Dysregulation of sphingolipid metabolism in pain.

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

Preparation and characterization of starch/PBAT film containing hydroxypropyl-ß-cyclodextrin/ethyl lauroyl arginate/cinnamon essential oil microcapsules and its application in the preservation of strawberry.

Cinnamon essential oil (CEO) was emulsified by hydroxypropyl-ß-cyclodextrin/ ethyl lauroyl arginate (HPCD/LAE) complex to make nanoemulsions, which were then incorporated into maltodextrin (MD) to prepare HPCD/LAE/CEO/MD microcapsules by spray drying. The starch/polybutylene adipate terephthalate (starch/PBAT, SP) based extrusion-blowing films containing above microcapsules were developed and used as packaging materials for strawberry preservation. The morphology, encapsulation efficiency, thermal and antibacterial properties of microcapsules with different formulations were investigated. The effects of microcapsules on the physicochemical and antimicrobial properties of SP films were evaluated. When the formula was 4 % HPCD/LAE-3% CEO-10% MD (HL-3C-MD), the microcapsule had the smallest particle size (3.3 µm), the highest encapsulation efficiency (84.51 %) of CEO and the best antibacterial effect. The mechanical and antimicrobial properties of the SP film were enhanced while the water vapor transmittance and oxygen permeability decreased with the incorporation of HL-3C-MD microcapsules. The films effectively reduced the weight loss rate (49.03 %), decay rate (40.59 %) and the total number of colonies (2.474 log CFU/g) and molds (2.936 log CFU/g), thus extending the shelf life of strawberries. This study revealed that the developed SP films containing HPCD/LAE/CEO microcapsules had potential applications in degradable bioactive food packaging materials.

RASSF1A promotes radiosensitivity in nasopharyngeal carcinoma by promoting FoxO3a and inhibiting the Nrf2/TXNRD1 signaling pathway.

Radiotherapy is widely used as the first-line treatment for nasopharyngeal carcinoma (NPC). However, the resistance of some patients to treatment lowers its clinical effectiveness. Compared to typical epithelial cells, NPC markedly lowers the Ras-association domain family 1A (RASSF1A) protein expression. RASSF1A overexpression sensitizes NPC cells to radiotherapy. Mechanistically, RASSF1A promotes the expression of Forkhead box O3a (FoxO3a) in the nucleus and inhibits the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway via binding to the Kelch-like ECH-associated protein 1 (Keap1) promoter. Through elevating intracellular ROS levels, RASSF1A overexpression inhibits the expression of thioredoxin reductase 1 (TXNRD1), a crucial Nrf2 target gene, and increases NPC sensitivity to radiation. Immunohistochemical staining of NPC tissue sections revealed that the expression of RASSF1A is negatively correlated with that of TXNRD1. The traditional Chinese medicine component andrographolide (AGP), which induces RASSF1A expression, increased the sensitivity of NPC cells to radiotherapy in vitro and in vivo. Our findings implied that RASSF1A increases the sensitivity of NPC to radiation by increasing FoxO3a expression in the nucleus, inhibiting the Nrf2/TXNRD1 signaling pathway, and elevating intracellular ROS levels. AGP targets RASSF1A and may be a promising adjuvant sensitizer for enhancing radiosensitivity in NPC.

Effects of different content of EGCG or caffeic acid addition on the structure, cooking, antioxidant characteristics and in vitro starch digestibility of extruded buckwheat noodles.

The effects of different types and content of polyphenol addition on the structure, cooking, antioxidant characteristics and in vitro starch digestibility of extruded buckwheat noodles were investigated in this study. The result showed epigallocatechin-3-gallate (EGCG) was more easily combined with starch to form complex than caffeic acid, and amylose tended to be combined with polyphenols to form more complex. Amylose had a protective effect on polyphenols during extrusion process, which led to a significant increase of polyphenol content and antioxidant activity of extruded noodles. The addition of polyphenol and high amylose corn starch (HACS) improved the cooking quality of extruded buckwheat noodles. The extruded buckwheat noodles with 20 % HACS and 1 % EGCG had the lowest cooking loss of 6.08 %. The addition of EGCG and HACS increased the content of resistant starch and reduced predicted glycemic index (pGI). The noodles with 20 % HACS and 3 % EGCG had the lowest pGI (63.38) and the highest resistant starch (RS) content (61.60 %). This study provides a theoretical basis for the development of low pGI extruded buckwheat noodles.

Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.

Nasopharyngeal carcinoma (NPC) is a type of head and neck tumor with noticeable regional and ethnic differences. It is associated with Epstein-Barr virus infection and has a tendency for local and distant metastasis. NPC is also highly sensitive to radiotherapy and chemotherapy. Over 70% of patients present with locoregionally advanced disease, and distant metastasis is the primary reason for treatment failure. A signal transducer and activator of transcription 3 (STAT3) promotes NPC oncogenesis through mechanisms within cancerous cells and their interactions with the tumor microenvironment, which is critical in the initiation, progression, and metastasis of NPC. Further, p-STAT3 is strongly associated with advanced NPC. Recent research on STAT3 has focused on its expression at the center of various oncogenic pathways. Here, we discuss the role of STAT3 in NPC and its potential therapeutic inhibitors and analogs for the treatment and control of NPC.

The IL-22 gene rs2227478 polymorphism significantly decreases the risk of colorectal cancer in a Han Chinese population.

