Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model.

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

Unveiling nature's potential weapon: Magnolol's role in combating bladder cancer by upregulating the miR-124 and inactivating PKC-δ/ERK axis.

BACKGROUND: Bladder cancer (BC) is a challenging disease to manage. Researchers have been investigating the potential of magnolol, a compound derived from Magnolia officinalis, as an anti-cancer agent. However, the exact regulatory mechanism of magnolol and its impact on the NF-κB signaling pathway in BC remain unclear. MATERIALS: To comprehensively evaluate its therapeutic potential, the researchers conducted a series of experiments using BC cell lines (TSGH8301, T24, and MB49) and in vivo animal models. RESULTS: The results of the study demonstrated that magnolol exhibits cytotoxic effects on BC cells by activating both the extrinsic and intrinsic apoptosis signaling pathways. Additionally, the expression of anti-apoptotic genes was downregulated by magnolol treatment. The researchers also uncovered the regulatory role of PKCδ/ERK and miR-124-3p in the NF-κB pathway, which may be influenced by magnolol. Treatment with magnolol led to the inactivation of PKCδ/ERK and an increase in miR-124-3p expression, effectively inhibiting NF-κB-mediated progression of BC. Importantly, the administration of magnolol did not result in significant toxicity in normal tissues, highlighting its potential as a safe adjunctive therapy with minimal adverse effects. CONCLUSION: These findings position magnolol as a promising therapeutic agent for the treatment of BC. By activating apoptosis signaling pathways and inhibiting NF-κB pathway through the upregulation of miR-124-3p and downregulation of PKCδ/ERK activation, magnolol holds promise for suppressing tumor progression and improving patient outcomes in BC. Further research and clinical trials are warranted to explore the full potential of magnolol in the future.

Klebsiella pneumoniae invasive syndrome with liver abscess and purulent meningitis presenting as acute hemiplegia: a case report.

BACKGROUND: Klebsiella pneumoniae can infect a variety of sites, with the risk of infection being higher in the immunocompromised state such as diabetes mellitus. A distinct invasive syndrome has been detected mostly in Southeast Asia in the past two decades. A common destructive complication is pyogenic liver abscess that can be complicated by metastatic endophthalmitis as well as the involvement of the central nervous system, causing purulent meningitis or brain abscess. CASE PRESENTATION: We report a rare case of an invasive liver abscess caused by K. pneumoniae, with metastatic infections of meninges. A 68-year-old man with type 2 diabetes mellitus presented to our emergency department as sepsis. Sudden disturbed consciousness was noticed with presentation of acute hemiplegia and gaze preference mimicking a cerebrovascular accident. CONCLUSIONS: The above case adds to the scarce literature on K. pneumoniae invasive syndrome with liver abscess and purulent meningitis. K. pneumoniae is a rare cause of meningitis and should raise suspicions about the disease in febrile individuals. In particular, Asian patients with diabetes presenting with sepsis and hemiplegia prompt a more thorough evaluation with aggressive treatment.

Accessing Apoptosis Induction and Metastasis Inhibition Effect of Magnolol on Triple Negative Breast Cancer In Vitro.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that still requires improvement in treatment. Magnolol extract, derived from the bark of Magnolia officinalis, has traditionally been used in Asia to treat sleeping disorders and anxiety, and as an anti-inflammatory agent. Several reports have indicated that magnolol may have the potential to inhibit the progression of hepatocellular carcinoma and glioblastoma. However, the anti-tumor effect of magnolol on TNBC remains unknown. MATERIALS AND METHODS: In this study, we used two TNBC cell lines, MDA-MB-231 and 4T1, to examine the cytotoxicity, apoptosis, and metastasis effects of magnolol. These were evaluated using MTT assay, flow cytometry, western blotting, and invasion/migration transwell assay, respectively. RESULTS: Magnolol significantly induced cytotoxicity and extrinsic/intrinsic apoptosis in both TNBC cell lines. It also decreased metastasis and associated protein expression in a dose-dependent manner. Furthermore, the anti-tumor effect was associated with the inactivation of the epidermal growth factor receptor (EGFR)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT3) signaling pathway. CONCLUSION: Magnolol may not only induce cell death in TNBC through apoptosis signaling activation but also by down-regulating EGFR/JAK/STAT3 signaling, which mediates TNBC progression.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

Magnolol Suppresses ERK/NF-κB Signaling and Triggers Apoptosis Through Extrinsic/Intrinsic Pathways in Osteosarcoma.

