Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy.

PURPOSE: We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen. METHODS: Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h). RESULTS: Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05). CONCLUSION: This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes Through the ROS/HIF-1α/GLUT1 Pathway.

Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model, we found that MEL significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation in LPS-treated macrophages, whereas this inhibitory effect of MEL was weakened in MH-S cells transfected with glucose transporter 1 (GLUT1) overexpressing lentivirus. Further experiments showed that MEL downregulated GLUT1 via inhibition of hypoxia-inducible factor 1 (HIF-1α). Notably, hydrogen peroxide (H2O2), a donor of reactive oxygen species (ROS), significantly increased the level of intracellular ROS and inhibited the regulatory effect of MEL on the HIF-1α/GLUT1 pathway. Interestingly, the protective effect of MEL was attenuated after the knockdown of melatonin receptor 1A (MT1) in MH-S cells. We also confirmed in vivo that MEL effectively downregulated the HIF-1α/GLUT1/NLRP3 pathway in the lung tissue of LPS-treated mice, as well as significantly ameliorated LPS-induced lung injury and improved survival in mice. Collectively, these findings revealed that MEL regulates the activation of the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages via the MT1 receptor, further alleviating sepsis-induced ARDS.

Mitochondrial energy metabolism correlates with an immunosuppressive tumor microenvironment and poor prognosis in esophageal squamous cell carcinoma.

Background: Reprogramming of mitochondrial energy metabolism (MEM) is an important hallmark of tumorigenesis and cancer progression. Currently, there are no studies that have examined MEM in the tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC), and relevant drug targets have not yet been identified. Methods: The ESCC single-cell transcriptome sequencing dataset, GSE145370, was analyzed, using the AUCell R package to screen for MEM-related genes in high-scoring cell populations. Monocle was used to infer cell differentiation and CellChat to analyze intercellular communication networks. Finally, transcription levels of prognostic genes were analyzed using a complementary DNA microarray from 15 patients with ESCC. Results: A total of 121 MEM-related genes were differentially expressed in seven cell populations in the TME, and four high-scoring cell populations were identified. As a result, the MEM state of T cells is significantly different from that of macrophages and epithelial cells, and signaling communication between T cells and macrophages is the strongest. These findings suggest that immunosuppression is related to metabolic reprogramming. Additionally, marker genes of high-scoring cells and the top10 receptor-ligand pairs may become new targets for rebuilding immune cell metabolism. Furthermore, the 4-MEM gene risk signature had good predictive power for overall survival and drug sensitivity. MAP1LC3A, APOE, APPL1, and NDUFA are novel potential immunotherapeutic targets for remodeling the TME. Finally, teal-time quantitative PCR was used to verify APOE and MAP1LC3A expression. Conclusion: MEM heterogeneity was observed in the immunosupressive TME of ESCC. Prognostic models based on MEM-related genes are helpful for screening early treatment patient groups and realizing personalized treatment. APOE and MAP1LC3A are potential target genes for the development of anti-ESCC drugs based on MEM-related genes.

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma.

Background: There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. Methods: Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. Results: MMP13 was found to be highly expressed in the "Pathologic Complete Response (pCR)" and "Complete Remission (CR)" and "Alive" groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the 0.70, and the model could well distinguish high-risk and low-risk subgroups. Conclusion: The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.

