Hyperspectral screen-image-synthesis meter with scattering-noise suppression.

The screen image synthesis (SIS) meter was originally proposed as a high-speed measurement tool, which fused the measured data from multiple sample-rotational angles to produce a whole-field measurement result. However, it suffered from stray light noise and lacked the capability of spectrum measurement. In this study, we propose an SIS system embedded with a snapshot hyperspectral technology, which was based on a dispersion image of the sparse sampling screen (SSS). When a photo was captured, it was transformed and calibrated to hyperspectral data at a specific sample-rotational angle. After the hyperspectral data in all sample-rotational angles were captured, an SIS image-fusion process was then applied to get the whole field hyperspectral data. By applying SSS to the SIS meter, we not only create a screen image synthesis hyperspectral meter but also effectively address the issue of stray-light noise. In the experiment, we analyze its correctness by comparing the hyperspectral value with a one-dimensional spectrum goniometer (ODSG). We also show the 2D color temperature coefficient distribution and compare it with the ODSG. Experimental results also demonstrate the feasibility in terms of both spectrum distribution meter and color coefficient temperature distribution meter.

Lemierre's Syndrome Caused by Klebsiella pneumoniae: A Case Report and Literature Review.

Lemierre's syndrome is a rare condition that involves anaerobic sepsis following pharyngitis and is characterized by a high mortality rate. It often manifests as a septic embolism within the internal jugular vein due to oropharyngeal infections, leading to vein wall inflammation. Despite modern antibiotics, Lemierre's syndrome remains underdiagnosed and poses a significant threat. We report the case of a 43-year-old man who has alcoholic liver cirrhosis and diabetes mellitus. Symptoms included chest pain, back pain, and neck swelling, with Klebsiella pneumoniae leading to the diagnosis of K. pneumoniae-associated Lemierre's syndrome. Furthermore, K. pneumoniae-associated Lemierre's syndrome is linked to diabetes mellitus and the elderly population. Notably, it showed a tendency for distant metastases, particularly in the lungs and brain. Additionally, central nervous system and renal involvement were observed in a smaller subset of cases.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

Far-infrared radiation alleviates cisplatin-induced vascular damage and impaired circulation via activation of HIF-1α.

Severe vascular damage and complications are often observed in cancer patients during treatment with chemotherapeutic drugs such as cisplatin. Thus, development of potential options to ameliorate the vascular side effects is urgently needed. In this study, the effects and the underlying mechanisms of far-infrared radiation (FIR) on cisplatin-induced vascular injury and endothelial cytotoxicity/dysfunction in mice and human umbilical vein endothelial cells (HUVECs) were investigated. An important finding is that the severe vascular stenosis and poor blood flow seen in cisplatin-treated mice were greatly mitigated by FIR irradiation (30 minutes/day) for 1-3 days. Moreover, FIR markedly increased the levels of phosphorylation of PI3K and Akt, and VEGF secretion, as well as the expression and the activity of hypoxia-inducible factor 1α (HIF-1α) in cisplatin-treated HUVECs in a promyelocytic leukemia zinc finger protein (PLZF)-dependent manner. However, FIR-stimulated endothelial angiogenesis and VEGF release were significantly diminished by transfection with HIF-1α siRNA. We also confirmed that HIF-1α, PI3K, and PLZF contribute to the inhibitory effect of FIR on cisplatin-induced apoptosis in HUVECs. Notably, FIR did not affect the anticancer activity and the HIF-1α/VEGF cascade in cisplatin-treated cancer cells under normoxic or hypoxic condition, indicating that the actions of FIR may specifically target endothelial cells. It is the first study to demonstrate that FIR effectively attenuates cisplatin-induced vascular damage and impaired angiogenesis through activation of HIF-1α-dependent processes via regulation of PLZF and PI3K/Akt. Taken together, cotreatment with the noninvasive and easily performed FIR has a therapeutic potential to prevent the pathogenesis of vascular complications in cancer patients during cisplatin treatment.

Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells.

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1ß, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia-reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1ß, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.

Inhibition of ß-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts.

BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.

Suppression of EGFR/PKC-δ/NF-κB Signaling Associated With Imipramine-Inhibited Progression of Non-Small Cell Lung Cancer.

