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MPPa-PDT induced apoptosis and autophagy through JNK and p38 MAPK signaling pathways in A549 cells

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BIOCELL 2024年第11期48卷 1603-1612页

作者： PINGHUA TU SHANSHAN WANG KELAN DENG XINJUN LI ZHANLING WU Department of respiratory and critical care medicine Xiaogan Hospital Afﬁliated to Wuhan University of Science and TechnologyDepartment of Respiratory and Critical Care MedicineXiaogan432000China

Objectives:The antitumor effects of pyropheophorbide-αmethyl ester-mediated photodynamic therapy(MPPa-PDT)were observed in several *** objective of this investigation was to examine the antineoplastic efﬁcacy of MPPa-PDT acting on lung carcinoma A549 cells and further elaborate ***:The viability of A549 cells was examined with cell counting kit-8 after MPPa-PDT *** 33342 staining,monodansylcadaverine(MDC)staining,and transmission electron microscopy were employed to observe apoptotic bodies and autophagic *** cytometry with Annexin V/propidium iodide(PI)labeling objectively assessed cell *** expression of associated proteins,including Caspase-3,Beclin-1,LC-3II,and mitogen-activated protein kinase(MAPK)families concluding c-jun NH2-terminal kinase(JNK),p38 MAPK,and extracellular signal-regulated kinase 1/2(ERK)were identiﬁed by Western ***:Prolonged exposure to MPPa-PDT gradually decreased lung cancer A549 cell *** and autophagy activity were higher in the MPPa-PDT cohort in comparison to the control ***,autophagy inhibition enhanced cell-killing efﬁcacy ***,the JNK and p38 MAPK pathways were implicated in MPPa-PDT-triggered apoptosis and ***:This study demonstrated that JNK and p38 MAPK were engaged in MPPa-PDT-mediated apoptosis and autophagy in lung carcinoma A549 cells.

关键词： Photodynamic therapy Lung carcinoma Apoptosis Autophagy

Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

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Science China(Life Sciences) 2016年第12期59卷 1297-1304页

作者： Yong Lu Hua Lin Kan Zhai Xiaojuan Wang Qiong Zhou Huanzhong Shi Department of respiratory and critical care medicine Beijing Chaoyang Hospital Capital Medical University Department of respiratory and critical care medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology

Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9-dependent mechanism.

关键词： malignant pleural effusion interleukin 17 Th9 cells

Effect of TRPV1 Channel on Proliferation and Apoptosis of Airway Smooth Muscle Cells of Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第4期34卷 504-509页

作者：赵丽敏况红艳张罗献吴纪珍陈献亮张晓宇马利军 Department of respiratory and critical care medicine Zhengzhou University People’s Hospital

Airway remodeling is an important pathological feature of asthma and the basis of severe asthma. Proliferation of airway smooth muscle cells （ASMCs） is a major contributor to airway remod- eling. As an important Ca2＋ channel, transient receptor potential vanilloid 1 （TRPV1） plays the key role in the cell pathological and physiological processes. This study investigated the expression and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel on the ASMCs proliferation and apoptosis in order to provide the scientific basis to treat asthmatic airway remodeling in clinical practice Immunofluorescence staining and reverse transcription polymerase chain reaction （RT-PCR） were used to detect the expression of TRPVI in rat ASMCs. Intracellular Ca2＋ was detected using the single cell confocal fluorescence microscopy measurement loaded with Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst 33258 staining were used to detect the proliferation and apoptosis of ASMCs in rats respectively. The data showed that：（1） TRPV1 channel was present in rat ASMCs. （2） TRPV1 channel agonist, capsaicin, increased the Ca2~ influx in a concentration-dependent manner （EC50=284.3＋58 nmol/L）. TRPV1 channel antagonist, capsazepine, inhibited Ca2＋ influx in rat ASMCs. （3） Capsaicin significantly increased the percentage of S＋G2M ASMCs and the absorbance of MTT assay. Capsazepine had the opposite effect. （4） Capsaicin significantly inhibited the apoptosis, whereas capsazepine had the opposite effect. These results suggest that TRPV1 is present and mediates Ca2＋ influx in rat ASMCs. TRPV1 activity stimulates proliferation of ASMCs in rats.

