Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria) and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM) in chicken embryo and human vascular endothelial cells (HUVECs). The matrix metalloproteinase-2 (MMP-2) activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS), exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs

Localized tail state distribution and hopping transport in ultrathin zinc-tin-oxide thin film transistor

Carrier transport properties of solution processed ultra thin (4 nm) zinc-tin oxide (ZTO) thin film transistor are investigated based on its transfer characteristics measured at the temperature ranging from 310K to 77K. As temperature decreases, the transfer curves show a parellel shift toward more postive voltages. The conduction mechanism of ultra-thin ZTO film and its connection to the density of band tail states have been substantiated by two approaches, including fitting logarithm drain current (log ID) to T-1/3 at 310K to 77K according to the two-dimensional Mott variable range hopping theory and the extraction of density of localized tail states through the energy distribution of trapped carrier density. The linear dependency of log ID vs. T-1/3 indicates that the dominant carrier transport mechanism in ZTO is the variable range hopping. The extracted value of density of tail states at the conduction band minimum is 4.75 x 10(20) cm(-3) eV(-1) through the energy distribution of trapped carrier density. The high density of localized tail states in the ultra thin ZTO film is the key factor leading to the room-temperature hopping transport of carriers among localized tail states. Published by AIP Publishing

Psoas muscle area is an independent survival prognosticator in patients undergoing surgery for long-bone metastases

Background: Predictive analytics is gaining popularity as an aid to treatment planning for patients with bone metastases, whose expected survival should be considered. Decreased psoas muscle area (PMA), a morphometric indicator of suboptimal nutritional status, has been associated with mortality in various cancers, but never been integrated into current survival prediction algorithms (SPA) for patients with skeletal metastases. This study investigates whether decreased PMA predicts worse survival in patients with extremity metastases and whether incorporating PMA into three modern SPAs (PATHFx, SORG-NG, and SORG-MLA) improves their performance. Methods: One hundred eighty-five patients surgically treated for long-bone metastases between 2014 and 2019 were divided into three PMA tertiles (small, medium, and large) based on their psoas size on CT. Kaplan–Meier, multivariable regression, and Cox proportional hazards analyses were employed to compare survival between tertiles and examine factors associated with mortality. Logistic regression analysis was used to assess whether incorporating adjusted PMA values enhanced the three SPAs' discriminatory abilities. The clinical utility of incorporating PMA into these SPAs was evaluated by decision curve analysis (DCA). Results: Patients with small PMA had worse 90-day and 1-year survival after surgery (log-rank test p 0.5 after the addition of adjusted PMA to these SPAs. Conclusions: Decreased PMA on CT is associated with worse survival in surgically treated patients with extremity metastases, even after controlling for three contemporary SPAs. Physicians should consider the additional prognostic value of PMA on survival in patients undergoing consideration for operative management due to extremity metastases

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan

Aims/Introduction To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. Materials and Methods In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. Results A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by −0.73% (95% confidence interval [CI] −0.80, −0.67), body weight was -1.61 kg (95% CI −1.79, −1.42), and systolic/diastolic blood pressure by −3.6/−1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (−0.82%) than switched therapy (−0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. Conclusions In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Delta Cord as a Radiological Localization Sign of Postoperative Adhesive Arachnoiditis: A Case Report and Literature Review

Postoperative adhesive arachnoiditis is an inflammatory response of the spinal leptomeninges that occurs after surgery and results in scar formation in the avascular nature of the arachnoid layer. Clinical manifestations of postoperative adhesive arachnoiditis include pain, sensory deficits, motor dysfunction, reflex abnormalities, and bladder or bowel impairment. In magnetic resonance imaging scans, signs of postoperative adhesive arachnoiditis can vary; however, some indicators can assist surgeons in locating the lesion accurately and, thus, in planning effective surgical interventions. This paper reports the case of a 37-year-old man with postoperative adhesive arachnoiditis after two surgeries for Chiari I malformation. This case illustrates the progressive development of the “delta cord sign”, which refers to the formation of a thick arachnoid band causing the spinal cord to adopt a triangular shape in the axial view. This phenomenon is accompanied by the sequential occurrence of syringomyelia. During intraoperative examination, we identified the presence of the delta cord sign, which had been formed by an arachnoid scar that tethered the dorsal spinal cord to the dura. This discovery enabled us to precisely pinpoint the location of the arachnoid scar and thus provided us with guidance that enabled us to avoid unnecessary exploration of unaffected structures during the procedure. Other localization signs were also reviewed

