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1.
Photochem Photobiol Sci ; 23(6): 1031-1039, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38839721

ABSTRACT

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

2.
Cell Div ; 19(1): 13, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632651

ABSTRACT

The anti-aging gene Klotho is implicated in the pathogenesis of preeclampsia (PE), which is a pregnancy disease characterized by hypertension and proteinuria. Oxidative stress is closely associated with the worse outcomes in PE, and Klotho can eliminate Reactive Oxygen Species (ROS), but it is still unclear whether Klotho regulates PE pathogenesis through modulating oxidative damages. Here, by analyzing the clinical data, we found that Klotho was aberrantly downregulated in PE umbilical cord serum and placental tissues, compared to their normal counterparts. In in vitro experiments, the human trophoblasts were subjected to hypoxic pressure to establish the PE models, and we confirmed that hypoxia also decreased the expression levels of Klotho in those trophoblasts. In addition, through performing functional experiments, we confirmed that hypoxia promoted oxidative damages, cell apoptosis and senescence, whereas suppressed cell invasion in human trophoblasts, which were all reversed overexpressing Klotho. The following mechanical experiments verified that Klotho increased the levels of nuclear Nrf2, total Nrf2, SOD2 and NQO1 to activate the anti-oxidant Nrf2/ARE signal pathway, and silencing of Nrf2 abrogated the protective effects of Klotho overexpression on hypoxic human trophoblasts. Consistently, in in vivo experiments, Klotho overexpression restrained oxidative damages and facilitated cell mitosis in PE rats' placental tissues. In conclusion, this study validated that Klotho activated the Nrf2/ARE signal pathway to eliminate hypoxia-induced oxidative damages, cell apoptosis and senescence to recover normal cellular functions in human trophoblasts, and our data supported that Klotho could be used as novel biomarker for PE diagnosis and treatment.

3.
J Clin Hypertens (Greenwich) ; 26(5): 474-482, 2024 May.
Article in English | MEDLINE | ID: mdl-38476059

ABSTRACT

Patients with systemic autoimmune diseases, such as systemic lupus erythematosus, were at a higher risk for preeclampsia. The causal relationship between immunological inflammation and preeclampsia (PE) remains uncertain. We aimed to investigate the causal relationship between circulating immune inflammation and PE. Genetically predicted blood immune cells and circulating inflammatory proteins were identified using two genome-wide association studies (GWAS). We used a two-sample Mendelian randomization (MR) method to determine whether circulating immunological inflammation causes PE. Our findings indicated that ten immunophenotypes were identified to be significantly associated with PE risk: CD62L- Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- myeloid Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell Absolute Count, CD62L- myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell Absolute Count, CD16 on CD14+ CD16+ monocyte, HLA DR+ Natural Killer Absolute Count, and T cell Absolute Count. Ninety-one inflammation-related proteins had no statistically significant effect on PE following false discovery rate (FDR) correction. Certain proteins exhibited unadjusted low p-values that merited mention. These proteins include interleukin-10 (OR = 0.76, 95%CI = 0.63-0.93, p = .006), fibroblast growth factor 21 (OR = 1.23, 95%CI = 1.01-1.47, p = .035), and Caspase 8 (OR = 0.65, 95%CI = 0.50-0.85, p = .001). The ELISA analysis demonstrated elevated levels of FGF-21 and decreased levels of IL-10 and Caspase-8 in the plasma of patients with PE. These findings reveal that immunophenotypes and circulating inflammatory proteins may induce PE, confirming the importance of peripheral Immunity-Inflammation in PE. The discovery has the potential to lead to earlier detection and more effective treatment techniques.


