Preoperative work-up and results of parathyroidectomy plus auto-transplantation for the elderly with secondary hyperparathyroidism.

BACKGROUND: Total parathyroidectomy for secondary hyperparathyroidism has low morbidity and mortality rates and requires a special workup in the preoperative period. METHODS: Neck echography and technetium-99m-sestamibi scintigraphy were performed preoperatively. Cardiac echography, a thallium-201 myocardial perfusion scan, and cardiac catheterization were performed if necessary. During surgery, we removed all the parathyroid glands and the upper thymus and autotransplanted 100 mg of the smallest gland into the subcutaneous tissue of the forearm. RESULTS: The success rate in three months after total parathyroidectomy was 91.7% without mortality. In the elderly (age ≤65 years, n = 35), bone pain, skin itching, general weakness, and insomnia improved three months after surgery, and grip strength increased significantly. One year after parathyroidectomy, the serum levels of Ca, P, alkaline phosphatase, and intact parathyroid hormone were all within the normal ranges. Except for the bone mineral density (BMD) of the radial distal one-third, the BMD of the lumbar spine (L2 to L4), femoral neck, femoral global, and radial global increased significantly. Furthermore, the bone density T-scores of the lumbar spine (L2 to L4), femoral neck, femoral global, radial distal one-third, and radial global improved significantly. CONCLUSIONS: After a meticulous preoperative workup, parathyroidectomy plus autotransplantation can be performed safely for the treatment of symptomatic secondary hyperparathyroidism in the elderly to improve their quality of life and decrease their incidence of bone fractures.

Combination of treatments with transoral endoscopic thyroidectomy vestibular approach (TOETVA) for Graves' disease.

Although the success rates of non-surgical treatments for Graves' disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient's goiter size was determined using four grades-from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20-48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20-850] mL) than in grade 2 patients (20 [10-200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease provides optimal cosmetic results with a high success rate.

Impact of Thyroid Incidentaloma on Liver Transplant: A Study of 1010 Recipients at a Single Center.

BACKGROUND Thyroid incidentalomas are typically nonpalpable thyroid nodules discovered during radiographic evaluation for a non-thyroid issue. Thyroid incidentalomas visualized by computed tomography (CT) and ¹8F-flurodeoxyglucose (FDG) positron emission tomography (PET) before living donor liver transplantation (LDLT) are rare. The aim of the study was to analyze the clinical impact of thyroid incidentalomas discovered prior to transplantation. MATERIAL AND METHODS This retrospective study recruited 1010 patients undergoing LDLT between 2010 and 2019. CT was performed on each patient, whereas PET was performed on randomized patients (n=498). RESULTS The prevalence and malignant risk of thyroid incidentaloma on CT was 2.3% (23/1010) and 13.0% (3/23), respectively. The prevalence of thyroid incidentaloma on PET was 3.0% (15/498). Approximately half of the FDG uptake on PET was diffuse uptake (n=7), whereas the other half was focal uptake (n=8). The malignant risk of PET incidentaloma with focal FDG uptake was 37.5% (3/8). Four asymptomatic thyroid cancers were identified incidentally. After total thyroidectomy followed by LDLT, these patients maintained cancer-free status. CONCLUSIONS Thyroid incidentalomas occurred at a rate of 2-3% in LDLT candidates. The malignant risk was 13.0% on CT incidentaloma, and 37.5% on PET incidentaloma with focal FDG uptake. Curative treatment of incidental thyroid cancer followed by LDLT without delay can achieve a favorable prognosis.

Changes in voice quality, swallowing, and pulmonary function after parathyroidectomy for secondary hyperparathyroidism.

OBJECTIVE: To find changes in voice quality, airway invasion during swallowing, pharyngeal residue after swallowing, acoustic and aerodynamic measurements and pulmonary function tests after total parathyroidectomy plus auto-transplantation for secondary hyperparathyroidism. METHODS: We recruited 38 patients who underwent successful surgery for secondary hyperparathyroidism in this study. Voice quality was evaluated using voice handicap index (VHI-10), eating assessment tool (EAT-10), voice impairment, and the grade, roughness, breathiness, asthenia, strain (GRBAS) scale. Acoustic and aerodynamic measurements included fundamental frequency (F0), maximal phonation time, high pitch, jitter, s/z, shimmer and noise-to-harmonic ratio. Vocal cord mobility, vocal cord closure, premature spillage, the penetration-aspiration scale and the Yale pharyngeal residue severity rating scale (PRSRS) after swallowing were examined using fiber-optic endoscopy. Pulmonary function tests included forced vital capacity, forced expiratory volume in 1 s, bronchodilator test, total lung capacity, diffusion capacity of the lung for carbon monoxide, alveolar volume, and distance and O2 desaturation of the 6 min walking test (6MWT). RESULTS: Four months after successful parathyroidectomy, VHI-10 improved significantly (p < 0.01); incomplete vocal cord closure decreased significantly (p < 0.01); the Yale PRSRS for vallecula and pyriform sinus improved significantly (p = 0.02 and p = 0.02); F0 and high pitch increased significantly (p < 0.01 and p = 0.01); O2 desaturation (<4%) of 6MWT improved significantly (p = 0.04). CONCLUSIONS: Parathyroidectomy for secondary hyperparathyroidism can improve the voice quality, vocal cord closure, the Yale PRSRS for vallecular and pyriform sinus and O2 desaturation of 6MWT, and increase F0 and high pitch.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection.