BACKGROUND/AIM: Osteosarcoma is an aggressive primary malignant bone tumor that occurs in childhood. Although the diagnostic and treatment options have been improved, osteosarcoma confers poor prognosis. Magnolol, an active component of Magnoliae officinalis cortex, has been widely applied in herb medicine and has been shown to have multiple pharmacological activities. However, whether magnolol possesses anti-osteosarcoma capacity remains unknown. MATERIALS AND METHODS: We examined magnolol is cytotoxicity, and whether it regulates apoptosis and oncogene expression using MTT, flow cytometry and Western blotting assays in osteosarcoma cells. RESULTS: Magnolol exerted toxicity towards U-2 OS cells by inducing intrinsic/extrinsic apoptosis pathways. Additionally, treatment of U-2 OS cells with magnolol inhibited MAPK1 mitogen-activated protein kinase 1 (ERK)/Nuclear factor kappa B (NF-B) signaling involved in tumor progression and reduced the expression of anti-apoptotic and metastasis-associated genes. CONCLUSION: Magnolol may induce apoptosis and inactivate ERK/NF-B signal transduction in osteosarcoma cells.

Magnolol Induces Apoptosis Through Extrinsic/intrinsic Pathways and Attenuates NF-κB/STAT3 Signaling in Non-small-cell Lung Cancer Cells.

BACKGROUND/AIM: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, and treatment outcomes are still poor. Magnolol, a hydroxylated biphenyl isolated from Magnolia officinalis, was found to be effective against hepatocellular carcinoma via inactivating nuclear-factor-kappa B (NF-B) signaling. However, whether magnolol targets not only NF-B but also other factors in NSCLC and may contribute to the suppression of tumor progression is unclear. MATERIALS AND METHODS: Cell viability, flow cytometry, and western blotting assays were used to identify the mechanism of magnolol action in human lung adenocarcinoma cell lines A549 and CL1-5-F4. RESULTS: Our results indicated that magnolol induced cytotoxicity through extrinsic/intrinsic apoptosis signaling and suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3)/NF-B and expression of their downstream proteins. CONCLUSION: Magnolol not only induced extrinsic and intrinsic apoptosis signaling but also inactivated STAT3/NF-B and attenuated their signaling of epithelial-mesenchymal transition and metastasis-related protein expression in NSCLC.

Exploring Hepatocellular Carcinoma Mortality Using Weighted Regression Estimation for the Cohort Effect in Taiwan from 1976 to 2015.

To estimate the cohort effects that remove the efficacy of age and the period in the age-period statistics of a contingency table, the multiphase method is put forward. Hepatocellular carcinoma (HCC) is one of the most common malignancies of the liver. Understanding the predictive effects of age, period, and cohort on HCC mortality trends may help to estimate the future HCC burden, identify etiological factors, and advise public health prevention programs. Estimates of future HCC mortality and the associated health burden were forecast using an age-period-cohort (APC) model of analysis. By running a regression of residuals that were isolated from the median polish stage of cohort classification, the study controlled for HCC mortality confounding variables and interpreted time trends in HCC rates. The literature shows that the weighted mean estimation derived from the confidence interval (CI) is relatively restricted (compared to the equal-weighted evaluation). This study aimed to illustrate the effects of age, period, and cohort on the incidence and mortality rates, along with the weight equivalent to the segment of death number caused by HCC in each cohort. The objective of that work was to evaluate the proposed method for appraising cohort effects within the age-period data of contingency tables. The weighted mean estimate from the regression model was found to be robust and thus warrants consideration in forecasting future HCC mortality trends. The final phase was factored in to calculate the magnitude of cohort effects. In conclusion, owing to the relatively constricted CI and small degree of uncertainty, the weighted mean estimates can be used for projections based on simple linear extrapolation.

