Insights into the interactions between etheric compounds and myofibrillar proteins using multi-spectroscopy, molecular docking, and molecular dynamics simulation.

This study aimed to examine how the addition of etheric compounds (EC) affects the characteristics of myofibrillar proteins (MP) and to understand underlying interaction mechanisms. Fourier transform infrared spectroscopy confirmed that the EC-MP complex was formed through hydrogen bonding. The addition of EC resulted in an increase in the α-helix content and a decrease in the ß-sheet content of MP, which would promote the protein unfolding. The unfolding of MP led to aggregation and formation of larger and non-uniform particles. As a result, the exposure of negative charge on the MP surface was enhanced, and zeta potential was decreased from -5.33 mV to -7.45 mV. Moreover, the EC-induced modification of MP conformation resulted in a less rigid three-dimensional network structure of MP gel and enhanced the discharge of aldehyde compounds (C > 6). Moreover, the rheological characteristics of MP were enhanced by the suppression of protein-protein interactions due to the MP unfolding. Molecular dynamics simulations revealed that anethole reduced the binding capacity of myosin to decanal by raising its binding energy from -22.22 kcal/mol to -19.38 kcal/mol. In the meantime, anethole competed for the amino acid residue (PHE165) where myosin connects to decanal. This caused the hydrogen bonds and hydrophobic contacts between the two molecules to dissolve, altering myosin's conformation and releasing decanal. The results might be useful in predicting and controlling the ability of proteins to release and hold onto flavors.

Consequences of using poly-ether-ether-ketone versus traditional implant on tibial cement penetration and short-term clinical outcomes during total knee arthroplasty: a randomized controlled trial.

BACKGROUND: The use of poly-ether-ether-ketone (PEEK) prosthesis during total knee arthroplasty (TKA) is a relatively new concept. Several studies have suggested that the thickness of cement penetration during TKA may affect the stability of the implants. The present study aimed to compare the cement penetration and clinical performance between PEEK and traditional cobalt chromium molybdenum (CoCrMo) prosthesis during TKA. METHODS: This study was a randomized controlled trial with level I of evidence. A total of 48 patients were randomly assigned to either the PEEK group (n = 24) or the CoCrMo group (n = 24). Mean bone cement penetration under the tibial baseplate was assessed radiographically in four zones in the anteroposterior view and two zones in the lateral view, in accordance with the Knee Society Scoring System. Furthermore, parameters such as the Knee Society Score (KSS), visual analogue scale (VAS) scores, complications and survivorship at 1 year postoperatively were also compared. RESULTS: According to the results of this study, the mean bone cement penetration exhibited no significant difference between PEEK and CoCrMo groups (2.49 ± 0.61 mm vs. 2.53 ± 0.68 mm, p = 0.85). Additionally, there were no remarkable differences in the KSS clinical score, functional score, and VAS score between the two groups. Moreover, complications and survivorship were also statistically compared between the groups and presented no significant differences. CONCLUSIONS: Based on the current findings, it can be concluded that PEEK implant present similar bone cement penetration, short-term clinical outcomes, and survivorship with traditional CoCrMo implant in TKA without added complications. Trial registration Chinese Clinical Trial Registry (ChiCTR2100047563).

Nuclear receptor coactivator 3 transactivates proinflammatory cytokines in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.

Tumor Immune Microenvironment Characteristics and Their Prognostic Value in Non-Small-Cell Lung Cancer.

INTRODUCTION: Cancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients. METHODS: Seventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine differences in survival. RESULTS: Compared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049). CONCLUSION: We profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Effectiveness of jejunostomy for enteral nutrition during complete thoracoscopic and laparoscopic Ivor-Lewis esophagectomy in thoracic segment esophageal carcinoma.

