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1.
Regen Biomater ; 11: rbae015, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487713

RESUMEN

The prognosis of glioblastoma (GBM) remains challenging, primarily due to the lack of a precise, effective imaging technique for comprehensively characterization. Addressing GBM diagnostic challenges, our study introduces an innovative dual-modal imaging that merges near-infrared (NIR) fluorescent imaging with magnetic resonance imaging (MRI). This method employs superparamagnetic iron oxide nanoparticles coated with NIR fluorescent dyes, specifically Cyanine 7, and targeted peptides. This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles, provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions, offering a comprehensive diagnostic tool for GBM. Notably, the probe traverses the blood-brain barrier, targeting GBM in vivo via peptides, producing clear and discernible images in both modalities. Cytotoxicity and histopathology assessments confirm the probe's favorable safety profile. These findings suggest that the dual-modal MR\NIR fluorescent imaging probe could revolutionize GBM prognosis and survival rates, which can also be extended to other tumors type.

2.
Huan Jing Ke Xue ; 44(11): 6025-6037, 2023 Nov 08.
Artículo en Chino | MEDLINE | ID: mdl-37973087

RESUMEN

The Kuaize River is a small typical karst watershed in the source area of the Pearl River as well as an important coal mining area in Eastern Yunnan with a fragile ecological environment. Strengthening the research on the water environment in the region plays an important role in supporting the comprehensive management of the ecological environment and water resources in the source region of the Pearl River. Through the systematic collection of surface water, karst groundwater, and mine water samples, mathematical statistics analysis, correlation analysis, ion ratio analysis, absolute principal component scores multiple linear regression(APCS-MLR), and other methods were used to study the characteristics of hydrochemical evolution and control factors in Kuaize River Basin. The results showed that the average pH value of surface water in Kuaize River Basin was 7.8, which was weakly alkaline. The main cations were Ca2+ and Na+, showing the characteristics of Ca2+>Na+>Mg2+>K+. The main anions were HCO3- and SO42-, showing the characteristics of HCO3->SO42->NO3->Cl-. The variation coefficients of Na+, SO42-, and NO3- in surface water were high, showing strong spatial variability. The water chemical type of the trunk stream was mainly HCO3-Ca, whereas the water chemical type of the tributary was relatively complex, mainly HCO3-Ca, HCO3-Ca·Na, and HCO3·SO4-Ca·Na. The chemical composition of surface water was mainly affected by rock weathering, cation exchange, and human activities. Ca2+, Mg2+, Na+, and HCO3- in surface water mainly came from the weathering of carbonate rock and silicate rock; SO42- mainly came from the oxidation of sulfide, such as pyrite in coal seams; K+, Cl-, and NO3- mainly came from domestic sewage and agricultural activities. The APCS-MLR receptor model analysis results showed that the surface water in the Kuaize River Basin was mainly affected by sulfide oxidation, carbonate weathering, weathering of silicate rock in mine water, domestic sewage, agricultural activities, and unknown sources. In general, the contribution rate of human activities such as mining, domestic sewage, and agricultural activities to the surface water reached 47.17%, indicating that human activities were the key driving factor of surface water chemistry in the Kuaize River Basin.

3.
Purinergic Signal ; 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870716

RESUMEN

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

4.
Huan Jing Ke Xue ; 44(10): 5498-5510, 2023 Oct 08.
Artículo en Chino | MEDLINE | ID: mdl-37827767

RESUMEN

TheWudu River is a typical mining-type watershed in the karst mountainous area of western Guizhou Province. Based on the collection of the main stream, tributaries, spring water, and mine water samples in Wudu River Basin, the hydrochemical characteristics and control factors of Wudu River Basin were studied using Gibbs diagram, Piper diagram, and mathematical statistics analysis, and the solute contribution rate of different sources was calculated. The results revealed that the pH value of the water in the Wudu River Basin ranged from 7.87 to 8.52, with an average of 8.14. The TDS values ranged from 135 to 243 mg·L-1, with an average of 191.7 mg·L-1. The major cations in natural river and spring water were Ca2+ and Mg2+, the major anion was HCO3-, and the hydrochemical type was HCO3-Ca. However, owing to the influence of mining activities, the major cations in some tributaries were Ca2+ and Na+, and the hydrochemical types transitioned to HCO3·SO4-Ca and HCO3·SO4-Ca·Na. The ion components of river water in Wudu River Basin were affected by mine water discharge and cation exchange, carbonate rock weathering, silicate rock weathering, and agricultural fertilization. The high concentration of SO42- and Na+in mine water was the primary source of SO42- and Na+in the tributaries of the Wudu River. The method for calculating chemical material balance showed that the contribution rate of carbonate rock weathering ranged from 44.12% to 86.92%, with an average of 74.32%. The contribution rate of mining activities ranged from 3.28% to 37.07%, with an average of 11.61%. Carbonate rock weathering was the main controlling factor of hydrochemical components in the Wudu River Basin; meanwhile, mining activities also had a certain impact on river water chemistry but they showed spatial heterogeneity. The average contribution rates of atmospheric precipitation, silicate rock weathering, agricultural activities, and domestic sewage were 3.75%, 4.67%, 2.85%, and 2.81%, respectively, which had a limited impact on the hydrochemical components of the basin.