BACKGROUND: Anti-depressants have been reported to own anti-tumor potential types of cancers; however, the role of imipramine in non-small cell lung cancer (NSCLC) has not been elucidated. Epidermal growth factor receptor (EGFR) was known to be one of the key regulators that control NSCLC progression. Whether EGFR would be the target of imipramine for suppressing tumor signaling transduction and results in anti-tumor potential is remaining unclear. METHODS: We used CL-1-5-F4 cells and animal models to identify the underlying mechanism and therapeutic efficacy of imipramine. Cytotoxicity, apoptosis, invasion/migration, DNA damage, nuclear translocation of NF-κB, activation of NF-κB, phosphorylation of EGFR/PKC-δ/NF-κB was assayed by MTT, flow cytometry, transwell, wound healing assay, comet assay, immunofluorescence staining, NF-κB reporter gene assay and Western blotting, respectively. Tumor growth was validated by CL-1-5-F4/NF-κB-luc2 bearing animal model. RESULTS: Imipramine effectively induces apoptosis of NSCLC cells via both intrinsic and extrinsic apoptosis signaling. DNA damage was increased, while, invasion and migration potential of NSCLC cells was suppressed by imipramine. The phosphorylation of EGFR/PKC-δ/NF-κB and their downstream proteins were all decreased by imipramine. Similar tumor growth inhibition was found in imipramine with standard therapy erlotinib (EGFR inhibitor). Non-obvious body weight loss and liver pathology change were found in imipramine treatment mice. CONCLUSION: Imipramine-triggered anti-NSCLC effects in both in vitro and in vivo model are at least partially attributed to its suppression of EGFR/PKC-δ/NF-κB pathway.

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.

Amentoflavone Induces Cell-cycle Arrest, Apoptosis, and Invasion Inhibition in Non-small Cell Lung Cancer Cells.

BACKGROUND/AIM: Amentoflavone, an effective compound derived from medicinal plants, has been shown to boost therapeutic efficacy of chemotherapy in non-small cell lung cancer (NSCLC). However, anti-NSCLC effect of amentoflavone is ambiguous. The major purpose of the present study was to verify the inhibitory effects of amentoflavone in NSCLC cells. MATERIALS AND METHODS: The effects of amentoflavone on growth and invasion of NSCLC CL-1-5-F4 cells were evaluated by cell viability assay, flow cytometry, colony formation assay, nuclear factor-kappa B (NF-κB) reporter gene assay, immunofluorescence staining, transwell invasion, and western blot assay. RESULTS: Amentoflavone effectively induced cell growth inhibition, G1 cell-cycle arrest, apoptosis, and suppression of invasion. Furthermore, amentoflavone not only triggered expression of p27, cleaved caspase-3, -8 also reduced NF-κB signaling, protein levels of matrix metalloproteinase (MMP)-2, -9, Cyclin-D1, and vascular endothelial growth factor (VEGF). CONCLUSION: Cell-cycle arrest, apoptosis induction, NF-κB signaling inhibition are associated with amentoflavone-inhibited growth and invasion of NSCLC cells.

Renal protective effect of sacubitril/valsartan in patients with heart failure.

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3-0.9). Kaplan-Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.

Parathyroid Hormone Induces Transition of Myofibroblasts in Arteriovenous Fistula and Increases Maturation Failure.

CONTEXT: Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown. OBJECTIVE: This work aimed to investigate the association between plasma PTH and AVF maturation. METHODS: Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion. RESULTS: In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin ß6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast. CONCLUSION: Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Combined protective effects of oligo-fucoidan, fucoxanthin, and L-carnitine on the kidneys of chronic kidney disease mice.

