Influences of Ipomoea batatas Anti-Cancer Peptide on Tomato Defense Genes.

AIMS: This study investigates the impact of IbACP (Ipomoea batatas anti-cancer peptide) on defense-related gene expression in tomato leaves, focusing on its role in plant defense mechanisms. BACKGROUND: Previously, IbACP was isolated from sweet potato leaves, and it was identified as a peptide capable of inducing an alkalinization response in tomato suspension culture media. Additionally, IbACP was found to regulate the proliferation of human pancreatic adenocarcinoma cells. OBJECTIVE: Elucidate IbACP's molecular influence on defense-related gene expression in tomato leaves using next-generation sequencing analysis. METHOD: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP for durations ranging from 0 h (control) to 24 h. RESULTS: IbACP induced jasmonic acid-related genes (LoxD and AOS) at 2 h, with a significant up-regulation of salicylic acid-dependent gene NPR1 at 24 h. This suggested a temporal antagonistic effect between jasmonic acid and salicylic acid during the early hours of IbACP treatment. Downstream ethylene-responsive regulator genes (ACO1, ETR4, and ERF1) were consistently down-regulated by IbACP at all times. Additionally, IbACP significantly up-regulated the gene expressions of suberization-associated anionic peroxidases (TMP1 and TAP2) at all time points, indicating enhanced suberization of the plant cell wall to prevent pathogen invasion. CONCLUSION: IbACP enhances the synthesis of defense hormones and up-regulates downstream defense genes, improving the plant's resistance to biotic stresses.

Increased late-onset glaucoma risk following vitrectomy for macular pucker or hole.

OBJECTIVES: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. METHODS: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. RESULTS: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. CONCLUSIONS: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

Pharmacological agents targeting drug-tolerant persister cells in cancer.

Current cancer therapy can be effective, but the development of drug resistant disease is the usual outcome. These drugs can eliminate most of the tumor burden but often fail to eliminate the rare, "Drug Tolerant Persister" (DTP) cell subpopulations in residual tumors, which can be referred to as "Persister" cells. Therefore, novel therapeutic agents specifically targeting or preventing the development of drug-resistant tumors mediated by the remaining persister cells subpopulations are needed. Since approximately ninety percent of cancer-related deaths occur because of the eventual development of drug resistance, identifying, and dissecting the biology of the persister cells is essential for the creation of drugs to target them. While there remains uncertainty surrounding all the markers identifying DTP cells in the literature, this review summarizes the drugs and therapeutic approaches that are available to target the persister cell subpopulations expressing the cellular markers ATP-binding cassette sub-family B member 5 (ABCB5), CD133, CD271, Lysine-specific histone demethylase 5 (KDM5), and aldehyde dehydrogenase (ALDH). Persister cells expressing these markers were selected as the focus of this review because they have been found on cells surviving following drug treatments that promote recurrent drug resistant cancer and are associated with stem cell-like properties, including self-renewal, differentiation, and resistance to therapy. The limitations and obstacles facing the development of agents targeting these DTP cell subpopulations are detailed, with discussion of potential solutions and current research areas needing further exploration.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. MATERIALS AND METHODS: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. RESULTS: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. CONCLUSION: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Caffeic acid alleviates skeletal muscle atrophy in 5/6 nephrectomy rats through the TLR4/MYD88/NF-kB pathway.

Skeletal muscle atrophy is a common complication of chronic kidney disease (CKD) that affects the quality of life and prognosis of patients. We aimed to investigate the effects and mechanisms of caffeic acid (CA), a natural phenolic compound, on skeletal muscle atrophy in CKD rats. Male Sprague-Dawley rats underwent 5/6 nephrectomy (NPM) and were treated with CA (20, 40, or 80 mg/kg/day) for 10 weeks. The body and muscle weights, renal function, hemoglobin, and albumin were measured. The histological, molecular, and biochemical changes in skeletal muscles were evaluated using hematoxylin-eosin staining, quantitative real-time PCR, malondialdehyde/catalase/superoxide dismutase/glutathione level detection, and enzyme-linked immunosorbent assay. Western blotting and network pharmacology were applied to identify the potential targets and pathways of CA, CKD, and muscle atrophy. The results showed that CA significantly improved NPM-induced muscle-catabolic effects, reduced the expression of muscle atrophy-related proteins (muscle atrophy F-box and muscle RING finger 1) and proinflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha, and IL-1ß), and attenuated muscle oxidative stress. Network pharmacology revealed that CA modulated the response to oxidative stress and nuclear factor kappa B (NF-κB) signaling pathway and that Toll-like receptor 4 (TLR4) was a key target. In vivo experiment confirmed that CA inhibited the TLR4/myeloid differentiation primary response 88 (MYD88)/NF-kB signaling pathway, reduced muscle iron levels, and restored glutathione peroxidase 4 activity, thereby alleviating ferroptosis and inflammation in skeletal muscles. Thus, CA might be a promising therapeutic agent for preventing and treating skeletal muscle atrophy in CKD by modulating the TLR4/MYD88/NF-κB pathway and ferroptosis.