5.
J Med Chem ; 66(13): 8628-8642, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37332162

RESUMEN

Nonsubstrate allosteric inhibitors of P-glycoprotein (Pgp), which are considered promising modulators for overcoming multidrug resistance (MDR), are relatively unknown. Herein, we designed and synthesized amino acids bearing amide derivatives of pyxinol, the main ginsenoside metabolite produced by the human liver, and examined their MDR reversal abilities. A potential nonsubstrate inhibitor (7a) was identified to undergo high-affinity binding to the putative allosteric site of Pgp at the nucleotide-binding domains. Subsequent assays confirmed that 7a (25 µM) was able to suppress both basal and verapamil-stimulated Pgp-ATPase activities (inhibition rates of 87 and 60%, respectively) and could not be pumped out by Pgp, indicating that it was a rare nonsubstrate allosteric inhibitor. Moreover, 7a interfered with Pgp-mediated Rhodamine123 efflux while exhibiting high selectivity for Pgp. Notably, 7a also markedly enhanced the therapeutic efficacy of paclitaxel, with a tumor inhibition ratio of 58.1%, when used to treat nude mice bearing KBV xenograft tumors.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Ratones , Humanos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Amidas/farmacología , Aminoácidos/farmacología , Ratones Desnudos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos
6.
Huan Jing Ke Xue ; 44(2): 740-751, 2023 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-36775598

RESUMEN

Tuochangjiang River is a typical mining-type watershed in the karst mountainous area of western Guizhou province. The study of its hydrochemical evolution characteristics and driving factors is of great significance to the local economic development and the scientific management of water resources. The samples of river water, spring water, and mine water in the Tuochangjiang River Basin were collected, and the sources of solutes and their contribution to the chemical components of river water were discussed by means of hydrochemical diagrams, mathematical statistics, and the absolute principal component scores-multivariate linear regression model (APCS-MLR). The results showed that the pH of the river water ranged between 7.30 to 8.31, and the TDS value ranged between 40 to 520 mg·L-1, which was mainly contributed by Ca2+, Na+, HCO3-, and SO42-. The dominant cations in river water were Ca2+ and Na+, the dominant anions were HCO3- and SO42-, and the main water chemistry transitioned from HCO3-Ca to HCO3-Ca·Na and HCO3·SO4-Ca·Na type, whereas that of the mine water was mainly the HCO3-Na and HCO3·SO4-Na types. The chemical composition of river water was affected by rock weathering, exchange adsorption of anions, mineral dissolution and precipitation, and human activities, in which Ca2+, Mg2+, and HCO3- were mainly derived from the weathering and dissolution of carbonate and silicate rocks, Na+and SO42- were mainly from the discharge of mining wastewater, and Cl- and NO3- were affected by domestic sewage and agricultural activities, respectively. APCS-MLR analysis further showed that the river water solutes mainly included five sources:discharge of mining wastewater, dissolution of soil minerals, geological background, agricultural activities, and unknown sources, and their contribution rates to river water were 23.49%, 35.04%, 13.87%, 7.96%, and 20.63%, respectively. Mining factors and soil factors were the most important sources of solutes in the river water, and they were the main driving factors for the hydrochemical evolution of the Tuochangjiang River Basin.

7.
Artículo en Inglés | MEDLINE | ID: mdl-36777630

RESUMEN

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

8.
Purinergic Signal ; 19(1): 99-111, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-34973115

RESUMEN

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.


