The Aryl Hydrocarbon Receptor Regulates Invasiveness and Motility in Acute Myeloid Leukemia Cells through Expressional Regulation of Non-Muscle Myosin Heavy Chain IIA.

Acute myeloid leukemia (AML) is the most prevalent type of hematopoietic malignancy. Despite recent therapeutic advancements, the high relapse rate associated with extramedullary involvement remains a challenging issue. Moreover, therapeutic targets that regulate the extramedullary infiltration of AML cells are still not fully elucidated. The Aryl Hydrocarbon Receptor (AHR) is known to influence the progression and migration of solid tumors; however, its role in AML is largely unknown. This study explored the roles of AHR in the invasion and migration of AML cells. We found that suppressed expression of AHR target genes correlated with an elevated relapse rate in AML. Treatment with an AHR agonist on patient-derived AML cells significantly decreased genes associated with leukocyte trans-endothelial migration, cell adhesion, and regulation of the actin cytoskeleton. These results were further confirmed in THP-1 and U937 AML cell lines using AHR agonists (TCDD and FICZ) and inhibitors (SR1 and CH-223191). Treatment with AHR agonists significantly reduced Matrigel invasion, while inhibitors enhanced it, regardless of the Matrigel's stiffness. AHR agonists significantly reduced the migration rate and chemokinesis of both cell lines, but AHR inhibitors enhanced them. Finally, we found that the activity of AHR and the expression of NMIIA are negatively correlated. These findings suggest that AHR activity regulates the invasiveness and motility of AML cells, making AHR a potential therapeutic target for preventing extramedullary infiltration in AML.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. RESULTS: We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. CONCLUSIONS: Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Kaempferol Inhibits Cervical Cancer Cells by Inducing Apoptosis and Autophagy via Inactivation of the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND/AIM: Kaempferol, a natural flavonoid, occurs abundantly in fruits and vegetables. It has various bioactivities, with antioxidant, anti-inflammatory, and other beneficial properties. The aim of this study was to investigate the in vitro effects of kaempferol on the proliferation, apoptosis, and autophagy of KB cells, a human cervical cancer cell line, and the corresponding action mechanisms. MATERIALS AND METHODS: The inhibitory efficacy of kaempferol on KB cervical cancer cells was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, migration assay, 4',6-diamidino-2-phenylindole staining, flow cytometry, acridine orange staining and western blotting. RESULTS: Kaempferol reduced KB cell viability and migration in a dose-dependent manner. Additionally, kaempferol-induced apoptosis was confirmed, and kaempferol treatment influenced levels of apoptotic proteins. Autophagy was detected upon visualization of characteristic autophagic vacuoles and acidic vesicular organelles, and verified using western blotting, which revealed elevated levels of autophagy-related proteins. Kaempferol-mediated apoptosis and autophagy were evidently attributable to reduced phosphorylation in the phosphoinositide 3-kinase (PI3K)/serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) pathway. This finding was validated using a pharmacological inhibition assay with the PI3K pathway inhibitor LY294002, which promoted KB cell apoptosis and autophagy. CONCLUSION: Our results suggest that kaempferol induces apoptosis and autophagy by inhibiting the PI3K/AKT/mTOR pathway in human cervical cancer cells, empirically showing the anticancer effects of kaempferol, and thereby presenting it as a potential anticancer therapeutic agent.

Food passage following proximal gastrectomy with double-tract reconstruction and its effect on nutritional status in early gastric cancer: a prospective single-center cohort study.

Purpose: Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) expectedly results in improved nutritional status and less body weight loss than conventional total gastrectomy in upper-third gastric cancer. This study aimed to investigate the food passage patterns following LPG-DTR and its effect on nutritional outcomes up to 1 year after surgery. Methods: This prospective cohort study recruited 10 patients with early gastric cancer scheduled for LPG-DTR. Nutritional indices and body composition were assessed every 3 months up to 12 months. Liquid and solid food transits were evaluated with fluoroscopic upper gastrointestinal study and radionuclide scintigraphy, respectively. Results: At 12 months, patients exhibited a body weight loss of 14.5% ± 3.6%. The main passage routes for liquid and solid foods differed, primarily via the interposed jejunum for liquids, whereas via both tracts for solids. The median half-life of solid food emptying from the remnant distal stomach was 105.1 minutes (range, 50.8-2,194.2 minutes), and duodenal passage of solid food was noted in 9 of 10 patients. Those with gastric half-emptying time >3 hours demonstrated greater weight loss (19.5% ± 1.4% vs. 12.5% ± 1.1%, P = 0.024) and more pronounced reduction in serum albumin levels (-0.5 ± 0.3 g/dL vs. 0.0 ± 0.2 g/dL, P = 0.024) after 12 months. Conclusion: LPG-DTR demonstrated varying food passage patterns depending on the food contents and delayed solid food emptying from the remnant stomach was associated with more substantial weight loss.

