Residual, regrowth, and new growth of radiofrequency ablation for benign thyroid nodules of different volumes: two-year follow-up results.

INTRODUCTION: Radiofrequency ablation (RFA) is recognized as an effective technique for the treatment of benign thyroid nodules (BTNs), although the long-term results are limited. This study aimed to evaluate the residual vital volume increase, regrowth, and new growth over a 2-year period after RFA among different nodule volume groups. SUBJECTS AND METHODS: This retrospective study evaluated 135 patients with 153 BTNs who underwent ultrasound guided RFA. The BTNs were categorized into small (<10 mL), medium (10-30 mL), and large (>30 mL) according to the initial volume of BTNs prior to ablation. The volume changes of each nodule were analyzed at 1, 3, 6, 12 and 24 months after RFA. New growth was defined as the growth in volume not found in the early follow-up on ultrasonography. RESULTS: The initial ablation ratio of all BTNs was 99.67%. The mean volume reduction ratio (VRR) of BTNs was 85.53% after 2-year follow-up. The small nodule group showed a lower VRR compared to the other two groups at the 1-month follow-up, and there was no difference of VRR at the subsequent follow-ups. The incidence of residual vital volume increase was 4.58%. The overall incidence of regrowth was 3.92% and the mean timing of regrowth was 16.71 months. New growth occurred in 18.95% of patients. No further treatment was required in the majority of cases. CONCLUSION: RFA achieved a clinically relevant volume reduction in different sizes of single BTNs which persisted for at least 2 years, thereby preventing the need for retreatment.

Ultrasound-Guided Moving Shot Radiofrequency Ablation of Benign Soft Tissue Neoplasm.

Background and Objective: To evaluate the effectiveness of radiofrequency ablation (RFA) using the moving-shot technique for benign soft tissue neoplasm. Materials and Methods: This retrospective study reviewed eight patients with benign soft tissue neoplasm presenting with cosmetic concerns and/or symptomatic issues who refused surgery. Six patients had vascular malformation, including four with venous malformation and two with congenital hemangioma. The other two patients had neurofibroma. All patients underwent RFA using the moving-shot technique. Imaging and clinical follow-up were performed in all patients. Follow-up image modalities included ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging. The volume reduction ratio (VRR), cosmetic scale (CS), and complications were evaluated. Results: Among the seven patients having received single-stage RFA, there were significant volume reductions between baseline (33.3 ± 21.2 cm3), midterm follow-up (5.1 ± 3.8 cm3, p = 0.020), and final follow-up (3.6 ± 1.4 cm3, p = 0.022) volumes. The VRR was 84.5 ± 9.2% at final follow-up. There were also significant improvements in the CS (from 3.71 to 1.57, p = 0.017). The remaining patient, in the process of a scheduled two-stage RFA, had a 33.8% VRR after the first RFA. The overall VRR among the eight patients was 77.5%. No complications or re-growth of the targeted lesions were noted during the follow-up period. Of the eight patients, two received RFA under local anesthesia, while the other six patients were under general anesthesia. Conclusions: RFA using the moving-shot technique is an effective, safe, and minimally invasive treatment for benign soft tissue neoplasms, achieving mass volume reduction within 6 months and significant esthetic improvement, either with local anesthesia or with general anesthesia under certain conditions.

LncRNAnet: long non-coding RNA identification using deep learning.

Motivation: Long non-coding RNAs (lncRNAs) are important regulatory elements in biological processes. LncRNAs share similar sequence characteristics with messenger RNAs, but they play completely different roles, thus providing novel insights for biological studies. The development of next-generation sequencing has helped in the discovery of lncRNA transcripts. However, the experimental verification of numerous transcriptomes is time consuming and costly. To alleviate these issues, a computational approach is needed to distinguish lncRNAs from the transcriptomes. Results: We present a deep learning-based approach, lncRNAnet, to identify lncRNAs that incorporates recurrent neural networks for RNA sequence modeling and convolutional neural networks for detecting stop codons to obtain an open reading frame indicator. lncRNAnet performed clearly better than the other tools for sequences of short lengths, on which most lncRNAs are distributed. In addition, lncRNAnet successfully learned features and showed 7.83%, 5.76%, 5.30% and 3.78% improvements over the alternatives on a human test set in terms of specificity, accuracy, F1-score and area under the curve, respectively. Availability and implementation: Data and codes are available in http://data.snu.ac.kr/pub/lncRNAnet.

