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1.
J Tradit Chin Med ; 44(4): 660-669, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39066526

RESUMEN

OBJECTIVE: To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese Medicine, we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3 (ATP/P2X3) receptor signaling system as an indicator of the body's energy state, commonly referred to as "Qi". METHODS: The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold (PTT) in mice, while also assessing adenosine (ADO) levels and adenylate energy charge (EC) at Zusanli (ST36). The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli (ST36). To shed light on the underlying mechanisms of acupuncture's effects, the study examined the impact of ATP, a P2X3 receptor antagonist, and adenosine disodium on PTT following acupuncture administration. RESULTS: Acupuncture at Zusanli (ST36) led to significant improvements in PTT in mice, with the most effective interventions being twirling for 2 min and needle retention for 28 min. These interventions also resulted in significant increases in ATP levels. The effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli (ST36), and pretreatment with a P2X3 receptor antagonist decreased PTT. Adenylate EC peaked at 30 min after intraperitoneal injection of ATP, and pretreatment with various doses of i.p. ATP 30 min prior to acupuncture increased PTT in a dose-dependent manner. Additionally, pretreatment with an i.p. or intramuscular injection of adenosine disodium enhanced the effects of acupuncture. CONCLUSION: This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture, revealing new avenues for achieving enhanced clinical outcomes.


Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Adenosina Trifosfato , Animales , Adenosina Trifosfato/metabolismo , Ratones , Masculino , Humanos , Umbral del Dolor/efectos de los fármacos , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X3/genética
2.
FASEB J ; 38(11): e23681, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38814725

RESUMEN

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.


Asunto(s)
Apoptosis , Proteína Forkhead Box O1 , Ghrelina , Ratones Endogámicos C57BL , Estrés Oxidativo , Receptores de Ghrelina , Daño por Reperfusión , Sirtuina 1 , Ghrelina/farmacología , Ghrelina/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Sirtuina 1/metabolismo , Animales , Ratones , Receptores de Ghrelina/metabolismo , Humanos , Masculino , Proteína Forkhead Box O1/metabolismo , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Intestinos/efectos de los fármacos , Células CACO-2
3.
Free Radic Biol Med ; 221: 111-124, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763207

RESUMEN

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.


Asunto(s)
Apoptosis , Canales de Calcio , Dinaminas , Ratones Endogámicos C57BL , Mitocondrias , Dinámicas Mitocondriales , Daño por Reperfusión , Animales , Humanos , Masculino , Ratones , Apoptosis/genética , Células CACO-2 , Calcio/metabolismo , Canales de Calcio/metabolismo , Canales de Calcio/genética , Modelos Animales de Enfermedad , Dinaminas/metabolismo , Dinaminas/genética , Intestinos/irrigación sanguínea , Intestinos/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Mitocondrias/genética , Dinámicas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Estrés Oxidativo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Daño por Reperfusión/prevención & control
4.
Heliyon ; 10(9): e29987, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38737278

RESUMEN

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 (r = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread. Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control.

5.
Free Radic Biol Med ; 214: 115-128, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38331008

RESUMEN

Sestrins are metabolic regulators that respond to stress by reducing the levels of reactive oxygen species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.


Asunto(s)
Ferroptosis , Isquemia Mesentérica , Daño por Reperfusión , Animales , Humanos , Ratones , Células CACO-2 , Ferroptosis/genética , Isquemia , Proteína 1 Asociada A ECH Tipo Kelch/genética , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Reperfusión , Daño por Reperfusión/genética , Transducción de Señal
6.
Neuro Oncol ; 26(2): 295-308, 2024 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-37772937

RESUMEN

BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.


Asunto(s)
Fibroblastos Asociados al Cáncer , Cordoma , Humanos , Cordoma/genética , Perfilación de la Expresión Génica , RNA-Seq , Estrés del Retículo Endoplásmico , Microambiente Tumoral
7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1018388