A glucuronogalactomannan isolated from Tetrastigma hemsleyanum Diels et Gilg: Structure and immunomodulatory activity.

A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.

A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth.

A 3D bioprinted neurovascular unit (NVU) model is developed to study glioblastoma (GBM) tumor growth in a brain-like microenvironment. The NVU model includes human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient-derived glioblastoma cells (JHH-520) are used for this study. Fluorescence reporters are used with confocal high content imaging to quantitate real-time microvascular network formation and tumor growth. Extensive validation of the NVU-GBM model includes immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing (scRNAseq) to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM-relevant cytokines. The scRNAseq reveals changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition cell population. The NVU-GBM model is used to test 18 chemotherapeutics and anti-cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening.

iDVEIP: A computer-aided approach for the prediction of viral entry inhibitory peptides.

With the notable surge in therapeutic peptide development, various peptides have emerged as potential agents against virus-induced diseases. Viral entry inhibitory peptides (VEIPs), a subset of antiviral peptides (AVPs), offer a promising avenue as entry inhibitors (EIs) with distinct advantages over chemical counterparts. Despite this, a comprehensive analytical platform for characterizing these peptides and their effectiveness in blocking viral entry remains lacking. In this study, we introduce a groundbreaking in silico approach that leverages bioinformatics analysis and machine learning to characterize and identify novel VEIPs. Cross-validation results demonstrate the efficacy of a model combining sequence-based features in predicting VEIPs with high accuracy, validated through independent testing. Additionally, an EI type model has been developed to distinguish peptides specifically acting as Eis from AVPs with alternative activities. Notably, we present iDVEIP, a web-based tool accessible at http://mer.hc.mmh.org.tw/iDVEIP/, designed for automatic analysis and prediction of VEIPs. Emphasizing its capabilities, the tool facilitates comprehensive analyses of peptide characteristics, providing detailed amino acid composition data for each prediction. Furthermore, we showcase the tool's utility in identifying EIs against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10.

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.

Effect of Acupoint Stimulation on Improving Gastrointestinal Motility in Patients After Gastrectomy: A Systematic Review and Meta-Analysis.

Introduction: Gastrointestinal immobility is experienced by many patients who undergo gastric surgery. This complication delays enteral nutrition, prolongs hospitalization, and causes discomfort. Acupoint stimulation is a popular alternative nonpharmacological treatment for gastrointestinal immobility. This study aimed to explore the effects of acupoint stimulation on gastrointestinal immobility after gastrectomy. Design: Systematic review and meta-analysis. Methods: Databases (PubMed, Cochrane, Joanna Briggs Institute EBP Database, Medline, CINAHL Complete, and Airiti library) were searched from their inception to April 2022 for relevant articles. Articles in Chinese and English were included, without limitations on year, region, or country. The inclusion criteria were studies with participants >18 years of age, postgastric surgery, and hospitalization. In addition, randomized controlled trials (RCTs) were included. Data were analyzed using random effects models, and data heterogeneity was investigated using subgroup analysis. Meta-analysis was performed using Review Manager 5.4 software. Results: We included 785 participants from six studies. Invasive and noninvasive acupoint stimulation reduced the time of gastrointestinal mobility better than usual care. In the control group, the time of first flatus was 43.56 ± 9.57 h to 108 ± 19.2 h, and the time of first defecation was 77.27 ± 22.67 h to 139.2 ± 24 h. In the experimental group, the time of first flatus and defecation was 36.58 ± 10.75 h to 79.97 ± 37.31 h and 70.56 ± 15.36 h to 108.55 ± 10.75 h, respectively. Subgroup analysis showed that invasive acupoint stimulation with acupuncture reduced the time of first flatus and defecation to 15.03 h (95% confidence interval [CI] = -31.06 to 1.01) and 14.12 h (95% CI = -32.78 to 4.54), respectively. Noninvasive acupoint stimulation, including acupressure and transcutaneous electrical acupoint stimulation (TEAS), reduced the time of first flatus and defecation to 12.33 h and (95% CI = -20.59 to -4.06) and 12.20 h (95% CI = -24.92 to 0.52), respectively. Conclusions: Acupoint stimulation improved the gastrointestinal immobility of postgastrectomy. In the included RCT articles, invasive and noninvasive stimulations were effective. However, noninvasive acupoint stimulation, such as with TEAS and acupressure, was more efficient and convenient than invasive stimulation. Overall, health care professionals with adequate training or under the supervision of an acupuncturist can effectively perform acupoint stimulation to improve the quality of postgastrectomy care. They can select commonly used and effective acupoints to enhance gastrointestinal motility. Clinical relevance: Acupoint stimulation, such as acupressure, electrical acupoint stimulation, or acupuncture, can be included in postgastrectomy routine care to improve gastrointestinal motility and reduce abdominal discomfort.