Paradigm Shift in Rhinoplasty with Virtual 3D Surgery Software and 3D Printing Technology.

Most Asians have a nose with a short columella and a low dorsum; augmentation rhinoplasty using implants is commonly performed in Asian countries to achieve a taller and more well-defined nasal dorsum. However, the current knowledge is insufficient to fully understand the various subjective desires of patients, reflect on them during surgery, or to objectively analyze the results after surgery. Advances in digital imaging technologies, such as 3D printing and 3D scanning, have transformed the medical system from hospital-centric to patient-centric throughout the medical field. In this study, we applied these techniques to rhinoplasty. First, we used virtual 3D plastic surgery software to enable surgical planning through objectified numerical calculations based on the visualized data of the patient's medical images rather than simple virtual plastic surgery. Second, the customized nasal implant was manufactured by reflecting the patient's anatomical shape and virtual 3D plastic surgery data. Taken together, we describe the surgical results of applying these rhinoplasty solutions in four patients. Our experience indicates that high fidelity and patient satisfaction can be achieved by applying these techniques.

Tschimganidine reduces lipid accumulation through AMPK activation and alleviates high-fat diet-induced metabolic diseases.

Obesity increases the risk of mortality and morbidity because it results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugs to treat obesity. We performed a screening assay using natural products with anti-adipogenic properties in 3T3-L1 cells and determined that tschimganidine, a terpenoid from the Umbelliferae family, inhibited adipogenesis. To evaluate the anti-obesity effects of tschimganidine in vivo. Mice were fed either a normal chow diet (NFD) or a high-fat chow diet (HFD) with or without tschimganidine for 12 weeks. Treatment with tschimganidine decreased lipid accumulation and adipogenesis, accompanied by reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased that of AKT. Depletion of AMPK relieved the reduction in lipid accumulation resulting from tschimganidine treatment. Moreover, tschimganidine administration drastically reduced the weight and size of both gonadal white adipose tissue (WAT) and blood glucose levels in high-fat diet-induced obese mice. We suggest that tschimganidine is a potent antiobesity agent, which impedes adipogenesis and improves glucose homeostasis. Tschimganidine can then be evaluated for clinical application as a therapeutic agent. [BMB Reports 2023; 56(4): 246-251].

Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPß) stability and accelerates adipogenesis and lipid accumulation.

Dysregulation of the ubiquitin-proteasome system has been implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes, and non-alcoholic fatty liver disease; however, the mechanisms controlling pathogenic metabolic disorders remain unclear. Transcription factor CCAAT/enhancer binding protein beta (C/EBPß) regulates adipogenic genes. The study showed that the expression level of C/EBPß is post-translationally regulated by the deubiquitinase ubiquitin-specific protease 1 (USP1) and that USP1 expression is remarkably upregulated during adipocyte differentiation and in the adipose tissue of mice fed a high-fat diet (HFD). We found that USP1 directly interacts with C/EBPß. Knock-down of USP1 decreased C/EBPß protein stability and increased its ubiquitination. Overexpression of USP1 regulates its protein stability and ubiquitination, whereas catalytic mutant of USP1 had no effect on them. It suggests that USP1 directly deubiquitinases C/EBPß and increases the protein expression, leading to adipogenesis and lipid accumulation. Notably, the USP1-specific inhibitor ML323-originally developed to sensitize cancer cells to DNA-damaging agents-decreased adipocyte differentiation and lipid accumulation in 3T3-L1 cells without cytotoxicity. Oral gavage of ML323 was administered to HFD-fed mice, which showed weight loss and improvement in insulin and glucose sensitivity. Both fat mass and adipocyte size in white adipose tissues were significantly reduced by ML323 treatment, which also reduced the expression of genes involved in adipogenesis and inflammatory responses. ML323 also reduced lipid accumulation, hepatic triglycerides, free fatty acids, and macrophage infiltration in the livers of HFD-fed mice. Taken together, we suggest that USP1 plays an important role in adipogenesis by regulating C/EBPß ubiquitination, and USP1-specific inhibitor ML323 is a potential treatment option and further study by ML323 is needed for clinical application for metabolic disorders.

