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1.
PLoS One ; 19(6): e0303442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885284

RESUMO

BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.


Assuntos
alfa-Globulinas , Biomarcadores , Infecções por HIV , Tenofovir , Microglobulina beta-2 , Humanos , Masculino , Microglobulina beta-2/urina , alfa-Globulinas/urina , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Infecções por HIV/complicações , Biomarcadores/urina , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Injúria Renal Aguda/urina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia
2.
J Inorg Biochem ; 256: 112574, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677004

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, which owned severe resistance to platinum-based anticancer agents. Herein, we report a new metal-arene complex, Ru-TPE-PPh3, which can be synthesized in vitro and in living cells with copper catalyzed the cycloaddition reaction of Ru-azide and alkynyl (CuAAC). The complex Ru-TPE-PPh3 exhibited superior inhibition of the proliferation of TNBC MDA-MB-231 cells with an IC50 value of 4.0 µM. Ru-TPE-PPh3 could induce the over production of reactive oxygen species (ROS) to initiate the oxidative stress, and further damage the mitochondria both functionally and morphologically, as loss of mitochondrial membrane potential (MMP) and cutting the supply of adenosine triphosphate (ATP), the disappearance of cristae structure. Moreover, the damaged mitochondria evoked the occurrence of mitophagy with the autophagic flux blockage and cell death. The complex Ru-TPE-PPh3 also demonstrated excellent anti-proliferative activity in 3D MDA-MB-231 multicellular tumor spheroids (MCTSs), indicating the potential to inhibit solid tumors in living cells. This study not only provided a potent agent for the TNBC treatment, but also demonstrated the universality of the bioorthogonally catalyzed lethality (BCL) strategy through CuAAC reation.


Assuntos
Antineoplásicos , Autofagia , Complexos de Coordenação , Mitocôndrias , Espécies Reativas de Oxigênio , Rutênio , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Autofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Rutênio/química , Rutênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Potencial da Membrana Mitocondrial/efeitos dos fármacos
3.
Inorg Chem ; 63(11): 5235-5245, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38452249

RESUMO

Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.


Assuntos
Antineoplásicos , Neoplasias , Cisplatino/farmacologia , Linhagem Celular Tumoral , Ciclo Celular , Mitocôndrias , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Neoplasias/metabolismo
4.
Inorg Chem ; 63(10): 4758-4769, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38408314

RESUMO

The efficiency of nitrogen mustards (NMs), among the first chemotherapeutic agents against cancer, is limited by their monotonous mechanism of action (MoA). And tumor hypoxia is a significant obstacle in the attenuation of the chemotherapeutic efficacy. To repurpose the drug and combat hypoxia, herein, we constructed an organo-Ir(III) prodrug, IrCpNM, with the composition of a reactive oxygen species (ROS)-inducing moiety (Ir-arene fragment)-a hypoxic responsive moiety (azo linker)-a DNA-alkylating moiety (nitrogen mustard), and realized DNA damage response (DDR)-mediated autophagy for hypoxic lung cancer therapy for the first time. Prodrug IrCpNM could upregulate the level of catalase (CAT) to catalyze the decomposition of excessive H2O2 to O2 and downregulate the expression of the hypoxia-inducible factor (HIF-1α) to relieve hypoxia. Subsequently, IrCpNM initiates the quadruple synergetic actions under hypoxia, as simultaneous ROS promotion and glutathione (GSH) depletion to enhance the redox disbalance and severe oxidative and cross-linking DNA damages to trigger the occurrence of DDR-mediated autophagy via the ATM/Chk2 cascade and the PIK3CA/PI3K-AKT1-mTOR-RPS6KB1 signaling pathway. In vitro and in vivo experiments have confirmed the greatly antiproliferative capacity of IrCpNM against the hypoxic solid tumor. This work demonstrated the effectiveness of the DNA damage-responsive organometallic prodrug strategy with the microenvironment targeting system and the rebirth of traditional chemotherapeutic agents with a new anticancer mechanism.