Anticancer Effects of α-Pinene in AGS Gastric Cancer Cells.

Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related mortality. Existing treatment strategies for gastric cancer often present numerous side effects. Consequently, recent studies have shifted toward devising new treatments grounded in safer natural substances. α-Pinene, a natural terpene found in the essential oils of various plants, such as Lavender angustifolia and Satureja myrtifolia, displays antioxidant, antibiotic, and anticancer properties. Yet, its impact on gastric cancer remains unexplored. This research assessed the effects of α-pinene in vitro using a human gastric adenocarcinoma cell-line (AGS) human gastric cancer cells and in vivo via a xenograft mouse model. The survival rate of AGS cells treated with α-pinene was notably lower than that of the control group, as revealed by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. This decline in cell viability was linked to apoptosis, as verified by 4',6-diamidino-2-phenylindole and annexin V/propidium iodide staining. The α-pinene-treated group exhibited elevated cleaved-poly (ADP-ribose) polymerase and B cell lymphoma 2 (Bcl-2)-associated X (Bax) levels and reduced Bcl-2 levels compared with the control levels. Moreover, α-pinene triggered the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 within the mitogen-activated protein kinase (MAPK) pathway. In the xenograft mouse model, α-pinene induced apoptosis through the MAPK pathway, devoid of toxicity. These findings position α-pinene as a promising natural therapeutic for gastric cancer.

Transcriptome dataset of two Pistacia species: Pistacia chinensis and Pistacia weinmannifolia.

Pistacia chinensis and Pistacia weinmannifolia are small trees and are distributed in East Asia, in particular China. The data on P. chinensis presented in this article is associated with the research article, "DOI: 10.5010/JPB.2019.46.4.274" [1]. Both P. chinensis and P. weinmannifolia have long been used as ethnobotanical plants to treat various illnesses, including dysentery, inflammatory swelling, rheumatism, liver diseases, influenza, lung cancer, etc. Many studies have been carried out to delve into the pharmaceutical properties of these Pistacia species using plant extracts, but genomic studies are very rarely performed to date. To enrich the genetic information of these two species, RNA sequencing was conducted using a pair-end Illumina HiSeq2500 sequencing system, resulting in 2.6 G of raw data from P. chinensis (Accession no: SRR10136265) and 2.7 G bases from P. weinmannifolia (Accession no: SRR10136264). Transcriptome shotgun assembly using three different assembly tools generated a total of 18,524 non-redundant contigs (N50, 1104 bp) from P. chinensis and 18,956 from P. weinmannifolia (N50, 1137 bp). The data is accessible at NCBI BioProject: PRJNA566127. These data would be crucial for the identification of genes associated with the compounds exerting pharmaceutical properties and also for molecular marker development.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). PATIENTS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. RESULTS: A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. CONCLUSIONS: Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Health risk assessment of uranium intake from private residential drinking groundwater facilities based on geological characteristics across the Republic of Korea.

Groundwater contributes to an average of 8 % of the total water source capacity in the Republic of Korea. Hence, private residential households in rural areas in Korea are still using groundwater for drinking without any regular water quality inspection. This can increase the risk of exposure to natural radionuclides like uranium through drinking groundwater. This study investigated the uranium level in drinking groundwater all over the country by analyzing 11,451 samples from private residential drinking groundwater facilities and compared the exposure amount and its associated carcinogenic and non-carcinogenic risk based on the geological characteristics of the aquifer. Results yield that although the average hazard quotient (HQ) and excess cancer risk (ECR) of exposure to natural uranium through drinking groundwater were respectively below 1 and 1 × 10-6 and do not indicate a potential health hazard, significantly high HQ and ECR up to respectively 70 and 4 × 10-4 in samples where the aquifer is the Jurassic granite observed. Accordingly, regular water quality investigation and onsite treatment methods are required to provide healthy drinking water in such areas.