关键词： transient receptor potential vanilloid 1 airway smooth muscle cells intracellular calcium proliferation apoptosis

Synthesis, Crystal Structure and Anti-lung Cancer Activity of a New Dy(Ⅱ) Complex

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Chinese Journal of Structural Chemistry 2017年第4期36卷 609-613页

作者：韩婧韩利梅邵松军夏婧范红 Department of respiratory medicine and critical care medicine West China Hospital Sichuan University Department of respiratory medicine and critical care medicine Institute of Respiratory Disease Guizhou Provincial People's Hospital Department of respiratory medicine The Second Affiliated Hospital of Xinjiang Medical University Nursing School of Guizhou Provincial People's Hospital

A new Dy-based coordination polymer, namely {[Dy（cptpy）_2（H_2O）_2]（TPT）（Cl）}_n（1, Hcptpy = 4-（4-carboxyphenyl）-4,2？：6？,4？？-terpyridine, TPT = 2,4,6-tri（4-pyridyl）-1,3,5-triazine, DMA = N,N-dimethylacetamide） has been solvothermally synthesized by the reactions of DyCl_3, Hcptpy and TPT in a mixture solvent of DMA and H_2O. Single-crystal X-ray structural analysis reveals that 1 is a 1D linear chain coordination polymer with quadrangle channels which are occupied by the TPT ligands. The compound has been characterized by singe-crystal analyses, thermogravimetry analyses and powder X-ray diffraction measurements. The antitumor activity of compound 1 and its corresponding organic ligands Hcptpy and TPT were then investigated against four human lung cancer cell lines（NCI-H460, Calu-3, A549 and NCI-H292） by MTT assay. It was found that compared with Hcptpy and TPT, compound 1 exerted rather potent activity against all of these cell lines.

关键词： coordination polymers 1D linear chain lung cancer

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia

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Biomedical and Environmental Sciences 2023年第5期36卷 397-405页

作者： YAN Wei SUN Xiao Yan WANG Meng ZHAO Fei Fan ZHOU Qing Tao Department of respiratory and critical care medicine Peking University Third HospitalBejing 100191China

Objective This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly *** This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target *** secondary endpoints were clinical response, vancomycin treatment duration, and vancomycinassociated acute kidney injury(VA-AKI) *** All patients were at least 60 years old(median age = 81 years). The proportion of patients with target trough concentration achievement(≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group(75.8% vs. 42.4%, P = 0.006).Forty-five patients(68.2%) achieved clinical success, the median duration of vancomycin therapy was10.0 days, and VA-AKI occurred in eight patients(12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration(mg/L) = 17.194-0.104 × creatinine clearance rate(mL/min) + 0.313 × vancomycin daily dose [mg/(kg·d)].Conclusion A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

关键词： Pneumonia Clinical trials Vancomycin Trough concentration Elderly patients

Targeting the ubiquitination/deubiquitination process to regulate immune checkpoint pathways

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Signal Transduction and Targeted Therapy 2021年第2期6卷 425-435页

作者： Jiaxin Liu Yicheng Cheng Ming Zheng Bingxiao Yuan Zimu Wang Xinying Li Jie Yin Mingxiang Ye Yong Song Department of respiratory and critical care medicine Afliated Jinling HospitalMedical School of Nanjing University210002 NanjingJiangsuChina Department of respiratory and critical care medicine Jining HospitalNanjing University School of Medicine210002 NanjingChina Department of Stomatology Jining HospitalMedical School of Nanjing UniversityNanjing 210002China Department of respiratory and critical care medicine Jinling HospitalNanjing Medical University210002 NanjingJiangsuChina

The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the ***,excessive responses cause detrimental effects,such as inflammation and autoimmune *** balance the immune responses and maintain immune homeostasis,there are immune checkpoints to terminate overwhelmed immune *** and tumor cells can also exploit immune checkpoint pathways to suppress immune responses,thus escaping immune *** a consequence,therapeutic antibodies that target immune checkpoints have made great breakthroughs,in particular for cancer *** the overall efficacy of immune checkpoint blockade(ICB)is unsatisfactory since only a small group of patients benefted from ICB ***,there is a strong need to search for other targets that improve the efficacy of *** is a highly conserved process which participates in numerous biological activities,including innate and adaptive immunity.A growing body of evidence emphasizes the importance of ubiquitination and its reverse process,deubiquitination,on the regulation of immune responses,providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic *** review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity,and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.

关键词： ubiquitin immunity process

Involvement of TRPC1 and Cyclin D1 in Human Pulmonary Artery Smooth Muscle Cells Proliferation Induced by Cigarette Smoke Extract

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Current Medical Science 2020年第6期40卷 1085-1091页

作者： Xun WANG Wen WANG Chan LIU Xiao-jun WU Department of respiratory and critical care medicine Renmin Hospital of Wuhan UniversityWuhan 430060China

