Identification of extracellular matrix-related biomarkers in colon adenocarcinoma by bioinformatics and experimental validation.

Backgrounds: Extracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis. Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial-mesenchymal transition (EMT). Results: Three potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model. Conclusion: The three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Comparative efficacy of concurrent training types on lower limb strength and muscular hypertrophy: A systematic review and network meta-analysis.

Objective: This study aims to compare, through quantitative analysis, the effectiveness of different endurance training types on increasing lower limb strength and muscle cross-sectional area (MCSA) in concurrent training. Methods: This systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [PROSPERO ID: CRD42023396886]. Web of Science, SportDiscuss, Pubmed, Cochrane, and Scopus were systematically searched from their inception date to October 20, 2023. Results: A total of 40 studies (841 participants) were included in this meta-analysis. MCSA analysis showed that, compared to resistance training alone, concurrent high-intensity interval running training and resistance training and concurrent moderate-intensity continuous cycling training and resistance training were more effective (SMD = 0.15, 95% CI = -0.46 to 0.76, and SMD = 0.07, 95% CI = -0.24 to 0.38 respectively), while other modalities of concurrent training not. Lower body maximal strength analysis showed that all modalities of concurrent training were inferior to resistance training alone, but concurrent high-intensity interval training and resistance training showed an advantage in four different concurrent training modalities (SMD = -0.08, 95% CI = -0.25 to 0.08). For explosive strength, only concurrent high-intensity interval training and resistance training was superior to resistance training (SMD = 0.06, 95% CI = -0.21 to 0.33). Conclusion: Different endurance training types have an impact on the effectiveness of concurrent training, particularly on lower limb strength. Adopting high-intensity interval running as the endurance training type in concurrent training can effectively minimize the adverse effects on lower limb strength and MCSA.

Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Efficacy of Different Exercises on Mild to Moderate Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.

PURPOSE: The aims of this study are to evaluate the effectiveness of different exercise interventions on patients with adolescent idiopathic scoliosis and to provide evidence-based exercise prescriptions for this population. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, CNKI, Chinese Biomedical Literature Database (CBM), VIP, and Wanfang Data Knowledge Service Platform were searched until January 2023. The data were pooled and a meta-analysis was conducted. RESULTS: A total of 19 studies were conducted with 778 participants. The Schroth exercises group (mean difference = -3.48, 95% confidence interval = -4.73 to -2.23, P < 0.00001) and strength training group (mean difference = -3.43, 95% confidence interval = -4.06 to -2.80, P < 0.00001) had better recovery of the Cobb angle than the other groups. The Cobb angle rehabilitation effect was good in the time of less than 60-min group. In addition, there was no significant difference found between the different intervention periods groups ( P > 0.05). CONCLUSIONS: Schroth exercise and strength training significantly improved Cobb angle of adolescent idiopathic scoliosis patients; exercising for less than 60 mins is effective for Cobb angle rehabilitation, but prolonging exercise time cannot improve training effectiveness; 12 wks of exercise significantly improved Cobb angle, but prolonged training periods did not have a significant impact.

Relationship between methods of monitoring training load and physiological indicators changes during 4 weeks cross-country skiing altitude training.

This study aimed to: (i) analyze the load characteristics of 4 weeks cross-country skiing altitude training; (ii) analyze the relationships between methods of monitoring training load and physiological indicators changes of elite male Chinese cross-country skiers during this period. Practitioners collected load data during 4 weeks of altitude training camp. Participants performed maximal oxygen uptake, lactate threshold, body composition, and skierg power test before and after the training camp to investigate the changes in physiological performance. Edwards TRIMP, Lucia TRIMP, and session rating of perceived exertion were collected as internal load. Training distance, time recorded by the Catapult module were collected as external load. The result revealed a " pyramid " pattern in the load characteristics during the altitude training camp. The correlation between luTRIMP and percent change in physiological indicators was highest. Percentage changes in lactate threshold velocity (r = .78 [95% CI -.01 to .98]), percentage changes in lactate threshold HR (r = .71 [95% CI .14- .99]), percentage changes in maximum HR (r = .83 [95% CI .19-1.00]), percentage changes in skierg power-to-weight ratio (r = .75 [95% CI -.28 to .98]) had very large relationships with luTRIMP. In cross-country skiing altitude training, training loads should be reasonably controlled to ensure that athletes do not become overly fatigued. Methods of training load monitoring that combine with athletes' physiological characteristics and program characteristics have the highest dose-response relationships, it is an important aspect of cross-country ski training load monitoring. The luTRIMP could be a good monitoring tool in cross-country skiing altitude training.