Tissue diagnosis necessary for small endoscopic ultrasound-suspected gastric gastrointestinal stromal tumors 2 cm or less in size: A prospective study focusing on the endoscopic incisional biopsy.

BACKGROUND AND AIM: The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Bite-on-bite forceps biopsy and EUS-guided tissue sampling yield variable results. This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs 2 cm or less in size and to evaluate the efficacy and safety of the endoscopic incisional biopsy (EIB) for these small tumors. METHODS: This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the bite-on-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate. RESULTS: Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups. CONCLUSIONS: Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions.

Synchronous but separate neuroendocrine tumor and high-grade dysplasia/adenoma of the gall bladder: A case report.

BACKGROUND: Gall bladder neuroendocrine tumors (GB-NETs) are rare, accounting for less than 0.5% of all NETs. They usually lack specific symptoms and are difficult to diagnose preoperatively. In most cases, GB-NETs are incidentally found after cholecystectomy for large polyps or cholelithiasis, causing acute or chronic cholecystitis. The coexistence of GB-NET and GB adenocarcinoma is very rare. CASE SUMMARY: We report a case of synchronous but separate GB-NET and adenoma with high-grade dysplasia in a patient who had undergone surgery for a progressively growing GB polypoid lesion. To the best of our knowledge, simultaneous separation of NETs and cancer in the GB has not been reported. CONCLUSION: Coexistent GB carcinoid tumor and adenocarcinoma is rare. A surveillance program is needed for these large GB polyps.

Induction of Apoptosis, Inhibition of MCL-1, and VEGF-A Expression Are Associated with the Anti-Cancer Efficacy of Magnolol Combined with Regorafenib in Hepatocellular Carcinoma.

While regorafenib was approved for the treatment of advanced HCC in 2017, with a partial response and survival benefit; other combination agents to facilitate the efficacy of regorafenib still need to be explored. Magnolol is a potential natural anti-tumor compound for many types of cancers. Combination indexes calculated on the basis of both in vitro and in vivo models have indicated a synergistic effect of the combination of regorafenib and magnolol. The overexpression of the VEGF-A protein significantly diminished regorafenib's inhibition of cell viability, while the transient knockdown of VEGF-A by siRNA effectively sensitized HCC cells to regorafenib. In addition, the inhibition of MCL-1 by siRNA combined with regorafenib allowed for a significantly greater inhibition of cell growth, compared to regorafenib alone. A lower protein expression level for VEGF-A and MCL-1 was found for the combination treatment of HCC in vitro and in vivo. A superior metastasis inhibition was also found in the combination group, as compared to the single-treatment groups, using a transwell assay, wound healing assay, and Western blotting. The caspase-dependent and -independent and DNA damage effects, as determined by flow cytometry and a comet assay, were increased by the combination therapy. Taken together, magnolol sensitized HCC to regorafenib, which was correlated with the reduction of VEGF-A and MCL-1 and the induction of apoptosis.

Noninferiority clinical trial comparing the bowel cleansing efficacy of sodium phosphate tablets (Quiklean®) with a polyethylene glycol/bisacodyl kit.

BACKGROUND: Efficient bowel cleansing is essential for a successful colonoscopy, but the ideal cleansing agent, volume, and pharmaceutical dosage form have yet to be determined. Small-volume cleansers enhance patient compliance. AIM: To compare the bowel cleansing efficacy of 32-tablet sodium phosphate (Quiklean®) with 2-L polyethylene glycol (PEG)/bisacodyl (Klean-Prep/ Dulcolax®) under identical dietary recommendations. METHODS: This multicenter, randomized, parallel-group, noninferiority clinical trial enrolled 472 outpatients, randomized 456 subjects, and scheduled 442 subjects to undergo colonoscopy (Quiklean® = 222 and Klean-Prep/Dulcolax® = 220). After bowel preparation, a colonoscopist performed the colonoscopy with video recorded for rating. The primary efficacy endpoint was the bowel cleansing quality using the Aronchick Scale. The secondary endpoints were the bowel cleansing efficacy of three colon segments, tolerability and acceptability, safety using the Ottawa bowel preparation scale, questionnaires by subjects, and monitoring of adverse events. RESULTS: Success rates (Excellent + Good) of the bowel cleansing quality by Aronchick Scale were 98.6% (n = 205) and 97.6% (n = 204) in the Quiklean® and Klean-Prep/Dulcolax® groups, respectively. Quiklean® demonstrated noninferiority over Klean-Prep/Dulcolax® in colon cleansing efficacy. Quicken showed better tolerability and acceptability in the overall experience (was rated as excellent; 24.0% vs 17.2%; P = 0.0016) and the taste of the study preparation (was rated as excellent, 23.1% vs 13.4%; P < 0.0001) than Klean-Prep/Dulcolax®. Safety profiles did not differ between the two groups. Our data indicate that Quiklean® is an adequate, well-tolerated bowel cleansing preparation compared with the standard comparator Klean-Prep/Dulcolax®. CONCLUSION: Quiklean® is sodium phosphate tablets available on Taiwan's market for bowel preparation; it potentially offers patients an alternative to standard large-volume bowel preparation regimens and may, therefore, increase positive attitudes toward colonoscopies and participation rates.