Chronic kidney disease (CKD) is a common global progressive disease, but there are no ideal drugs for the treatment. Fucoidan and fucoxanthin, and L-carnitine are one of the very few natural products that have a therapeutic effect on CKD in animal experiments. However, the combined effects of these compounds on CKD are unknown. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Oligo-fucoidan and fucoidan were extracted from Laminaria japonica. We fed CKD mice with the two compounds and L-carnitine to evaluate the combined effects on CKD. Oligo-fucoidan and fucoidan inhibited renal fibrosis and reduced serum creatine in CKD mice to a greater extent than any single compound. L-carnitine had no measurable effect on renal fibrosis but promoted the protective effect of the mixture of oligo-fucoidan and fucoidan on renal function in CKD mice. In the two-month safety test, the combined mixture further improved renal function and did not elevate serum aspartate aminotransferase and alanine aminotransferase levels in CKD mice. Furthermore, the weights of CKD mice treated with the combination increased to the normal level. We also found that all oligo-fucoidan, fucoxanthin, and L-carnitine inhibit H2O2-induced apoptosis and activated Akt in rat renal tubular cells. Our results confirm that oligo-fucoidan, fucoxanthin, and L-carnitine have a combined protective effect on the kidneys. The combined mixture may be beneficial for CKD patients.

Anticancer Efficacy and Mechanism of Amentoflavone for Sensitizing Oral Squamous Cell Carcinoma to Cisplatin.

BACKGROUND/AIM: Nuclear factor kappa B (NF-κB) inactivation and apoptosis activation have been shown to enhance the anticancer effect of cisplatin in oral squamous cell carcinoma (OSCC). Amentoflavone may suppress NF-κB activity and trigger apoptosis in different types of cancer. The aim of this study was to investigate the anticancer effect and mechanism of amentoflavone in combination with cisplatin in OSCC. MATERIALS AND METHODS: We investigated the combination effect and mechanism of amentoflavone and cisplatin via cell viability analysis, flow cytometry-based apoptosis analyses, transwell migration/invasion assay, immunofluorescence staining and western blotting assay. RESULTS: Both amentoflavone and QNZ (NF-κB inhibitor) significantly increased cisplatin-induced cytotoxicity. Amentoflavone reduced cisplatin-triggered NF-κB activity and enhanced cisplatin-induced intrinsic caspase-dependent and independent apoptotic pathways. Moreover, amentoflavone augments cisplatin-suppressed invasion and migration ability of OSCC cells. CONCLUSION: Inactivation of NF-κB and induction of apoptosis through intrinsic caspase-dependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin.

Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula.

While the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.

Far-infrared radiation prevents decline in ß-cell mass and function in diabetic mice via the mitochondria-mediated Sirtuin1 pathway.

Insulin deficiency in type 2 diabetes mellitus (DM) involves a decline in both pancreatic ß-cell mass and function. Enhancing ß-cell preservation represents an important therapeutic strategy to treat type 2 DM. Far-infrared (FIR) radiation has been found to induce promyelocytic leukemia zinc finger protein (PLZF) activation to protect the vascular endothelium in diabetic mice. The influence of FIR on ß-cell preservation is unknown. Our previous study reveals that the biologically effective wavelength of FIR is 8-10 µm. In the present study, we investigated the biological effects of FIR (8-10 µm) on both survival and insulin secretion function of ß-cells. FIR reduced pancreatic islets loss and increased insulin secretion in nicotinamide-streptozotocin-induced DM mice, but only promoted insulin secretion in DM PLZF-/- mice. FIR-upregulated PLZF to induce an anti-apoptotic effect in a ß cell line RIN-m5f. FIR also upregulated mitochondrial function and the ratio of NAD+/NADH, and then induced Sirtuin1 (Sirt1) expression. The mitochondria Complex I inhibitor rotenone blocked FIR-induced PLZF and Sirt1. The Sirt1 inhibitor EX527 and Sirt1 siRNA inhibited FIR-induced PLZF and insulin respectively. Sirt1 upregulation also increased CaV1.2 expression and calcium influx that promotes insulin secretion in ß-cells. In summary, FIR-enhanced mitochondrial function prevents ß-cell apoptosis and enhances insulin secretion in DM mice through the Sirt1 pathway.

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.

Study protocol for a prospective observational study to investigate the role of luminal pressure on arteriovenous fistula maturation.