Assessment of poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride-induced developmental neurotoxicity via oxidative stress mechanism: Integrative approaches with neuronal cells and zebrafish.

Poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride (PHMB) is a biocide with a broad spectrum of antibacterial activity. Its use as a disinfectant and preservative in consumer products results in human exposure to PHMB. Toxicity studies on PHMB mainly focus on systemic toxicity or skin irritation; however, its effects on developmental neurotoxicity (DNT) and the underlying mechanisms are poorly understood. In this study, the DNT effects of PHMB were evaluated using IMR-32 and SH-SY5Y cell lines and zebrafish. In both cell lines, PHMB concentrations ≥ 10 µM reduced neurite outgrowth, and cytotoxicity was observed at concentrations up to 40 µM. PHMB regulated expression of neurodevelopmental genes and induced reactive oxygen species (ROS) production and mitochondrial dysfunction. Treatment with N-acetylcysteine reversed the toxic effects of PHMB. Toxicity tests on zebrafish embryos showed that PHMB reduced viability and heart rate and caused irregular hatching. PHMB concentrations of 1-4 µM reduced the width of the brain and spinal cord of transgenic zebrafish and attenuated myelination processes. Furthermore, PHMB modulated expression of neurodevelopmental genes in zebrafish and induced ROS accumulation. These results suggested that PHMB exerted DNT effects in vitro and in vivo through a ROS-dependent mechanism, highlighting the risk of PHMB exposure.

Comparison of Prognostic Value Between Stimulated and Nonstimulated Thyroglobulins in Differentiated Thyroid Cancer: A Retrospective Study.

Purpose: The growing incidence of differentiated thyroid cancer (DTC) demands dependable prognostic factors to guide follow-up and treatment plans. This study investigated the prognostic value of response to therapy (RTT) assessment using TSH stimulated-thyroglobulin (sti-Tg) and nonstimulated-thyroglobulin (nonsti-Tg) and evaluates whether RTT using nonsti-Tg (nonstiRTT) can replace RTT using sti-Tg (stiRTT) in clinical practice to improve patients' quality of life during assessment. Methods: We enrolled 419 DTC patients who underwent total thyroidectomy, radioactive iodine (RAI) therapy, and Tg assessment. Patients with structural incomplete responses were excluded. Initial RTT assessments based on the 2015 American Thyroid Association guidelines (excellent response; ER, indeterminate response, biochemical incomplete response) were performed 6-24 months after RAI therapy. The second RTT assessments were performed 6-24 months after the first assessment. Statistical analysis for recurrence-free survival (RFS) was done with the log-rank test for stiRTT and nonstiRTT. Results: Although initial stiRTT and nonstiRTT were significant predictors for RFS (p < 0.0001), stiRTT provided better RFS prediction than nonstiRTT. The RFS analysis of the second RTT assessment demonstrated statistical significance only for stiRTT (p < 0.0001). In 116 patients classified as ER on initial stiRTT, there was no RFS difference between patients classified as ER on either second stiRTT or nonstiRTT. Conclusion: The prognostic power of stiRTT surpasses that of nonstiRTT in both the initial and second RTT assessment. Nevertheless, among patients classified as ER on initial stiRTT, a second stiRTT may not be required for those classified as ER on the second nonstiRTT. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00811-8.

Piperlongumine induces apoptosis via the MAPK pathway and ERK­mediated autophagy in human melanoma cells.

Piperlongumine (PL) is an amide alkaloid with diverse pharmacological effects against cancer, bronchitis and asthma; however, research on its efficacy against melanoma is lacking. The present study investigated the anticancer effects of PL on A375SM and A375P human melanoma cells. PL decreased the survival rate of A375SM and A375P cells, as shown by MTT assay, increase of apoptotic cells by DAPI staining. And PL induced apoptosis by decreasing the expression of the anti­apoptotic protein Bcl­2 and increasing that of the pro­apoptotic proteins cleaved­PARP and Bax. PL also induced apoptosis in A375SM and A375P cells via the MAPK pathway, increasing expression of the MAPK pathway proteins, phosphorylated­(p­ERK), p­JNK p­p38. These proteins were confirmed by western blot. In addition, A375SM and A375P cells treated with PL showed an increased number of acidic vesicular organelles by acridine orange staining. Also, autophagy induced by the expression of 1A/1B­light chain 3, Beclin 1and mTOR was investigated through western blot. When PL was applied following treatment with autophagy inhibitors 3­methyladenine and hydroxychloroquine, autophagy exhibited a cytoprotective effect against apoptosis in MTT assay. Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.