Asunto(s)
Diabetes Mellitus Experimental , Neuropatías Diabéticas , Neuralgia , Ratas , Animales , Ratas Sprague-Dawley , Diabetes Mellitus Experimental/metabolismo , Calcio/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacología , Receptores Purinérgicos P2X3/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/farmacología , Ganglios Espinales/metabolismo , Neuralgia/metabolismo , Hiperalgesia/metabolismo , Neuropatías Diabéticas/metabolismo
9.
Purinergic Signal ; 19(1): 29-41, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35218450

RESUMEN

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.


Asunto(s)
Diabetes Mellitus , Neuropatías Diabéticas , Electroacupuntura , Ratas , Animales , Hiperalgesia/metabolismo , Regulación hacia Abajo , Ganglios Espinales/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Neuropatías Diabéticas/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Diabetes Mellitus/metabolismo
10.
Transl Pediatr ; 11(8): 1374-1388, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36072542

RESUMEN

Background: Near-infrared spectroscopy (NIRS) is a non-invasive approach that measures cerebral regional oxygen saturation (rScO2). In this study, we evaluated the evidence on the validity of NIRS and the interchangeability between NIRS and common invasive approaches by exploring the correlation and consistency and comparing the mean and standard deviation between the NIRS rScO2 and jugular bulb venous oxygen saturation (SjvO2) as well as central venous oxygen saturation (ScvO2) in the perioperative period of children with congenital heart disease (CHD). Methods: We searched electronic bibliographic databases (PubMed, The Cochrane Library and Embase) and screened the studies that met the inclusion criteria. We included cross-sectional studies of CHD pediatric patients in the perioperative period receiving both tests for NIRS rScO2 and SjvO2 or NIRS rScO2 and ScvO2. Methodological quality assessment and heterogeneity analyses were performed. We qualitatively summarized the results of Bland-Altman's analysis. Meta-regression, subgroup analyses, and sensitivity analyses were carried out to explore the causes of heterogeneity. Results: There was no significant difference in Cohen's d between rScO2 and ScvO2 or between rScO2 and SjvO2 (Cohen's d =0.06, 95% CI: -0.16 to 0.28; Cohen's d =0.03, 95% CI: -0.25 to 0.31, respectively) and notable heterogeneity existed (I2=76.0%, P<0.001; I2=73.6%, P<0.001, respectively). A positive linear correlation was present between rScO2 and ScvO2 or between rScO2 and SjvO2 (r=0.58, 95% CI: 0.54 to 0.63; r=0.60, 95% CI: 0.54 to 0.66, respectively) and the heterogeneity was not significant (I2=36.7%, P=0.065; I2=12.7%, P=0.328, respectively). In most studies, the 95% limits of agreements of Bland-Altman's analysis were large. No evidence of publication bias was observed. Conclusions: The rScO2 measured by NIRS reflected the SjvO2 and ScvO2 monitored by invasive measurements in the perioperative period of children with CHD to some extent. However, wide limits of agreements between rScO2 and SjvO2 as well as ScvO2 indicated that NIRS and SjvO2 as well as ScvO2 are not interchangeable. Whether NIRS plays a prominent role in monitoring cerebral oxygen saturation in children with CHD needs further research.

11.
Huan Jing Ke Xue ; 43(4): 1885-1897, 2022 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-35393812

RESUMEN

In order to serve the water resources management of the Xiaohuangni River basin, this study explored the hydrochemical composition characteristics and ion sources of surface water in the basin. Samples of main stream and tributary river water and mine water were systematically collected. By means of a Piper diagram, Gibbs diagram, ion ratio coefficient, and mathematical statistical analysis, we analyzed the hydrochemical composition, spatial distribution characteristics, and main control factors of the Xiaohuangni River and evaluated the solute contribution rates of different sources. The results showed that the pH of the Xiaohuangni River basin ranged between 7.17 to 9.14, with an average of 8.00, which is generally considered weakly alkaline. Additionally, the total dissolved solids ranged between 154 mg·L-1 to 460 mg·L-1, with an average of 257.39 mg·L-1, which was equivalent to that of the main stream of the Xijiang River. The dominant cation was Ca2+, accounting for 69% of the total cations; the dominant anions were HCO3- and SO42-, accounting for 65% and 30% of the total anions, respectively. The main chemical type of the main stream was HCO3-Ca. Affected by mining activities, the tributaries transitioned from HCO3-Ca to HCO3·SO4-Ca and HCO3·SO4-Ca·Na type. River water solute was mainly controlled by the weathering of carbonate rock and silicate rock, with the participation of sulfuric and carbonic acid. The contribution rate of carbonate weathering to river water solute was 63%, and that of silicate weathering was 16.33%. Meanwhile, human activities contributed markedly to the dissolved solutes of the Xiaohuangni River basin, in which the contribution rate of mining activities was 13.4%, and the contribution rate of agricultural activities and domestic sewage was 4%.


