Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

AIM:This study aims to investigate the role of ferroptosis in the myocardium of mice with lipopoly-saccharide(LPS)-induced sepsis and in the injury of H9c2 rat cardiomyocytes,and to explore the regulatory function of microRNA-351-5p(miR-351-5p)in this context.METHODS:An in vivo model of sepsis-induced cardiomyopathy was established in mice through intraperitoneal injection of LPS.Twenty-four mice were randomly divided into negative control(NC)group,LPS group,and LPS+ferroptosis inhibitor ferrostatin-1(Fer-1)group.Hematoxylin-eosin(HE)staining was conducted to assess cardiac injury,and plasma levels of creatine kinase(CK)and lactate dehydrogenase(LDH)were also measured.Additionally,the levels of Fe2+and malondialdehyde(MDA)in plasma were quantified,and the mRNA levels of acyl-CoA synthetase long chain family member 4(ACSL4)and prostaglandin-endperoxide synthase 2(PTGS2)were de-tected by RT-qPCR.In vitro,H9c2 cardiomyocytes were stimulated with LPS to create cellular models,followed by treat-ment with Fer-1,inhibitor NC,or miR-351-5p inhibitor.Cell viability was evaluated using CCK8 assay,intracellular re-active oxygen species(ROS)were measured by flow cytometry,intracellular Fe2+levels were assessed using a fluorescence probe,and the protein expression of glutathione peroxidase 4(GPX4)and ACSL4 was analyzed by Western blot.The MDA and reduced glutathione(GSH)levels were measured using commercial kits.MicroRNA(miRNA)sequencing was performed on the LPS-stimulated H9c2 cardiomyocyte models,with differential miRNAs identified and subsequently vali-dated using RT-qPCR.RESULTS:The mice in LPS group exhibited significant myocardial tissue dysregulation com-pared with NC group,with enlarged space,increased plasma CK and LDH levels(P<0.05),elevated Fe2+and MDA levels in myocardial tissues(P<0.05),and increased mRNA levels of ACSL4 and PTGS2(P<0.05).In contrast,the mice in LPS+Fer-1 group demonstrated improved myocardial tissue structure,reduced space,decreased plasma CK and LDH levels(P<0.05),and lower Fe2+and MDA levels in myocardial tissues(P<0.05),along with decreased mRNA level of PTGS2(P<0.05).In H9c2 cardiomyocytes,cell viability,intracellular GSH level,and GPX4 protein level were significantly reduced in LPS group compared with NC group(P<0.05),while ROS,MDA,Fe2+,and ACSL4 protein levels were elevated(P<0.05).The cells in LPS+Fer-1 group showed increased viability,intracellular GSH level,and GPX4 protein level compared with LPS group(P<0.05),alongside reduced ROS,MDA,Fe2+,and ACSL4 levels(P<0.05).miRNA sequencing revealed a significant decrease in several miRNAs,with miR-351-5p showing the most pro-nounced reduction.In LPS+miR-351 inhibitor group,H9c2 cell viability significantly declined(P<0.05),and the levels of GSH and GPX4 were notably lowered(P<0.05),while ROS,MDA,Fe2+and ACSL4 protein levels were significantly elevated(P<0.05).However,in LPS+miR-351 inhibitor+Fer-1 group,the cell viability increased(P<0.05),and the GSH level rose significantly(P<0.05),with corresponding decreases in intracellular ROS,Fe2+and ACSL4 protein levels(P<0.05).CONCLUSION:Inhibition of ferroptosis attenuated sepsis-induced myocardial injury,and inhibition of miR-351-5p promotes sepsis-induced ferroptosis of H9c2 cardiomyocytes.