Regulation of anti-inflammatory and antioxidant responses by methanol extract of Mikania cordata (Burm. f.) B. L. Rob. leaves via the inactivation of NF-κB and MAPK signaling pathways and activation of Nrf2 in LPS-induced RAW 264.7 macrophages.

Mikania cordata (Burm. f.) B.L. Rob. has been traditionally used in tropical countries throughout Asia and Africa to treat gastric ulcers, dyspepsia, and dysentery. However, the mechanisms responsible for its anti-inflammatory and antioxidant activities are not fully understood. Therefore, this study sought to investigate the anti-inflammatory and antioxidant effects of methanol extracts of M. cordata (MMC) on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and elucidate its underlying regulatory mechanism. MMC significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 macrophages by downregulating the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels. Moreover, MMC effectively reduced the mRNA expression levels and production of pro-inflammatory cytokines, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). These suppressive effects of MMC on pro-inflammatory mediators and cytokines were mediated through the inhibition of transforming growth factor beta-activated kinase 1 (TAK1), which subsequently blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). MMC also upregulated the nuclear factor erythroid-2-related factor 2 (Nrf2) by inducing the degradation of Kelch-like ECH-related protein 1 (Keap1), an Nrf2-specific E3 ligase. Accordingly, MMC enhanced Nrf2 target gene expression of anti-oxidative regulators such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, it had minimal effect on the DPPH radical scavenging capacity in vitro. Collectively, these findings demonstrate that MMC holds promise as a potential therapeutic agent for alleviating inflammation-related diseases and oxidative stress.

Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway.

Currently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor growth in vivo. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that piperine reduced the viability of HSC-3 cells and 4',6-diamidino-2-phenylindole staining, annexin-V/propidium iodide staining, and analysis of apoptosis-related protein expression confirmed that piperine induces apoptosis in HSC-3 cells. Additionally, piperine-induced autophagy was confirmed by the observation of increased acidic vesicular organelles and autophagy marker proteins, demonstrating that autophagy in HSC-3 cells induces apoptosis. Mechanistically, piperine induced apoptosis and autophagy by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in HSC-3 cells. We also confirmed that piperine inhibits oral cancer tumor growth in vivo via antitumor effects related to apoptosis and PI3K signaling pathway inhibition. Therefore, we suggest that piperine can be considered a natural anticancer agent for human oral cancer.

Piperlongumine Induces Apoptosis and Cytoprotective Autophagy via the MAPK Signaling Pathway in Human Oral Cancer Cells.

Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.

Piperlongumine induces apoptosis and autophagy via the PI3K/Akt/mTOR pathway in KB human cervical cancer cells.

Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer, the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper, exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4',6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine. PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

Fusion Assessment of Oblique Lumbar Interbody Fusion Using Demineralized Bone Matrix: A 2-Year Prospective Study.