BACKGROUND: The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM: This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD: From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS: There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION: The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BACKGROUND With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. MATERIAL AND METHODS From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. RESULTS Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). CONCLUSIONS Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy.

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

BACKGROUND: Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. METHODS: We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. RESULTS: During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

Scarless Completion Thyroidectomy After Initial Transoral Approach for Differentiated Thyroid Cancer: How and When to Start?

BACKGROUND: With growing literature, the feasibility of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been confirmed as a valid method for managing differentiated thyroid cancer. Completion thyroidectomy (CT) is recommended in patients who have been diagnosed with differentiated thyroid cancer after unilateral lobectomy by TOETVA. In this retrospective study, the authors addressed the critical questions of how and when to do the second operation of CT to avoid a neck scar. MATERIALS AND METHODS: The authors retrospectively reviewed our patients who had received TOETVA in our hospital from August 2016 to December 2019. Those who received CT after initial TOETVA as cTOETVA were further separated according to the approaching methods. Demographic data, operative variables, and postoperative variables were collected and analyzed. RESULTS: A total of 97 patients were enrolled using TOETVA. Malignancies were present in 42 patients (43.3%) using TOETVA. There were 3 approaching methods of cTOETVA and separated into reopen transcervical approach (re-TCA), retransoral TOETVA (re-TOETVA), and transaxillary approach (TAA) groups. There were no significant complications among patients for cTOETVA. Of the 8 patients for the cTOETVA, 3 received re-TCA, 3 re-TOETVA, and 2 TAA. CONCLUSIONS: The outcomes are encouraging and demonstrate the feasibility of scarless completion thyroidectomy after initial TOETVA. The re-TOETVA procedure should be completed within 14 days after the initial TOETVA procedure, TAA beyond 14 days, and re-TCA may be completed at any time. The cTOETVA techniques using re-TOETVA or TAA have better cosmetic results than re-TCA in oncological equivalency.

The Perioperatively Altered Neutrophil-to-Lymphocyte Ratio Associates with Impaired DNA Damage Response in Liver Transplantation Recipients with Hepatocellular Carcinoma.

Increasing evidence has suggested that elevated systemic inflammation with a high neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis after liver transplantation (LT). The ongoing molecular events involved in poor survival remain unclear. This retrospective study evaluated LT recipients whose data was collected at Kaohsiung Chang Gung Memorial Hospital between 2005 and 2014. Clinical records of 347 patients with hepatocellular carcinoma from seven days before LT to 30 days after LT illustrated that longitudinal values of lymphocytes, RBC, and hemoglobin were persistently low in patients with peritransplant high NLR (PTH-NLR, pre-LT ≥ 4 and post-LT ≥ 5), which indicated a significantly worse survival rate in association with increased RDW-CV and pancytopenia when compared to other patients (p = 0.008). We further found that PTH-NLR patients had decreased DNA damage response (DDR) genes and detoxifying enzymes of ADH and ALDH families, and increased mitochondrial stress response genes in their liver tissues. Reduced lineage markers of liver progenitor cells were also observed in PTH-NLR patients signifying the presence of unresolved impairments after LT. Our results demonstrate the association between hematopoietic deficiencies and lack of protection against DDR with PTH-NLR in LDLT recipients with HCC and may imply abnormal hematological and organismal defects in those patients.

Association Between Recurrent Laryngeal Nerve Calibre and Body Figure: A Preoperative Tool to Assess Thin-Diameter Nerves in Thyroidectomy.

