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1.
Pak J Med Sci ; 40(6): 1087-1092, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952500

RESUMEN

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.

2.
ACS Chem Neurosci ; 15(13): 2432-2444, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38916052

RESUMEN

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.


Asunto(s)
Dolor Crónico , Neuralgia , Humanos , Neuralgia/terapia , Neuralgia/tratamiento farmacológico , Neuralgia/epidemiología , Animales , Dolor Crónico/epidemiología , Dolor Crónico/fisiopatología , Dolor Crónico/terapia , Dolor Crónico/tratamiento farmacológico , Ketamina/uso terapéutico , Ketamina/farmacología , Depresión/tratamiento farmacológico , Depresión/terapia , Comorbilidad , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/terapia , Trastorno Depresivo/fisiopatología
3.
Brain Res ; 1841: 149085, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876320

RESUMEN

As a cutting-edge technology of connecting biological brain and external devices, brain-computer interface (BCI) exhibits promising applications on extensive fields such as medical and military. As for the disable individuals with four limbs losing the motor functions, it is a potential treatment way to drive mechanical equipments by the means of non-invasive BCI, which is badly depended on the accuracy of the decoded electroencephalogram (EEG) singles. In this study, an explanatory convolutional neural network namely EEGNet based on SimAM attention module was proposed to enhance the accuracy of decoding the EEG singles of index and thumb fingers for both left and right hand using sensory motor rhythm (SMR). An average classification accuracy of 72.91% the data of eight healthy subjects was obtained, which were captured from the one second before finger movement to two seconds after action. Furthermore, the character of event-related desynchronization (ERD) and event related synchronization (ERS) of index and thumb fingers was also studied in this study. These findings have significant importance for controlling external devices or other rehabilitation equipment using BCI in a fine way.

4.
Micromachines (Basel) ; 15(5)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38793158

RESUMEN

As a cutting-edge technology, animal robots based on living organisms are being extensively studied, with potential for diverse applications in the fields of neuroscience, national security, and civil rescue. However, it remains a significant challenge to reliably control the animal robots with the objective of protecting their long-term survival, and this has seriously hindered their practical implementation. To address this issue, this work explored the use of a bio-friendly neurostimulation system that includes integrated stimulation electrodes together with a remote wireless stimulation circuit to control the moving behavior of rat robots. The integrated electrodes were implanted simultaneously in four stimulation sites, including the medial forebrain bundle (MFB) and primary somatosensory cortex, barrel field (S1BF). The control system was able to provide flexibility in adjusting the following four stimulation parameters: waveform, amplitude, frequency, and duration time. The optimized parameters facilitated the successful control of the rat's locomotion, including forward movement and left and right turns. After training for a few cycles, the rat robots could be guided along a designated route to complete the given mission in a maze. Moreover, it was found that the rat robots could survive for more than 20 days with the control system implanted. These findings will ensure the sustained and reliable operation of the rat robots, laying a robust foundation for advances in animal robot regulation technology.

5.
Microsyst Nanoeng ; 10: 64, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784374

RESUMEN

Flexible sensors have been widely studied for use in motion monitoring, human‒machine interactions (HMIs), personalized medicine, and soft intelligent robots. However, their practical application is limited by their low output performance, narrow measuring range, and unidirectional force detection. Here, to achieve flexibility and high performance simultaneously, we developed a flexible wide-range multidimensional force sensor (FWMFS) similar to bones embedded in muscle structures. The adjustable magnetic field endows the FWMFS with multidimensional perception for detecting forces in different directions. The multilayer stacked coils significantly improved the output from the µV to the mV level while ensuring FWMFS miniaturization. The optimized FWMFS exhibited a high voltage sensitivity of 0.227 mV/N (0.5-8.4 N) and 0.047 mV/N (8.4-60 N) in response to normal forces ranging from 0.5 N to 60 N and could detect lateral forces ranging from 0.2-1.1 N and voltage sensitivities of 1.039 mV/N (0.2-0.5 N) and 0.194 mV/N (0.5-1.1 N). In terms of normal force measurements, the FWMFS can monitor finger pressure and sliding trajectories in response to finger taps, as well as measure plantar pressure for assessing human movement. The plantar pressure signals of five human movements collected by the FWMFS were analyzed using the k-nearest neighbors classification algorithm, which achieved a recognition accuracy of 92%. Additionally, an artificial intelligence biometric authentication system is being developed that classifies and recognizes user passwords. Based on the lateral force measurement ability of the FWMFS, the direction of ball movement can be distinguished, and communication systems such as Morse Code can be expanded. This research has significant potential in intelligent sensing and personalized spatial recognition.