Subject(s)
Genome-Wide Association Study , Inflammation , Mendelian Randomization Analysis , Pre-Eclampsia , Humans , Female , Pre-Eclampsia/immunology , Pre-Eclampsia/blood , Pre-Eclampsia/genetics , Mendelian Randomization Analysis/methods , Pregnancy , Inflammation/immunology , Inflammation/blood , Inflammation/genetics , Interleukin-10/blood , Interleukin-10/genetics , Dendritic Cells/immunology , Adult , Immunophenotyping/methods
4.
Aging (Albany NY) ; 16(3): 2320-2339, 2024 02 07.
Article in English | MEDLINE | ID: mdl-38329424

ABSTRACT

ALG3 has significant modulatory function in the process of tumor development. Yet how ALG3 involves in the advancement of different malignancies isn't fully understood. We performed a pan-cancer assessment on ALG3 utilizing datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to examine its tumor-related roles across malignancies and its link to particular molecules and cells in the tumor microenvironment (TME). Furthermore, we focused on breast cancer to examine the influence of ALG3-mediated signaling pathways and intercellular interactions in the advancement of tumors. The biological effects of ALG3 were verified by breast cancer cells. Enhanced ALG3 expression was discovered to be substantially linked to patients' grim prognoses in a number of malignancies. Furthermore, the expression of ALG3 in the TME was linked to the infiltration of stromal and immune cells, and ALG3-related immune checkpoints, TMB, and MSI were also discovered. We also discovered that cancer patients having a high level of ALG3 exhibited a lower probability of benefiting from immunotherapy. Furthermore, our research found that KEGG enrichment, single-cell RNA and spatial sequencing analyses were effective in identifying key signaling pathways in ALG3-associated tumor growth. In vitro, knockdown of ALG3 could decrease the proliferation of breast cancer cells. In summary, our research offers a comprehensive insight into the advancement of tumors under the mediation of ALG3. ALG3 appears to be intimately associated with tumor development in the TME. ALG3 might be a viable treatment target for cancer therapy, particularly in the case of breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Biomarkers , Immunotherapy , RNA , Spatial Analysis , Prognosis , Tumor Microenvironment/genetics , Mannosyltransferases
5.
Quant Imaging Med Surg ; 13(10): 7269-7280, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37869277

ABSTRACT

Background: Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma that predominantly affects adolescents and young adults. Early diagnosis of ASPS is crucial for optimal therapeutic planning and improving prognosis, but its diagnostic features are not well delineated. This study aimed to retrospectively analyze the imaging features of ASPS with an emphasis on the dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) findings to identify imaging findings that might suggest the diagnosis to radiologists. Methods: The imaging features of 34 patients with pathologically proven limb ASPS were retrospectively analyzed. A total of 23 underwent DCE-MRI, and 12 underwent DWI. Results: Among the 34 cases of ASPS, 31 tumors were in the lower extremities, and 3 were in the upper extremities. The maximum tumor diameters ranged from 3.0 to 19.4 cm (mean, 8.7±3.96 cm). A total of 28 cases had well-defined borders. The masses demonstrated heterogeneous high signal intensity on T2-weighted imaging (T2WI) and the fat-suppressed (FS) T2WI sequence and slight hyperintensity on T1-weighted imaging (T1WI). A total of 25 lesions had thin hypointense bands on T1WI and T2WI. Intra- and peri-tumoral tubular areas of flow void were exhibited on both T1WI and T2WI in all cases. A total of 12 cases showed a high signal on DWI, and the mean apparent diffusion coefficient (ADC) value was (0.86±0.07)×10-3 mm2/s [range, (0.6-1.4)×10-3 mm2/s]. Persistent remarkable enhancement of the lesion was displayed on contrast-enhanced scans. The time-intensity curves (TICs) of 23 masses showed early arterial enhancement and slow washout of contrast. Conclusions: ASPS most commonly presents in the lower extremities of adolescents or young adults. Hyperintense T1WI, T2WI, and DWI signals, low ADC, flow voids, early arterial enhancement are frequent MRI features.

6.
J Transl Med ; 21(1): 349, 2023 05 26.
Article in English | MEDLINE | ID: mdl-37237321

ABSTRACT

Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.