Associations of air pollution and greenness with global burden of breast cancer: an ecological study.

Despite the significance of the associations of air pollution and greenness with the risk of breast cancer, this topic has not been investigated on a global scale. We conducted an ecological study using 7 years of data from 162 countries. Disability-adjusted life years (DALYs) and incidence data were used to represent the breast cancer disease burden. Particulate matter with a diameter < 2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and the normalized difference vegetation index (NDVI) were adopted as our exposures. We employed generalized linear mixed models to explore the relationship between air pollution and greenness on breast cancer disease burden. The rate ratio (RR) and its 95% confidence interval (CI) indicate the effect size. There is a positive association between air pollution and the burden of breast cancer disease. Contrarily, per interquartile range increment in NDVI was negatively associated with DALYs and incidence. In terms of air pollutants and breast cancer, NDVI seems to have a significant influence on the relationship between these two conditions. A higher amount of greenness helps to alleviate the negative association of air pollution on breast cancer. PM2.5 and O3 play a mediating role in the relationship between greenness and breast cancer disease burden. In areas with higher levels of greenness, there is a possibility that the inverse association between air pollutants and the burden of breast cancer may be influenced.

Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 µM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

Moderate-intensity continuous training has time-specific effects on the lipid metabolism of adolescents.

Background and Objectives: Moderate-intensity continuous training (MICT) is used to observe lipidomic effects in adults. However, the efects of MICT on lipid metabolism in adolescents remain unclear. Therefore, we aimed to longitudinally characterize the lipid profile in adolescents during different periods of 6-week MICT. Methods: Fifteen adolescents undertook bicycle training at 65% of maximal oxygen consumption. Plasma samples were collected at four time points (T0, T1, T2, and T3). Targeted lipidomics was assessed by ultra-performance liquid chromatography-tandem mass spectrometry to characterize the plasma lipid profiles of the participants to identify the lipids present at differing concentrations and changes in lipid species with time. Results: MICT afected the plasma lipid profiles of the adolescents. The concentrations of diglycerides, phosphatidylinositol, lysophosphatidic acid, lysophosphatidylcholine, and lysophosphatidylethanolamine were increased at T1, decreased at T2, and increased again at T3. Fatty acids (FAs) showed an opposite trend. Ether-linked alkylphosphatidylcholine and triglycerides were significantly increased and remained high. Sphingolipid concentrations initially decreased and then remained low. Therefore, a single bout of exercise had substantial efects on lipid metabolism, but by T3, fewer lipid species were present at significantly diferent concentrations and the magnitudes of the remaining diferences were smaller than those at earlier times. Among all the changed lipids, only DG(14:1/18:1), HexCer(d18:1/22:1) and FA(22:0) showed no significant correlations with any other 51 lipids (P < 0.05). Glycerides and phospholipids showed positive correlations with each other (P < 0.05), but FAs were significantly negatively correlated with glycerides and phospholipids while positively with other FAs (P < 0.05). Pathway enrichment analysis showed that 50% of the metabolic pathways represented were related to lipid metabolism and lipid biosynthesis. Conclusion: MICT increases ether-linked alkylphosphatidylcholine and triglyceride concentrations. Diglyceride, phosphatidylinositol, and lysophosphatidylcholine concentrations initially rise and then decrease 6 weeks after MICT, but FA concentrations show an opposite trend. These changes might correlate with lipid metabolism or biosynthesis pathways.

Residential surrounding greenness is associated with improved lung function in adults: a cross-sectional study in eastern China.