6.
Chem Biol Interact ; 395: 111015, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38663797

RESUMEN

Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.


Asunto(s)
Ácido Clodrónico , Células Estrelladas Hepáticas , Lipopolisacáridos , Liposomas , Cirrosis Hepática , Macrófagos , Ratas Sprague-Dawley , Animales , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Liposomas/química , Lipopolisacáridos/farmacología , Ácido Clodrónico/farmacología , Ácido Clodrónico/química , Ácido Clodrónico/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/inducido químicamente , Ratas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Células RAW 264.7 , Ratones , Tetracloruro de Carbono/toxicidad
7.
Sci Total Environ ; 925: 171704, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38492586

RESUMEN

Greenhouse gas emissions are considered the culprit of extreme high temperatures, and low-carbon transformation has become a global consensus. The low-carbon action by enterprises is an inevitable choice if they are to adapt to economic and social needs. Green innovation is an important measure for enterprises to respond to the challenges of low-carbon transformation. This study mainly discusses the causal relationship between extreme high temperatures and green innovation of enterprises. Using China's industrial enterprise database, we construct county-annual panel data from 2000 to 2013. Results show that extreme high temperatures improve the level of green innovation of enterprises. After a series of robustness tests, the results remain. Mechanism analysis shows that extreme high temperatures increase the environmental concerns of the government, the public, and society, thus strengthening government regulation, public participation, and social supervision as well as encouraging enterprises to carry out green innovation. Our heterogeneous analysis shows that in the eastern region with a high level of legal system and economic development, it is easier to promote green innovation for enterprises. In addition, large-scale enterprises are more willing to carry out green innovation after experiencing a heat wave.

8.
J Environ Manage ; 354: 120300, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38359625

RESUMEN

Global warming has accentuated the effects of extreme heat on health. Health insurance, functioning as a risk management tool, has the potential to alleviate these impacts. Consequently, this paper investigates the correlation between extreme heat events and the demand for health insurance in China. Using data from the China Health and Nutrition Survey, we have observed a substantial increase in the likelihood of residents purchasing health insurance during extreme heat events. To be specific, for every extra day of extreme heat events annually, there is a 0.3% increase in the probability of purchasing health insurance. This effect is not uniform across different demographic groups. It is particularly pronounced among middle-aged and elderly individuals, rural residents, those with lower educational levels, higher income brackets, and individuals residing in underprivileged areas with limited access to green spaces and healthcare facilities. Furthermore, our study indicates that the increased frequency of extreme heat events not only impacts individuals' physical health but also triggers negative emotions, which in turn drive risk-averse behavior related to health insurance purchases. These findings carry substantial policy implications for mitigating the economic consequences of climate change.


Asunto(s)
Calor Extremo , Persona de Mediana Edad , Anciano , Humanos , Calor Extremo/efectos adversos , China , Seguro de Salud , Cambio Climático , Calentamiento Global
9.
Artículo en Inglés | MEDLINE | ID: mdl-38401113

RESUMEN

Objective: This study aims to investigate the impact of patient-centered health education on individuals with type 2 diabetes coexisting with hyperlipidemia. Methods: A cohort of 80 patients with type 2 diabetes and hyperlipidemia attending our hospital from February 2022 to August 2022 were randomly assigned to either the health education group or the control group. While the control group received routine health education, the health education group received additional patient-centered health education. Subsequently, we compared blood glucose and lipid levels, negative emotions, quality of life, and the incidence of unhealthy eating or overweight between the two groups post-education. Results: Following the health education intervention, the health education group exhibited superior improvements in blood glucose and lipid levels compared to the control group. Moreover, there was a significant decrease in SAS and SDS scores and a notable increase in quality of life compared to the control group. The health education group also demonstrated a lower incidence of unhealthy eating or overweight. Conclusions: Patient-centered health education for individuals with type 2 diabetes and hyperlipidemia proves effective in enhancing glucose and lipid metabolism, mitigating negative emotions, improving quality of life, and reducing unhealthy habits.