Asunto(s)
Contaminantes Químicos del Agua , Calidad del Agua , Carbonatos , Monitoreo del Ambiente/métodos , Humanos , Agua/análisis , Contaminantes Químicos del Agua/análisis
12.
Zhongguo Zhen Jiu ; 42(2): 173-8, 2022 Feb 12.
Artículo en Chino | MEDLINE | ID: mdl-35152582

RESUMEN

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION: The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.


Asunto(s)
Diabetes Mellitus Experimental , Electroacupuntura , Neuralgia , Animales , Diabetes Mellitus Experimental/terapia , Masculino , Neuralgia/etiología , Neuralgia/terapia , Ratas , Ratas Sprague-Dawley , Médula Espinal , Asta Dorsal de la Médula Espinal
13.
Front Immunol ; 13: 1029656, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36591295

RESUMEN

Objective: To explore multi-aspect radiologic assessment of immunotherapy response in intracranial malignancies based on a semi-automatic segmentation technique, and to explore volumetric thresholds with good performance according to RECIST 1.1 thresholds. Methods: Patients diagnosed with intracranial malignancies and treated with immunotherapy were included retrospectively. In all MR images, target lesions were measured using a semi-automatic segmentation technique that could intelligently generate visual diagrams including RECIST 1.1, total volume, and max. 3D diameter. The changes in parameters were calculated for each patient after immunotherapy. The ROC curve was used to analyze the sensitivity and specificity of the size change of the legion. This was useful to find new volumetric thresholds with better efficiency in response assessment. The changes in total volume were assessed by conventional volumetric thresholds, while RECIST 1.1 thresholds were for the max. 3D diameter. A chi-square test was used to compare the concordance and diagnostic correlation between the response assessment results of the three criteria. Results: A total of 20 cases (average age, 58 years; range, 23 to 84 years) and 58 follow-up MR examinations after immunotherapy were included in the analysis. The P-value of the chi-square test between RECIST 1.1 and total volume is 0 (P <0.05), same as that in RECIST 1.1 and max. 3D diameter. The kappa value of the former two was 0.775, and the kappa value for the latter two was 0.742. The above results indicate a significant correlation and good concordance for all three criteria. In addition, we also found that the volumetric assessment had the best sensitivity and specificity for the immunotherapy response in intracranial malignancies, with a PR threshold of -64.9% and a PD threshold of 21.4%. Conclusions: Radiologic assessment of immunotherapy response in intracranial malignancy can be performed by multiple criteria based on semi-automatic segmentation technique on MR images, such as total volume, max. 3D diameter and RECIST 1.1. In addition, new volumetric thresholds with good sensitivity and specificity were found by volumetric assessment.


Asunto(s)
Neoplasias Encefálicas , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Inmunoterapia , Imagen por Resonancia Magnética/métodos
14.
Regen Biomater ; 8(6): rbab062, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34868634

RESUMEN

Glioblastoma (GBM) is the most aggressive malignant brain tumour, with a median survival of 3 months without treatment and 15 months with treatment. Early GBM diagnosis can significantly improve patient survival due to early treatment and management procedures. Magnetic resonance imaging (MRI) using contrast agents is the preferred method for the preoperative detection of GBM tumours. However, commercially available clinical contrast agents do not accurately distinguish between GBM, surrounding normal tissue and other cancer types due to their limited ability to cross the blood-brain barrier, their low relaxivity and their potential toxicity. New GBM-specific contrast agents are urgently needed to overcome the limitations of current contrast agents. Recent advances in nanotechnology have produced alternative GBM-targeting contrast agents. The surfaces of nanoparticles (NPs) can be modified with multimodal contrast imaging agents and ligands that can specifically enhance the accumulation of NPs at GBM sites. Using advanced imaging technology, multimodal NP-based contrast agents have been used to obtain accurate GBM diagnoses in addition to an increased amount of clinical diagnostic information. NPs can also serve as drug delivery systems for GBM treatments. This review focuses on the research progress for GBM-targeting MRI contrast agents as well as MRI-guided GBM therapy.