Assuntos
Neoplasias Pulmonares , Pró-Fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Pró-Fármacos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Peróxido de Hidrogênio , Hipóxia , Autofagia , Dano ao DNA , DNA , Linhagem Celular Tumoral , Microambiente Tumoral
5.
J Inorg Biochem ; 251: 112427, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37979498

RESUMO

Breast cancer is the most commonly diagnosed cancer and second­leading cause of cancer deaths in women. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in promoting breast cancer cell proliferation, invasion, angiogenesis, and metastasis, and the high expression of STAT3 is related to the occurrence and poor chemotherapy sensitivity of breast cancer. Iridium(III) complexes Ir-PTS-1- 4 containing a pterostilbene-derived ligand were synthesized to inhibit the STAT3 pathway in breast cancer. Ir-PTS-4 inhibited the proliferation of breast cancer cells by suppressing the expression of phosphorylated STAT3 and STAT3-related cyclin D1, arresting cell cycle in the S-phase, inducing DNA damage and reactive oxygen species (ROS) generation, eventually leading to autophagic cell death. The cell metastasis and invasion were also inhibited after Ir-PTS-4 treatment. Besides, Ir-PTS-4 exhibited excellent anti-proliferation activity in 3D multicellular tumor spheroids, showing potential for the treatment of solid tumors. This work presents the rational design of metal-based anticancer agents to block the STAT3 pathway for simultaneously inhibiting breast cancer proliferation and metastasis.


Assuntos
Antineoplásicos , Neoplasias da Mama , Irídio , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Irídio/farmacologia , Irídio/uso terapêutico , Fator de Transcrição STAT3/metabolismo
6.
Medicine (Baltimore) ; 102(48): e36383, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050207

RESUMO

BACKGROUND: Corneal pregnancy is rare and difficult to detect in the early stages. Due to the abundant blood supply in this area, a rupture can result in massive internal bleeding, shock, and even death. Therefore, immediate surgery is necessary, and patients must replenish their blood volume as soon as possible to ensure blood supply to important organs. For those whose blood pressure cannot immediately rise, surgery should be performed while resisting shock to buy time. CASE SUMMARY: We present the case of a 34-year-old Chinese woman at 19 weeks of gestation who had a corneal pregnancy. No abnormalities were detected in the examinations in the first trimester. This patient was 19 weeks pregnant and sought medical advice due to sudden lower abdominal pain, syncope, and hemorrhagic shock. After rescue and treatment, she recovered and was discharged from the hospital, afterwards, the patient gave birth to a child 7 years later. CONCLUSION: The early diagnosis of cornual pregnancy is mainly based on ultrasound. However, there is a high incidence of missed diagnosis and misdiagnosis of this disease. Patients may face serious and life-threatening conditions in case of the rupture of cornual pregnancy. This disease can be mainly treated by surgery.


Assuntos
Gravidez Cornual , Ruptura Uterina , Gravidez , Feminino , Criança , Humanos , Adulto , Ruptura Uterina/diagnóstico , Ruptura Uterina/etiologia , Ruptura Uterina/cirurgia , Hemorragia/complicações , Dor Abdominal , Ultrassonografia/efeitos adversos
7.
Arch Med Sci ; 19(6): 1760-1767, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058726

RESUMO

Introduction: Anti-coagulant unfractionated heparin of low molecular weight (ACUHlmw) therapy is popularly practised in the therapy of recurrent miscarriages (RMC) due to its anti-coagulant properties. However, several in vitro investigations have hypothesized about the possible immunological effects of ACUHlmw. Material and methods: We examined pregnant women with cryptic RMC (cRMC) to determine whether ACUHlmw could regulate the immune reaction in vivo during their pregnancy. In this study, a total of 51 women were subjected to tinzaparin and 48 patients were considered as control women on the basis of an open single-centre randomized controlled trial. During different fertilization weeks (FW) 7, 19, 29, and 35 plasma samples were acquired for eleven chemokine and cytokine levels and then investigated by multiplex bead technology and selected to portray T-helper subset-related immunity. Results: We did not find any difference in chemokine C-C motif ligand-2, -17, -22, chemokine C-X-C motif ligand-1, -8, -12, -13 or cytokine interleukin-6 when a mixed linear model test was carried out on ACUHlmw in both the study and control women. However, differences were observed in the mixed linear model test on ACUHlmw in both the study and control women during pregnancy of the Th1/Th17 related chemokine C-X-C motif ligand-10 (p = 0.01), -11 (p < 0.001) and chemokine C-C motif ligand-20 (p = 0.04) respectively. Conclusions: A positive outcome of ACUHlmw therapy in vivo was observed, thus establishing its potential proinflammatory effect. During 2nd and 3rd trimesters, the observed harmonious enlargement in Th1/Th17 related chemokine and cytokine levels does not recommend a fruitful immunological impact of ACUHlmw therapy in vivo.