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.

Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice.

Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPARγ, C/EBPα, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPARγ. Galectin-1 overexpression resulted in increased PPARγ expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1-/-) mice and fed a 60% HFD. After 10 weeks, Lgals1-/- mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1-/-mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1-/- mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNFα, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1-/- mice. In addition, Lgals1-/-mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.

A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling.

Vinpocetine, a phosphodiesterase (PDE) type-1 inhibitor, increases cAMP and cGMP levels and is currently used for the management of cerebrovascular disorders, such as stroke, cerebral hemorrhage, and cognitive dysfunctions. In this study, we first determined that vinpocetine effectively suppressed adipogenesis and lipid accumulation. However, we questioned which molecular mechanism is involved because the role of PDE in adipogenesis is still controversial. Vinpocetine decreased adipogenic cell signaling, including the phosphorylation of ERK, AKT, JAK2, and STAT3, and adipokine secretion, including IL-6, IL-10, and IFN-α. Interestingly, vinpocetine increased the phosphorylation of HSL, suggesting the induction of the lipolysis pathway. Moreover, vinpocetine increased UCP1 expression via increasing cAMP and PKA phosphorylation. The administration of vinpocetine with a normal-chow diet (NFD) or a high-fat diet (HFD) in mice attenuated body weight gain in mice fed both the NFD and HFD. These effects were larger in the HFD-fed mice, without a difference in food intake. Vinpocetine drastically decreased fat weight and adipocyte cell sizes in gonadal and inguinal white adipose tissues and in the liver in both diet groups. Serum triacylglycerol levels and fasting blood glucose levels were reduced by vinpocetine treatment. This study suggested that vinpocetine prevents adipocyte differentiation through the inhibition of adipogenesis-associated cell signaling in the early stages of adipogenesis. Moreover, upregulating cAMP levels leads to an increase in lipolysis and UCP1 expression and then inhibits lipid accumulation. Therefore, we suggest that vinpocetine could be an effective agent for treating obesity, as well as improving cognition and cardiovascular function in older individuals.

Benign and malignant thyroid nodules: US differentiation--multicenter retrospective study.