10.
Acta Pharmacol Sin ; 45(4): 704-713, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38097715

RESUMEN

Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, S1R has become a novel target for antidepression therapy. With a rapid and sustained antidepressant effect, ketamine may also interact with S1R. In this study, we investigated whether the antidepressant action of ketamine was related to S1R activation. Depression state was evaluated in the tail suspension test (TST) and a chronic corticosterone (CORT) procedure was used to induce despair-like behavior in mice. The neuronal activities and structural changes of pyramidal neurons in medial prefrontal cortex (mPFC) were assessed using fiber-optic recording and immunofluorescence staining, respectively. We showed that pharmacological manipulation of S1R modulated ketamine-induced behavioral effect. Furthermore, pretreatment with an S1R antagonist BD1047 (3 mg·kg-1·d-1, i.p., for 3 consecutive days) significantly weakened the structural and functional restoration of pyramidal neuron in mPFC caused by ketamine (10 mg·kg-1, i.p., once). Ketamine indirectly triggered the activation of S1R and subsequently increased the level of BDNF. Pretreatment with an S1R agonist SA4503 (1 mg·kg-1·d-1, i.p., for 3 consecutive days) enhanced the sustained antidepressant effect of ketamine, which was eliminated by knockdown of BDNF in mPFC. These results reveal a critical role of S1R in the sustained antidepressant effect of ketamine, and suggest that a combination of ketamine and S1R agonists may be more beneficial for depression patients.


Asunto(s)
Antidepresivos , Factor Neurotrófico Derivado del Encéfalo , Ketamina , Receptor Sigma-1 , Animales , Humanos , Ratones , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Ketamina/farmacología , Neuronas , Corteza Prefrontal/metabolismo , Receptor Sigma-1/agonistas
11.
Adv Sci (Weinh) ; 10(27): e2300424, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37544916

RESUMEN

Aging is always accompanied by chronic diseases which probably attribute to long-term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes-associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.


Asunto(s)
Vía de Señalización Hippo , Células Madre Mesenquimatosas , Ratones , Animales , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/genética , Factores de Transcripción/metabolismo , Células Madre Mesenquimatosas/metabolismo , Inflamación/metabolismo
12.
Iran J Public Health ; 52(7): 1410-1417, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37593502

RESUMEN

Background: We aimed to probe into the occupational exposure causes and mental status of infectious diseases in pre-hospital emergency medical personnel. Methods: Forty medical personnel with occupational exposure to infectious diseases who participated in pre-hospital emergency work in 120 emergency center of The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China were selected as respondents from February 2018 to February 2021. The occupational exposure modes, exposure degrees, exposure sites, exposure sources and exposure causes of infectious diseases were summarized, and the mental status of emergency medical personnel after occupational exposure to infectious diseases was analyzed. Results: In the occupational exposure modes of infectious diseases, needle stick injuries were overtly higher than mucosal pollution, hematic and humoral pollution and incised wound by glass (P<0.05). In exposure degrees, slight bleeding was notably higher than excessive bleeding, bleeding and no bleeding (P<0.05). The hand was distinctly higher than the eye in exposure sites (P<0.05). In exposure sources, hepatitis B virus was visibly higher than hepatitis C virus, HIV, syphilis, intravenous drug, hemorrhagic fever and unknown cause (P<0.05). The scores of somatic symptoms, anxiety, depression, fear, interpersonal sensitivity, hostility, compulsion and paranoia in medical personnel were clearly higher than the norm in Chinese adults after occupational exposure to infectious diseases (P<0.05), with no statistical significance in the comparison of psychotic scores. Conclusion: The occupational exposure risk of infectious diseases among pre-hospital emergency medical personnel is high. It is necessary to strengthen pre-job training and education and improve standardized management for protection.