15.
Front Immunol ; 12: 790674, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899760

RESUMEN

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system with poor prognosis. Although the field of immunotherapy in glioma is developing rapidly, glioblastoma is still prone to recurrence under strong immune intervention. The major challenges in the process of immunotherapy are evaluating the curative effect, accurately distinguishing between treatment-related reactions and tumor recurrence, and providing guidance for clinical decision-making. Since the conventional magnetic resonance imaging (MRI) is usually difficult to distinguish between pseudoprogression and the true tumor progression, many studies have used various advanced imaging techniques to evaluate treatment-related responses. Meanwhile, criteria for efficacy evaluation of immunotherapy are constantly updated and improved. A standard imaging scheme to evaluate immunotherapeutic response will benefit patients finally. This review mainly summarizes the application status and future trend of several advanced imaging techniques in evaluating the efficacy of GBM immunotherapy.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Inmunoterapia , Imagen por Resonancia Magnética , Impresión Molecular , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Animales , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , Glioblastoma/diagnóstico por imagen , Glioblastoma/inmunología , Glioblastoma/patología , Humanos , Inmunoterapia/efectos adversos , Espectroscopía de Resonancia Magnética , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento
16.
Front Immunol ; 12: 751407, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34659255

RESUMEN

Objectives: For colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer. Methods: We searched the PubMed and Ovid MEDLINE databases up to May 1, 2021 and screened studies for eligibility. Thirteen studies published from 2015 to 2021 with 5062 patients were included finally. We extracted and calculated hazard ratios (HRs) and odds ratios (ORs) of overall survival (OS) and objective response rates (ORRs) and their 95% confidence intervals (95% CIs). Pooled HR and OR were evaluated to compare OS and ORR between TMB-high and TMB-low groups in colorectal cancer patients. Meanwhile, we assessed heterogeneity with the I2 statistic and p-values and performed publication bias assessments, sensitivity analyses, and subgroup analyses to search the cause of heterogeneity. Results: The TMB-high patient group had a longer OS than the TMB-low patient group (HR = 0.68, 95% CI: 0.51, 0.92, p = 0.013) among colorectal cancer patients receiving ICIs. In addition, the TMB-high patient group was superior in terms of ORR (OR = 19.25, 95% CI: 10.06, 36.82, p < 0.001) compared to the TMB-low patient group. Conclusions: In conclusion, this meta-analysis revealed that TMB can be used as a potential predictive biomarker of colorectal cancer patients receiving ICI therapy. Nevertheless, this finding is not stable enough. Therefore, many more randomized controlled trials are needed to prove that TMB is reliable enough to be used clinically to predict the efficacy of immunotherapy in colorectal cancer. And the most relevant biomarker remains to be determined when TMB high overlaps with other biomarkers like MSI and TILs.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios de Cohortes , Humanos , Mutación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
17.
Front Cell Dev Biol ; 9: 679684, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34222249

RESUMEN

OBJECTIVE: Immediate early response 5 (IER5) plays a core role in cell cycle and response to irradiation. However, its role in glioma remains unclear. We aimed to evaluate its prognostic significance in glioma based on The Cancer Genome Atlas data resource. METHODS: The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were employed to explore the relationship between IER5 expression and clinicopathological features. Kaplan-Meier and Cox regression analyses were implemented to investigate the relationship of IER5 with prognosis. A nomogram to estimate the impact of IER5 on prognosis was created based on the Cox multivariate data. We performed gene set enrichment analysis (GSEA) to determine the key signaling cascades associated with IER5. Immunohistochemistry was performed to examine IER5 expression in a tissue microarray (TMA) of glioma samples. RESULTS: Immediate early response 5 gene expression was elevated in glioma patients. The level of IER5 was significantly correlated with WHO grade [OR = 6.71 (4.34-10.68) for G4 vs. G2 and G3], IDH (isocitrate dehydrogenase enzyme) status [OR = 13.35 (8.92-20.46) for wild-type (WT) vs. mutated (Mut)], epidermal growth factor receptor status [OR = 8.42 (4.32-18.43) for Mut vs. WT], age [OR = 0.27 (0.18-0.41) for ≤ 60 years vs. >60 years], and histological type [OR = 7.13 (4.63-11.31] for glioblastoma vs. astrocytoma, oligoastrocytoma, and oligodendroglioma). Univariate analyses revealed that high IER5 expression was linked to short overall survival (OS) [hazard ratio (HR): 3.747; 95% confidence interval (CI): 2.847-4.933; and P < 0.001]. High IER5 expression was linked to poor OS in multivariate analyses (HR: 2.474; 95% CI: 1.552-3.943; and P < 0.001). TMA results showed that high IER5 protein levels were related to short OS (HR: 1.84; 95% CI: 1.10-3.07; and P = 0.021) and poor disease-specific survival (HR: 1.82; 95% CI: 1.09-3.04; and P = 0.023). GSEA showed that many tumor related pathways were enriched differentially in the IER5-high expression group. The C-index and calibration plots of the nomogram showed an effective estimation performance in glioma patients. CONCLUSION: Herein, we established that IER5 plays a critical role in glioma progression and prognosis, which might be an important biomarker for the prognosis of glioma patients.

