IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

Nanoscale mapping of temperature-dependent conduction in an epitaxial VO2 film grown on an Al2O3 substrate

Vanadium dioxide (VO₂) is one of the extensively studied strongly correlated oxides due to its intriguing insulator–metal transition near room temperature. In this work, we investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy (C-AFM). We observed that only the regions near the grain boundaries are conductive, producing intriguing donut patterns in C-AFM images. Such donut patterns were observed in the entire measured temperature range (300–355 K). The current values near the grain boundaries increased by approximately two orders of magnitude with an increase in the temperature, which is consistent with the macroscopic transport data. The spatially-varied conduction behavior is ascribed to the coexistence of different monoclinic phases, i.e., M1 and M2 phases, based on the results of temperature-dependent Raman spectroscopy. Furthermore, we investigated the conduction mechanism in the relatively conductive M1 phase regions at room temperature using current–voltage (I–V) spectroscopy and deep data analysis. Bayesian linear unmixing and k-means clustering showed three distinct types of conduction behavior, which classical C-AFM cannot resolve. We found that the conduction in the M1 phase regions can be explained by the Poole–Frenkel mechanism. This work provides deep insight into IMT behavior in the epitaxial VO₂ thin film at the nanoscale, especially the coexistence and evolution of the M1 and M2 phases. This work also highlights that I–V spectroscopy combined with deep data analysis is very powerful in investigating local transport in complex oxides and various material systems.

We investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy and deep data analysis.     

Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells

AIM OF THE STUDY: The traditional Chinese medicine Cordyceps sinensis (CS) (Clavicipitaceae) improves pulmonary function and is used to treat respiratory disease. Here, we compare the efficacy and mechanisms of action of Cordyceps sinensis and Cordyceps militaris (CM) (Clavicipitaceae) in Calu-3 human airway epithelial monolayer model. MATERIAL AND METHODS: The extracts of Cordyceps sinensis and Cordyceps militaris, as well as their isolated compounds, cordycepin and adenosine, stimulated ion transport in a dose-dependent manner in Calu-3 monolayers. In subsequent experiments, transport inhibitor bumetanide and carbonic anhydrase inhibitor acetazolamide were added after Cordyceps sinensis and Cordyceps militaris extracts to determine their effects on Cl- and HCO3- movement. RESULTS: The results suggested that Cordyceps sinensis and Cordyceps militaris extracts may affect the anion movement from the basolateral to apical compartments in the airway epithelia. CONCLUSIONS: Basolateral Na+-K+-2Cl- cotransporter and apical cAMP-dependent cystic fibrosis transmembrane conductance regulator Cl- channel are involved in the process. The results provide the first evidence for the pharmacological mechanism of Cordyceps sinensis and Cordyceps militaris on respiratory tract.     

Gleditsia sinensis thorns inhibit the production of NO through NF-kappaB suppression in LPS-stimulated macrophages

The thorns of Gleditsia sinensis LAM. (Leguminosae) have been used in traditional medicine for the treatment of inflammatory diseases including swelling, suppuration, carbuncle and skin diseases in China and Korea. In this study, we investigated the mechanism responsible for anti-inflammatory effects of Gleditsia sinensis thorns in RAW 264.7 macrophages. The aqueous extract of Gleditsia sinensis thorns (AEGS) inhibited LPS-induced NO secretion as well as inducible nitric oxide synthase (iNOS) expression, without affecting cell viability. Furthermore, AEGS suppressed LPS-induced NF-kappaB activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). These results suggest that AEGS has the inhibitory effects on LPS-induced NO production and iNOS expression in macrophages through blockade in the phosphorylation of MAPKs, following IkappaB-alpha degradation and NF-kappaB activation.     

Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation in a rat model of arthritis induced by Freund's complete adjuvant

Aim of study

In this study, we have investigated the analgesic and anti-arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete adjuvant (FCA).

Materials and methods

Sprague–Dawley rats were induced with monoarthritis by single unilateral injection of FCA into the knee joint. The TCM combination was administered to the rats daily by intraperitoneal injection (50 mg/(kg day)) or via oral administration (500 mg/(kg day)) for 7 days before induction of arthritis and 7 days after. Extension angle that provoked struggling behavior, and size and blood flow of the rat knees were measured to give indexes of allodynia, edema, and hyperemia, respectively. The extent of cell infiltration, tissue proliferation, and erosions of joint cartilage provided additional indexes of the arthritis condition.