AIM:This study aims to investigate the role of ferroptosis in the myocardium of mice with lipopoly-saccharide(LPS)-induced sepsis and in the injury of H9c2 rat cardiomyocytes,and to explore the regulatory function of microRNA-351-5p(miR-351-5p)in this context.METHODS:An in vivo model of sepsis-induced cardiomyopathy was established in mice through intraperitoneal injection of LPS.Twenty-four mice were randomly divided into negative control(NC)group,LPS group,and LPS+ferroptosis inhibitor ferrostatin-1(Fer-1)group.Hematoxylin-eosin(HE)staining was conducted to assess cardiac injury,and plasma levels of creatine kinase(CK)and lactate dehydrogenase(LDH)were also measured.Additionally,the levels of Fe2+and malondialdehyde(MDA)in plasma were quantified,and the mRNA levels of acyl-CoA synthetase long chain family member 4(ACSL4)and prostaglandin-endperoxide synthase 2(PTGS2)were de-tected by RT-qPCR.In vitro,H9c2 cardiomyocytes were stimulated with LPS to create cellular models,followed by treat-ment with Fer-1,inhibitor NC,or miR-351-5p inhibitor.Cell viability was evaluated using CCK8 assay,intracellular re-active oxygen species(ROS)were measured by flow cytometry,intracellular Fe2+levels were assessed using a fluorescence probe,and the protein expression of glutathione peroxidase 4(GPX4)and ACSL4 was analyzed by Western blot.The MDA and reduced glutathione(GSH)levels were measured using commercial kits.MicroRNA(miRNA)sequencing was performed on the LPS-stimulated H9c2 cardiomyocyte models,with differential miRNAs identified and subsequently vali-dated using RT-qPCR.RESULTS:The mice in LPS group exhibited significant myocardial tissue dysregulation com-pared with NC group,with enlarged space,increased plasma CK and LDH levels(P<0.05),elevated Fe2+and MDA levels in myocardial tissues(P<0.05),and increased mRNA levels of ACSL4 and PTGS2(P<0.05).In contrast,the mice in LPS+Fer-1 group demonstrated improved myocardial tissue structure,reduced space,decreased plasma CK and LDH levels(P<0.05),and lower Fe2+and MDA levels in myocardial tissues(P<0.05),along with decreased mRNA level of PTGS2(P<0.05).In H9c2 cardiomyocytes,cell viability,intracellular GSH level,and GPX4 protein level were significantly reduced in LPS group compared with NC group(P<0.05),while ROS,MDA,Fe2+,and ACSL4 protein levels were elevated(P<0.05).The cells in LPS+Fer-1 group showed increased viability,intracellular GSH level,and GPX4 protein level compared with LPS group(P<0.05),alongside reduced ROS,MDA,Fe2+,and ACSL4 levels(P<0.05).miRNA sequencing revealed a significant decrease in several miRNAs,with miR-351-5p showing the most pro-nounced reduction.In LPS+miR-351 inhibitor group,H9c2 cell viability significantly declined(P<0.05),and the levels of GSH and GPX4 were notably lowered(P<0.05),while ROS,MDA,Fe2+and ACSL4 protein levels were significantly elevated(P<0.05).However,in LPS+miR-351 inhibitor+Fer-1 group,the cell viability increased(P<0.05),and the GSH level rose significantly(P<0.05),with corresponding decreases in intracellular ROS,Fe2+and ACSL4 protein levels(P<0.05).CONCLUSION:Inhibition of ferroptosis attenuated sepsis-induced myocardial injury,and inhibition of miR-351-5p promotes sepsis-induced ferroptosis of H9c2 cardiomyocytes.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Liver cancer is a malignant tumor with a high mortality rate.With the continuous development of targeted drugs,immunotherapy and other technological means,translational therapy has become a consensus in the treatment of advanced liver cancer.The liver's inherent immune tolerance,tumor tissue,and various immune components constitute a dynamically changing liver cancer microenvironment.The immune escape in the microenvironment of liver cancer is the main obstacle to current immunotherapy.Cellular immunity is an important component of anti-tumor immunity,and the status and function of immune cells are closely related to cancer prognosis.This article reviews the progress of tumor infiltrating lymphocytes in the tumor microenvironment of hepatocellular carcinoma,in order to benefit the exploring of targeted antitumor therapy.

Non-small cell lung cancer(NSCLC)is one of the most prevalent and deadliest cancers worldwide.While the use of targeted therapies and immunotherapies in precision medicine has improved outcomes for some patients,a significant portion of individuals still fail to benefit,emphasizing the need to investigate the underlying mechanisms of resis-tance.Survival analyses have shown that NSCLC patients with SMARCA4 mutations often have poor prognoses.SMARCA4,the core ATPase subunit of the SWI/SNF chromatin remodeling complex,plays a critical role in regulating gene transcription by modifying chromatin accessibility.This influences essential cellular processes such as differentiation and cell cycle regula-tion,and SMARCA4 is widely regarded as a tumor suppressor.This review will explore the role of SMARCA4 mutations in tumor progression,its clinicopathological features in NSCLC,its impact on treatment outcomes,and potential therapeutic strategies.