8.
Med Sci Monit ; 30: e943403, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38059305

RESUMO

The authors requested retraction after reviewing the manuscript and determining that there were errors in the data. Reference: Yanli Hong, Yanyun Yin, Yong Tan, Ke Hong, Huifang Zhou. The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome. Med Sci Monit, 2019; 25: 395-401. DOI: 10.12659/MSM.912341.

9.
Angew Chem Int Ed Engl ; 62(48): e202312897, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-37830171

RESUMO

Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation (LPO) with the potential for antitumor immunity activation. In this study, a nonferrous cyclopentadienyl metal-based ferroptosis inducer [Ir(Cp*)(Bet)Cl]Cl (Ir-Bet) was developed by a metal-ligand synergistic enhancement (MLSE) strategy involving the reaction of [Ir(Cp*)Cl]2 Cl2 with the natural product Betulin. The fusion of Betulin with iridium cyclopentadienyl (Ir-Cp*) species as Ir-Bet not only tremendously enhanced the antiproliferative activity toward cancer cells, but also activated ferritinophagy for iron homeostasis regulation by PI3K/Akt/mTOR cascade inhibition with a lower dosage of Betulin, and then evoked an immune response by nuclear factor kappa-B (NF-κB) activation of Ir-Cp* species. Further immunogenic cell death (ICD) occurred by remarkable ferroptosis through glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) deactivation and ferritinophagy. An in vivo vaccination experiment demonstrated desirable antitumor and immunogenic effects of Ir-Bet by increasing the ratio of cytotoxic T cells (CTLs)/regulatory T cells (Tregs).


Assuntos
Ferroptose , Irídio/farmacologia , Fosfatidilinositol 3-Quinases , Ferro/metabolismo , Glutationa
10.
Immunol Res ; 71(6): 929-940, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37405561

RESUMO

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.


Assuntos
Células T Matadoras Naturais , Encefalopatia Associada a Sepse , Sepse , Humanos , Encefalopatia Associada a Sepse/diagnóstico , Encefalopatia Associada a Sepse/epidemiologia , Estudos Prospectivos , Prognóstico , Albumina Sérica
11.
Dalton Trans ; 52(20): 6922-6933, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37158602

RESUMO

Breast cancer (BC) is one of the most common malignant tumors and often accompanied by inflammatory processes. Inflammation is an essential component of the tumor microenvironment, which might influence tumor proliferation and metastasis. Herein, three metal-arene complexes MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru were prepared by tethering the non-steroidal anti-inflammatory drug meclofenamic acid (MA). Among them, MA-bip-Ru and MA-bpy-Ir showed lower cytotoxicity towards cancer cells, but MA-bpy-Ru showed significantly high selectivity and cytotoxicity towards MCF-7 cells through the autophagic pathway and exhibited no toxicity against normal HLF cells, showing potential for selective treatment of tumor cells. MA-bpy-Ru could also effectively destroy the 3D multicellular tumor spheroids, demonstrating its potential for clinical application. Besides, MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru exhibited anti-inflammatory properties superior to MA, notably downregulating the expression of cyclooxygenase-2 (COX-2) and inhibiting the secretion of prostaglandin E2 in vitro. These findings demonstrated that MA-bpy-Ru was capable of intervening in inflammatory processes and showed the potential of MA-bpy-Ru to act as a selective anticancer agent, thus presenting a new mechanism of action for metal-arene complexes.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclo-Oxigenase 2 , Ácido Meclofenâmico , Rutênio/farmacologia , Humanos
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(3): 295-301, 2023 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-36946166

RESUMO

OBJECTIVES: To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants. METHODS: China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). RESULTS: A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05). CONCLUSIONS: Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.