Subject(s)
Gastrointestinal Microbiome , Humans , Intestines/physiology , Gastrointestinal Motility , Dysbiosis
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 292: 122410, 2023 May 05.
Article in English | MEDLINE | ID: mdl-36736049

ABSTRACT

Biothiols mainly include cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), which play an important role in life activities and abnormal changes in their concentrations are closely related to certain diseases. Therefore, the quantitative tracking and analysis of biothiols in living organisms has become a hot research topic in recent years. In this work, a coumarin-based fluorescent probe COUN was designed and synthesized for the comparable color recognition of Cys/Hcy and GSH by introducing the phenylethynyl group as the recognition site of biothiols, which showed significant fluorescence enhancement and green fluorescence under the UV light at 365 nm. The probe specifically recognized Hcy, showing 40-fold fluorescence enhancement and strong green fluorescence at 492 nm. Moreover, there was a good linear relationship between the fluorescence intensity of the probe and certain concentrations of Cys/Hcy and GSH, with detection limits of 36.6 nM, 86.4 nM, and 174 nM, respectively. The recognition mechanism of COUN to distinguish Cys/Hcy and GSH was studied by TDDFT calculations. More importantly, COUN was successfully used for imaging biothiols in living cells. The results showed that this probe could provide an effective contribution to the understanding of the role of biothiols, especially Hcy.


Subject(s)
Cysteine , Fluorescent Dyes , Cysteine/analysis , Glutathione/analysis , Coumarins , Spectrometry, Fluorescence/methods , Homocysteine
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 292: 122443, 2023 May 05.
Article in English | MEDLINE | ID: mdl-36753868

ABSTRACT

There is an urgent need to develop highly sensitive and selective fluorescence probes for ONOO- in mitochondria. Herein, we reported a ratiometric fluorescent probe COUS with coumarin-cyanine hybrid as fluorophore and C = C bonds as reaction sites of ONOO-. The probe COUS was sensitive and selective to ONOO-, and had a large fluorescence emission shift (239 nm) as well as a low detection limit (41.88 nM). Moreover, COUS showed the mitochondrial targeting ability, and the targeting moiety could dissociate from the probe when reacting with ONOO-, which enabled COUS to accurately detect ONOO- in mitochondria.


Subject(s)
Fluorescent Dyes , Peroxynitrous Acid , Fluorescent Dyes/chemistry , Peroxynitrous Acid/analysis , Mitochondria/chemistry , Coumarins/analysis , Fluorescence
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 284: 121778, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36049300

ABSTRACT

Monitoring intracellular pH using ratiometric fluorescent probes can provide further insights into various biological processes including many diseases. Although ratiometric fluorescent probes with dual emission can efficiently exclude interferences (probe concentration, instrumental efficiency, and environmental conditions) compared with traditional off-on fluorescent probes, development of pH-responsive fluorescent probes with dual emission remains relatively unexplored and challenging. Herein we reported a new hemicyanine-based ratiometric fluorescent probe 1 with a hydroxyl group. The probe 1 exhibits dual emission and shows a real-time and selective fluorescence response to micro-environmental pH conditions in a range of 6.0 âˆ¼ 8.0. Further studies revealed that 1 could exclusively enter and accumulate into mitochondria and monitor the pH micro-environmental conditions through fluorescence imaging in HepG2 cells. We suggest that this probe might be used as a probe to elucidate the role of pH in many physiological processes.