Objective: To evaluate the relationship between bolus volume and hyoid displacement in dysphagia patients with nasopharyngeal carcinoma after radiation therapy. Methods: Twenty-three nasopharyngeal carcinoma patients with dysphagia were recruited and their swallowing of 3, 5, 10 and 20ml of liquid food was studied fluoroscopically. The vertical and horizontal displacement of the hyoid as well as its time in motion were measured, and the relationship between the bolus volume, hyoid displacement and time in motion time was evaluated. Results: The largest vertical displacement of the hyoid (1.01±0.65cm) was observed when swallowing a 10ml bolus. The hyoid showed the smallest average horizontal displacement (0.39±0.34cm), when swallowing a 3ml bolus. The average motion time of the hyoid was (2.11±0.65) seconds. It was shorter when swallowing a 10 or 20ml bolus than when dealing with a smaller one. Hyoid motion time was negatively correlated with the horizontal displacement of the hyoid bone, and the volume of a swallow was negatively correlated with the hyoid motion time but positively correlated with the penetration-aspiration scale score. Conclusion Bolus volume affects hyoid displacement and hyoid motion time in nasopharyngeal carcinoma patients with dysphagia after radiation therapy. For patients with a penetration-aspiration scale score of 5 or less, the optimum bolus volume is 5 to 10ml.

Objective To investigate the regulation effect of emodin on human embryonic liver L02 cells strain farnesoid X receptor (FXR) pathways.Methods By using Guggulsterones,FXR genes were intervened with in L02 cells as model group,in three different concentrations of emodin (50.0 μ mol/L,25.0 μmol/L,12.5 μmol/L) of emodin in the model group cells,FXR,small heterodimer parter (SHP),UDP-glucuronosyltransferase 2B4 (UGT2 B4),bile salt export pump(BSEP) mRNA and protein expressions were detected by real-time fluorescent quantitative PCR and Western blot test.Results (1) The relative expressions of FXR mRNA and protein in the model group (0.240 ± 0.021,0.385 ±0.119) decreased significantly than those of control group (1.000 ± 0.088,1.000 ± 0.223),the differences were statistically significant (t =14.62,4.21,all P ＜ 0.01).Compared with the model group,the relative expressions of FXR mRNA in the high,the middle and the low-dose emodin groups (0.755 ±0.083,0.817 ±0.097,0.547 ± 0.080) were significantly higher (t =10.42,10.03,6.39,all P ＜ 0.01).The relative expressions of FXR protein in the medium-dose group (0.865 ± 0.203) increased significantly (t =3.53,P ＜ 0.01).The relative expressions of FXR mRNA in the high and the medium-dose groups (0.755 ± 0.083,0.817 ± 0.097) were higher than those in the low-dose group (0.547 ± 0.080),the differences were statistically significant (t =3.11,3.70,all P ＜ 0.01).(2)The relative expressions of SHP,UGT2B4,BSEP mRNA and protein in the model group (0.148 ±0.025,0.205 ± 0.039,0.184 ± 0.020;0.458 ± 0.130,0.255 ± 0.170,0.303 ± 0.100) were significantly lower than those in the control group (1.000 ±.0.099,1.000 ±0.104,1.000 ±0.125;1.000 ±0.129,1.000 ±0.157,1.000 ±0.162),the differences were statistically significant (t =14.50,12.44,11.19,5.13,5.57,6.33,all P ＜ 0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high,the middle and the low-dose groups (0.610 ± 0.058,0.514 ± 0.041,0.707 ± 0.062;0.755 ± 0.108,0.800 ± 0.086,0.727 ± 0.076;0.470 ± 0.070,0.582 ± 0.050,0.500±0.108) were significantly lower than those in the model group (0.148 ± 0.025,0.205 ± 0.039,0.184 ± 0.020),the differences were statistically significant (t =12.75,9.38,13.94,9.46,10.90,11.96,7.53,10.31,5.00,all P ＜0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high and the middle-dose emodin group (0.658 ±0.091,0.624 ±0.113,0.607 ±0.097;0.868 ±0.194,0.883 ±0.099,0.913 ±0.131) were significantly higher than those in the low-dose