BACKGROUND: While benefits of greenness exposure to health have been reported, findings specific to lung function are inconsistent. The purpose of this study is to assess the correlations of greenness exposure with multiple lung function indicators based on chronic obstructive pulmonary disease (COPD) monitoring database from multiple cities of Anhui province in China. METHODS: We assessed the greenness using the annual average of normalized difference vegetation index (NDVI) with a distance of 1000-meter buffer around each local community or village. Three types of lung function indicators were considered, namely indicators of obstructive ventilatory dysfunction (FVC, FEV1, FEV1/FVC, and FEV1/FEV3); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25%, FEF50%, FEF75%, MMEF, FEV3, FEV6, and FEV3/FVC). Linear mixed effects model was used to analyze associations of greenness exposure with lung function through adjusting age, sex, educational level, occupation, residence, smoking status, history of tuberculosis, family history of lung disease, indoor air pollution, occupational exposure, PM2.5, and body mass index. RESULTS: A total of 2768 participants were recruited for the investigations. An interquartile range (IQR) increase in NDVI was associated with better FVC (153.33mL, 95%CI: 44.07mL, 262.59mL), FEV1 (109.09mL, 95%CI: 30.31mL, 187.88mL), FEV3 (138.04mL, 95%CI: 39.43mL, 236.65mL), FEV6 (145.42mL, 95%CI: 42.36mL, 248.47mL). However, there were no significant associations with PEF, FEF25%, FEF50%, FEF75%, MMEF, FEV1/FVC, FEV1/FEV6, FEV3/FVC. The stratified analysis displayed that an IQR increase in NDVI was related with improved lung function in less than 60 years, females, urban populations, nonsmokers, areas with medium concentrations of PM2.5 and individuals with BMI of less than 28 kg/m2. Sensitivity analyses based on another greenness indice (enhanced vegetation index, EVI) and annual maximum of NDVI remained consistent with the main analysis. CONCLUSIONS: Our findings supported that exposure to greenness was strongly related with improved lung function.

Development of the "hidden" multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease.

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aß aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized. The in vitro results showed that compound 3f indicated significant selective MAO-B inhibitory activity (IC50 = 0.67 µM) and remarkable anti-inflammatory property. It also significantly inhibited self-induced Aß1-42 aggregation and showed remarkable neuroprotective effects on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f was a selective metal chelator and could inhibit Cu2+-induced Aß1-42 aggregation. Based on this, the carbamate fragment was introduced to compound 3f to obtain carbamate derivatives. The biological activity results exhibited that compound 4b showed good BBB permeability, good AChE inhibitory potency (IC50 = 5.3 µM), moderate BuChE inhibitory potency (IC50 = 12.4 µM), significant MAO-B inhibitory potency, anti-inflammation potency on LPS-induced BV-2 cells and neuroprotective effects on Aß25-35-induced PC12 cell injury. Compared with 3f, compound 4b did not show obvious chelation property. Significantly, compound 4b could be activated by AChE/BuChE following inhibition of AChE/BuChE to liberate an active multifunctional chelator 3f, which was consistent with our original intention. More importantly, compounds 3f and 4b presented favorable ADME properties and good stability in artificial gastrointestinal fluid, blood plasma and rat liver microsomes. The in vivo results suggested that compound 4b (0.0195 µg/mL) could significantly improve dyskinesia and reaction capacity of the AlCl3-induced zebrafish AD model by increasing the level of ACh. Together our data suggest that compound 4b was a promising "hidden" multifunctional agent by AChE/BuChE, and this strategy deserved further development for the treatment of AD.

OsCIP1, a secreted protein, binds to and stabilizes OsCR4 to promote aleurone layer development, seed germination and early seedling growth in rice.

The receptor kinase CRINKLY 4 (CR4) and its orthologs are known for their essential roles in cell differentiation and their shuttling between plasma membrane and cytoplasmic vesicles, a unique feature tied to their extracellular domain. However, the extracellular regulators of CR4 have been little known. Here we identified an OsCR4 Interacting Protein 1 (OsCIP1) (also named as OsLTPL36 in rice) by a yeast two-hybrid screen using the extracellular domain of OsCR4 (OsCR4E) as bait. OsCIP1/OsLTPL36 harbors a signal peptide and is localized to the outer surface of the plasma membrane. It interacted with the TNFR subdomain of OsCR4, causing an increase in OsCR4 recycling to the plasma membrane. oscip1, in which OsCR4 protein was decreased, exhibited thinner aleurone layer, late germination and delayed growth; while OsCIP1-overexpressing plants, in which OsCR4 protein was increased, displayed enhanced growth at the early seedling stage. OsCIP1 was cleaved between W61 and Q62, and the resulting C-terminal half exhibited a greater affinity for OsCR4E than did its precursor. Abolishing this cleavage site compromises OsCIP1's ability to promote seedling growth. Our results provide valuable clues for the regulation of CR4 activity and its functions in aleurone layer cell differentiation by a secreted small protein in rice.