Subject(s)
Fluorescent Dyes , Carbocyanines , HeLa Cells , Humans , Hydrogen-Ion Concentration
10.
Int J Nanomedicine ; 17: 5565-5579, 2022.
Article in English | MEDLINE | ID: mdl-36444199

ABSTRACT

Introduction: Second near-infrared photothermal therapy (NIR-II PTT) has become a promising strategy for treating cancer in terms of safety and potency. However, the application of NIR-II PTT was limited in the treatment of deep-buried solid tumors due to the low dose of NIR-II absorption nanomaterials and the inadequate laser energy in the deep tumor. Methods: Herein, the authors report the engineering of NIR-II absorbing polyaniline nanorods, termed HPW@PANI Nanorods, for in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial infusion for the treatment of orthotopic hepatocellular carcinoma in the rabbit. HPW@PANI Nanorods were prepared via chemical oxidant polymerization of aniline under phosphotungstic acid, which exhibited effective NIR-II absorption for hyperthermia ablation cells. Results: HPW@PANI Nanorods were fast and efficiently deposited into primary orthotopic transplantation VX2 tumor in rabbits via transarterial infusion. Furthermore, an optical fiber was interventionally inserted into the primary VX2 tumor to transmit 1064nm laser energy for in situ NIR-II PTT, which could ablate primary tumor, inhibit distant tumor, and suppress peritoneal metastasis. Conclusion: This study provides new insights into the application of in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial injection of NIR-II absorption nanomaterials to treat deep-buried tumors.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanotubes , Animals , Rabbits , Photothermal Therapy , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Aniline Compounds
11.
Opt Express ; 30(12): 21362-21376, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-36224857

ABSTRACT

The digital twin of optical systems can imitate its response to outer environments through connecting outputs from data-driven optical element models with numerical simulation methods, which could be used for system design, test and troubleshooting. Data-driven optical element models are essential blocks in digital twins. It can not only transform data obtained from sensors in real optical systems to states of optical elements in digital twins, but also simulate behaviors of optical elements with real measurements as prior conditions. For ground based optical telescopes, the digital twin of atmospheric turbulence phase screens is an important block to be developed. The digital twin of atmospheric turbulence phase screens should be able to generate phase screens with infinite length and high similarities to real measurements. In this paper, we propose a novel method to build the digital twin of atmospheric turbulence phase screens. Our method uses two deep neural networks to learn mapping functions between the space of parameters and the space of phase screens and vice versa. Meanwhile, a forecasting deep neural network is proposed to generate parameters for the next phase screen according to parameters extracted from a previous phase screen. The method proposed in this paper could be used to directly produce phase screens with infinite length and of any temporal or spatial power spectral density that follows statistical distributions of real measurements, which makes it an appropriate block in digital twins of ground based optical systems.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121406, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-35617838

ABSTRACT

A novel near-infrared fluorescent probe CyOE based on hemicyanine dye containing acetyl as a recognition site is reported. The probe CyOE shows high selectivity and sensitivity (LOD = 82 nM, 2.58 ppb), as well as good water solubility and quantitative detectability of hydrazine in the concentration range of 0-75 µM (R2 = 0.993). Moreover, CyOE has a significant increase in fluorescence at 735 nm with the addition of N2H4, which provides a rapid, colorimetric and gas-phase detection method for N2H4 in both aqueous solution and real water samples. In addition, CyOE is successfully utilized to visualize hydrazine in cells with low cytotoxicity and high cell permeability.


Subject(s)
Fluorescent Dyes , Hydrazines , Carbocyanines , Fluorescent Dyes/toxicity , Gases , HeLa Cells , Humans , Spectrometry, Fluorescence/methods , Water
13.
Bioinorg Chem Appl ; 2021: 2495958, 2021.
Article in English | MEDLINE | ID: mdl-35003236

ABSTRACT

TTRE, a photosensitizer molecule, has excellent biofluorescence imaging performance and effective antitumor properties for breast cancer. However, its application in breast cancer treatment is limited due to poor tumor selectivity and lack of targeting ability. In this study, TTRE and trastuzumab were combined to synthesize Tra-TTR-A, a novel near-infrared fluorescent nanoprobe for HER2 positive breast cancer. The targeting and antitumor abilities of Tra-TTR-A in breast cancer were also investigated. Like TTRE, Tra-TTR-A has a stable structure with remarkable optical properties and in vivo imaging capacity. However, Tra-TTR-A not only inhibits tumor growth by generating reactive oxygen species but also kills tumor cells by trastuzumab. In this study, Tra-TTR-A, a new type of near-infrared fluorescent nanoprobe that targets HER2-positive breast cancer, was successfully synthesized. Tra-TTR-A could be used in in vivo imaging, targeted photodynamic therapy, and diagnosis and treatment for breast cancer.