Assuntos
Displasia Broncopulmonar , Ventilação de Alta Frequência , Ventilação não Invasiva , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Ventilação com Pressão Positiva Intermitente , Extubação , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Pressão Positiva Contínua nas Vias Aéreas
13.
J Inorg Biochem ; 243: 112195, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36996696

RESUMO

Combination of novel immunomodulation and traditional chemotherapy has become a new tendency in cancer treatment. Increasing evidence suggests that blocking the "don't eat me" signal transmitted by the CD47 can promote the phagocytic ability of macrophages to cancer cells, which might be promising for improved cancer chemoimmunotherapy. In this work, we conjugated CPI-alkyne modified by Devimistat (CPI-613) with ruthenium-arene azide precursor Ru-N3 by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to construct Ru complex CPI-Ru. CPI-Ru exhibited satisfactory cytotoxicity towards the K562 cells while nearly non-toxic towards the normal HLF cells. CPI-Ru has been demonstrated to cause severe damage to mitochondria and DNA, ultimately inducing cancer cell death through the autophagic pathway. Moreover, CPI-Ru could significantly downregulate the expression of CD47 on the surface of K562 accompanied by the enhanced immune response by targeting the blockade of CD47. This work provides a new strategy for utilizing metal-based anticancer agents to block CD47 signal to achieve chemoimmunotherapy in chronic myeloid leukemia treatment.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Rutênio , Humanos , Rutênio/farmacologia , Antígeno CD47/genética , Antígeno CD47/metabolismo , Azidas , Imunização , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Fagocitose
14.
ACS Appl Bio Mater ; 6(2): 722-732, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36626248

RESUMO

The rational design of cancer theranostics with natural diagnostic information and therapeutic behavior has been considered to be a big challenge, since common theranostics from photothermal and photodynamic therapy need to be activated with external stimuli of photoirradiation to enable the chemotherapeutic effects. In this contribution, we have designed and synthesized a series of simple theranostic agents, TPA-N-n (n = 4, 8, 12), which could accumulate at the tumor site over 48 h and indicate superior antiproliferative performance in vivo. TPA-N-n was constructed with electron donor triphenylamine-acceptor benzothiadiazole-mitochondria-targeting moiety pyridinium. Complex TPA-N-8 indicated the best cytotoxicity to cancerous HeLa cells, with an IC50 value of 4.3 µM, and could self-assemble to a nanosphere with a size of 161.2 nm in the DMSO/PBS solution. It is worth noting that TPA-N-8 could accumulate in the mitochondria and produce major ROS species O2•- and OH• as well as small amounts of 1O2 without photoirradiation. Oxidative DNA damage is initiated due to the imbalance of intracellular redox homeostasis from the significant ROS storm. Multimodal synergistic therapy for HeLa cells was activated, as the PINK1-mediated mitophagy from the damaged mitochondria and DNA damage responsive (DDR) induced necroptosis and autophagy. This work not only provided a successful D-A type theranostic agent with superior anticancer performance from multimodal synergistic therapy but also further demonstrated the high efficacy of a mitochondria-targeting strategy for cancer treatment.


Assuntos
Mitocôndrias , Nanosferas , Neoplasias , Humanos , Células HeLa , Mitocôndrias/efeitos dos fármacos , Nanosferas/química , Nanosferas/uso terapêutico , Neoplasias/tratamento farmacológico , Medicina de Precisão/métodos , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
15.
ChemMedChem ; 18(5): e202200614, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36578101

RESUMO

Inhibition of histone deacetylase (HDAC) has been demonstrated to be an effective strategy for cancer treatment. In this work, we have developed a new agent Ir-VPA, which exhibits the cell death mode switching between apoptosis and autophagy due to the distinct level of HDAC6 inhibition. Ir-VPA indicates the best anticancer activity to HeLa cells, and could be hydrolyzed due to the high expression of the esterase in HeLa cells. Ir-VPA could accumulate in nuclei, induce severe DNA damages and cell cycle arrest at G2/M phase. The anticancer mechanism of Ir-VPA to HeLa cells was dependent on the HDAC6 inhibitory performance, as the caspase dependent apoptosis at low concentration (IC50 ) and autophagy with the autophagy flux blockage at high concentration (2×IC50 ). This is resulted from the distinct inhibitory levels of HDAC6, as moderate/complete inhibition at the concentration of IC50 /2×IC50 .In the presence of autophagic inhibitor chloroquine, the apoptotic population elevated from 32.7 % to 61.7 %, indicating that Ir-VPA could activate apoptotic process through the autophagolysosome fusion inhibition. Ir-VPA also exhibits excellent antiproliferative behavior to 3D HeLa multicellular tumor spheroids (MCTSs). This work not only provided a new HDAC6 inhibitor and novel anticancer mechanism for the effective treatment of cervical cancer, but also demonstrated the strategy to conjugate the metal fragment with active organic drug to enhance the anticancer performance.