Low Dose Olanzapine in the Prevention and Treatment of Carboplatin Induced Nausea and Vomiting: A Prospective Clinical Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine the effectiveness and safety of 5 mg olanzapine (OLZ) in preventing vomiting and nausea caused by carboplatin chemotherapy. METHODS: All patients with malignant tumors (n = 113) who underwent Carboplatin (AUC ≥ 5) treatment were randomly categorized into two groups: the standard group (n = 57) and the OLZ regimen (n = 56). The major endpoints of the trial were the TC (total control) between two groups during the OP (Overall phase, 0-120 hours), DP (delayed phase, 25-120 hours), and AP (acute phase, 0-24 hours). The secondary endpoints were the CR (complete response) and TP (total protection) during AP, OP, and DP. The time of first vomiting was compared between the two groups using Kaplan-Meier curves. The impact of CINV on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). OLZ-related side effects were also recorded. RESULTS: (1) The primary endpoint TC rates were more favorable in the OLZ regimen group than in the standard group during the AP 87.50% (49/56) vs. 63.15% (36/57) P = 0.003, OP 62.50% (35/56) vs. 31.57% (18/57) P = 0.001, and DP 64.28% (36/56) vs. 33.33% (19/57) P = 0.001. (2) The secondary endpoints TP were 82.14% (46/56) vs. 63.15% (36/57), P = 0.024, 83.92% (47/56) vs. 63.15% (36/57). P = 0.012 during the DP and OP. There was no statistical significance during AP between the two groups. The CR rates were not statistically different between the two groups during the three periods, P > 0.05; (3) The first vomiting time in the OLZ group was delayed compared with the standard group (P = 0.248). The effect on life quality (score ≥ 108) assessed by FLIE was 62.50% vs. 43.48% between the two groups, P < 0.05. The primary side effects of OLZ are fatigue (85%) and somnolence (75%). The primary side effects of the standard group are fatigue (77%) and loss of appetite (85%). CONCLUSION: The 5 mg OLZ-based triple antiemetic regimen is effective and safe in preventing vomiting and nausea induced by Carboplatin.

A Bibliometric Analysis of Mesenchymal Stem Cell-Derived Exosomes in Acute Lung Injury/Acute Respiratory Distress Syndrome from 2013 to 2022.

Background: Mesenchymal stem cell-derived exosomes (MSC-exosomes) have been found to effectively improve the systemic inflammatory response caused by acute lung injury and acute respiratory distress syndrome (ALI/ARDS), regulate systemic immune disorders, and help injured cells repair. The purpose of this study was to take a holistic view of the current status and trends of MSC-exosomes research in ALI/ARDS. Methods: Bibliometrix, Citespace and VOSviewer software were used for bibliometric analysis of the data. We analysed the world trends, country distribution, institution contribution, most relevant journals and authors, research hotspots, and research hotspots related to Coronavirus Disease 2019 (COVID-19) based on the data collected. Results: China possessed the largest number of publications, while the USA had the highest H-index and the number of citations. Both China and the USA had a high influence in this research field. The largest number of publications in the field of MSC-exosomes and ALI/ARDS were mainly from the University of California system. Stem Cell Research & Therapy published the largest number of papers in this scope. The author with the greatest contribution was LEE JW, and ZHU YG published an article in Stem Cell with the highest local citation score. The most frequent keyword and the latest research hotspot were "NF-κB" and "Coronavirus Disease 2019". Furthermore, our bibliometric analysis results demonstrated that MSC-exosomes intervention and treatment can effectively alleviate the inflammatory response caused by ALI/ARDS. Conclusion: Our bibliometric study suggested the USA and China have a strong influence in this field. COVID-19-induced ALI/ARDS had become a hot topic of research.

Hsa_Circ_0104206 is An Oncogenic circRNA in Colon Cancer by Targeting Mir-188-3p/CCNA2 Axis.

The identification of specific biomarkers is essential to improve cancer therapy, and circular RNAs (circRNAs) have great potency to be biomarkers. We harbor the goal to unveil the role of circ_0104206 in colon cancer (CC). The relative expressions of circ_0104206, miR-188-3p and CCNA2 in different groups were studied using real-time quantitative PCR (qPCR) or western blotting. The proliferative and migratory capacity of cancer cells were monitored via CCK-8, colony formation and Transwell assays. The transplanted tumor models were generated to analyze circ_0104206's role in vivo. The putative relationship between miR-188-3p and circ_0104206 or CCNA2 by bioinformatics tools was testified through dual-luciferase or RIP assay. The abnormal elevation of circ_0104206 expression was observed in CC. Circ_0104206 silencing repressed CC cell proliferative and migratory behaviors, and also decelerated tumor development in animal models. MiR-188-3p was directly targeted by circ_0104206, and its inhibitor had the ability to reverse the anticancer effects of circ_0104206 silencing on CC cells. CCNA2 was a target downstream of circ_0104206/miR-188-3p network. Moreover, the repressive effects of CCNA2 absence on cell proliferation and migration were attenuated by miR-188-3p inhibitor. In conclusion, Circ_0104206 plays oncogenic roles in CC via the implication of miR-188-3p/CCNA2 network, which further discloses CC pathogenesis and supplies potential markers for CC.