13.
J Coll Physicians Surg Pak ; 33(4): 411-415, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37190713

RESUMEN

OBJECTIVE:  To investigate whether insulin resistance (IR) affects the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Place and Duration of the Study: The Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from September 2017 to December 2021. METHODOLOGY: This study retrospectively analysed 324 patients with DLBCL who were divided into a non-IR group (251 cases) and IR group (73 cases) according to IR. The authors collected clinical data of the study population and calculated the overall survival (OS) of patients through inpatient case data or follow-up. The Cox regression method was used to assess the prognostic factors of the patients. The Kaplan-Meier method was used for drawing the survival curve of IR on OS of the DLBCL patients. RESULTS: The IR group had older age, higher international prognostic index (IPI), later stage, and higher insulin levels. The five-year OS rate was 46% in the IR group and 66% in the non-IR group. Compared with the non-IR group, the IR group showed a poor prognosis (OS: adjusted HR 1.23, 95% CI: 1.02-1.41, p = 0.031). CONCLUSION: IR was one of the factors leading to poor prognosis in patients with DLBCL, and attention should be paid to this risk factor. KEY WORDS: Insulin resistance, Diffuse large B-cell lymphoma, Overall survival, Prognosis.


Asunto(s)
Resistencia a la Insulina , Linfoma de Células B Grandes Difuso , Humanos , Estudios Retrospectivos , Supervivencia sin Enfermedad , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Protocolos de Quimioterapia Combinada Antineoplásica
14.
Adv Sci (Weinh) ; 10(18): e2300350, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37085918

RESUMEN

The malignant transformation of hepatic progenitor cells (HPCs) in the inflammatory microenvironment is the root cause of hepatocarcinogenesis. However, the potential molecular mechanisms are still elusive. The HPCs subgroup is identified by single-cell RNA (scRNA) sequencing and the phenotype of HPCs is investigated in the primary HCC model. Bulk RNA sequencing (RNA-seq) and proteomic analyses are also performed on HPC-derived organoids. It is found that tumors are formed from HPCs in peritumor tissue at the 16th week in a HCC model. Furthermore, it is confirmed that the macrophage-derived TWEAK/Fn14 promoted the expression of inhibitor of differentiation-1 (ID1) in HPCs via NF-κB signaling and a high level of ID1 induced aberrant differentiation of HPCs. Mechanistically, ID1 suppressed differentiation and promoted proliferation in HPCs through the inhibition of HNF4α and Rap1GAP transcriptions. Finally, scRNA sequencing of HCC patients and investigation of clinical specimens also verified that the expression of ID1 is correlated with aberrant differentiation of HPCs into cancer stem cells, patients with high levels of ID1 in HPCs showed a poorer prognosis. This study provides important intervention targets and a theoretical basis for the clinical diagnosis and treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteómica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Transducción de Señal/genética , Carcinogénesis/genética , Células Madre/metabolismo , Microambiente Tumoral , Proteína 1 Inhibidora de la Diferenciación/genética
15.
Ann Transl Med ; 11(2): 135, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36819504

RESUMEN

Background: Total ear avulsion is one of the most serious auricular traumas. Its surgical procedure is complicated and involves high technical difficulty. The auricular blood vessels mostly contain capillaries, and capillary anastomosis reconstruction is difficult. Right ear vascular anastomosis and auricle replantation under microscope are very few cases of successful replantation of total ear avulsion. The lack of blood supply in the amputated ear leads to postoperative blood supply disturbance. At present, there are no reports on the application of hyperbaric oxygen therapy following the replantation of severed ears. Hyperbaric oxygen therapy was used to promote the recovery of vascular microcirculation, reduce complications and improve the survival rate of postoperative ear transplantation. Case Description: We present a rare case of total ear avulsion in a 53-year-old Chinese man. The patient complained of cutting injury of the right auricle for more than 1 hour. The patient had a history of hypertension for 4 years, and his blood pressure was well controlled by regular administration of valsartan. This paper reports on the treatment experience in a case of microscope-assisted auricular replantation, targeted postoperative treatment, early intervention with hyperbaric oxygen therapy, and individualized nursing care. After 16 days of careful treatment, the patient's avulsion ear survived and he was discharged from the hospital. After 6 months of continuous follow-up, the auricular shape and hearing of the patient reached the ideal standard. Conclusions: Precise medical and nursing cooperation coupled with meticulous management of the patient throughout the entire process are key factors for the survival of the severed ear. The combined application of microscopic techniques and hyperbaric oxygen therapy improves blood circulation to the anastomosed vessels, accelerates the healing of the replanted ear, and shortens the length of hospital stay. Early hyperbaric oxygen treatment can make postoperative wound heal quickly. Early intervention of hyperbaric oxygen therapy after ear avulsion is helpful to the recovery of patients with ear avulsion. However, the initiation time and duration of intervention need to be further optimized and more evidence is needed to support it.

