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Clinical evidence suggests that lymphangiogenesis and lymphatic metastasis are important processes during the progression of prostate cancer. Vascular endothelial growth factor (VEGF)-C was shown to be a key regulator in these processes. Our previous studies demonstrated that lysophosphatidic acid (LPA), a low-molecular-weight lipid growth factor, enhances VEGF-C expression in human endothelial cells. We previously demonstrated that the LPA receptor plays an important role in lymphatic development in zebrafish embryos. However, the effects of LPA on VEGF-C expression in prostate cancer are not known. Herein, we demonstrate that LPA up-regulated VEGF-C expression in three different human prostate cancer cell lines. In PC-3 human prostate cancer cells, the enhancing effects of LPA were mediated through both LPA1 and LPA3. In addition, reactive oxygen species (ROS) production and lens epithelium-derived growth factor (LEDGF) expression were involved in LPA1/3-dependent VEGF-C expression. Furthermore, autotaxin (ATX), an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA1/3 of PC-3, conditioned medium (CM) - induced human umbilical vein endothelial cell (HUVEC) lymphatic markers expression was also blocked. In summary, we found that LPA enhances VEGF-C expression through activating LPA1/3-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer. [ABSTRACT FROM AUTHOR]

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide- induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. [ABSTRACT FROM AUTHOR]

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) has been demonstrated to induce insulin resistance (IR) and lipolysis, raising the possibility that ET-1 may also contribute to the elevated fatty acid levels in IR-associated comorbidities. We attempted to evaluate whether ET-1 also affects the long-chain fatty acid (LCFA) utilization in 3T3-L1 adipocytes. The effects of chronic ET-1 exposure on basal and insulin-stimulated LCFA uptake, and LCFA uptake kinetics were examined in 3T3-L1 adipocytes. Chronic exposure to ET-1 induced IR and suppressed basal and insulin-stimulated LCFA uptake. Given that insulin acutely stimulates LCFA uptake, there was dramatically similar trend of dose-response curves for ET-1-suppressed LCFA uptake, and also similar corresponding IC50 values, between basal and insulin-stimulated states, reflecting that ET-1 predominantly suppresses basal LCFA uptake. Results of LCFA kinetics, western blots, and CD36 inhibition using sulfosuccinimidyl oleate (SSO) revealed that suppression of LCFA uptake by ET-1 is associated with downregulation of CD36. ET type A receptor (ETAR) antagonist BQ-610 reversed the IR induction and the ET-1-suppressed LCFA uptake. Exogenous replenishment of phosphatidylinositol (PI) 4, 5-bisphosphate (PIP2) prevented IR induction, but not the suppression of LCFA uptake by ET-1. Pharmacological inhibition of the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) completely blocked the ET-1-suppressed LCFA uptake. Serving as an inducer of IR, ET-1 also chronically suppresses LCFA uptake via PIP2-independent and ERK-dependent pathway. The interplay between impaired glucose disposal and diminished LCFA utilization, induced by ET-1, could worsen the dysregulation of adipose metabolism and energy homeostasis in insulin-resistant states. [ABSTRACT FROM AUTHOR]

Abstract  To form a low noise figure and uniform shortpass band in optical fiber communications an improved automatic filtered power control (AFPC) pumping method is proposed here. A modulated single laser signal was entered in a closed feedback loop, in which the erbium-doped fiber amplifier (EDFA) was used as a part of the AFPC loop. Owing to the constant filtered signal and the quadrature phase shift delay inside the feedback loop, an optical pass band was uniformly formed. This EDFA attains high performance with a low noise figure simultaneously. The method was successfully applied to the fabrication of practical 12.0 m length of erbium-doped fiber pumped at 980 nm wavelength and 20 dBm power. Experiments prove that the signal gain of the loop remain flat in the range of 18.2 to 22.4 dB with a worst case error of ±0.5 dB and the noise figure was reduced by 2.2 dB at optimal, which correspond to a shortpass range of 40 nm band pass from 1525 nm to 1565 nm in wavelength. Of course, it should be possible to extent the system performance to all pumping configurations for semiconductor optical amplifiers. This provides the simplest and most economical way to transmit a well-defined band of modulated laser signal and to reject all other unwanted radiation. [ABSTRACT FROM AUTHOR]

The article reports on how the authors reached their clinical decision of whether cardiac rehabilitation improved the quality of life of a man with coronary artery disease who received percutaneous transluminal coronary angioplasty (PTCA) with the insertion of a stent. The authors, who are physical therapists, conducted literature searches through the MEDLINE medical electronic database and initially searched with the keywords cardiac rehabilitation, exercise training, and PTCA. The authors summarize the clinical trials that they read. Based on their findings through the literature search, the authors conclude that cardiac rehabilitation did improve patients' quality of life after PTCA.