Inadvertent recurrent laryngeal nerve (RLN) injury is a major complication of thyroidectomy. This study aimed to investigate the association between preoperative clinical parameters and RLN size prediction. Total thyroidectomy and thyroid lobectomy data were collected between January 2014 and April 2017. Routine identification of the recurrent laryngeal nerves was performed, while intraoperative findings (nerve diameter, thyroid gland weight, intraoperative neuromonitoring (IONM) use, and signal recording) and demographic data were collected for analysis. A total of 848 patients with 1357 RLNs at risk were enrolled in this study. RLN diameter was thinner in females, those with body height <160 cm, and those with a BMI <25 (all p < 0.001). RLN diameter was directly proportional to age, body weight, height, and BMI. RLN diameter was thinner (1.71 mm vs. 1.55 mm, p = 0.039) and branched nerve incidence was higher (18.5% vs. 29.7%, p = 0.09) in the postoperative RLN injury group. Branched nerves were more frequently encountered in female patients (female vs. male: 28.8% vs. 18.7%, p = 0.004). The risk of RLN palsy in intraoperative IONM loss patients was 27 times higher compared to that in IONM normal patients (1.55% vs. 30%, p < 0.001). Thinner nerves did not yield a higher rate of IONM signal loss. Thinner nerves and higher palsy rates could be anticipated in females, younger age groups, those with shorter stature, and those with low BMI. RLN diameter was not associated with the rate of IONM signal loss.

Ability of the post-operative ALBI grade to predict the outcomes of hepatocellular carcinoma after curative surgery.

The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) (p = 0.011), alpha-fetoprotein levels (AFP) (p < 0.001), low platelet count (p = 0.008), liver cirrhosis (p < 0.001), and the first year of ALBI grade after resection (p < 0.001) were independent predictors for RFS. Additionally, old age (p = 0.006), DM (p = 0.002), AFP (p = 0.027), and ALBI grade at the first year after resection (p < 0.001) were independent risk factors for poor liver-related survival. Patients with post-operative ALBI grades II/III had older age (p = 0.019), hypoalbuminemia (p = 0.038), DM (p = 0.043), and high stages of pTNM (p = 0.021). The post-operative ALBI grade is better for predicting the outcomes in HCC patients after curative hepatectomy than the pre-operative ALBI grade.

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.

The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.

Effect of soil organic matter on petroleum hydrocarbon degradation in diesel/fuel oil-contaminated soil.

The purpose of this study is to investigate the effect of soil organic matter (SOM) content levels on the biodegradation of total petroleum hydrocarbons (TPH). Batch experiments were conducted with soils with 2% or 10% organic matter that had been contaminated by diesel or fuel oil. In addition to the TPH (diesel or fuel oil) degradation efficiency, a comprehensive investigation was conducted on the TPH-degrading microbial community using molecular tools including oligonucleotide microarray technique and terminal restriction fragment length polymorphism analysis (T-RFLP). TPH was reduced from 10,000 mg/kg to 1849-4352 mg/kg dry weight soil. Higher biodegradation efficiencies and kinetic rate constants were observed in higher SOM contents. Hydrocarbon fractional analyses were conducted to explain the optimal operation with relatively low resin and aromatic fractions detected at the end of the remediation. The bacterial and fungal counts in the 10% SOM were approximately 10 CFU/g to 102 CFU/g above those in the 2% SOM, and the lowest fungal level was found when the least TPH degradability was measured. The internal transcribed spacer microarray identified the microorganisms that were introduced and proved their survival. The associated growth pattern confirmed that different kinds of contamination oils affected the microbial community diversity over time. Both the microarray and T-RFLP profiles indicated that Gordonia alkanivorans, G. desulfuricans, and Rhodococcus erythoropolis were the dominant bacteria, while Fusarium oxysporum and Aspergillus versicolor were the dominant fungi. The T-RFLP-derived nonmetric multidimensional scaling concluded that the dynamics of the microbial communities were impacted by the TPH degradation stages.

Successful Modified Transoral Endoscopic Parathyroidectomy Vestibular Approach For Secondary Hyperparathyroidism With Ectopic Mediastinal Glands.

BACKGROUND: Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation. MATERIALS AND METHODS: We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center. RESULTS: There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to <300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications. CONCLUSION: m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.

Application of molecular biological tools for monitoring efficiency of trichloroethylene remediation.

Trichloroethylene (TCE) is one of the most ubiquitous halogenated organic compounds of concerns of carcinogens in groundwater in Taiwan. Bioremediation has been recognized as a cost-effective approach in reducing TCE concentration. Five pilot-scale wells were constructed to monitor TCE concentrations in contaminated groundwater. With injection of EOS®, TCE was effectively degraded to 42%-93% by the end of 175 days. The biostimulation with EOS® was useful in establishing a micro-site anaerobic but with limited contribution. Dilution of the aquifer movement also caused the TCE reduction among injection and monitoring wells. The degradability was affected by the location and the proximity from the injection well. TCE concentrations found to be negatively correlated with the associated Dehalococcoides spp. and functional genes levels. Dhc concentration of 108 copies L-1 caused the initial 40% of TCE degradation. The well with the optimal degradation owned tceA of 109 cells L-1. T-RFLP results indicate the wells with the superior TCE degradability also performed the highest Shannon index number (means the highest diversity), which occurred on the same day that Dhc levels started to enlarge. Desulfovibrio desulfuricans and Desulfuromonas chloroethenica were predominant species identified in the T-RFLP fingerprint profile. In brief, a variety of different factors including well locations, geochemical indicators, and microbial contribution were useful to explain the site-specific optimal TCE remediation approach. The consistence among TCE degradation, Dhc growing pattern, functional gene levels, and the dynamics of the microbial community structure present the novelty of this study.

