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Abstract Lung squamous cell carcinoma (LUSC) represents a minor proportion of nonsmall cell lung cancer (NSCLC) harboring a poor prognosis. Herein, retrospective medical record research was performed to investigate real‐world treatment patterns and identify the prognostic factors among LUSC patients. A total of 173 patients with a median age of 68 years were enrolled for analysis. Males were predominant (n = 143, 83%) and current or ex‐smokers contributed to 78% of the entire cohort. Pleura and lung were the most common metastatic sites, whereas brain metastasis was only 7%. After diagnosis, however, only 107 patients (62%) had received first‐line chemotherapy. In the chemotherapy cohort, median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 11.1 months, respectively. After multivariable analysis, bone metastasis and the use of first‐line single‐agent chemotherapy independently predicted shorter PFS. For baseline characteristics, male sex, metastasis to lung, pleura, liver, and bone independently predicted worse OS. Regarding the treatment pattern, patients who had undergone standard first‐line doublet therapy and employed targeted therapies after disease progression linked to longer OS. In the real world, even those who underwent chemotherapy still had poor outcome. The findings may help clinicians to orchestrate the treatment strategies for LUSC patients and provide further direction of large‐scale studies.

The effects of Lycium barbarum polysaccharides (LBP) and plasmon-activated water (PAW) against IFN-γ/TNF-α induced inflammation in human colon Caco-2 cells were investigated. Cells were divided into the control, induction, LBP treatment (100–500 μg/mL), and combination groups with PAW. Inflammation was induced 24 h with 10 ng/mL IFN-γ when cell confluency reached >90%, and various doses of LBP with or without PAW were treated for 3 h, and subsequently 50 ng/mL TNF-α was added for another 24 h to provoke inflammation. Combination of LBP with PAW significantly decreased the secretion of IL-6 and IL-8. Cyclooxygenase-2 and inducible NO synthase expression was attenuated in all LBP-treated groups with or without PAW. NLRP3 inflammasome and related protein PYCARD expression were inhibited by LBP at the highest dose (500 μg/mL). All doses of LBP alone significantly decreased p-ERK expression, but combination with PAW increased p-ERK expression compared to those without PAW. Additionally, 250 and 500 μg/mL of LBP with or without PAW inhibited procaspase-3/caspase-3 expression. Therefore, LBP possesses anti-inflammation and anti-apoptosis by inhibiting the secretion of inflammatory cytokines and the expression of NLRP3 inflammasome-related protein. The combination with PAW exerts additive or synergistic effect on anti-inflammation.

Background: To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. Methods: This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. Results: Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are ‘true’ totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely ‘cluster 3’, as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.

Mutations in PLA2G6 gene cause PLA2G6-associated neurodegeneration, including recessive familial type 14 of Parkinson's disease (PARK14). Previously, we identified PARK14 patients with compound heterozygous c.991G > T/c.1077G > A (p.D331Y/p.M358IfsX) mutations. The c.1077G > A mutation led to a four base-pairs deletion and frameshift mutation (p.M358IfsX) of PLA2G6 mRNA. We established induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a female patient with compound heterozygous c.991G > T/c.1077G > A (p.D331Y/ p.M358IfsX) mutations by using Sendai-virus delivery system. The iPSCs exhibited pluripotency and in vivo differentiation potential. The iPSCs can be used for studying the molecular pathogenic mechanism of PARK14.

MicroRNAs (miRs) downregulate or upregulate the mRNA level by binding to the 3′-untranslated region (3′UTR) of target gene. Dysregulated miR levels can be used as biomarkers of Parkinson’s disease (PD) and could participate in the etiology of PD. In the present study, 45 brain-enriched miRs were evaluated in serum samples from 50 normal subjects and 50 sporadic PD patients. The level of miR-204-5p was upregulated in serum samples from PD patients. An upregulated level of miR-204-5p was also observed in the serum and substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Expression of miR-204-5p increased the level of α-synuclein (α-Syn), phosphorylated (phospho)-α-Syn, tau, or phospho-tau protein and resulted in the activation of endoplasmic reticulum (ER) stress in SH-SY5Y dopaminergic cells. Expression of miR-204-5p caused autophagy impairment and activation of c-Jun N-terminal kinase (JNK)-mediated apoptotic cascade in SH-SY5Y dopaminergic cells. Our study using the bioinformatic method and dual-luciferase reporter analysis suggests that miR-204-5p positively regulates mRNA expression of dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) by directly interacting with 3′UTR of DYRK1A. The mRNA and protein levels of DYRK1A were increased in SH-SY5Y dopaminergic cells expressing miR-204-5p and SN of MPTP-induced PD mouse model. Knockdown of DYRK1A expression or treatment of the DYRK1A inhibitor harmine attenuated miR-204-5p-induced increase in protein expression of phospho-α-Syn or phospho-tau, ER stress, autophagy impairment, and activation of JNK-mediated apoptotic pathway in SH-SY5Y dopaminergic cells or primary cultured dopaminergic neurons. Our results suggest that upregulated expression of miR-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated ER stress and apoptotic signaling cascade.