OBJECTIVE: Although several studies have reported successful fusion rates after oblique lumbar interbody fusion (OLIF) using allografts or dimerized bone matrix (DBM) instead of autografts, whether OLIF can achieve satisfactory solid fusion without the use of autografts remains unclear. This study investigated the real fusion rates after OLIF using allografts and DBM, which were evaluated using both dynamic radiographs and computed tomography scans. METHODS: We enrolled 79 consecutive patients who underwent minimally invasive OLIF followed by percutaneous pedicle screw fixation. All patients were treated with OLIF between L2 and L5 and underwent radiographic and clinical follow-ups at 12, 18, and 24 months after surgery. Radiographic assessment of fusion was performed using the modified BrantigaSteffee-Fraser (mBSF) scale, which was categorized as follows: grades I (radiographic pseudoarthrosis), II (indeterminate fusion), and III (solid radiographic fusion). Other radiologic and clinical outcomes were evaluated using the following parameters: vertebral slippage distance, disc height, subsidence, Oswestry Disability Index (ODI), and visual analogue scale (VAS). RESULTS: Clinical outcomes demonstrated significant improvements in the VAS scores for back pain, leg pain, and ODI after surgery. Subsidence was present in 34 cases (35.4%) at 12 months postoperatively, which increased to 47.9% and reached 50.0% at 1.5 years and 2 years after surgery, respectively. The solid fusion rate after OLIF was 32.3% at 1 year, increased to 58.3% at 1.5 years, and reached 72.9% at 2 years. Radiographic pseudoarthrosis was 24.0% at 1 year, which decreased to 6.3% at 1.5 years and 3.1% at 2 years. CONCLUSION: OLIF is a safe and effective surgical procedure for the treatment of degenerative lumbar diseases. The mBSF scale, which simultaneously evaluates both dynamic angles and bone bridge formation, offers great reliability for the radiological assessment of fusion. Moreover, OLIF using allografts and DBM, which is performed on one or 2 levels at L2-5, can achieve satisfactory fusion rates within 2 years after surgery.

Nationwide Survey for Pediatric Gastrostomy Tube Placement in Korea.

BACKGROUND: Various methods have been implemented for pediatric gastrostomy tube placement. We aimed to investigate the performance status of pediatric gastrostomy in South Korea and to present indications and appropriate methods for domestic situations. METHODS: A survey was conducted among pediatric endoscopists who performed upper gastrointestinal endoscopy in Korea. The questionnaire consisted of 16 questions on gastrostomy performance status. RESULTS: Among the 48 institutions where the survey was applied, 36 (75%) responded. Of the 36 institutions, gastrostomy was performed in 31 (86.1%). The departments in which gastrostomy was performed were pediatrics at 26 institutions (81.3%), surgery at 24 institutions (75.0%), internal medicine at 9 institutions (28.1%), and radiology at 7 institutions (21.9%). There were 18 institutions (66.7%) using the pull method for percutaneous endoscopic gastrostomy (PEG) and nine institutions (33.3%) using the push method. When performing gastrostomies, fundoplication procedures were performed in 19 institutions (61.3%), if deemed necessary. However, 12 institutions (38.7%) answered that gastrostomy was always implemented alone. Complications after gastrostomy included buried bumper syndrome, wound infection, leakage, tube migration, and incorrect opening site in the stomach, but the number of cases with complications was very small. CONCLUSION: In Korea, a pediatric gastrostomy is implemented in various ways depending on the institution. Clinicians are concerned about choosing the most effective methods with fewer complications after the procedure. In our study, we reported only a few complications. Korea has good accessibility for pediatric gastrointestinal endoscopy, and this survey showed that it is a safe procedure that can be considered initially in pediatric gastrostomy. This study is expected to help to create optimal pediatric PEG guidelines in Korea.

Metanephrine Negative Pheochromocytoma: A rare case report of dopamine-secreting tumor in an adolescent patient with NF1.

Pheochromocytoma (PCC) occurs in 4% of pediatric neurofibromatosis type 1 (NF1) patients and is mostly characterized by epinephrine and norepinephrine secretion. Herein, we report the first case of a dopamine-secreting PCC in a 13-year-old patient with NF1, in whom a left adrenal mass was incidentally found on abdominal computed tomography (CT) during hypertension workup. Fractionated 24-h urine metanephrine excretion was normal but urine dopamine level was elevated. On 123I-metaiodobenzylguanidine (MIBG) single photon emission tomography/CT (SPECT/CT), focal MIBG uptake was observed. Our multidisciplinary team determined that surgery would be difficult to perform because the tumor was small and the symptoms were vague, with only increased dopamine level. After six months, the tumor increased in size on abdominal CT, with focal significant uptake of the lesion on 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET/CT. Laparoscopic resection was performed, and the mass was histologically confirmed as PCC. Currently, the vital signs of the patient are stable, urine dopamine levels are normal, and there is no abnormal uptake of 18F-FDOPA PET/CT. This study reports a case of a rare dopamine-secreting PCC. When metanephrine is negative in patients at high risk of PCC, focused examination and multidisciplinary approach are needed.