A Rare Case of Spontaneous Pseudo-Aneurysm Rupture of an Extra-Anatomical Axillo-Femoral Bypass Graft: A Case Report.

BACKGROUND: Sudden onset of chest wall bulging is a rare chief symptom in the emergency department (ED). However, it may represent life-threatening diseases, such as tumor bleeding, aneurysm rupture, or subcutaneous emphysema. CASE REPORT: We present an 89-year-old woman who visited our ED with a chief symptom of abrupt bulging of the right chest wall accompanied with severe pain. The patient had a history of peripheral artery disease and 10-year post-extra-anatomical axillo-femoral bypass (AxFB) status. After several examinations, the patient was diagnosed as having spontaneous pseudo-aneurysm rupture of an extra-anatomical AxFB graft. Emergency endovascular intervention with stent insertion was performed immediately, and the patient was eventually discharged successfully. WHY SHOULD EMERGENCY PHYSICIANS BE AWARE OF THIS?: Although spontaneous pseudo-aneurysm rupture of an extra-anatomical AxFB graft is rare, the disease may consequently lead to a fatal outcome once misdiagnosed, and prompt intervention is warranted. Therefore, we should always consider the differential diagnosis of this disease in patients with a bulging chest wall and history of AxFB graft placement.

The In Vivo Radiosensitizing Effect of Magnolol on Tumor Growth of Hepatocellular Carcinoma.

BACKGROUND/AIM: Radiation (RT) induced ERK/NF-κB in hepatocellular carcinoma (HCC) has been reported in our previous works; it weakens the toxicity of RT or triggers a radioresistance effect. Thus, combining RT with a suitable NF-κB inhibitor may sensitize HCC to RT. Magnolol, a bioactive compound, was known to have anti-inflammatory and anti-tumor functions. Here, we aimed to investigate whether magnolol may enhance anti-HCC efficacy of RT in vivo. MATERIALS AND METHODS: We established a Hep3B bearing mouse to evaluate the efficacy of the combination treatment of magnolol and RT. RESULTS: Most significantly, tumor volume and tumor weight inhibition was found in the combination group. Tumor immunohistochemistry staining also illustrated the suppression of RT-induced ERK/NF-κB-related proteins expression by magnolol. In addition, intrinsic apoptosis-related proteins, such as caspase-3 and -9, were markedly increased in the combination group. CONCLUSION: Magnolol may effectively enhance anti-HCC ability of RT by downregulating the expression of ERK/NF-κB-related proteins and increasing the expression of apoptosis-related proteins.

Suppression of PKCδ/NF-κB Signaling and Apoptosis Induction through Extrinsic/Intrinsic Pathways Are Associated Magnolol-Inhibited Tumor Progression in Colorectal Cancer In Vitro and In Vivo.