Objective: The purpose of the study is to report and to analyze the complications following intratympanic injections (ITI) of steroids. The occurrence rate of complications at different ITI sites, four quadrants of eardrum, was also compared. Methods: A retrospective clinical review in a medical center. Each patient received ITI twice in a week for 2â3 consecutive weeks as a salvage therapy for sudden sensorineural hearing loss. Post-injection complications, especially transient dizziness and vertigo, were recorded. Patients with acute or chronic vertigo episodes in 1 month were excluded. Results: A total of 59 patients with sudden sensorineural hearing loss and a total of 278 times of ITI were performed in 1 year. The post-injection complications included pain, tongue numbness, transient dizziness, vertigo, tinnitus, and a small persistent perforation. There was no significant difference in the occurrence of these complications between the injections sites on the 4 quadrants of the tympanic membrane. However, there was statistical significance in the post-injection vertiginous episode after IT injections to posterior-inferior quadrant (Q3) and posterior-superior quadrant (Q4) compared to anterior-superior quadrant (Q1) and anterior-inferior quadrant (Q2) (PÂ =Â 0.0113). Conclusion: IT injection is recommended to be applied to the Q2 since the Q1 and Q4 injections are more likely to induce the adverse effect of tongue numbness, while the Q3 and Q4 areas are more likely to induce post-injection vertigo. Keywords: Intratympanic injection, Sudden deafness, Complications, Vertigo

Background/AimsBalsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-κB (NF-κB) activity. Parthenolide (PT) inhibits NF-κB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-κB in a representative human colorectal carcinoma cell line, HCT116.MethodsWe counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis.ResultsPT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-κB p65 subunit and the phosphorylation of inhibitor of NF-κB. Moreover, PT and balsalazide dramatically enhanced NF-κB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8.ConclusionsCombination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.

Background: Neuromuscular electric stimulation (NMES) induces repeated muscular contraction, possibly promoting the perfusion/oxygenation of the regional tissues. It remains unclear how NMES influences vascular hemodynamic property and segmental fluid distribution/composition in paretic extremities of hemiplegic patients. Methods: Eleven hemiplegic patients aged 62.6 ± 12.5 years in the subacute stage of stroke received NMES for paretic wrist extensor and flexor muscles 30 min daily, 5 days per week for 4 weeks. The non-paretic upper extremities (NPUE) that did not receive NMES served as control. Distribution of fluid to intra/extracellular milieu and arterial hemodynamic properties were determined by using the multi-frequency bioelectrical impedance and pulse wave analysis, respectively. Results: Compared with NPUE without NMES, paretic upper extremity (PUE) with NMES revealed a significantly less decrease in arterial blood flow, impedance quotient, slope quotient, and less increase in crest width and crest time of arterial pulse wave. NMES for 4 weeks increased body cell mass in PUE. Furthermore, NPUE without NMES reduced intracellular water, whereas PUE with NMES retarded loss of intracellular water after stroke. Conclusion: NMES therapy increases body cell mass, attenuates reduction of intracellular water, and alleviates arterial hemodynamic disturbance in PUE in subacute stroke. However, stroke-related physical deconditioning may negatively regulate body composition and impair hemodynamic function in NPUE.

The first electrochemical method to prepare Au-containing nancomplexes with controllable particle size via roughening gold substrates with oxidation-reduction cycles (ORC) of various scans in 0.1 N KCI aqueous solutions without the addition of any stabilizer is reported. The prepared nanocomplex size increases from 2 to 50 nm with the increase of the ORC scan from 25 to 400 cycles.