We previously showed that chronic insulin infusion induces insulin resistance, hyperendothelinemia, and hypertension in rats (C. C. Juan, V. S. Fang, C. F. Kwok, J. C. Perng, Y. C. Chou, and L. T. Ho. Metabolism 48: 465-471, 1999). Endothelin-1 (ET-l), a potent vasoconstrictor, is suggested to play an important role in maintaining vascular tone and regulating blood pressure, and insulin increases ET-1 production in vivo and in vitro. In the present study, BQ-610, a selective endothelin A receptor antagonist, was used to examine the role of ET-1 in insulin-induced hypertension in rats. BQ-610 (0.7 mg/ml; 0.5 ml/kg body wt) or normal saline was given intraperitoneally two times daily for 25 days to groups of rats infused with either saline or insulin (2 U/day via sc-implanted osmotic pumps), and changes in plasma levels of insulin, glucose, and ET-1 and the systolic blood pressure were measured over the experimental period, whereas changes in insulin sensitivity were examined at the end of the experimental period. Plasma insulin and ET-1 levels were measured by RIA, plasma glucose levels using a glucose analyzer, systolic blood pressure by the tail-cuff method, and insulin sensitivity by an oral glucose tolerance test. Our studies showed that insulin infusion caused sustained hyperinsulinemia in both saline- and BQ-610-injected rats over the infusion period. After pump implantation (2 wk), the systolic blood pressure was significantly higher in insulin-infused rats than in saline-infused rats in the saline-injected group (133 ± 3.1 vs. 113 ± 1.1 mmHg, P < 0.05) but not in the BQ-610-injected group (117 ± 1.2 vs. 117 ± 1.8 mmHg). Plasma ET-1 levels in both sets of insulin-infused rats were higher than in saline-infused controls (2.5 ± 0.6 and 2.5 ± 0.8 vs. 1.8 ± 0.4 and 1.7 ± 0.3 pmol/l, P < 0.05). Oral glucose tolerance tests showed that BQ-610 treatment did not prevent the insulin resistance caused by chronic insulin infusion. No significant changes were found in insulin sensitivity and blood pressure in saline-infused rats treated with BQ-610. In a separate experiment, insulin infusion induced the increase in arterial ET-1 content, hypertension, and subsequent plasma ET-1 elevation in rats. These results suggest that, in the insulin infusion rat model, ET-1 plays a mediating role in the development of hypertension, but not of insulin resistance. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis. Since the expression and function of LPA receptors are critical for cellular effects, selective antagonists may represent a potential treatment for a broad range of illnesses, such as cardiovascular diseases, idiopathic pulmonary fibrosis, voiding dysfunctions, and various types of cancers. More new LPA receptor antagonists have shown their therapeutic potentials, although most are still in the preclinical trial stage. This review provided integrative information and summarized preclinical findings and recent clinical trials of different LPA receptor antagonists in cancer progression and resistance. Targeting LPA receptors can have potential applications in clinical patients with various diseases, including cancer. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor‐like lipid mediator that regulates various physiological functions via activating multiple LPA G protein‐coupled receptors. Here, we study the roles of LPA and LPA receptors in premature aging. We report that the protein level of LPA3 was highly downregulated through internalization and the lysosomal degradation pathway in Progerin‐transfected HEK293 cells. By treating Progerin HEK293 cells with an LPA3 agonist (OMPT, 1‐Oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate) and performing shRNA knockdown of the Lpa3r transcript in these cells, we showed that LPA3 activation increased expression levels of antioxidant enzymes, consequently inhibiting ROS accumulation and ameliorating cell senescence. LPA3 was shown to be downregulated in HGPS patient fibroblasts through the lysosomal pathway, and it was shown to be crucial for ameliorating ROS accumulation and cell senescence in fibroblasts. Moreover, in a zebrafish model, LPA3 deficiency was sufficient to cause premature aging phenotypes in multiple organs, as well as a shorter lifespan. Taken together, these findings identify the decline of LPA3 as a key contributor to the premature aging phenotypes of HGPS cells and zebrafish. [ABSTRACT FROM AUTHOR]