Effect of dimethoxycurcumin beyond degradation of androgen receptor

AbstractBackgroundAndrogen receptor (AR) plays an important role in the pathogenesis of prostate cancer and acne. Dimethoxycurcumin is a newly found enhancer of AR degradation, which highlights its potential for treatment of AR-related disorders. Follicular hyperkeratosis is one essential factor in the complicated pathogenesis of acne, in which some dermatopathologists have observed overexpressed psoriasin, an activator protein (AP)-1-targeted gene product.MethodsWe used the HaCaT cell line to determine the effect of dimethoxycurcumin on expression of AP-1 subunits and AP-1-targeted genes, psoriasin and cyclin D1, by luciferase reporter assay, western blotting and reverse transcriptase polymerase chain reaction. We also used flow cytometry to analyze changes in cell populations in response to increasing dose of dimethoxycurcumin.ResultsDimethoxycurcumin inhibits psoriasin promoter activities at the basal or enhanced level induced by exogenous c-Jun/c-Fos heterodimeric AP-1. Expression of endogenous c-Jun and c-Fos, two important subunits of dimeric AP-1, was downregulated at the mRNA or protein level by dimethoxycurcumin in HaCaT cells. Inhibition of endogenous cyclin D1 occurred at both the transcript and protein levels. A shift of subpopulations of cells into sub-G1 phase was consistent with reduced cyclin D1, corresponding to dimethoxycurcumin treatment.ConclusionIdentification of AP-1 transcription factor as a specific target for dimethoxycurcumin-downregulated molecules in human keratinocytes suggests that this novel chemical modulates various AP-1–related events in the epidermis, including cell-cycle progression and its role as an inflammatory reservoir. We provided evidence for this because expression of cyclin D1 and psoriasin, two AP-1-regulated gene products, was inhibited by dimethoxycurcumin in HaCaT and HeLa cells. Cyclin D1 is an important cell-cycle regulator, whereas psoriasin is a potent cytokine for innate immunity. We anticipate that more diseases will benefit from this curcumin analog in the near future

Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer

Objective: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). Materials and methods: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. Results: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-müllerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). Conclusion: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine

Exploring the Influence of Solvents on Electrochemically Etched Porous Silicon Based on Photoluminescence and Surface Morphology Analysis

Porous silicon (PSi) has promising applications in optoelectronic devices due to its efficient photoluminescence (PL). This study systematically investigates the effects of various organic solvents and their concentrations during electrochemical etching on the resulting PL and surface morphology of PSi. Ethanol, n-butanol, ethylene glycol (EG) and N,N-dimethylformamide (DMF) were employed as solvents in hydrofluoric acid (HF)-based silicon etching. The PL peak position exhibited progressive blue-shifting with increasing ethanol and EG concentrations, accompanied by reductions in the secondary peak intensity and emission linewidth. Comparatively, changes in n-butanol concentration only slightly impacted the main PL peak position. Additionally, distinct morphological transitions were observed for different solvents, with ethanol and n-butanol facilitating uniform single-layer porous structures at higher concentrations in contrast to the excessive etching caused by EG and DMF resulting in PL quenching. These results highlight the complex interdependencies between solvent parameters such as polarity, volatility and viscosity in modulating PSi properties through their influence on surface wetting, diffusion and etching kinetics. The findings provide meaningful guidelines for selecting suitable solvent conditions to tune PSi characteristics for optimized device performance