The first electrochemical pathway to prepare Au-containing nanocomplexes with the mean diameter of 2 nm in 0.1 N KCI aqueous solutions without addition of any stabilizer is reported. The electrochemical activities of AuCI4-nanocomplexes existing in the aqueous solution during oxidation-reduction cycles (ORC) treatment for roughening Au substrate are found that can be used to fabricate Au/PPy core-shell nanocomposites with extremely high conductivities and further prepare elemental Au(0) nanoparticles.

A strategy to electrodeposit polypyrrole (PPy) or roughened silver substrates, accomplished by a triangular-wave oxidation-reduction cycle (ORC) for three scans in an aqueous solution containing 0.1 N KCl is studied. Different view on how Raman spectroscopy has proved to be an effective means to evaluate the structure situation of PPy in various states.

Copper is underpotentially deposited on electrochemically roughened Au(111) by using the applications of self-assembled monolayers (SAMs). The characteristics of autopolymerizaion and electropolymerization are studied.

The polypyrrole (PPy) films were electrochemically deposited on roughened gold substrates with different predominant crystalline orientations of (111) and (220) respectively. The result indicates that the (220) crystalline orientation of gold was partially changed into (111) one after gold was roughened with oxidation-reduction cycles (ORC) treatment.

The first electrochemical oxidation-reduction cycle procedure to roughen gold substrates in 0.1 N HCl aqueous solutions containing 1 nM rutile TiO2 nanoparticles under the irradaition of UV light is presented. The SERS spectrum of polypyrrole electrodeposited on the corresponding roughened gold substrate exhibits a 5-fold higher intensity compared to that without he contribution of TiO2 nanoparticles.

Polypyrrole (PPy) films were electrodeposited on electrochemically roughened gold substrates modified by argon plasma treatment. The surface-enhanced Raman scattering (SERS) spectroscopy of polypyrrole electrodeposited on this roughened gold substrate modified by argon plasma treatment exhibits a higher intensity by 8-fold, as compared with the SERS of PPy electrodeposited on an unmodified roughened gold substrate.

Size-controlled gold nanoparticles, ranging from 2 to 15 nm in diameter, were prepared from gold substrates in 0.1 N HCl aqueous solutions without the addition of any stabilizers by sonoelectrochemical methods. It was observed that the ratio of gold nanoparticles to gold containing nanocomplexes in solutions could be controlled by adjusting the sonoelectrochemical reduction time.

A study in which polypyrrole (PPy) films are electrodeposited on gold substrates roughened by a triangular-wave oxidation-reduction cycle (ORC) in 0.1 N HCl aqueous solution is reported. The surface-enhanced Raman scattering (SERS) spectroscopy of PPy with Au monolayers/PPy/roughened Au substrate is described that exhibits a higher intensity by 1 order of magnitude and a better resolution, as compared with the normal SERS of PPy electrodeposited on a roughened Au substrate.

Background/Aims: Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. Methods: SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death. The wound healing, Transwell migration, and Matrigel invasion assays were performed to investigate the effect of PT on cell migration/invasion. Western blotting was used to establish the signaling pathway of apoptosis and cell migration/invasion. Results: PT exerts antiproliferative effect and induces apoptotic cell death of SW620 cells. In addition, PT prevents cell migration and invasion in a dose-dependent manner. Moreover, PT markedly suppressed migration/invasion-related protein expression, including E-cadherin, ß-catenin, vimentin, Snail, cyclooxygenase-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 in SW620 cells. PT also inhibited the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and activated apoptosis terminal factor (caspase-3) in a dose-dependent manner. Conclusions: Our results suggest that PT is a potential novel therapeutic agent for aggressive CRC treatment. [ABSTRACT FROM AUTHOR]

Recently, the nuclear factor (NF)-κB inhibitor parthenolide (PT) was identified as a promising anticancer agent for the promotion of cancer cell apoptosis. Additionally, our previous study demonstrated that PT administration suppresses tumor growth in a xenograft model of colorectal cancer cells via regulation of the B-cell lymphoma-2 (Bcl-2) family. However, the role of PT in the development of colitis-associated colon cancer (CAC) is poorly understood. Therefore, the aim of the present study was to investigate the effects of PT administration on CAC using a murine model. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were administered to induce experimental CAC in the following three groups of treated mice: i) AOM and DSS plus vehicle; ii) AOM, DSS and 2 mg/kg PT; and iii) AOM, DSS and 4 mg/kg PT. It was demonstrated that the histological acuteness of AOM/DSS-induced CAC was significantly reduced following the administration of PT, resulting in decreased NF-κB p65 expression levels via a blockade of phosphorylation and subsequent degradation of inhibitor of κB-α (IκBα). Furthermore, PT administration appeared to enhance the process of carcinogenesis via the downregulation of the antiapoptotic proteins Bcl-2 and Bcl-extra large, mediated by inhibition of NF-κB activation. Apoptosis and caspase-3 expression were markedly increased in the PT-treated group. These findings indicate that PT inhibits IκBα phosphorylation and NF-κB activation, resulting in the initiation of apoptosis and the eventual suppression of CAC development. The beneficial effects of PT treatment observed in the experimental CAC model indicate the potential chemopreventive and therapeutic role of PT in CAC. [ABSTRACT FROM AUTHOR]