Abstract Background Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. Methods The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. Results The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2‐butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2‐butoxyethyl) phosphate (r = 0.88, p

Abstract Purpose Previous research shows conflicting views on the relationship between obesity and osteoporosis, partly due to variations in obesity classification and the nonlinear nature of these relationships. This study investigated the association between adiposity indices and osteoporosis, diagnosed using dual-energy X-ray absorptiometry (DXA), employing nonlinear models and offering optimal thresholds to prevent further bone mineral density decline. Methods In 2019, a prospective study enrolled males over 50 years and postmenopausal women. Anthropometric measurements, blood biochemistry, and osteoporosis measured by DXA were collected. Associations between adiposity indices and osteoporosis were analyzed using a generalized additive model and segmented regression model. Results The study included 872 women and 1321 men. Indices such as abdominal volume index (AVI), visceral adiposity index (VAI), waist circumference (WC), hip circumference, body mass index (BMI), waist-to-hip ratio, and waist-to-height ratio (WHtR) were inversely associated with osteoporosis. In women, the relationship between the risk of osteoporosis and the adiposity indices was U-shaped, with thresholds of WC = 94 cm, AVI = 17.67 cm2, BMI = 25.74 kg/m2, VAI = 4.29, and WHtR = 0.61, considering changes in bone mineral density. Conversely, men exhibited a linear patterns for the inverse association. Conclusion The impact of obesity and adiposity on osteoporosis varies significantly between women and men. In postmenopausal women, the relationship is nonlinear (U-shaped), with both very low and very high adiposity linked to higher osteoporosis risk. In men over 50, the relationship is linear, with higher adiposity associated with lower osteoporosis risk. The study suggests that maintaining specific levels of adiposity could help prevent osteoporosis in postmenopausal women.

Temperature-dependent photoluminescence (PL) and time-resolved photoluminescence (TRPL) are measured for the (Ga1-xZnx)(N1-xOx) solid solution with x = 0.22 to study its luminescence properties. PL result shows that the material exhibits visible luminescence at around 1.87 eV (663 nm) with a broad emission band even at room temperature. The origin of luminescence mechanism can be attributed to the radiative recombination of the electrons bound to donors and the holes bound to acceptors. The investigation from the integrated PL intensity and TRPL as a function of temperature indicates that the activation energy for thermalizing the electrons bound to a donor dominates the luminescence behavior in the (Ga1-xZnx)(N1-xOx) solid solution. [ABSTRACT FROM AUTHOR]

Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, whileMETTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced crosslinking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and downregulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and upregulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated thatMETTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow. [ABSTRACT FROM AUTHOR]

We have studied the variations in the temperature-dependent absorption edge of a bulk InSe-layered semiconductor using photoconductivity (PC) measurements. From both the X-ray diffraction (XRD) and Raman experimental results, the structural phase of the as-prepared InSe sample was confirmed to be γ-polytype. Upon heating from 15 K to 300 K, the absorption edge of PC spectra was found to shift significantly toward lower energy, and the absorption edge as a function of temperature was further analyzed by the Varshni’s relationship and Bose–Einstein empirical equation. The Urbach energy as a function of temperature was obtained by fitting the absorption tail below the absorption coefficient of the PC spectrum, and the effective phonon energy can be derived from the temperature-dependent steepness parameter associated with Urbach energy. Our study indicates that the broadening of the absorption edge in the as-synthesized bulk γ-InSe is caused by a combination of electron/exciton–phonon interactions and thermal/structural disorder.