16.
Cancer Cell Int ; 22(1): 362, 2022 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-36403057

RESUMEN

BACKGROUND: Transarterial chemoembolization (TACE) has been shown to prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, the long-term survival remains dismal. Targeting macrophage and neutrophil infiltration is a promising strategy. The CCL2/CCR2 and CXCLs/CXCR2 axes are required for recruitment of macrophages and neutrophils, respectively, in HCC. We investigated the feasibility of CCL2/CCR2 and CXCLs/CXCR2 as therapeutic targets in combination with TACE for treating HCC. METHODS: Expression of CCL2/CCR2 and CXCLs/CXCR2 was analyzed in the primary rat HCC model and one HCC cohort. The relationship between expression levels, neutrophil and macrophage infiltration, hepatocarcinogenesis progression in the rat model, and survival of HCC patients was assessed. The anti-tumor effects of blocking the CCL2/CCR2 and CXCLs/CXCR2 axes by CCR2 and CXCR2 antagonists in combination with TACE were evaluated in HCC rats. The numbers of macrophages, neutrophils, and hepatic progenitor cells were further determined to explore the underlying mechanisms. RESULTS: High macrophage and neutrophil infiltration and CXCL8 expression were associated with poor prognosis in the TCGA liver cancer dataset. High expression of CCL2/CCR2 and CXCL8/CXCR2 in clinical HCC specimens was associated with reduced survival. Expression of CCL2/CCR2 and CXCL1/CXCR2 was correlated with hepatocarcinogenesis progression in the primary rat HCC model. Blockade of CCL2/CCR2 and CXCLs/CXCR2 enhanced the anti-tumor effect of TACE treatment in this model. Blocking the CCL2/CCR2 and CXCLs/CXCR2 axes with CCR2 and CXCR2 antagonists in TACE-treated rats reduced macrophage and neutrophil infiltration and hepatic progenitor cell activation and thus overcame TACE resistance in HCC. CONCLUSIONS: The results demonstrate the translational potential of immunotherapy targeting the CCL2/CCR2 and CXCLs/CXCR2 axes in combination with TACE therapy for the treatment of HCC.

17.
Int J Pharm ; 629: 122346, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36334635

RESUMEN

Macrophages in the liver have capacities of capturing and phagocytosing nanocarriers. Macrophages also play an important role in the inflammatory microenvironment and in the tumorigenesis, development and progression of hepatocellular carcinoma (HCC). Several studies have shown that depletion of macrophages is a viable strategy for drug delivery and tumor microenvironment regulation. We prepared liposomes containing doxorubicin and clodronate using an ammonium sulfate gradient and thin film hydration method. The repressive therapeutic effects of liposomes were compared by intrasplenic injection at different stages of a primary HCC model induced by diethylnitrosamine (DEN) in rats. Doxorubicin-liposome (DOX-LIP) and clodronate-liposome (CL-LIP) about 180-200 nm were successfully prepared and characterized. We found that DOX-LIP combined with CL-LIP could effectively inhibit the occurrence and development of liver cancer without major organ damage and side effects. The combination of doxorubicin and clodronate liposomes notably decreased hepatic CD68 + macrophages, enriched DOX in plasma and accumulated it for a long time in the liver and spleen, thus improving the tumor microenvironment, inhibiting the activation of hepatic progenitor cells (HPCs) and promoting the apoptosis of tumor cells, and finally producing the inhibitory and therapeutic effects of HCC in rats. Results of this study were expected to provide a new prospect for the chemotherapy of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratas , Animales , Liposomas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Ácido Clodrónico/farmacología , Ácido Clodrónico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Doxorrubicina , Macrófagos/patología , Línea Celular Tumoral , Microambiente Tumoral
18.
Front Oncol ; 12: 877982, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646705