RESUMEN

Objective To investigate the clinical efficacy of Yiqi Huayu Decoction(mainly composed of Astragali Radix,Dioscoreae Rhizoma,Poria,fried Euryales Semen,Ecliptae Herba,Rosae Laevigatae Fructus,charred Crataegi Fructus,Ligustri Lucidi Fructus,Salviae Miltiorrhizae Radix et Rhizoma,and Leonuri Herba)combined with Calcium Dobesilate in the treatment of diabetic nephropathy(DN)with qi deficiency and blood stasis syndrome,and to observe the effect of the therapy on vascular endothelial growth factor(VEGF)and insulin-like growth factor 1(IGF-1).Methods Ninety patients with DN of qi deficiency and blood stasis type were randomly divided into an observation group and a control group,with 45 patients in each group.All patients received basic hypoglycemic therapy and treatment for controlling blood pressure and regulating lipid metabolism disorders.Moreover,the patients in the control group were given Calcium Dobesilate orally,and the patients in the observation group were given Yiqi Huayu Decoction combined with Calcium Dobesilate.The course of treatment lasted for 3 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters and serum VEGF and IGF-1 levels in the two groups of patients were observed before and after the treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 3 months of treatment,the total effective rate of the observation group was 91.11%(41/45),and that of the control group was 75.56%(34/45).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After one month and 3 months of treatment,the TCM syndrome scores of both groups were significantly lower than those before treatment(P<0.05),and the scores after 3 months of treatment in the two groups were significantly lower than those after one month of treatment(P<0.05).The intergroup comparison showed that the reduction of TCM syndrome scores of the observation group was significantly superior to that of the control group after one month and 3 months of treatment(P<0.01).(3)After treatment,the levels of renal function parameters such as serum creatinine(Scr),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)in the two groups of patients were significantly improved compared with those before treatment(P<0.05),and the observation group's effect on the improvement of all renal function parameters was significantly superior to that of the control group(P<0.01).(4)After treatment,the serum VEGF and IGF-1 levels in the two groups of patients were significantly lower than those before treatment(P<0.05),and the observation group's effect on the decrease of serum VEGF and IGF-1 levels was significantly superior to that of the control group(P<0.01).(5)In the course of treatment,no significant adverse reactions occurred in the two groups of patients,with a high degree of safety.Conclusion Yiqi Huayu Decoction combined with Calcium Dobesilate exerts certain therapeutic effect in treating DN patients with qi deficiency and blood stasis syndrome.The combined therapy can effectively down-regulate the serum levels of VEGF and IGF-1,significantly improve the renal function,and alleviate the clinical symptoms of the patients,with a high degree of safety.

8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1019603

RESUMEN

Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.

9.
Journal of Shenyang Medical College ; (6): 179-182,187, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1020612

RESUMEN

Gut microbiota participates in numerous physiological and metabolic processes in the human body,directly affecting human health.The imbalance of gut microbiota may lead to many diseases.This article reviews the types of gut microbiota,the impact of gut microbiota on different populations,and the relationship between gut microbiota abnormalities and diseases,in order to better explain the important role of gut microbiota in human health and diseases,and provide the theoretical basis for further understanding the relationship between gut microbiota and human health.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1023170

RESUMEN

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031507

RESUMEN

This paper summarized the clinical experience of using the method of “returning fire to its origin” for treatment of paroxysmal sympathetic hyperactivity (PSH). According to the causes and clinical characteristics of PSH, the author believes that the deficiency of kidney qi, and the loss of yin and yang are the basis of the pathogenesis of PSH. Fright causes qi to be chaotic as the triggering mechanism of PSH. The key mechanism of PSH is that the deficiency yang with upper manifestation, and the fire does not return to its origin. The treatment should be nourishing yin and astringing yang, by taking modified Yinhuo Decoction (引火汤) internally, and receiving warm moxibustion as the first choice externally with selected acupoints Guanyuan (CV 4), Mingmen (GV 4), and bilateral Yongquan (KI 1); For prevention, attention should be paid to take care of stomach qi, support healthy qi, and cultivate original qi.

12.
Acta Pharmaceutica Sinica ; (12): 413-417, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1016660

RESUMEN

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

13.
World J Clin Cases ; 11(32): 7833-7851, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38073678

RESUMEN

BACKGROUND: The Nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor has attracted much attention in the context of neurological diseases. However, none of the studies have systematically clarified this field's research hotspots and evolution rules. AIM: To investigate the research hotspots, evolution patterns, and future research trends in this field in recent years. METHODS: We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods: (((((TS=(NFE2 L2)) OR TS=(Nfe2 L2 protein, mouse)) OR TS=(NF-E2-Related Factor 2)) OR TS=(NRF2)) OR TS=(NFE2L2)) OR TS=(Nuclear factor erythroid2-related factor 2) AND (((((((TS=(neurological diseases)) OR TS=(neurological disorder)) OR TS=(brain disorder)) OR TS=(brain injury)) OR TS=(central nervous system disease)) OR TS=(CNS disease)) OR TS=(central nervous system disorder)) OR TS=(CNS disorder) AND Language = English from 2010 to 2022. There are just two forms of literature available: Articles and reviews. Data were processed with the software Cite-Space (version 6.1. R6). RESULTS: We analyzed 1884 articles from 200 schools in 72 countries/regions. Since 2015, the number of publications in this field has increased rapidly. China has the largest number of publications, but the articles published in the United States have better centrality and H-index. Among the top ten authors with the most published papers, five of them are from China, and the author with the most published papers is Wang Handong. The institution with the most articles was Nanjing University. To their credit, three of the top 10 most cited articles were written by Chinese scholars. The keyword co-occurrence map showed that "oxidative stress", "NRF2", "activation", "expression" and "brain" were the five most frequently used keywords. CONCLUSION: Research on the role of NRF2 in neurological diseases continues unabated. Researchers in developed countries published more influential papers, while Chinese scholars provided the largest number of articles. There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases. NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases. However, despite decades of research, our knowledge of NRF2 transcription factor in nervous system diseases is still limited. Further studies are needed in the future.