Assuntos
Inibidores de Histona Desacetilases , Ácido Valproico , Humanos , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Células HeLa , Ácido Valproico/farmacologia , Linhagem Celular Tumoral , Apoptose , Morte Celular , Autofagia , Histona Desacetilase 1
16.
J Inorg Biochem ; 238: 112057, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370504

RESUMO

It is a major challenge to design novel multifunctional metal-based chemotherapeutic agents for anti-tumor and anti-metastasis applications. Two complexes (OA-Ir and OA-Ru) were synthesized via CuAAC (copper-catalyzed azide-alkyne cycloaddition) reaction from nontoxic Ir-N3 or Ru-N3 species and low toxic alkynyl precursor OA-Alkyne, and exhibited satisfactory anti-tumor and anti-metastasis pharmacological effects. Conjugation of Oleanolic acid (OA) and metal-arene species significantly enhanced the cytotoxicity in A2780 cells compared to the precursors through mitochondrial-induced autophagy pathway. Moreover, the two complexes could inhibit the cell metastasis and invasion through damage of actin dynamics and down-regulation of MMP2/MMP9 proteins. Combination of two precursors improved the lipophilicity and biocompatibility, simultaneously enhanced the cell uptake and the mitochondrial accumulation of metal-arene complexes, which caused mitochondrial membrane potential damage, oxidative phosphorylation, ATP depletion and autophagy. Besides, OA-Ir and OA-Ru displayed excellent activity to disintegrate the 3D multicellular tumor spheroids, showing potential for the treatment of solid tumors. This work provides a new way for developing novel metal-based complexes via CuAAC reaction for simultaneously inhibiting tumor proliferation and metastasis.


Assuntos
Complexos de Coordenação , Neoplasias Ovarianas , Rutênio , Humanos , Feminino , Rutênio/farmacologia , Irídio/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Alcinos
17.
World J Gastrointest Surg ; 15(12): 2919-2925, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38222016

RESUMO

BACKGROUND: Esophageal atresia (EA) is a life-threatening congenital malformation in newborns, and the traditional repair approaches pose technical challenges and are extremely invasive. Therefore, surgeons have been actively investigating new minimally invasive techniques to address this issue. Magnetic compression anastomosis has been reported in several studies for its potential in repairing EA. In this paper, the primary repair of EA with magnetic compression anastomosis under thoracoscopy was reported. CASE SUMMARY: A full-term male weighing 3500 g was diagnosed with EA gross type C. The magnetic devices used in this procedure consisted of two magnetic rings and several catheters. Tracheoesophageal fistula ligation and two purse strings were performed. The magnetic compression anastomosis was then completed thoracoscopically. After the primary repair, no additional operation was conducted. A patent anastomosis was observed on the 15th day postoperatively, and the magnets were removed on the 23rd day. No leakage existed when the transoral feeding started. CONCLUSION: Thoracoscopic magnetic compression anastomosis may be a promising minimally invasive approach for repairing EA.