RESUMEN

Background: Hepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence. Methods: T3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated in vitro. We assessed the effect of T3-lipo on hepatocarcinogenesis in diethylnitrosamine (DEN)-induced primary HCC in rats and examined the biodistribution of T3 and T3-lipo by high-performance liquid chromatography-mass spectrometry. Furthermore, we explored the potential molecular mechanism of T3-lipo in hepatocarcinogenesis by immunohistochemistry and immunofluorescence analyses, Bio-Plex assays, real-time polymerase chain reaction analysis, and Western blotting assays. Results: Compared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways. Conclusions: T3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.

19.
Cancer Med ; 11(22): 4283-4296, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35674129

RESUMEN

BACKGROUND & AIMS: Capsaicin, a functional component of chili pepper, possesses anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to determine the property of capsaicin against hepatocarcinogenesis in vivo and investigate the role of the SIRT1/SOX2 pathway in the mode of action of capsaicin in hepatic progenitor cells (HPCs), which is related to hepatocarcinogenesis. MATERIALS & METHODS: We prepared a diethylnitrosamine-induced liver cancer model in rats to examine hepatocarcinogenesis, and delivered liposomal capsaicin through the subcutaneous transposition of the spleen to the liver. Liver sections from rats and hepatocarcinoma patients were stained for the markers of HPCs or SIRT1/SOX2 signaling. SIRT1/SOX2 signalling expression was measured using immunoprecipitation and western blot. RESULTS: We found that capsaicin significantly inhibited hepatocarcinogenesis. Notably, capsaicin inhibited HPCs activation in vivo but did not induce apoptosis in the normal hepatic progenitor cell line in rats in vitro. This suggests that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs. Moreover, capsaicin can induce this inhibition by reducing the stability of SOX2. SIRT1 is overexpressed in liver cancer and acts as a tumor promoter via SOX2 deacetylation. Using immunoprecipitation, we identified direct binding between SIRT1 and SOX2. The capsaicin treatment resulted in SIRT1 downregulation which reduced deacetylation, and increased nuclear export as well as subsequent ubiquitous degradation of SOX2. CONCLUSIONS: Altogether, we report that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs via SIRT1/SOX2 signaling. It may serve as a promising therapeutic candidate for liver cancer.


Asunto(s)
Neoplasias Hepáticas , Factores de Transcripción SOXB1 , Sirtuina 1 , Animales , Ratas , Capsaicina/farmacología , Carcinogénesis , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Células Madre/metabolismo , Factores de Transcripción SOXB1/metabolismo
20.
Nanomaterials (Basel) ; 12(7)2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35407273

RESUMEN

The flexible pressure sensor has attracted much attention due to its wearable and conformal advantage. All the same, enhancing its electrical and structural properties is still a huge challenge. Herein, a flexible integrated pressure sensor (FIPS) composed of a solid silicone rubber matrix, composited with piezoelectric powers of polyacrylonitrile/Polyvinylidene fluoride (PAN/PVDF) and conductive silver-coated glass microspheres is first proposed. Specifically, the mass ratio of the PAN/PVDF and the rubber is up to 4:5 after mechanical mixing. The output voltage of the sensor with composite PAN/PVDF reaches 49 V, which is 2.57 and 3.06 times that with the single components, PAN and PVDF, respectively. In the range from 0 to 800 kPa, its linearity of voltage and current are all close to 0.986. Meanwhile, the sensor retains high voltage and current sensitivities of 42 mV/kPa and 0.174 nA/kPa, respectively. Furthermore, the minimum response time is 43 ms at a frequency range of 1-2.5 Hz in different postures, and the stability is verified over 10,000 cycles. In practical measurements, the designed FIPS showed excellent recognition abilities for various gaits and different bending degrees of fingers. This work provides a novel strategy to improve the flexible pressure sensor, and demonstrates an attractive potential in terms of human health and motion monitoring.

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