14.
Huan Jing Ke Xue ; 40(2): 738-746, 2019 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-30628338

ABSTRACT

Polyvinylidene fluoride (PVDF) hollow fiber ultrafiltration membranes were modified with carbon nanotubes (CNT). Hybrid pre-ozonation and CNT modification were investigated by experimentally manipulating the ozonation process, threshold flux, and membrane fouling. The results showed that the threshold fluxes of the unmodified membrane and hybrid process were 45 L·(m2·h)-1 and 81 L·(m2·h)-1, respectively. Additionally, the fouling rate of the hybrid process was about 0.00137 kPa·min-1·L-1·m2·h, which was notably lower compared to other process. The results showed that the filtration volume under threshold flux was higher than that under critical flux with the same CNT loading mass and ozone dosage. This comparison indicated that membrane fouling was alleviated under threshold flux and that the corresponding operation period was extended. Through the carbon balance experiment, the fouling capacity and recoverability improved remarkably after CNT modification. Additionally, ozonation could enhance the recoverability of membranes. The hybrid process examined in this study could dramatically improve the permeability and extend the operation time of the ultrafiltration membrane.

15.
Free Radic Biol Med ; 131: 382-392, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30578918

ABSTRACT

Reactive oxygen species (ROS) play a critical role in total body irradiation (TBI)-induced hematopoietic system injury. However, the mechanisms involved in ROS production in hematopoietic stem cells (HSCs) post TBI need to be further explored. In this study, we demonstrated that hematopoietic system injury in mice radiated with TBI was effectively alleviated when the blood circulation environment was changed via the injection of serum from non-radiated mice. Serum injection increased the survival of radiated mice and ameliorated TBI-induced hematopoietic system injury through attenuating myeloid skew, increasing HSC frequency, and promoting the reconstitution of radiated HSCs. Serum injection also decreased ROS levels in HSCs and regulated oxidative stress-related proteins. A serum proteome sequence array showed that proteins related to tissue injury and oxidative stress were regulated, and a serum-derived exosome microRNA sequence assay showed that the PI3K-Akt and Hippo signaling pathways were affected in radiated mice injected with serum from non-radiated mice. Furthermore, a significant increase in cell viability and a decrease in ROS were observed in radiated lineage-c-kit+ cells treated with serum-derived exosomes. Similarly, an improvement in the impaired differentiation of HSCs was observed in radiated mice injected with serum-derived exosomes. Taken together, our observations suggest that serum from non-radiated mice alleviates HSC injury in radiated mice by improving the systemic environment after radiation, and exosomes contribute to this radioprotective effect as important serum active component.


Subject(s)
Blood Proteins/pharmacology , Exosomes/transplantation , Hematopoietic Stem Cells/drug effects , Hematopoietic System/drug effects , Radiation-Protective Agents/pharmacology , Serum/physiology , Animals , Blood Proteins/chemistry , Blood Proteins/isolation & purification , Dose-Response Relationship, Radiation , Exosomes/chemistry , Gene Expression Regulation , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/radiation effects , Hematopoietic System/cytology , Hematopoietic System/radiation effects , Hippo Signaling Pathway , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-kit/metabolism , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Serum/chemistry , Signal Transduction , Survival Analysis , Whole-Body Irradiation
16.
Huan Jing Ke Xue ; 39(8): 3744-3752, 2018 Aug 08.
Article in Chinese | MEDLINE | ID: mdl-29998682