BACKGROUND: Although jejunostomy is widely used in complete thoracoscopic and laparoscopic minimally invasive Ivor-Lewis esophagectomy, its clinical effectiveness remains undefined. This study aimed to assess the therapeutic and side effects of jejunostomy in patients undergoing Ivor-Lewis esophagectomy for thoracic segment esophageal carcinoma. METHODS: A total of 1400 patients with esophageal carcinoma who underwent minimally invasive esophagectomy in the Thoracic Surgery of our hospital from 2015 to 2018 were retrospectively evaluated. Of these, 356 and 1044 were treated with nasojejunal feeding tubes (Nasojejunal group) and by jejunostomy (Jejunostomy group), respectively. Clinicopathologic factors, postoperative complications and tubule-related complications between the two groups were compared. RESULTS: Both groups were well-balanced for clinicopathological data, except tumor location, which was significantly different (P < 0.001). Operation time (208.8 ± 53.5 min vs. 218.1 ± 43.2 min) was shorter in the Jejunostomy group compared with the Nasojejunal group, while intraoperative (26.6 ± 10.4 min vs 18.4 ± 9.1 min) and postoperative (38.6 ± 6.9 min vs 18.5 ± 7.6 min) indwelling times of nutrition tubes were prolonged (all P < 0.05). Postoperative pulmonary infection (17.0% vs 22.2%), incision infection (0.2% vs 1.1%), nutrient tube slippage (0.2% vs 5.1%) and nutrient reflux 1 (0.1% vs 5.6%) rates were reduced in the Jejunostomy group compared with the Nasojejunal group (P < 0.05). Meanwhile, ileus rates perioperatively (1.7% vs 0.3%) and at 3 postoperative months (1.7% vs 0.3%) were both higher in the Jejunostomy group compared with the Nasojejunal group. CONCLUSIONS: Jejunostomy is a reliable enteral nutrition method in Ivor-Lewis esophagectomy for thoracic segment esophageal carcinoma.

Mechanism research of miR-34a regulates Axl in non-small-cell lung cancer with gefitinib-acquired resistance.

BACKGROUND: To investigate the regulatory mechanism behind miR-34a-altered Axl levels in non-small-cell lung cancer (NSCLC) with gefitinib-acquired resistance. METHODS: The expression of miR-34a, Axl, Gas6 and related downstream signaling proteins in the EGFR mutant NSCLC cell lines were determined by qRT-PCR and Western blot; PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells were established by transfecting the parent cells with a miR-34a overexpressing virus, then the expression of Axl, Gas6 and the downstream channel-related proteins were also compared in PC9-Gef-miR-34a and HCC827-Gef-miR-34a and drug-resistant strains. The survival rate of the cells were measured by CCK8 assay. A luciferase reporter detected whether Axl was the target of miR-34a. Finally, a tumor-bearing nude mouse model was established to verify the relationship between the expression of miR-34a, Axl and Gas6 mRNA in vivo. RESULTS: The expression levels of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream proteins in PC9-Gef and HCC827-Gef cell lines were higher than those in PC9 and HCC827 parental cell lines, while the expression of miR-34a was lower than it was in the parental cell lines (P < 0.05). The expression of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream signaling proteins in PC9-Gef and HCC827-Gef cell lines was higher than the expression in PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells, which overexpressed miR-34a (P < 0.05). CONCLUSION: The miR-34a regulation of Axl plays an important role in NSCLC-acquired gefitinib resistance, and their expression is inversely correlated, which suggests that they can be used as prognostic markers or potential therapeutic targets for NSCLC.

Flow synthesis, characterization, anticoagulant activity of xylan sulfate from sugarcane bagasse.

High-value utilization of hemicellulose is critical to improve the append value of integrated biorefineries. In this research, the alkali-soluble sugarcane bagasse hemicellulose was sulfated using chlorosulfonic acid and N,N-dimethylformamide/LiCl under homogeneous conditions. With the aid of flow technique, a rapid, mild, and efficient method for the synthesis of xylan sulfate with high molecular weight and controllable degree of substitution was achieved. The results showed that the reaction time and the degradation of xylan chain were drastically reduced compared to the "in flask" batch conditions. High molecular weight of the product (Mw = 148,217) with a reasonable degree of substitution (DS = 1.49) could be obtained even at room temperature in 10 min under the present flow system. Anticoagulant experiments showed good anticoagulant activity of the resultant xylan sulfate, which could significantly prolong the activated partial thromboplastin time and thrombin time. This work not only provides a novel method for the synthesis of xylan sulfate, but also offers new opportunities for the production of other functional polysaccharide derivatives under the flow reaction conditions.