PURPOSE: To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) criteria for the depiction of benign and malignant thyroid nodules by using tissue diagnosis as the reference standard. MATERIALS AND METHODS: This study had institutional review board approval, and informed consent was waived. From January 2003 through June 2003, 8024 consecutive patients had undergone thyroid US at nine affiliated hospitals. A total of 831 patients (716 women, 115 men; mean age, 49.5 years +/- 13.8 [standard deviation]) with 849 nodules (360 malignant, 489 benign) that were diagnosed at surgery or biopsy were included in this study. Three radiologists retrospectively evaluated the following characteristics on US images: nodule size, presence of spongiform appearance, shape, margin, echotexture, echogenicity, and presence of microcalcification, macrocalcification, or rim calcification. A chi(2) test and multiple regression analysis were performed. Sensitivity, specificity, and positive and negative predictive values were obtained. RESULTS: Statistically significant (P < .05) findings of malignancy were a taller-than-wide shape (sensitivity, 40.0%; specificity, 91.4%), a spiculated margin (sensitivity, 48.3%; specificity, 91.8%), marked hypoechogenicity (sensitivity, 41.4%; specificity, 92.2%), microcalcification (sensitivity, 44.2%; specificity, 90.8%), and macrocalcification (sensitivity, 9.7%; specificity, 96.1%). The US findings for benign nodules were isoechogenicity (sensitivity, 56.6%; specificity, 88.1%; P < .001) and a spongiform appearance (sensitivity, 10.4%; specificity, 99.7%; P < .001). The presence of at least one malignant US finding had a sensitivity of 83.3%, a specificity of 74.0%, and a diagnostic accuracy of 78.0%. For thyroid nodules with a diameter of 1 cm or less, the sensitivity of microcalcifications was lower than that in larger nodules (36.6% vs 51.4%, P < .05). CONCLUSION: Shape, margin, echogenicity, and presence of calcification are helpful criteria for the discrimination of malignant from benign nodules; the diagnostic accuracy of US criteria is dependent on tumor size.

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK).

Weight loss ≥ 5 percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with antiadipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications. [BMB Reports 2017; 50(11): 566-571].

Galectin-3 activates PPARγ and supports white adipose tissue formation and high-fat diet-induced obesity.

Galectin-3, a ß-galactoside-binding lectin, is elevated in obesity and type 2 diabetes mellitus, and metformin treatment reduces these galectin-3 levels. However, the role of galectin-3 in adipogenesis remains controversial. We found that 17-month-old galectin-3-deficient (lgals3(-/-)) mice had decreased body size and epididymal white adipose tissue (eWAT) without related inflammatory diseases when fed normal chow. Galectin-3 knockdown significantly reduced adipocyte differentiation in 3T3-L1 cells and also decreased the expression of peroxisome proliferator-activated receptor (PPAR)-γ, ccaat-enhancer-binding protein α, and ccaat-enhancer-binding protein ß. Endogenous galectin-3 directly interacted with PPARγ, and galectin-3 ablation reduced the nuclear accumulation and transcriptional activation of PPARγ. After a 12-week high-fat diet (60% fat), lgals3(-/-) mice had lower body weight and eWAT mass than lgals3(+/+) mice. Moreover, the expression of PPARγ and other lipogenic genes was drastically decreased in the eWAT and liver of lgals3(-/-) mice. We suggest that galectin-3 directly activates PPARγ and leads to adipocyte differentiation in vitro and in vivo. Furthermore, galectin-3 might be a potential therapeutic target in metabolic syndromes as a PPARγ regulator.

Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression.

Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase- 1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin- 3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.

Epidemiologic survey of head and neck cancers in Korea.

Head and neck cancers have never been systematically studied for clinical purposes yet in Korea. This epidemiological survey on head and neck cancer patients was undertaken from January to December 2001 in 79 otorhinolaryngology resident-training hospitals nationwide. The number of head and neck cancer patients was 1,063 cases in the year. The largest proportion of cases arose in the larynx, as many as 488 cases, which accounted for 45.9%. It was followed by, in order of frequency, oral cavity (16.5%), oropharynx (10.0%), and hypopharynx (9.5%). The male:female ratio was 5:1, and the mean age was 60.3 yr. Surgery was the predominant treatment modality in head and neck cancers: 204 (21.5%) cases were treated with only surgery, 198 (20.8%) cases were treated with surgery and radiotherapy, 207 cases (21.8%) were treated with combined therapy of surgery, radiotherapy, and chemotherapy. Larynx and hypopharynx cancers had a stronger relationship with smoking and alcohol drinking than other primary site cancers. Of them, 21 cases were found to be metastasized at the time of diagnosis into the lung, gastrointestinal tract, bone, or brain. Coexisting second primary malignancies were found in 23 cases. At the time of diagnosis, a total of 354 cases had cervical lymph node metastasis accounting for 42.0%.