Symptom Clusters in Lymphoma Survivors Before, During, and After Chemotherapy: A Prospective Study 
.

OBJECTIVES: To explore symptom clusters (SCs) in lymphoma survivors before, during, and after chemotherapy. . SAMPLE & SETTING: 61 lymphoma survivors from a medical center in central Taiwan were enrolled in the study. . METHODS & VARIABLES: A prospective observational study design was adopted. The MD Anderson Symptom Inventory was used to measure symptoms. The 13 symptoms assessed by the MD Anderson Symptom Inventory were evaluated after diagnosis and before chemotherapy (T1), after the fourth cycle of chemotherapy (T2), and after completion of chemotherapy (T3). Data were analyzed using mean, frequency, and latent profile analysis. . RESULTS: Three SCs were identified at T1, four at T2, and three at T3. Fatigue was the predominant symptom in each SC for the participants over time. Fatigue, disturbed sleep, and numbness constituted an SC at T2 and T3. An SC consisting of multiple psychological symptoms was found only at T1. IMPLICATIONS FOR NURSING: This study describes methods for grouping SCs. An SC of fatigue, disturbed sleep, and numbness was identified at T2 and T3. By familiarizing themselves with this SC, clinicians can be attentive to patients' concurrent symptoms and implement early prevention measures and timely symptom management.

Alleviation of Hyperuricemia by Strictinin in AML12 Mouse Hepatocytes Treated with Xanthine and in Mice Treated with Potassium Oxonate.

Hyperuricemia, an abnormally high level of blood uric acid, is a major risk factor for gout. Although xanthine oxidase inhibitors were clinically used to lower blood uric acid level, the concerned side effects restricted their utilization. In this study, strictinin, an abundant polyphenol in Pu'er tea, was evaluated for its preventive effects on hyperuricemia. The results showed that the xanthine oxidase activity, uric acid production, and inflammation in AML12 mouse hepatocytes treated with xanthine were significantly reduced by the supplementation of strictinin. Detailed analyses revealed that strictinin inhibited xanthine-induced NLRP3 inflammasome activation. Consistently, the elevated blood uric acid level and the enhanced xanthine oxidase activity in mice treated with potassium oxonate were effectively diminished by strictinin supplementation. Moreover, for the first time, strictinin was found to promote healthy gut microbiota. Overall, strictinin possesses a great potential to be utilized as a functional ingredient for the prevention of hyperuricemia.

CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer.

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Natural history of lung squamous cell brain metastases in patients treated with radiosurgery: a thirty-year experience at a tertiary medical center.

PURPOSE: In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS. METHOD: We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis. RESULTS: We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p < 0.001), use of immunotherapy(p < 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors. CONCLUSION: In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS.

Clerodane diterpene induces apoptosis/anoikis and suppresses migration and invasion of human bladder cancer cells through the histone deacetylases, integrin-focal adhesion kinase, and matrix metalloproteinase 9 signalling pathways.