Predictors for Necrosis after Single-Digit Replantation: A Retrospective Analysis of 946 Patients.

BACKGROUND: Digital necrosis (DN) is a serious complication after replantation. However, predisposing factors, as reported less, remain controversial. The purpose of this study was to explore risk factors of necrosis after single-digit replantation by means of a retrospective study. METHODS: Patients who underwent single-digit replantations in our hospital between June of 2014 and October of 2020 were included. The authors regarded DN as the failure group and digital survival as the success group. The factors were conducted by univariate and multivariate analysis. RESULTS: The survival rate in our study was 78.8% (745 of 946). The results of univariate analysis showed that there were significant differences in the levels of D-dimer (first), menstrual cycle, injury level, and starting and finishing time of surgery between different groups. In multivariate analysis, age, injury level, duration of surgery, and D-dimer (first) were identified as the risk factors for DN in the entire and male population. In addition, regarding male patients, ischemia time was also found to be a risk factor for DN. In terms of female patients, the menstrual period and menopause were related to DN. CONCLUSIONS: Many factors, including age, ischemia time, injury level, menstrual period, menopause, and duration of surgery, were related to DN after digital replantation. D-dimer (first) was first found as a predicted factor for DN. In addition, these results also showed that the starting and ending times of surgery were associated with DN by univariate analysis. Preoperative measures should be taken to lower the incidence of DN. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Targeted Lipidomics and Inflammation Response to Six Weeks of Sprint Interval Training in Male Adolescents.

Lipids play an important role in coordinating and regulating metabolic and inflammatory processes. Sprint interval training (SIT) is widely used to improve sports performance and health outcomes, but the current understanding of SIT-induced lipid metabolism and the corresponding systemic inflammatory status modification remains controversial and limited, especially in male adolescents. To answer these questions, twelve untrained male adolescents were recruited and underwent 6 weeks of SIT. The pre- and post-training testing included analyses of peak oxygen consumption (VO2peak), biometric data (weight and body composition), serum biochemical parameters (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, testosterone, and cortisol), inflammatory markers, and targeted lipidomics. After the 6-week SIT, the serum C-reactive protein (CRP), interleukin (IL)-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß significantly decreased (p < 0.05), whereas IL-6 and IL-10/TNF-α significantly increased (p < 0.05). In addition, the targeted lipidomics revealed changes in 296 lipids, of which 33 changed significantly (p < 0.05, fold change > 1.2 or <1/1.2). The correlation analysis revealed that the changes in the inflammatory markers were closely correlated with the changes in some of the lipids, such as LPC, HexCer, and FFA. In conclusion, the 6-week SIT induced significant changes in the inflammatory markers and circulating lipid composition, offering health benefits to the population.

Higher aorta dose increased neutrophil-to-lymphocyte ratio resulting in poorer outcomes in stage II-III non-small cell lung cancer.

BACKGROUND: This study focused on the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the dose of organs at risk in patients with stage II-III non-small cell lung cancer (NSCLC) receiving intensity-modulated radiotherapy. METHODS: The clinical characteristics and dosimetric parameters of 372 patients were collected retrospectively. A high NLR was defined as that ≥1.525. Survival analysis was conducted using the Kaplan-Meier and Cox regression analysis. Least absolute shrinkage and selection operator (LASSO) analysis was conducted to select appropriate dosimetric parameters. The risk factors of NLR were evaluated using univariate and multivariate logistic regression analyses. RESULTS: Patients with a high NLR had poorer progression-free survival (PFS) (p = 0.011) and overall survival (OS) (p = 0.061). A low NLR (<1.525) predicted better PFS (hazard ratio [HR] 0.676, 95% confidence interval [CI]: 0.508-0.900, p = 0.007) and OS (HR 0.664, 95% CI: 0.490-0.901, p = 0.009). The aorta dose differed between the low and high NLR groups (all <0.1) in the univariate analysis. An aorta V10 was confirmed as a significant risk factor for a high NLR (odds ratio [OR] 1.029, 95% CI: 1.011-1.048, p = 0.002). Receiving chemotherapy before (OR 0.428, 95% CI: 0.225-0.813, p = 0.010) and during (OR 0.491, 95% CI: 0.296-0.815, p = 0.006) radiotherapy were predictive factors of a low NLR. CONCLUSION: The aorta dose was significantly associated with a high NLR. Patients with stage II-III NSCLC with a high NLR had poorer prognosis. Receiving chemotherapy before and/or during radiotherapy predicted a low NLR.

Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease.

A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1ß and NO. In addition, compound 3f presented significant neuroprotective effect on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.

Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy.

PURPOSE: Lymphopenia is a common adverse effect of radiation therapy (RT). Little is known about the difference in lymphopenia between intensity modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiation therapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Clinical and dosimetric parameters were collected from 343 patients who received definitive IMRT or PCIRT for NSCLC. Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) ≤0.5 × 103 cells/µL. Overall survival (OS) was analyzed using the Kaplan-Meier method. Propensity score matching was performed between the IMRT and PCIRT groups. Least absolute shrinkage and selection operator analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL. RESULTS: Compared with the IMRT group, the PCIRT group was less likely to develop SRL (P < .001). Compared with the non-SRL group, the SRL group showed significant association with poorer OS, with a median survival time of 29.2 versus 15.0 months (P = .046). IMRT was an independent risk factor of SRL (P = .004). A lower ALC before RT (P = .030) and larger planning target volume (PTV) (P = .002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organs at risk in PCIRT were lower than those in IMRT (P < .001). Thoracic vertebra V5 (P = .002) and aorta V5 (P = .026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model. CONCLUSIONS: Compared with IMRT, PCIRT could reduce SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in patients with NSCLC.

Chronic intermittent hypoxia impaired collagen synthesis in mouse genioglossus via ROS accumulation: A transcriptomic analysis.

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets.

m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis.

Radiotherapy is a valid treatment for nasopharyngeal carcinoma (NPC), and radioresistance is the main cause of local NPC treatment failure. However, the underlying mechanisms and valuable markers of radioresistance for NPC remain have not been established. In this study, we observed that the m6A mRNA demethylase fat mass and obesity-associated protein (FTO) was significantly upregulated in radioresistant NPC tissues and cells relative to parental radiosensitive NPC tissues and cells. FTO enhances radioresistance by repressing radiation-induced ferroptosis in NPC. Mechanistically, FTO acts as an m6A demethylase to erase the m6A modification of the OTUB1 transcript and promote the expression of OTUB1, thereby inhibiting the ferroptosis of cells induced by radiation and finally triggering the radiotherapy resistance of NPC. Furthermore, our in vivo experiment results showed that the FTO inhibitor, FB23-2, and the ferroptosis activator, erastin, altered tumor responsiveness to radiotherapy in NPC cell lines and patient-derived xenografts. Our findings reveal, for the first time, that FTO enhances NPC radiotherapy resistance by withstanding radiation-induced ferroptosis, suggesting that FTO may serve as a potential therapeutic target and valuable prognostic biomarker in patients with NPC.

[Inhibitory effect of paeoniflorin on CAL27 cells of tongue squamous cell carcinoma and its mechanism].

PURPOSE: To investigate the inhibitory effect of paeoniflorin(PF) with different concentrations on CAL27 cells of tongue squamous cell carcinoma in vitro and its possible mechanism. METHODS: CCK-8 technique and clone formation trial were used to detect the effect of PF on the proliferation and clone formation of CAL27 cells. Scratch test and Transwell method was used to detect the effects of PF on migration and invasion of CAL27 cells. Staining of Hoechst33342 was employed to evaluate the influence of PF on apoptosis of CAL27 cells, while Western blot was utilized to investigate the effect of PF on the expression of NF-κB pathway related proteins and EMT related proteins. The effect of PF on NO production in CAL27 cells was detected by nitric oxide detection kit. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: PF inhibited proliferation, migration, and invasion of CAL27 cells in vitro in a concentration-dependent way. Moreover, PF caused apoptosis of CAL27 cells. PF impeded NF-κB pathway activity, decreased the expression of P-P65, further reduced the expression of iNOS and MMP-9, suppressed the production of NO, and concurrently inhibited Vimentin,promoted E-cadherin. CONCLUSIONS: Paeoniflorin inhibits the proliferation, migration and invasion of CAL27 cells, which may play an anti-cancer role by inhibiting the activation of NF-κB pathway and EMT.