15.
J Exp Clin Cancer Res ; 42(1): 285, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37891669

RESUMEN

BACKGROUND: Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism. METHODS: A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models. RESULTS: ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy. CONCLUSION: Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.


Asunto(s)
Neoplasias Encefálicas , Ferroptosis , Glioblastoma , Animales , Ratones , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Paclitaxel Unido a Albúmina/farmacología , Paclitaxel Unido a Albúmina/uso terapéutico , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Ratones Desnudos , Proteómica , Resistencia a Antineoplásicos , Daño del ADN , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Integr Plant Biol ; 65(10): 2262-2278, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37565550

RESUMEN

Cadmium (Cd) toxicity severely limits plant growth and development. Moreover, Cd accumulation in vegetables, fruits, and food crops poses health risks to animals and humans. Although the root cell wall has been implicated in Cd stress in plants, whether Cd binding by cell wall polysaccharides contributes to tolerance remains controversial, and the mechanism underlying transcriptional regulation of cell wall polysaccharide biosynthesis in response to Cd stress is unknown. Here, we functionally characterized an Arabidopsis thaliana NAC-type transcription factor, NAC102, revealing its role in Cd stress responses. Cd stress rapidly induced accumulation of NAC102.1, the major transcript encoding functional NAC102, especially in the root apex. Compared to wild type (WT) plants, a nac102 mutant exhibited enhanced Cd sensitivity, whereas NAC102.1-overexpressing plants displayed the opposite phenotype. Furthermore, NAC102 localizes to the nucleus, binds directly to the promoter of WALL-ASSOCIATED KINASE-LIKE PROTEIN11 (WAKL11), and induces transcription, thereby facilitating pectin degradation and decreasing Cd binding by pectin. Moreover, WAKL11 overexpression restored Cd tolerance in nac102 mutants to the WT levels, which was correlated with a lower pectin content and lower levels of pectin-bound Cd. Taken together, our work shows that the NAC102-WAKL11 module regulates cell wall pectin metabolism and Cd binding, thus conferring Cd tolerance in Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cadmio/toxicidad , Cadmio/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pectinas/metabolismo , Pared Celular/metabolismo , Raíces de Plantas/metabolismo
17.
Virol J ; 20(1): 122, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37312198

RESUMEN

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.


Asunto(s)
COVID-19 , Orthomyxoviridae , Infecciones del Sistema Respiratorio , Niño , Humanos , Adolescente , Niño Hospitalizado , Pandemias , COVID-19/epidemiología , China/epidemiología , Infecciones del Sistema Respiratorio/epidemiología
18.
Org Lett ; 25(24): 4562-4566, 2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37314148

RESUMEN

An electrochemical method for the decarboxylative silylation of α,ß-unsaturated carboxylic acids was developed. A variety of alkenylsilanes could be obtained in satisfactory yields and excellent selectivities under external oxidant- and metal-free conditions. Mechanistic studies showed that the formation of the silyl radical was mediated by NHPI, which produces the hydrogen atom transfer (HAT) reagent phthalimide N-oxyl (PINO) via multiple-site concerted proton-electron transfer (MS-CPET).


Asunto(s)
Hidrógeno , Protones , Estructura Molecular , Transporte de Electrón , Ácidos Carboxílicos
20.
Front Surg ; 10: 1156337, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215354

RESUMEN

Background: Spontaneous hemorrhage of gastro-omental hemangioma is a rare disease. The treatment strategy for this disease changes as it develops. In the acute stage, surgery is the first priority, among which laparoscopic treatment should be the most frequently considered option in large general hospitals. Due to the rarity of this disease, such cases have rarely been reported. Case description: We present the first report of two eldely cases with gastro-omental hemangioma with hemorrhage by laparoscopic treatment. Both cases were initially admitted with upper abdominal pain, and abdominal computed tomography (CT) scan revealed masses alongside the greater curvature of the stomach. Laparoscopic surgery was conducted immediately in both patients. The two cases recovered well after surgery, and no obvious abnormalities were observed in the follow-up period. Conclusion: Gastro-omental hemangioma rupture remains an uncommon cause of intraperitoneal hemorrhage. Timely diagnosis and surgery are paramount for treatment. Medical institutions with the correct technology and equipment should perform laparoscopic treatment to minimize surgical trauma and promote rapid recovery of patients with abdominal apoplexy.

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