18.
Medicine (Baltimore) ; 101(35): e30293, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107545

RESUMO

BACKGROUND: Cellular angiofibroma (CAF), a rare benign mesenchymal tumor, is histologically characterized by abundant thick-walled vessels with a spindle cell component. As one of the female reproductive system tumors, its clinical and pathological features are not well characterized. METHODS: A 47-year-old woman presented for the removal of intrauterine device on October 28, 2021, as she had achieved menopause one year back. The patient had no discomfort or awareness of any mass in her vagina. She has history of breast cancer and papillary thyroid cancer. Till date, no progression of thyroid cancer or breast cancer has been observed. Her menstrual cycle was regular, and she had one child delivered vaginally. RESULTS: Pelvic examination revealed a mass sized 2.5 × 2.0 cm located near the fornix in the upper segment of the left vaginal wall. Thin prep cytologic test (TCT) revealed negative intraepithelial lesion or malignancy (NILM). HPV test was negative and leucorrhea routine inspection cleanliness II degree. No cervical mass was detected by ultrasound examination. The patients underwent the operation for intrauterine device removal plus vaginal tumor resection on November 1, 2021. Postoperative antibiotics (intravenous cefuroxime sodium 0.75 g bid for 1 day) were administered to prevent infection. The patient showed no signs of recurrence at one-month follow-up. CONCLUSION: In summary, CAF is a rare benign soft tissue tumor. Surgery is the only treatment method, and the definitive diagnosis of CAF is based on histopathological examination of surgical specimen. Long-term follow-up is needed for surveillance of recurrence.


Assuntos
Angiofibroma , Neoplasias da Mama , Angiofibroma/diagnóstico , Angiofibroma/patologia , Angiofibroma/cirurgia , Cefuroxima , Feminino , Humanos , Pessoa de Meia-Idade , Sódio , Vagina/patologia , Vagina/cirurgia
19.
World J Clin Cases ; 10(21): 7531-7538, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36157998

RESUMO

BACKGROUND: A patient with type III Kummell's disease had a ruptured posterior cortex of the fractured vertebral body, which caused spinal cord compression. An open surgery was considered the best choice of operation. However, the patient and her family refused open surgery and instead demanded a minimally invasive surgical treatment such as percutaneous vertebroplasty (PVP). After preoperative discussion, we finally adopted the novel therapy of traditional Chinese medicine manipulative reduction (TCMMR) combined with PVP. CASE SUMMARY: A patient with type III Kummell's disease exhibiting bone block-induced spinal cord compression was admitted to our hospital. She suffered from a variety of medical disorders but refused open surgery, and instead asked for PVP surgery. TCMMR, in parallel with PVP, was used to restore the height of the compressed vertebral body and reduce the symptoms of spinal cord compression by the bone block in order to strengthen the vertebral body and prevent further collapse. The surgery was very successful. The height of the compressed vertebra was restored, and the symptom of spinal cord compression by bone block was reduced successfully via TCMMR. The fractured vertebra was solidified by the PVP. The pain visual analog score declined from preoperative 7 scores to postoperative 2 scores, and the Frankel spinal cord scale increased from preoperative D degree to postoperative E degree. CONCLUSION: The new method has advantages in treating patients with type III Kummell's disease who cannot be treated with open surgery.

20.
World J Clin Cases ; 10(22): 7973-7981, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36158505

RESUMO

BACKGROUND: Delayed arterial symptomatic epidural hematoma (SEH) on the 14th day after posterior lumbar interbody fusion (PLIF) is rare but it may lead to severe complications if not identified and treated in a timely manner. After diagnosis of the current case, early surgical removal of the hematoma and strict hemostasis treatment was accomplished. This case report highlights the importance of swift diagnosis and treatment in SEH patients. CASE SUMMARY: A 41-year-old male patient with a single-segment lumbar disc herniation underwent left-side PLIF. On the 14th post-operative day, the patient complained of lumbar incision pain with sudden onset accompanied by left limb radiation pain and aggravated cauda equina symptoms. Magnetic resonance imaging examination and a puncture blood draw at the incision site confirmed a delayed arterial SEH. Emergency surgical removal of the hematoma and hemostasis was performed. About 70 mL of hematoma was found in the left incision. Continuous bleeding was found in the anterior branch of the transverse process of the 4th lumbar artery in the muscle area about 2 cm below the transverse process of the 4th lumbar vertebra. A blood jet of about 10 cm in height was observed and bipolar electrocoagulation was used to stop the bleeding. Post-operative lumbar incision pain and left lower limb pain were relieved immediately and gradually disappeared. There was no recurrence during the 12-mo follow-up. CONCLUSION: For delayed arterial SEH on the 14th day after PLIF, preventive measures including pre-, intra- and post-operative prevention should be implemented.

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