In this study, we examine the effect of chemokine (C-C motif) ligand 5 (CCL5)/Regulated on Activation Normal T cell Expressed and Secreted (RANTES), a pro-inflammatory cytokine on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We found CCL5 expression was increased during osteogenic differentiation of hMSCs and CCL5 expression is dependent on the presence of dexamethasone. Knocking down endogenous CCL5 expression blocked osteogenesis, as revealed by decreasing alkaline phosphatase (ALP) activity and a reduction in the expression levels of ALP, bone sialoprotein (BSP), and osteopontin (OPN). Of note, the overexpression of CCL5 was sufficient to increase ALP expression and activity. Moreover, the down-regulation of chemokine (C-C motif) receptor 1 (CCR1), one of the CCL5 receptors, significantly decreased the osteogenesis of hMSCs. Interestingly, the down-regulation of CCR1, but not CCL5, was sufficient to affect the cell numbers during the process of osteogenesis. Our findings reveal that both CCL5 and CCR1 are required for osteogenesis of human MSCs, CCL5 is sufficient for the osteogenesis, and provide a novel link between dexamethasone and CCL5 in human osteogenesis. [ABSTRACT FROM AUTHOR]

Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we report innovative breakthroughs for efficient and safe HD by using a plasmon-induced dialysate comprising Au nanoparticles (NPs)-treated (AuNT) water that is distinguishable from conventional deionized (DI) water. The diffusion coefficient of K3Fe(CN)6 in saline solution can be significantly increased from 2.76, to 4.62 × 10-6 cm s-1, by using AuNT water prepared under illumination by green light-emitting diodes (LED). In vitro HD experiments suggest that the treatment times for the removals of 70% BUN and Crea are reduced by 47 and 59%, respectively, using AuNT water instead of DI water in dialysate, while additionally suppressing NO release from lipopolysaccharide (LPS)-induced inflammatory cells. [ABSTRACT FROM AUTHOR]

In the electrochemical oxidation–reduction cycles (ORC) treatment for preparing surface-enhanced Raman scattering (SERS)-active substrates, chloride electrolyte was generally selected because this facilitates the metal dissolution-deposition process that is known to produce SERS-active roughened surfaces. In this work, SERS-active Ag substrates were electrochemically prepared in HCl solutions containing supplemental electrolytes of HNO3. Encouragingly, the SERS of Rhodamine 6G (R6G) adsorbed on this developed Ag substrate exhibits a higher intensity by 15-fold of magnitude, as compared with that of R6G adsorbed on a roughened Ag substrate prepared in HCl solution. Moreover, limit of detection for probe molecules of R6G can be significantly reduced to 2 × 10−15M. Also, the significant improvements in thermal stability and anti-aging of SERS-active Ag substrates proposed in this work are observed. [ABSTRACT FROM AUTHOR]

In this work, different conditions for electrochemically roughening silver substrates were investigated to obtain the best surface-enhanced Raman scattering (SERS) performance. Experimental results indicate that Ag electrodes can be cycled in deoxygenated aqueous solutions containing 0.1 N HCl from −0.3 to +0.2 V vs. Ag/AgCl at 25 mV s−1 for five scans to obtain the strongest SERS effects. Using this substrate, the SERS intensity of adsorbed Rhodamine 6G (R6G) can be increased 9-fold, compared with that of R6G adsorbed on an Ag substrate prepared using the general literature methods. Moreover, the SERS enhancement capabilities of the newly developed Ag substrate seriously decays at 200 °C, compared to 125 °C for the generally roughened Ag substrates. The reduction of the SERS intensity upon aging is also lessened for this newly developed substrate. Further investigations revealed that surface morphology and the Cl content on the roughened Ag substrates have significant influence on the corresponding SERS performances. [ABSTRACT FROM AUTHOR]