Myelosuppression Caused by Nanoparticle Albumin-Bound Paclitaxel in the Northern Chinese Population and the Role of Body Composition.

The aim of this study was to examine the relationship between lean body mass (LBM) and the incidence and severity of neutropenia in patients with malignant tumors from Northern China who have received nanoparticle albumin-bound paclitaxel. Twenty-six patients with pathologically confirmed malignant tumors were prospectively included in this study. These 26 patients were divided into Group A (sarcopenia) and Group B (nonsarcopenia). Group A comprised 50% (13/26) of the patients, while Group B comprised the other 50% (13/26). There was no statistically significant difference between both groups in terms of body surface area (P = .052). The incidence of neutropenia in Group A was 76.9% compared to 61.5% in Group B (P = .0673). The incidence of Grade 3 and severe neutropenia was 76.9% versus 61.5% in Groups A and B, respectively (P = .645). These 26 patients were divided into Groups 1 and 2 based on the administered nab-paclitaxel dose per kilogram of LBM, with both groups receiving a body surface area dose of 260 mg/m2 . Group 1 received a nab-paclitaxel dose of 14.19 mg/kg of LBM, whereas Group 2 received 11.37 mg/kg of LBM. In Group 1, the incidence of neutropenia was 71.4%, whereas it was 66.7% in Group 2. Grade 3 or higher neutropenia incidence was 28.6% in Group 1 versus 16.7% in Group 2. Patients with sarcopenia in northern China experienced a higher incidence of severe neutropenia after receiving nab-paclitaxel than patients without sarcopenia. Higher drug dose intensity per unit of LBM may be a contributing factor.

4-octyl itaconate ameliorates alveolar macrophage pyroptosis against ARDS via rescuing mitochondrial dysfunction and suppressing the cGAS/STING pathway.

Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1ß release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.

Pt/MXene-Based Flexible Wearable Non-Enzymatic Electrochemical Sensor for Continuous Glucose Detection in Sweat.

Wearable non-invasive sensors facilitate the continuous measurement of glucose in sweat for the treatment and management of diabetes. However, the catalysis of glucose and sweat sampling are challenges in the development of efficient wearable glucose sensors. Herein, we report a flexible wearable non-enzymatic electrochemical sensor for continuous glucose detection in sweat. We synthesized a catalyst (Pt/MXene) by the hybridization of Pt nanoparticles onto MXene (Ti3C2Tx) nanosheets with a broad linear range of glucose detection (0-8 mmol/L) under neutral conditions. Furthermore, we optimized the structure of the sensor by immobilizing Pt/MXene with a conductive hydrogel to enhance the stability of the sensor. Based on Pt/MXene and the optimized structure, we fabricated a flexible wearable glucose sensor by integrating a microfluidic patch for sweat collection onto a flexible sensor. We evaluated the utility of the sensor for the detection of glucose in sweat, and the sensor could detect the glucose change with the replenishment and consumption of energy by the body, and a similar trend was observed in the blood. An in vivo glucose test in sweat indicated that the fabricated sensor is promising for the continuous measurement of glucose, which is essential for the treatment and management of diabetes.

Marine-Derived Natural Product HDYL-GQQ-495 Targets P62 to Inhibit Autophagy.

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFPKI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFPKI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis.

Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

Association between Body Composition and Peripheral Neurotoxicity in Cancer Patients from North China Taking Nab-Paclitaxel.

Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.

Dynamic changes in the body composition during chemotherapy for gastrointestinal tumors in the context of active nutrition intervention.