Clerodane diterpene, a class of bicyclic diterpenoids, is found in hundreds of plant species. 16-hydroxycleroda-3,13-dien-15,16-olide (CD) can be isolated from the plant Polyalthia longifolia and has been applied against oral cancer and glioma by xenograft model. In this study, we aim to explore its antitumour action by examining its histone deacetylase (HDAC) activity and integrin-associated intracellular signalling pathway on T24 human bladder cancer (BC) cells. Our results revealed that CD-inhibited colony formation, HDAC activity, HDAC (1, 2 and 3) mRNA and cell spreading on fibronectin-coated surfaces in a concentration-dependent manner. Furthermore, decreased cFLIP and increased caspase-8 cleavage accompanied CD-induced cell death. At non-toxic concentrations, CD blocked the migration and invasion of T24 cells. CD hindered migration and invasion by the downregulation of fibronectin, integrin α5ß1, ß-catenin, FAK, vinculin and Rho A, as well as by reduction of phosphorylated glycogen synthase kinase 3ß (pGSK3ß), pSrc, pstat3 and pNFκB. We observed that the MMP9 gene was closely linked with prognosis of patients with bladder cancer. MMP9 protein levels and activity were largely attenuated by CD in a concentration-dependent manner. In conclusion, CD-induced caspase-8-dependent apoptosis and suppressed migration and invasion by blocking several intracellular signalling pathways, including downregulation of HDAC activity and integrin-FAK and MMP9 pathways.

Trajectories of symptom severity predicts quality of life change in newly diagnosis lymphoma survivors: An initial study.

OBJECTIVE: This study aimed to explore the subgroups of symptom severity and impact of their trajectories on quality of life in lymphoma survivors. METHODS: Secondary data were analysed from a prospective study with four-time measures: before treatment (T1), during treatment (T2), treatment completion (T3) and 10 weeks after treatment (T4). Data were analysed using descriptive statistics, group-based trajectory model and generalised estimation equation. RESULTS: Fifty nine of 61 participants completed three-time measure (mean age = 60.43 years, male-predominant). The changes in symptom severity over time were divided into two subgroups: slight-stable group (n = 54, 89%) and mild-fickle group (n = 7, 11%). Pain, tiredness and sleeping trouble were the predominant symptoms. The quality of life change in the slight-stable group was significantly better than that of the mild-fickle group (B = 13.35, SE = 3.53, p < 0.001). The overall quality of life at T2, T3 and T4 was better than it was at T1. CONCLUSION: The different trajectories of symptom severity significantly influenced quality of life changes in lymphoma survivors. Healthcare providers must be aware that there is a group of lymphoma survivors with relatively severe symptoms when newly diagnosed, compared to the opposite. More attention must be paid to this group, in addition to providing in-time symptom management.

Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg attenuate LPS-induced acute lung injury by modulating TLR4/COX-2/NF-κB signaling pathway.

Tetrastigma Hemsleyanum Diels et Gilg (Sanyeqing, SYQ), a traditional herb native to China, has been widely used in the treatment of inflammatory diseases, febrile convulsions and dysentery. Previous studies have demonstrated the hypoglycemic, anti-inflammatory and anti-pyretic effects of polysaccharides from SYQ (SYQP). However, the role of SYQP in acute lung injury (ALI) remained unknown. Our present study aimed to explore the protective effects of SYQP in ALI and explained its underlying mechanism. In vivo, Balb/c mice were intragastrically administered with SYQP and dexamethasone (DXMS) for 14 days which were intratracheally instilled (IT) with LPS at the last day. In vitro, A549 cells were pretreated with SYQP, DXMS or TAK-242, following by LPS stimulation for 24 h. The histopathological results showed that SYQP remarkably alleviated pulmonary macrophage infiltration and myeloperoxidase (MPO) levels. Additionally, SYQP evidently suppressed wet/dry (W/D) ratio of lung and white blood cells (WBC) in bronchoalveolar lavage fluid (BALF). Moreover, SYQP markedly reduced TNF-α, IL-6, IL-1ß and COX-2 levels both in vivo and in vitro. Meanwhile, SYQP significantly attenuated oxidative stress through upregulating the levels of SOD and GSH-Px and downregulating the expressions of MDA and LDH in vivo, which was confirmed by in vitro results that SYQP could increase SOD activity and decrease MDA and NO contents. Importantly, a decline in protein expressions of TLR4, COX-2, NF-κB p50, phospho-NF-κB p65 and phospho-IκB-α was detected in vivo and in vitro. Taken together, our results demonstrated that SYQP ameliorated LPS-induced ALI by alleviating inflammation and oxidative stress via attenuating TLR4/COX-2/NF-κB signaling pathway.

The impact of a multispecialty operative team on colorectal cancer surgery: A retrospective study from a would-be medical center in Taiwan.

Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015. The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients. A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups. A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15). The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.

Glutathione peroxidase 8 expression on cancer cells and cancer-associated fibroblasts facilitates lung cancer metastasis.

Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro-metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p-FAK and p-Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer-associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra-terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro-metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8-mediated lung cancer metastasis.