The small molecule NSM00191 specifically represses the TNF-α/NF-кB axis in foot and ankle rheumatoid arthritis.

The activation of TNF-α/NF-кB signaling is involved in the regulation of a wide range of biological processes, such as cell proliferation, differentiation and apoptosis, eventually causing a number of diseases, such as cancer and inflammation. Here, we found that TNF-α/NF-кB signaling was activated in a large number of blood samples taken from foot and ankle rheumatoid arthritis (RA) patients. By applying a microarray assay to the human synovial sarcoma cell line SW982 and the human fibroblast-like synoviocyte cell line HFLS-RA, as well as in their corresponding p65 knockdown and -overexpressing cells, we identified and verified the activation of many p65 targets, including cytokines (e.g., TNF-α and IL-6), chemokines (e.g., MCP-1 and PANTES), protein receptors (e.g., CD-40 and MHC-1), and inducible enzymes (e.g., COX2). In addition, we subjected microRNAs from foot and ankle RA patients to a microRNA-specific microarray and found that miR-7-5p targeted the 3'-UTR of p65, negatively regulating its expression. By applying an in vitro screen to identify small molecules that specifically inhibited the interaction between TRADD and TNFR2, we found that NSM00191 strongly inhibited the activation of TNF-α/NF-кB signaling in vitro and in vivo, causing the downregulation of NF-кB targets and the decrease of arthritis scores. Collectively, our findings shed new light on the regulation of the TNF-α/NF-кB axis and might provide a new avenue for RA treatment.

[Video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in thoracic cavity: analysis of 60 cases].

OBJECTIVE: To investigate the feasibility and safety of video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. METHODS: The clinical data of 120 patients who underwent esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity from March to December 2011 was analyzed retrospectively. In the video-assisted thoracoscopic surgery group, there were 60 patients [41 male and 19 female patients with aver age of (62 ± 7) years old] who underwent video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. In the routine thoracotomy group, there were 60 patients [39 male and 21 female patients with aver age of (62 ± 9) years old] who underwent routine thoracotomy esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. Operation time, intra-operative blood loss, postoperative total thoracic drainage in 3 days, total number of harvested lymph nodes, hospitalization, cost of hospitalization and complications were compared between the two groups. RESULT: The operations were carried out successfully in two groups. There was no perioperative death in all patients. There was no statistical difference in intra-operative blood loss, postoperative total thoracic drainage and cost of hospitalization between the two groups. Operation time of rideo-assisted thoracoscopic surgery group was significantly longer than that of thoracotomy group ((188 ± 38) minutes vs. (138 ± 50) minutes, t = 6.171, P = 0.000), but postoperative hospitalization was significantly lower ((14 ± 3) d vs. (18 ± 6) d, t = -4.093, P = 0.000) and total number of harvested lymph nodes was lower (17 ± 9 vs. 21 ± 11, t = -2.058, P = 0.042). There was significantly statistical difference in total postoperative main complication (25.0% vs. 48.3%, χ(2) = 7.033, P = 0.008). And postoperative incisional infection of VATE group patients was significantly lower than that of thoracotomy group patients (6.7% vs. 25.0%, χ(2) = 7.566, P = 0.006). CONCLUSIONS: Video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity is technically feasible and safe, with minimized trauma and quick recovery. The recent result is satisfactory.

Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomsis.

We retrospectively analyzed the clinical data of 112 patients who underwent esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity from October 2011 to June 2013. First, the gastric tube was created with the aid of linear stapling device by removing the stomach and dissecting lymph nodes under laparoscopy and making a 3-4 cm incision through the subxiphoid area in the upper abdomen. Second, the thoracic esophagus and lymph nodes were dissected during thoracoscopic procedure. Gastric tube was inserted into the chest cavity and placed in the posterior mediastinum. The thoracic gastro-esophageal anastomosis was stapled with a circular stapler. Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis is technically feasible and safe, with minimized trauma, less operative blood loss and quick recovery.