ABSTRACT

Polyvinylidene fluoride (PVDF) hollow fiber ultrafiltration membranes were modified with carbon nanotube (CNT). Combined with the ozonation process, the effect of the hybrid pre-ozonation and CNT modification on fouling alleviation was investigated. The impacts of CNT loading mass and ozone dosage on the variation of flux and antifouling ability of the membrane modules were evaluated. Under a critical flux of 144 L·(m2·h)-1, CNT loading mass of 3 g·m-2, and ozone dosage(O3/DOC) of 0.22 mg·mg-1, the results revealed that the filtration volume of the hybrid process was promoted to 850 L·m-2, which was about 4.5 times higher than that of the original unmodified membrane. With a flux of 18 L·(m2·h)-1 and 15 day operation, the filtration volume was promoted to 3000 L·m-2, which was 10 times that of the unmodified membrane. The fouling membrane surface was observed using confocal laser scanning electron microscopy (CLSM). The results demonstrated that more living bacteria were present on the membrane surface of the unmodified membrane, which showed a rapid transmembrane pressure (TMP) increase. Both pre-ozonation and CNT modification decreased the total amount of microorganisms and the amount of the living bacteria as well, which mitigated the increase in TMP. After pre-ozonation, the presence of a CNT layer on the membrane surface further decreased the number of living bacteria. Although the CNT layer captured some dead bacteria, it had no obvious relationship with the increase in TMP.


Subject(s)
Bacteria/growth & development , Biofouling , Nanotubes, Carbon , Ultrafiltration , Water Purification , Membranes, Artificial , Ozone
17.
Front Pharmacol ; 9: 334, 2018.
Article in English | MEDLINE | ID: mdl-29867453

ABSTRACT

The proteasome inhibitor is a target therapy for multiple myeloma (MM) patients, which has increased the overall survival rate of multiple myeloma in clinic. However, relapse and toxicity are major challenges for almost all MM patients. Thus, there is an urgent need for an effective and less toxic combination therapy. Here, we demonstrated that a natural compound, resveratrol (RSV) displayed anti-proliferative activity in a dose- and time-dependent manner in a panel of MM cell lines. More importantly, a low concentration of RSV was synergistic with a low dose of the proteasome inhibitor carfilzomib (CFZ) to induce apoptosis in myeloma cells. Further studies showed that mitochondria was a key regulatory site after RSV/CFZ combination treatment. RSV induced the release of second mitochondria-derived activator of caspase (Smac) in a dose-dependent manner and kept the Smac in a high level after combination with CFZ. Also, RSV was additive with CFZ to increase reactive oxygen species (ROS) production. Moreover, a stress sensor SIRT1, with deacetylase enzyme activity, was remarkably downregulated after RSV/CFZ combination, thereby significantly decreasing its target protein, survivin in MM cells. Simultaneously, autophagy was invoked after RSV/CFZ combination treatment in myeloma cells. Further inhibition of autophagy could increase more ROS production and apoptosis, indicating a close linkage between autophagy and proteasome to modulate the oxidative stress. Together, these findings suggest that induction of multiple stress responses after RSV/CFZ combination is a major mechanism to synergistically inhibit MM cell growth and reduce the toxicity of CFZ in MM cells. This study also provides an important rationale for the clinic to consider an autophagy inhibitor for the combination therapy in MM patients.