18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(5): 592-598, 2020 Sep.
Artículo en Chino | MEDLINE | ID: mdl-32975070

RESUMEN

Transcranial magnetic stimulation (TMS), as a non-invasive neuromodulation technique, has achieved certain results in the study of brain function localization, treatment of nervous and mental diseases, but its mechanism of action and physiological effects are difficult to be clarified. The signals in blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is capable of reflecting the activities of brain tissue neurons. TMS-fMRI combines the advantages of two techniques to monitor changes in excitability of the TMS stimulation site and the distal brain region with which it is functionally linked. In this review, we elaborates the advances, limitations and future expectations of real-time interleaved TMS-fMRI. From the perspective of application progress, in the field of brain functional connectivity network research, TMS-fMRI can observe the dynamic connection between brain networks with a resolution of 100 ms, which is an important progress in the exploration of time-specific functional connectivity of brain regions. However, the TMS-fMRI on spatial specificity of functional connectivity of brain regions is still unclear, and future studies can focus on this aspect. In addition, TMS-fMRI can assess the effect of TMS on the cerebral cortex and the interaction between brain regions, help us understand the neural mechanism behind attention control, and study the brain's processing of somatosensory sensation. Nevertheless, TMS-fMRI can only observe the correlation between excitability of different brain regions under the stimulation of TMS, but the mechanism of this phenomenon and whether the correlation between brain regions is specific needs more research. Futhermore, TMS-fMRI can also be used to study the pathogenesis and therapeutic effect of neurological and psychiatric diseases, and the effects of psychoactive compounds on brain regions. Nonetheless, currently TMS-fMRI is still difficult to be widely used in clinical practice, so more efforts are needed in the study of clinical indications of TMS-fMRI. There are two major technical problems of TMS-fMRI. One major problem is that it is difficult for TMS coils to accurately position specific areas of cerebral cortex in MRI scanner. Another major problem is that TMS coils affect the static magnetic field (B0), resulting in image artifacts, spatial distortion and local signal loss of echo-Planar (EP) images. Nowadays, researchers have solved the two major problems through continuous technical updates, but TMS-fMRI still has problems in parameter setting, user experience, simplicity and universality of application and other aspects, which is the direction of future technological progress.


Asunto(s)
Mapeo Encefálico , Estimulación Magnética Transcraneal , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Tiempo
19.
Nanomedicine (Lond) ; 12(5): 555-570, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28181458

RESUMEN

Mesenchymal stem cells (MSCs) have a significant self-renewal capacity and can differentiate into a variety of cell types. Cell labeling is crucial as it is difficult to detect cell fate after transplantation in vivo. MSCs labeled with iron oxide nanoparticles (IONPs), which can be tracked by MRI, have tremendous potential in regenerative medicine and oncological research. As a part of nanoparticle, the iron oxide core is a key aspect that can exhibit adverse or beneficial effects on MSCs labeled for tracking. Some IONPs exhibit adverse effects, such as cytotoxicity and apoptosis, while other IONPs exhibit beneficial functions that can promote both MSC proliferation and homing efficiency. This review reveals the cytotoxic mechanisms and potential functions of the iron oxide core of IONPs in cell labeling as well as strategies for minimizing the intracellular effects of IONPs.


Asunto(s)
Rastreo Celular/métodos , Compuestos Férricos/química , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas/química , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/química
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