Background: The painDETECT questionnaire (PDQ) is a useful tool for screening of patients with neuropathic pain. This study aimed to translate the PDQ into the Malay language (PDQ-M) and to achieve cross-cultural adaptation of the questionnaire for use in Malaysia. Methods: The translation and cultural adaptation process of the English version of PDQ was performed based on international guidelines. Subsequently, 97 patients with neuropathic and nociceptive pain based on clinician's diagnoses were recruited to complete three-type numeric rating scale (NRS) of pain followed by PDQ-M. Results: On the basis of cognitive debriefing, several changes of the translated PDQ-M were made. A total of 53 patients with neuropathic pain and 44 with nociceptive pain (54.6% females, 45.4% males, mean age 52.4 years ± 14.2) were recruited into this study. The most common class of analgesia prescribed for patients with neuropathic pain was anti-convulsant, whereas co-analgesic therapy, which includes NSAID and COX-2 inhibitor, was the most prescribed for patients with nociceptive pain. Combination analgesia was used in 32.1% of those with neuropathic pain, and 11.4% of patients with nociceptive pain. The median time taken for respondents to complete the questionnaire was 420 seconds. In regression analysis, active smoking (beta 0.586, p<0.001) and female gender (beta -0.422, p=0.008) were associated with higher PDQ-M scores only among those with neuropathic pain. Conclusions: The Malay version of the painDETECT questionnaire was translated and cross-culturally adapted for ease of understanding among the local population via careful face-to-face interview. [ABSTRACT FROM AUTHOR]

Background/Purpose: Hip fractures are associated with physical dysfunction, and poor quality of life in the elderly. Post-acute care (PAC) would facilitate functional recovery in patients with hip fractures after surgeries. Taiwan has proposed a nationwide PAC program for hip fractures since 2017, but little has been known about its effectiveness. Therefore, this study aimed to evaluate the efficacy and cost-effectiveness of the PAC program for hip fracture patients in Taiwan. Methods: This was a prospective study. Patients aged ≥ 65 years with hip fractures after surgeries were recruited and divided into home-based, hospital-based, and control groups. Outcome measures included pain, physical function (sit-to-stand test, Barthel Index [BI], and Harris hip score [HHS]), and quality of life (EuroQol instrument [EQ-5D]). Direct medical and non-medical costs were recorded. Cost-effectiveness ratio (CER) was calculated as the amount of New Taiwanese Dollars (NTDs) paid per BI and EQ-5D unit improvement. Results: Forty-one patients participated in this study, with 17, 12, and 12 in the home-based, hospital-based, and control groups, respectively. The home-based group showed significant improvements in BI and HHS compared to the controls (p = 0.018 and p = 0.029, respectively). The hospital-based group demonstrated significant improvement in EQ-5D compared to the controls (p = 0.015). The home-based PAC program demonstrated the best CER for BI (NTD 554) and EQ-5D (NTD 41948). Conclusion: Both PAC programs would significantly improve the physical function and quality of life in patients with hip fractures. However, the home-based PAC provided the best CER for BI and EQ-5D.

We report the characteristics of reflectance spectra of the 15- and 20-period ZnTe/ZnSe distributed Bragg reflector grown on GaAs (001) substrates by molecular beam epitaxy. The reflectance spectra measured at various incident angles and polarizations were investigated by the theoretical curves simulated using transfer matrix method. The wavelength variation of the refractive indices described by Sellmeier equation and random thickness model were also considered for the interpretation of the experimentally observed curves. An omnidirectional reflection range defined from the edge of incident-angle-dependent reflection band with TE and TM polarizations is about 15 nm, and is consistent with the observed experimental curves. The results showed that the selected ZnTe and ZnSe materials are suitable for constructing multilayer structures having omnidirectional reflection band. [ABSTRACT FROM AUTHOR]

We reported the photoconduction properties of tungsten disulfide (WS2) nanoflakes obtained by the mechanical exfoliation method. The photocurrent measurements were carried out using a 532 nm laser source with different illumination powers. The results reveal a linear dependence of photocurrent on the excitation power, and the photoresponsivity shows an independent behavior at higher light intensities (400–4000 Wm−2). The WS2 photodetector exhibits superior performance with responsivity in the range of 36–73 AW−1 and a normalized gain in the range of 3.5–7.3 10−6 cm2V−1 at a lower bias voltage of 1 V. The admirable photoresponse at different light intensities suggests that WS2 nanostructures are of potential as a building block for novel optoelectronic device applications.