Results

FCA injection produced significant allodynia, edema, hyperemia, immune cell infiltration, synovial tissue proliferation, and erosions of joint cartilage in the ipsilateral knees compared with the contralateral saline-injected knees. Intraperitoneal injection of the TCM combination (50 mg/(kg day)) suppressed allodynia, edema, and hyperemia in the inflamed knees, and oral administration (500 mg/(kg day)) suppressed edema and hyperemia. Histological examination showed that the TCM administered by either route reduced immune cell infiltration and erosion of joint cartilage.

Conclusions

These findings suggest the Lingzhi and SMS formulation has analgesic and anti-inflammatory effects in arthritic rat knees, and concur to previous clinical studies that showed the TCM combination reduced pain in rheumatoid arthritis patients, and extends its possible benefit to suppression of inflammatory symptoms in these patients.     

Fabrication of Large-Area Mullite–Cordierite Composite Substrates for Semiconductor Probe Cards and Enhancement of Their Reliability

This work aims to fabricate a large-area ceramic substrate for the application of probe cards. Mullite (M) and cordierite (C), which both have a low thermal expansion coefficient, excellent resistance to thermal shock, and high durability, were selected as starting powders. The mullite–cordierite composites were produced through different composition ratios of starting powders (M:C = 100:0, M:C = 90:10, M:C = 70:30, M:C = 50:50, M:C = 30:70, and M:C = 0:100). The effects of composition ratio and sintering temperature on the density, porosity, thermal expansion coefficient, and flexural strength of the mullite–cordierite composite pellets were investigated. The results showed that the mullite–cordierite composite pellet containing 70 wt% mullite and 30 wt% cordierite sintered at 1350 °C performed exceptionally well. Based on these findings, a large-area mullite–cordierite composite substrate with a diameter of 320 mm for use in semiconductor probe cards was successfully fabricated. Additionally, the changes in sheet resistance and flexural strength were measured to determine the effect of the environmental tests on the large-area substrate such as damp heat and thermal shock. The results indicated that the mullite–cordierite composite substrate was extremely reliable and durable.     

Advanced parental age is an independent risk factor for term low birth weight and macrosomia

We aimed to investigate association between parental age and the risks of term low birth weight and macrosomia.This was a retrospective cohort study using a national database including 2,245,785 term singleton live births with complete parental age data. Old parental age was defined as 35 years or older. Odd ratios (OR) for term low birth weight and macrosomia were analyzed using univariate and multivariate logistic regression analysis.Neonatal sex, maternal occupation, parity, nationality, age, and paternal age were significant factors of term low birth weight and macrosomia, in univariate analysis. In multivariate analysis, old maternal age (≥35 years old) showed increased odds of term low birth weight and macrosomia (aOR = 1.122, 95% CI: 1.083 –1.162; and aOR = 1.166, 95% CI: 1.143 – 1.189, respectively). Similarly, old paternal age (≥35 years old) showed increased odds of term low birth weight and macrosomia (aOR = 1.090, 95% CI: 1.058 –1.122; and aOR = 1.101, 95% CI: 1.083 – 1.119, respectively). Maternal education that lasted more than 12 years had reduced odds of term low birth weight and macrosomia (OR = 0.817, 95% CI: 0.792 –0.842; and OR = 0.894, 95% CI: 0.879 – 0.91, respectively). Paternal education that lasted more than 12 years also had reduced odds of term low birth weight and macrosomia (OR = 0.865, 95% CI: 0.84 –0.892; and OR = 0.897, 95% CI: 0.881 – 0.913, respectively).This study suggests that not only maternal age but also paternal age are significantly associated with term low birth weight and macrosomia. In addition, parental education levels are also associated with term low birth weight and macrosomia.     

New series of isoniazid hydrazones linked with electron-withdrawing substituents

A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L⁻¹) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125–0.250 μmol L⁻¹), high value of selectivity index (SI) and IC₅₀ between 0.0218 and 0.326 mmol L⁻¹. Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.