Magnolol is one of the hydroxylated biphenyl compounds from the root and stem bark of Magnolia officinalis, which shown to possess anti-colorectal cancer (CRC) effects. However, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human CRC has not been elucidated. Thus, we investigated the inhibitory mechanism of magnolol on human and mouse CRC (HT-29 and CT-26) in vitro and in vivo. Results from reporter gene assay indicated that both magnolol and rottlerin (PKCδ inhibitor) reduced the endogenous NF-κB activity. In addition, indolactam V (PKCδ activator)-induced NF-κB signaling was significantly suppressed with both magnolol and rottlerin treatment. Results from Western blotting also indicated that phosphorylation of PKCδ and NF-κB -related proteins involved in tumor progression were effectively decreased by magnolol treatment. The invasion capacity of CRC cells was also attenuated by both magnolol and rottlerin. Furthermore, magnolol triggered Fas/Fas-L mediated extrinsic apoptosis and mitochondria mediated intrinsic apoptosis were validated by flow cytometry. Most importantly, tumor growth in both HT-29 and CT-26 bearing mice were suppressed by magnolol, but no pathologic change was detected in mice kidney, spleen, and liver. As confirmed by immunohistochemistry (IHC) staining from tumor tissue, PKCδ/NF-κB signaling and downstream proteins expression were decreased, while apoptotic proteins expression was increased in the magnolol treated group. According to these results, we suggest that the induction of apoptosis through extrinsic/intrinsic pathways and the blockage of PKCδ/NF-κB signaling are associated with the magnolol-inhibited progression of CRC.

Apoptosis induction and ERK/NF-κB inactivation are associated with magnolol-inhibited tumor progression in hepatocellular carcinoma in vivo.

Although hepatitis B and/or hepatitis C virus were recognized as major risk factor for the development of hepatocellular carcinoma (HCC), certain occupational, environmental, and lifestyle factors also play key roles in HCC tumorigenesis. Moreover, in molecular signaling route, extracellular signal-regulated kinase (ERK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was found to be overexpressed and linked to poor prognosis in HCC. Thus, to identify possible nature compound that can suppress ERK/NF-κB may be benefit to HCC patient. Magnolol, a natural compound derived from herbal plant Magnolia officinalis, has been recognized as a liver protection and antitumor reagent. However, whether magnolol-inhibited HCC progression correlates with disruption of ERK/NF-κB signaling is remained unclear. In this studies, we performed SK-Hep1/luc2 HCC bearing animal model to investigate the anticancer efficacy and mechanism of magnolol on tumor progression. Tumor size and tumor growth rate were dramatically suppressed after treatment of magnolol. In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. Most important, major extrinsic and intrinsic apoptosis signaling factors, including active caspase-8 and caspase-9 were both enhanced by magnolol. This study indicated that apoptosis induction through extrinsic/intrinsic pathways and blockage of ERK/NF-κB activation were associated with magnolol-inhibited tumor progression in HCC in vivo.

Protein Kinase B Inactivation Is Associated with Magnolol-Enhanced Therapeutic Efficacy of Sorafenib in Hepatocellular Carcinoma In Vitro and In Vivo.

Although sorafenib, an oral multikinase inhibitor, was approved as a treatment drug of advance hepatocellular carcinoma (HCC), treatment efficacy still requires improvement. Searching for the adjuvant reagent for enhancing sorafenib efficacy remains as a critical issue. Sorafenib has been proved to suppress extracellular signal-regulated kinases (ERK) in HCC; however, protein kinase B (AKT) was not affected by it. Targeting AKT in combination with sorafenib could be an important breakthrough point of HCC treatment. Many herbal compounds and composite formulas have been shown to enhance anti-HCC activity of sorafenib. Magnolol is a bioactive compound extracted from the bark of the Magnolia officinalis and has been shown to induce apoptosis and inhibit cell invasion in HCC in vitro. However, whether magnolol sensitizes HCC to sorafenib is ambiguous. In this study, we indicated that magnolol significantly enhanced sorafenib-diminished tumor cell growth, expression of anti-apoptotic proteins, and migration/invasion ability compared to sorafenib alone. Magnolol significantly boosted sorafenib-induced extrinsic/intrinsic dependent apoptosis pathways in HCC. Notably sorafenib could not reduce protein level of AKT (Ser473), but expression of AKT (Ser473) was significantly decreased by magnolol or magnolol combined with sorafenib. LY294002 as specific AKT inhibitor was used to confirm that AKT inactivation may promote anticancer effect of sorafenib. Taken together, AKT inhibition is associated with magnolol-enhanced the therapeutic effect of sorafenib in HCC. We suggested magnolol as the potential adjuvant which may enhance therapeutic benefits of sorafenib in patients with HCC.