INTRODUCTION: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis due to its higher patency and lower infection rate. However, its suboptimal maturation rate is a major weakness. Although substantial risk factors for AVF maturation failure have been disclosed, modifiable risk factors remain unknown. During the AVF maturation process, an elevated luminal pressure is required for outward remodeling; however, excessively high luminal pressure may also be detrimental to AVF maturation, which remains to be defined. We hypothesized that higher AVF luminal pressure is harmful to its maturation, and investigate its potential as a modifiable factor to improve AVF maturation. METHODS AND ANALYSIS: This prospective study includes patients undergoing surgical creation for a native AVF. The exclusion criteria were as follows: age <20 years, inability to sign an informed consent, and failure to create a native AVF due to technical difficulties. Demographic and laboratory profiles will be collected before AVF surgery. Vascular sonography will be performed within 1 week of AVF creation to measure the diameters, flow rates, and flow volumes of AVF and its branched veins. The pressure gradient within AVF will be estimated from the blood flow rates using the modified Bernoulli equation. The primary outcome is spontaneous AVF maturation defined as provision of sufficient blood flow for hemodialysis within 2 months of its creation without any interventional procedures. The secondary outcome is assisted AVF maturation, which is defined as AVF maturation within 2 months from its creation aided by any interventional procedure before the successful use of AVF. DISCUSSION: While contemporary theory for AVF maturation failure focuses on disturbed wall shear stress, complicate assumptions and measurement preclude its clinical applicability. AVF luminal pressure, which may be manipulated pharmaceutically and surgically, may be a target to improve the outcome of AVF maturation. TRIAL REGISTRATION: This study has been registered at the protocol registration and results system. The Protocol ID: NCT04017806.

Detecting the limits of the biological effects of far-infrared radiation on epithelial cells.

Far-infrared radiation (FIR) exerts numerous beneficial effects on health and cell physiology. Recent studies revealed that the biological effects of FIR are independent of thermal effects. There is no proper method for measuring the parameters of the non-thermal biological effects of FIR, which limits its biomedical application. In this study, we established a cell detection platform using epithelial cell migration to measure the limits of the biological effects of FIR. FIR promoted the migration of rat renal tubular epithelial cells as revealed by our standardized detection method. We defined the ratio of the FIR-promoted migration area to the migration area of the control group as the FIR biological index (FBI). An increase of the FBI was highly associated with FIR-promoted mitochondrial function. Through FBI detection, we revealed the limits of the biological effects of FIR, including effective irradiation time, wavelengths, and temperature. FBI detection can be used to clarify important parameters of the biological effects of FIR in biomedical studies and health industry applications.

Fluoxetine Induces Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits ERK/NF-κB-Modulated Anti-Apoptotic and Invasive Potential in Hepatocellular Carcinoma Cells In Vitro.

The aim of the present study was to verify the effects of fluoxetine on dysregulation of apoptosis and invasive potential in human hepatocellular carcinoma (HCC) SK-Hep1 and Hep3B cells. Cells were treated with different concentrations of fluoxetine for different times. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used for testing the effects of fluoxetine on cell viability. The regulation of apoptosis signaling, and anti-apoptotic, proliferation, and metastasis-associated proteins after fluoxetine treatment were assayed by flow cytometry and Western blotting assay. The detection of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation after fluoxetine treatment was performed by NF-κB reporter gene assay. The results demonstrated that fluoxetine significantly reduced cell viability, cell migration/invasion, NF-κB, extracellular signal-regulated kinases (ERK) activation, and expression of anti-apoptotic (Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (C-FLIP), Myeloid cell leukemia-1 (MCL-1), X-Linked inhibitor of apoptosis protein (XAIP), and Survivin), proliferation (Cyclin-D1), angiogenesis (vascular endothelial growth factor (VEGF)), and metastasis-associated proteins (matrix metalloproteinase-9 (MMP-9)). Fluoxetine also significantly induced apoptosis, unregulated extrinsic (activation of first apoptosis signal protein and ligand (Fas/FasL), and caspase-8) and intrinsic (loss of mitochondrial membrane potential (ΔΨm) pathways and increased Bcl-2 homologous antagonist killer (BAK) apoptosis signaling. Taken together, these results demonstrated that fluoxetine induced apoptosis through extrinsic/intrinsic pathways and diminished ERK/NF-κB-modulated anti-apoptotic and invasive potential in HCC cells in vitro.