Objective: To explore the dynamic changes in the body composition during chemotherapy in patients with gastrointestinal malignancies in the context of active nutrition intervention. Methods: Patients with gastrointestinal malignancies receiving first-line chemotherapy in the Department of Medical Oncology of Ordos Central Hospital from September 2019 to January 2022 were included in this study. The Nutritional Risk Screening form 2002, Patient-Generated Subjective Global Assessment form, bioelectrical impedance analysis, and dynamic changes in L3 skeletal muscle index (SMI) (L3SMI) were assessed at baseline and after chemotherapy. The recommended protocol of the Nutrition Guidelines for Cancer Patients in China 2020 was adopted as the active nutrition intervention. Chemotherapy-related toxic adverse reactions and the degree of toxicity were recorded with the adoption of the Common Terminology Criteria for Adverse Events version 4.0 by the National Institutes of Health. The type of toxicity Chemotherapy-Induced Nauseaand Vomiting(CINV) and hematological. Results: Fifty cases were enrolled in the study, and 38 cases completed the dynamic follow-ups. The average follow-up time was 125.63 d. In the context of active nutrition intervention, the prevalence of sarcopenia decreased from 26.3% before chemotherapy to 21.1% after chemotherapy. The average L3SMI decreased from 38.77 cm2/m2 to 38.04 cm2/m2, with a reduction of 1.41% ± 8.49% (P = 0.177). The SMI remained stable or increased in 57.9% (22/38) of patients. The benefit of active nutrition intervention was greater in the sarcopenic group than in the non-sarcopenic group (P = 0.033). There was an increased incidence of chemotherapy-related toxic adverse reactions of ≥ grade 3 during chemotherapy in the sarcopenic group compared with the muscle retention/gain group (P = 0.089). Conclusion: Active nutrition intervention might decrease the degree of reduction of L3SMI and the incidence of sarcopenia in patients with gastrointestinal tumors and raise the proportion of patients with stable or increased SMI during chemotherapy.

The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases.

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle is disrupted. Itaconate is derived from cis-aconitate decarboxylation by cis-aconitate decarboxylase (ACOD1) in the mitochondrial matrix and is also known as immune-responsive gene 1 (IRG1). Studies have demonstrated that itaconate plays an important role in regulating signal transduction and posttranslational modification through its immunoregulatory activities. Itaconate is also an important bridge among metabolism, inflammation, oxidative stress, and the immune response. This review summarizes the structural characteristics and classical pathways of itaconate, its derivatives, and the compounds that release itaconate. Here, the mechanisms of itaconate action, including its transcriptional regulation of ATF3/IκBζ axis and type I IFN, its protein modification regulation of KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, and TFEB, and succinate dehydrogenase and glycolytic enzyme metabolic action, are presented. Moreover, the roles of itaconate in diseases related to inflammation and oxidative stress induced by autoimmune responses, viruses, sepsis and IRI are discussed in this review. We hope that the information provided in this review will help increase the understanding of cellular immune metabolism and improve the clinical treatment of diseases related to inflammation and oxidative stress.

Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation.

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment of restenosis by the paracrine function of extracellular vesicles (EVs). However, the risk of tumorigenicity and poor cell survival limits its clinical applications. In this study, we for the first time applied a highly efficient and robust three-dimensional (3D) protocol for hiPSC differentiation into endothelial cells (ECs) with subsequent isolation of EVs from the derived hiPSC-EC (ECs differentiated from hiPSCs), and validated their therapeutic effect in intimal hyperplasia (IH) models. We found that intravenously (iv) injected EVs could accumulate on the carotid artery endothelium and significantly alleviate the intimal thickening induced by the carotid artery ligation. To elucidate the mechanism of this endothelial protection, we performed miRNA expression profiling and found out that among the most conserved endothelial miRNAs, miR-126 was the most abundant in hiPSC-EC-produced EVs (hiPSC-EC-EV). MiR-126 depletion from hiPSC-EC-EV can hinder its protective effect on human umbilical vein endothelial cells (HUVECs) in an inflammatory process. A variety of functional in vitro studies revealed that miR-126 was able to prevent endothelial apoptosis after inflammatory stimulation, as well as promote EC migration and tube formation through autophagy upregulation. The latter was supported by in vivo studies demonstrating that treatment with hiPSC-EC-EV can upregulate autophagy in mouse carotid artery ECs, thereby preventing IH and modulating vascular homeostasis via remodeling of the vascular intima. Our findings suggest a regulatory mechanism for the therapeutic effect on arterial restenosis by autophagy regulation, and provide a potential strategy for clinical treatment of the disease.

