography and performed ultrasound-guided core-needle biopsy of breast microcalcification before preoperative excisional biopsy. RESULTS: All 38 lesions were successfully located and biopsied for pathological examination. Carcinoma was present in 9 lesions: ductal carcinoma in situ (DCIS) (6/38) and intraductal carcinoma with early infiltration (3/38). For 29 benign lesions, there were mastopathies (25/38), atypical ductal hyperplasia (ADH)(3/38) and intraductal papiloma (1/38). Breast microcalcification was detected in all lesions by ultrasound-guided core-needle biopsy. The detection rate of breast cancer detected was 30.8% and the diagnostic accuracy 100%. CONCLUSIONS: For patients with unpalpable lesions, ultrasound negativity and abnormal mammography, mammography-guided wire-localization plus ultrasound-guided core-needle biopsy of breast microcalcification is accurate, safe and feasible. And it may avoid the effects of preoperative excisional biopsy for patients with sentinel node biopsy. The procedure is worthy of wider clinical applications.