To examine the role of IL-22 gene in colorectal cancer (CRC) susceptibility, we identified causative genetic polymorphisms in promoter region of IL-22 gene and explored the mechanism underlying their contribution to CRC development in a Chinese population of Hubei province. 13 target single nucleotide polymorphisms (SNPs) in IL-22 gene promoter were genotyped in 787 CRC patients (426 colon cancer and 361 rectal cancer) and 800 normal controls. The results demonstrated that the rs2227478 T > C polymorphism was significantly associated with the risk of colon cancer, rectal cancer and CRC, and the C allele was associated with a decreased cancer risk than the T allele. In CRC tissue samples, the subjects with CT+CC genotypes of rs2227478 had lower levels of IL-22 mRNA than the subjects with TT genotypes. Further functional analysis revealed that the transcription repressor Sp1 possessed a higher binding affinity to the C allele than the T allele. Collectively, the rs2227478 T > C is a functional genetic polymorphism that significantly reduces the CRC risk in a Han Chinese population.

Characterization of chitosan film with cinnamon essential oil emulsion co-stabilized by ethyl-Nα-lauroyl-l-arginate hydrochloride and hydroxypropyl-ß-cyclodextrin.

To improve the antimicrobial properties of chitosan films, cinnamon essential oil (CEO) nanoemulsion (1% and 3% v/v CEO) stabilized by ethyl-Nα-lauroyl-l-arginate hydrochloride (LAE) alone or co-stabilized by LAE and hydroxypropyl-ß-cyclodextrin (HPCD) were incorporated into chitosan matrix. The micromorphology, physical and antimicrobial properties of the composite films were compared. The dense structure of the CEO nanoemulsion co-stabilized by LAE and HPCD reduced the water vapor permeability and water content. The incorporation of the CEO nanoemulsion co-stabilized by LAE and HPCD, reduced the adverse effects of CEO on the mechanical properties and microstructure of the film, and even slightly increased the tensile strength. In addition, the antimicrobial properties of chitosan films were enhanced due to the encapsulation and emulsification effect of HPCD and LAE on CEO. This work indicated that the prepared chitosan based edible films had the potential to be used in the field of food packaging to improve food safety.

Replication study and meta-analysis of selected genetic variants and polycystic ovary syndrome susceptibility in Asian population.

PURPOSE: Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous association studies have identified multiple PCOS-susceptible loci, but there is no consistent conclusion, which calls for further investigations. METHODS: In the present case-control study, FSHR gene variants (rs2268361, rs6165, and rs6166), LHCGR gene variant (rs13405728), THADA gene variant (rs13429458), DENND1A gene variants (rs10818854 and rs2479106), and INSR gene variants (rs2059807 and rs1799817) were genotyped with Sanger sequencing in a total of 400 PCOS women and 480 healthy women. RESULTS: After Bonferroni correction, our results showed that rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807 were significantly associated with PCOS risk in Chinese women. To improve the statistical strength, a further meta-analysis in Asian population was conducted. Although rs6166 and rs1799817 were not associated with PCOS risk in the present study, they were identified to be strongly associated with PCOS risk in the pooled Koreans and Chinese respectively. No significant association with PCOS risk was consistently found for rs2268361 or rs6165. Moreover, the pooled results further confirmed the significant association with PCOS risk for rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807. CONCLUSIONS: Collectively, the rs6166, rs13405728, rs13429458, rs2479106, rs10818854, rs2059807, and rs1799817 may indeed be the genetic risk factors for PCOS in Asian population, which requires further investigation using larger independent sets of samples in different ethnic populations.

Effects of zein stabilized clove essential oil Pickering emulsion on the structure and properties of chitosan-based edible films.

Clove essential oil (CLO) Pickering emulsions were prepared with zein colloid particles as stabilizer, and the effects of CLO Pickering emulsion incorporation on the structure, mechanical, barrier and antimicrobial properties of chitosan-based edible films were explored. CLO Pickering emulsions with 3% w/v zein and 50% v/v CLO had smaller particle size and more even distribution. Incorporation of CLO Pickering emulsion in the films decreased the water vapor permeability and tensile strength, but the elongation at break firstly increased then decreased with the maximum value of 19.2% when the content of emulsion was 0.4%. Scanning electron microscopy revealed the formation of microstructure-sized holes in the films by the addition of CLO Pickering emulsion. The emulsified oil droplets were uniformly distributed, due to the good compatibility between oil phase and chitosan matrix. The antimicrobial properties of the films were strengthened by CLO Pickering emulsion incorporation and mainly depended on its concentration.

Characterization of chitosan based polyelectrolyte films incorporated with OSA-modified gum arabic-stabilized cinnamon essential oil emulsions.

Octenyl succinic anhydride (OSA) modified gum arabic (GA) was synthesized and used as an emulsifier to stabilize cinnamon essential oil (CEO) emulsions. The structure and properties of chitosan based polyelectrolyte films incorporated with above OSA-GA stabilized CEO emulsions were investigated. Results showed that OSA modification introduced the hydrophobic groups, which greatly influenced the emulsification capability of GA. The antimicrobial activities of CEO emulsions were significantly enhanced by the synergistic effect of GA modification and ultrasonic treatment. When the proportions of CEO emulsion increased, the improved water barrier properties but deteriorated tensile properties of films were observed. The retention of CEO during storage was prolonged to 20 days and the release of CEO in food simulant was effectively inhibited as emulsion ratios increased to 20%, indicating the effectiveness of the system for CEO delivery. As a result, the antimicrobial activities of films significantly enhanced with the innovative incorporation of OSA-GA stabilized CEO emulsions.