Synbiotic Combination of Djulis (Chenopodium formosanum) and Lactobacillus acidophilus Inhibits Colon Carcinogenesis in Rats.

Djulis is a functional grain containing prebiotic dietary fiber, which has an anti-cancer potential. This study examined the preventive effect of djulis alone or in combination with Lactobacillus acidophilus on colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS). Rats were divided into five groups and fed B (AIN-93G, blank), C (AIN-93G, control), D (10% djulis), DLA (10% djulis plus 5 × 106 cfu L. acidophilus/g), and DHA (10% djulis plus 5 × 107 cfu L. acidophilus/g) diets, respectively. All rats except for those in group B received three doses of DMH (40 mg/kg) by intraperitoneal injection and 3% DSS in drinking water. After 10 weeks of feeding, the colon was analyzed for precancerous lesions and biomarkers. DMH and DSS treatment induced aberrant crypt foci (ACF), especially in the distal colon. D, DLA, and DHA significantly reduced the numbers of total ACF, sialomucin-producing ACF (SIM-ACF), and mucin-depleted foci (MDF) in the distal colon compared to C. Additionally, DLA and DHA further downregulated the expressions of proliferating cell nuclear antigen (PCNA) and cyclooxygenase-2 (COX-2) and regulated apoptosis-related proteins. These results suggest that synbiotic combination of djulis and L. acidophilus shows the best inhibitory effect on colon carcinogenesis via regulation of proliferative, inflammatory, and apoptotic pathways.

Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity.

BACKGROUND/AIMS: We aimed to investigate gastrointestinal symptoms, clinical characteristics, and psychological factors in subjects with and without sleep disturbance (SD) in a health screening cohort. METHODS: We enrolled 2,752 consecutive subjects during their health checkups. All participants underwent an evaluation with questionnaires. Demographic characteristics and biochemical data were recorded. SD was confirmed when Pittsburgh Sleep Quality Index score was greater than 5. RESULTS: Among the study population (n = 2,674), 956 (36%) individuals had SD. SD was associated with female gender, older age, lower level of education, higher systolic blood pressure, higher serum high-density lipoprotein levels and higher prevalence of functional dyspepsia and irritable bowel syndrome (IBS). SD subjects also had more depression, more anxiety, more severe gastrointestinal reflux disease symptoms and higher prevalence of non-erosive reflux disease (NERD; p < 0.001). SD was -independently associated with female gender (OR 1.75, p < 0.001), older age (OR 1.03, p < 0.001), NERD (OR 1.88, p = 0.004), IBS (OR 1.51, p = 0.043), and depression (OR 1.16, p < 0.001) by multivariate analysis. CONCLUSIONS: Future studies will be needed to clarify the interrelationships among SD, psychological stress, and functional gastrointestinal disorders.

Magnolol Induces Apoptosis and Inhibits ERK-modulated Metastatic Potential in Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: The aim of the present study was to evaluate the anti-cancer effect of magnolol in hepatocellular carcinoma (HCC) cells in vitro. MATERIALS AND METHODS: HCC SK-Hep1 cells were treated with different concentrations of magnolol or PD98059 [extracellular-signal-regulated kinase (ERK) inhibitor] for 48 h, and then cell viability, apoptosis, signal transduction, expression of anti-apoptotic and metastasis-related proteins, and cell invasion were investigated by [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, flow cytometry, nuclear factor kappa B (NF-ĸB) reporter gene, western blotting, and cell invasion assays. RESULTS: Magnolol significantly induced accumulation of sub-G1 phase and caspase-3 activation and inhibited NF-ĸB activation, cell invasion, expression of phosphorylated ERK (pERK), anti-apoptotic and metastatic-related proteins. ERK inactivation was required for magnolol-induced inhibition of metastatic potential of SK-Hep1 cells. CONCLUSION: Taken together, these results indicated that magnolol not only induced apoptosis, but also inhibited ERK-modulated metastatic potential of HCC SK-Hep1 cells.