The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization.

Mitophagy is a vital process that controls mitochondria quality, dysregulation of which can promote cancer. Oncoprotein mucin 1 (MUC1) targets mitochondria to attenuate drug-induced apoptosis. However, little is known about whether and how MUC1 contributes to mitochondrial homeostasis in cancer cells. We identified a novel role of MUC1 in promoting mitophagy. Increased mitophagy is coupled with the translocation of MUC1 to mitochondria, where MUC1 interacts with and induces degradation of ATPase family AAA domain-containing 3A (ATAD3A), resulting in protection of PTEN-induced kinase 1 (Pink1) from ATAD3A-mediated cleavage. Interestingly, MUC1-induced mitophagy is associated with increased oncogenicity of cancer cells. Similarly, inhibition of mitophagy significantly suppresses MUC1-induced cancer cell activity in vitro and in vivo. Consistently, MUC1 and ATAD3A protein levels present an inverse relationship in tumor tissues of breast cancer patients. Our data validate that MUC1/ATAD3A/Pink1 axis-mediated mitophagy constitutes a novel mechanism for maintaining the malignancy of cancer cells, providing a novel therapeutic approach for MUC1-positive cancers.

A Comparison of the Efficacy of 5 mg Olanzapine and Aprepitant in the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting.

Objective: The significance of this article is to talk about aprepitant and olanzapine 5 mg, compare them, and deeply explore the safety or effectiveness during the whole process of multiple-day cisplatin chemotherapy-induced vomiting and nausea. Methods: This trial was randomized and prospective. It is needed to receive cisplatin chemotherapy (25 mg/m2/d) for three days. Its patients would need to choose to use 5 mg olanzapine or aprepitant for this treatment, combined with 5-HT3 receptor antagonist plus dexamethasone. The primary endpoints were the total protection (TP) during the acute phase (AP) (0-24 hours), delayed phase (DP) (25-120 hours), and overall phase (OP) (0-120 h) between the two groups. The secondary endpoints were the complete response (CR) and total control (TC) during the three phases. The first time of the whole process is particularly important and needs to be observed vigorously. However, the time of the patient's first vomiting symptom is also compared accurately by using the Kaplan-Meier curve. The functional life index vomiting (FLIE) was used to calculate and carefully evaluate the serious impact of nausea and vomiting (CINV) induced by the whole chemotherapy process on the quality of life. About olanzapine, its related symptoms and other side effects and aprepitant were also recorded. Results: (1) The primary endpoint TP rates of the olanzapine and aprepitant groups were similar; for the AP, they were 94.23% (98/104) vs. 95.45% (98/106) P=0.61(P=0.61); for the DP, they were 54.81% (57/104) vs. 54.72% (58/106) (P=0.99), and for the OP, the values were 53.79% (58/105) and 55.31% (56/104), respectively (P=0.99). The secondary endpoints, the TC rates, and CR rates were also comparable in the three phases (P > 0.05). (2) After research and display, the results showed that there was no significant difference between the two groups when they were used for the first time of vomiting and the FLIE index (P > 0.05). (3) The main olanzapine-related adverse event was drowsiness, while that of aprepitant was constipation. Conclusion: The efficacy of 5 mg olanzapine was similar to that of aprepitant, and it also showed an advantageous economic potency ratio in preventing CINV induced by multiple-day cisplatin chemotherapy with increased sedation side effects.

Bibliometric analysis of global research trends on pyroptosis in lung disease.

Background: Pyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease. Methods: On February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results. Result: 1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: "NOD-like receptor3 (NLRP3) inflammasome", "inflammation", "oxidative stress", and "acute lung injury (ALI)". Conclusion: The research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.