Cigarette smoking contributes to the development of pulmonary artery hypertension(PAH).As the basic pathological change of PAH,pulmonary vascular remodeling is considered to be related to the abnormal proliferation of pulmonary artery smooth muscle cells(PASMCs).However,the molecular mechanism underlying this process remains not exactly *** aim of this research was to study the molecular mechanism of PASMCs proliferation induced by *** PASMCs(HPASMCs)were divided into 6 groups:0%(control group),cigarette smoking extract(CSE)-treated groups at concentrations of 0.5%,1%,2%,5%,10%CSE *** proliferation was observed after 24 *** were divided into two groups:0(control group),0.5%CSE *** mRNA and protein expression levels of transient receptor potential channel 1(TRPC1)and cyclin D1 in HPASMCs after CSE treatment were respectively detected by RT-PCR and Western *** intracellular calcium ion concentration was measured by the calcium probe in each *** the negative control group and TRPC1-siRNA transfection group,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein were *** were compared with one-way ANOVA(for multiple-group comparison)and independent t-test(for two-group comparison)followed by the least significant difference(LSD)test with the computer software SPSS *** was found that 0.5%and 1%CSE could promote the proliferation of HPASMCs(P<0.05),and the former was more effective than the latter(P<0.05),while 3%and above CSE had inhibitory effect on HPASMCs(P<0.05).The mRNA and protein expression levels of TRPC1 and cyclin D1 in 0.5%and 1%CSE groups were significantly higher than those in the control group(P<0.05),while those in 3%CSE group were significantly decreased(P<0.05).Moreover,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein in TRPC1-siRNA transfection group were significantly reduced as compared with those in the negative control group(P<

关键词： cigarette smoke extract human pulmonary artery smooth muscle cells transient receptor potential channel 1 cyclin D1

Severe Klebsiella pneumoniae pneumonia complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism:A case report

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World Journal of Clinical Cases 2022年第30期10卷 11101-11110页

作者： Xiao-Li Bao Nan Tang Yang-Zhong Wang Department of respiratory and critical care medicine Chongqing University Fuling HospitalChongqing 408000China

BACKGROUND Klebsiella pneumoniae(***)is a clinically common Gram-negative bacillus that can cause community-and hospital-acquired infections and lead to pneumonia,liver abscesses,bloodstream infections,and other infectious diseases;however,severe pneumonia caused by hypervirulent ***(hv Kp)complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism is rarely seen in the clinical setting and has not been reported in the *** SUMMARY A 51-year-old man was hospitalized with fever and *** mild pain in the middle and upper abdomen began at dawn on the 3rd day following admission and developed into persistent severe pain in the left upper abdomen 8h *** on chest computed tomography(CT),bronchoscopy,bronchoalveolar lavage fluid metagenomic next-generation sequencing,abdominal aortic CT angiography(CTA),and culture of the superior mesenteric artery embolus,adult community-acquired severe hv Kp pneumonia complicated by acute intraabdominal multiple arterial thrombosis and bacterial embolism was ***,he recovered and was discharged from the hospital after receiving effective meropenem anti-infection,endovascular contact thrombolytic,and systemic anticoagulant therapies and undergoing percutaneous thrombus *** days later,the patient returned to the hospital for abdominal CTA examination,which indicated blocked initial common pathway of the celiac trunk and superior mesenteric artery,and local ***,celiac trunk artery stenting was performed in Chongqing Hospital,and postoperative recovery was *** We report a case of hv Kp severe pneumonia complicated by acute intra-abdominal multiple arterial thrombosis and bacterial embolism and suggest that clinicians should consider the possibility of a Gram-negative bacillus infection and conduct effective pathogen detection in a timely fashion when managing patients with severe community-acquired pneumonia befo

关键词： Klebsiella pneumoniae Severe pneumonia Acute mesenteric ischemia Superior mesenteric artery embolism Case report

Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice:Involvement of TGF-β1/Smads Signaling Pathway

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Current Medical Science 2019年第5期39卷 748-753页

作者： Wen WANG Gan ZHA Jin-jing ZOU Xun WANG Chun-nian LI Xiao-jun WU Department of respiratory and critical care medicine Rentnin Hospital of Wuhan UniversityWuhan 430060China

Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease(COPD),its underlying mechanisms were not clear until *** aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract(CSE).Twenty SPF C57BL/6 mice were randomly divided into PBS control group,COPD model group,low-dose berberine group and high-dose berberine group,5 mice in each *** neutrophils and macrophages were examined by Wright's *** levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid(BALF)were detennined by enzyme-linked immunosorbent *** expression levels of TGF-β1,Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western *** was found that CSE increased the number of inflammation cells in BALF,elevated lung inflammation scores,and enhanced the TGF-β1/Smads signaling activity in ***-dose berberine restrained the alterations in the COPD mice induced by *** was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD ***-β1/Smads signaling pathway might be involved in the *** findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation.

关键词： berberine cigarette smoke extract chronic obstructive pulmonary disease TGF-β1/Smads signaling pathway