18.
Free Radic Biol Med ; 113: 59-70, 2017 12.
Article in English | MEDLINE | ID: mdl-28939421

ABSTRACT

It has been well established that reactive oxygen species (ROS) play a critical role in ionizing radiation (IR)-induced hematopoietic injury. Theaflavin (TF), a polyphenolic compound from black tea, has been implicated in the regulation of endogenous cellular antioxidant systems. However, it remains unclear whether TF could ameliorate IR-induced hematopoietic injury, particularly the hematopoietic stem cell (HSC) injury. In this study, we explored the potential role of TF in IR-induced HSC injury and the underlying mechanism in a total body irradiation (TBI) mouse model. Our results showed that TF improved survival of irradiated wild-type mice and ameliorated TBI-induced hematopoietic injury by attenuating myelosuppression and myeloid skewing, increasing HSC frequency, and promoting reconstitution of irradiated HSCs. Furthermore, TF inhibited TBI-induced HSC senescence. These effects of TF were associated with a decline in ROS levels and DNA damage in irradiated HSCs. TF reduced oxidative stress mainly by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream targets in irradiated Lineage-c-kit+ positive cells. However, TF failed to improve the survival, to increase HSC frequency and to reduce ROS levels of HSCs in irradiated Nrf2-/- mice. These findings suggest that TF ameliorates IR-induced HSC injury via the NRF2 pathway. Therefore, TF has the potential to be used as a radioprotective agent to ameliorate IR-induced hematopoietic injury.


Subject(s)
Biflavonoids/pharmacology , Catechin/pharmacology , DNA Damage , Hematopoietic Stem Cells/drug effects , NF-E2-Related Factor 2/drug effects , Radiation Injuries, Experimental/prevention & control , Radiation, Ionizing , Signal Transduction , Animals , Biflavonoids/therapeutic use , Catechin/therapeutic use , DNA/radiation effects , Hematopoietic Stem Cells/radiation effects , Male , Mice , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Radiation-Protective Agents/pharmacology , Reactive Oxygen Species , Whole-Body Irradiation
19.
Sci Total Environ ; 601-602: 691-702, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28577404

ABSTRACT

The quality of groundwater used for human consumption and irrigation in the Hetao Basin of Inner Mongolia, China is affected by elevated salinity as well as high arsenic (As) concentrations. However, the origin of high salinity and its potential impact on As mobility in the Basin remain unclear. This study explores both issues using stable isotopic compositions and Cl/Br ratios of groundwater as well as the major ions of both groundwater and leachable salts in aquifer sediments. Limited variations in δ18O and δ2H (-11.13 to -8.10, -82.23 to -65.67) with the wide range of Total Dissolved Solid (TDS, 351-6734mg/L) suggest less contribution of direct evaporation to major salinity in groundwater. Deuterium excess shows that non-direct evaporation (capillary evaporation, transpiration) and mineral/evaporite dissolution contribute to >60% salinity in groundwater with TDS>1000mg/L. Non-direct evaporation, like capillary evaporation and transpiration, is proposed as important processes contributing to groundwater salinity based on Cl/Br ratio and halite dissolution line. The chemical weathering of Ca, Mg minerals and evaporites (Na2SO4 and CaSO4) input salts into groundwater as well. This is evidenced by the fact that lacustrine environment and the arid climate prevails in Pleistocene period. Dissolution of sulfate salts not only promotes groundwater salinity but affects As mobilization. Due to the dissolution of sulfate salts and non-direct evaporation, groundwater SO42- prevails and its reduction may enhance As enrichment. The higher As concentrations (300-553µg/L) are found at the stronger SO42- reduction stage, indicating that reduction of Fe oxide minerals possibly results from HS- produced by SO42- reduction. This would have a profound impact on As mobilization since sulfate is abundant in groundwater and sediments. The evolution of groundwater As and salinity in the future should be further studied in order to ensure sustainable utilization of water resource in this water scarce area.

20.
Int J Mol Sci ; 18(5)2017 Apr 29.
Article in English | MEDLINE | ID: mdl-28468251

ABSTRACT

Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress.


Subject(s)
Coriandrum/chemistry , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/radiation effects , Radiation Injuries/drug therapy , Radiation-Protective Agents/therapeutic use , Rutin/therapeutic use , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Cells, Cultured , DNA Damage/drug effects , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/pathology , Male , Mice, Inbred C57BL , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Radiation Injuries/genetics , Radiation Injuries/metabolism , Radiation Injuries/pathology , Radiation, Ionizing , Radiation-Protective Agents/chemistry , Reactive Oxygen Species/metabolism , Rutin/chemistry
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