ZNF479 downregulates metallothionein-1 expression by regulating ASH2L and DNMT1 in hepatocellular carcinoma.

Decreased expression of metallothionein-1 (MT-1) is associated with a poor prognosis in hepatocellular carcinoma (HCC). Here, we found that MT-1 expression was suppressed by 14-3-3ε, and MT-1 overexpression abolished 14-3-3ε-induced cell proliferation and tumor growth. We identified that 14-3-3ε induced expression of ZNF479, a novel potential transcriptional regulator by gene expression profiling and ZNF479 contributed to 14-3-3ε-suppressed MT-1 expression. ZNF479 induced the expression of DNMT1, UHRF1, and mixed-lineage leukemia (MLL) complex proteins (ASH2L and Menin), and increased tri-methylated histone H3 (H3K4me3) levels, but suppressed H3K4 (H3K4me2) di-methylation. ZNF479-suppressed MT-1 expression was restored by silencing of ASH2L and DNMT1. Furthermore, ZNF479 expression was higher in HCC tissues than that in the non-cancerous tissues. Expression analyses revealed a positive correlation between the expression of ZNF479 and DNMT1, UHRF1, ASH2L, and Menin, and an inverse correlation with that of ZNF479, ASH2L, Menin, and MT-1 isoforms. Moreover, correlations between the expression of ZNF479 and its downstream factors were more pronounced in HCC patients with hepatitis B. Here, we found that ZNF479 regulates MT-1 expression by modulating ASH2L in HCC. Approaches that target ZNF479/MLL complex/MT-1 or related epigenetic regulatory factors are potential therapeutic strategies for HCC.

Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53.

Focal adhesion kinase (FAK) plays an important role in vascular development, including the regulation of endothelial cell (EC) adhesion, migration, proliferation, and survival. 3'-deoxyadenosine (cordycepin) is known to suppress FAK expression, cell migration, and the epithelial⁻mesenchymal transition in hepatocellular carcinoma (HCC). However, whether cordycepin affects FAK expression and cellular functions in ECs and the specific molecular mechanism remain unclear. In this study, we found that cordycepin suppressed FAK expression and the phosphorylation of FAK (p-FAK) at Tyr397 in ECs. Cordycepin inhibited the proliferation, wound healing, transwell migration, and tube formation of ECs. Confocal microscopy revealed that cordycepin significantly reduced FAK expression and decreased focal adhesion number of ECs. The suppressed expression of FAK was accompanied by induced p53 and p21 expression in ECs. Finally, we demonstrated that cordycepin suppressed angiogenesis in an in vivo angiogenesis assay and reduced HCC tumor growth in a xenograft nude mice model. Our study indicated that cordycepin could attenuate cell proliferation and migration and may result in the impairment of the angiogenesis process and tumor growth via downregulation of FAK and induction of p53 and p21 in ECs. Therefore, cordycepin may be used as a potential adjuvant for cancer therapy.

Prognostic Significance of 14-3-3ε, Aldo-keto Reductase Family 1 B10 and Metallothionein-1 in Hepatocellular Carcinoma.

BACKGROUND/AIM: Expression of 14-3-3ε is associated with prognostic outcomes of hepatocellular carcinoma (HCC) patients. Metallothionein-1 (MT-1) proteins and aldo-keto-reductase family 1 B10 (AKR1B10) are considered potential tumor regulators of HCC. The aim of this study, was to examine the prognostic value of 14-3-3ε, MT-1 and AKR1B10 expression in HCC. MATERIALS AND METHODS: The expression levels of 14-3-3ε, MT-1 and AKR1B10 in HCC cell lines and paraffin-embedded tissues were examined by western blotting and immunohistochemical analysis. RESULTS: 14-3-3ε positivity was significantly associated with decreased MT-1 expression in HCC. Patients with decreased MT-1 expression had worse survival rates and a higher risk of metastasis than 14-3-3ε-positive HCC patients with unchanged MT-1 expression. Distinct expression patterns of 14-3-3ε/MT-1/AKR1B10 were significantly associated with the metastatic incidence and survival rates of HCC patients. Patients with negative 14-3-3ε staining in primary tumors had better prognostic outcomes. In contrast, patients with positive 14-3-3ε staining, decreased MT-1 expression and no increase in AKR1B10 expression in primary tumors had the worst overall and disease-free survival rates and the highest metastatic risk. CONCLUSION: 14-3-3ε, AKR1B10, and MT-1 act as potential prognostic biomarkers of HCC.