group (0.458 ±0.130,0.255 ±0.170,0.303 ±0.100),the differences were statistically significant (t =2.18,3.13,3.78,3.05,5.53,6.41,all P ＜ 0.01).The relative expression of SHP and BSEP protein in the low-dose group (0.645 ±0.135,0.572 ±0.076) increased,the differences were statistically significant (t =1.73,P ＜ 0.05,t =3.72,P ＜ 0.01).The relative expression of BSEP protein in the high and the medium-dose groups (0.607 ±0.097,0.913 ± 0.131) was significantly higher than those in the low-dose group (0.572 ± 0.076),the differences were statistically significant (t =1.99,3.90,all P ＜ 0.01).The relative expressions of SHP and UGT2B4 mRNA in the high and the low-dose group (0.610 ±0.058,0.470 ±0.070;0.514 ± 0.041,0.582 ± 0.050) were significantly lower than those in the medium-dose group (0.800 ± 0.086),the differences were statistically significant (t =3.75,6.47,3.83,3.42,all P ＜ 0.01).The expression levels of UGT2B4 and BSEP in the high and the low-dose groups (0.624 ± 0.113,0.644 ± 0.097;0.607 ± 0.097,0.572 ± 0.076) were significantly lower than those in the medium-dose group (0.883 ± 0.099,0.913 ± 0.131),the differences were statistically significant (t =4.27,2.98,6.30,3.90,all P ＜ 0.01).Conclusions Guggulsterones can inhibit FXR and downstream genes SHP,UGT2B4,BSEP expressions in L02,and emodin can enhance FXR gene expression,promote SHP,UGT2B4,BSEP gene expression,inhibit cholestasis pathway,protection of liver cell,which shows a dosage discreapancy.

Objective To observe the effect of low tidal volume lung protective ventilation management strategy on postoperative outcome of elderly patients with poor pulmonary function after abdominal surgery.Methods Eighty patients of poor pulmonary function undergoing open gastrointestinal surgery,male 64 cases,female 16 cases,aged over 65 years old,ASA physical status Ⅱ or Ⅲ,NYHA cardiac function Ⅱ or Ⅲ grade,expected operation time 2-4 h were screened.The patients were randomly divided into 2 groups: protective ventilation management group (group P) and conventional mechanical ventilation group (group C),40 cases in each group.Multi-mode anesthetic management was performed in both groups.The respiratory parameters were adjusted according to the group after tracheal intubation,and the respiratory rate was adjusted to maintain PETCO2 35-45 mm Hg.The blood gas evaluated postoperative oxygen and postoperative spontaneous breathing recovery time,recovery time,extubation time,PACU time,gastrointestinal function recovery time,ambulation time,hospital stay and cost of hospitalization were recorded.The occurrence of major complications were observed at 30 days after surgery.Results PaO2 of group C was significantly decreased at 1 and 3 days after surgery than that before operation (P<0.05),PaCO2 of group C was significantly higher at 1 and 3 days after surgery than that of group P (P<0.05);PACU residence time of group P was (76.63±29.72) min,significantly shorter than that of group C [(93.80±42.90) min] (P<0.05);The difference spontaneous breathing recovery time,awake time,extubation time,exhaust time,ambulation time,postoperative hospitalization time and hospitalization expenses of two group was not statistically significant.Within 30 d after operation,2 cases (5%) of respiratory failure patients,3 cases (7.5%) of pneumonia in group P;5 cases (12.5%)of respiratory failure patients,3 cases (7.5%) of pneumonia,postoperative hemorrhage in 1 cases (2.5%) and 1 cases (2.5%) delirium in group C,there was no significant difference of the main complications in 30 d after operation between two groups.Conclusion Under the condition of this research,low tidal volume lung protective ventilation management strategy can improve elderly patients with poor pulmonary function after abdominal surgery postoperative oxygen and help to reduce the occurrence of postoperative adverse reactions.