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1.
Int J Med Sci ; 18(15): 3488-3497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522175

RESUMO

Background: This study is to compare the efficacy of short-axis hydrodissection with long-axis hydrodissection for patients with mild-to-moderate carpal tunnel syndrome (CTS). Methods: Forty-seven patients with mild-to-moderate CTS were enrolled in a prospective, randomized, single-blinded, controlled trial (6 months follow-up). With ultrasound guidance, patients in both groups (short-axis or long-axis groups) were injected with normal saline (5 mL per session). Assessments were performed before and 2 weeks after the injection, as well as at 1, 3, and 6 months post-intervention. The primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score and secondary outcomes included the cross-sectional area of the median nerve and electrophysiological studies. Results: Forty-four patients (21 wrists in the short-axis group and 23 wrists in the long-axis group) completed the study. Compared with the baseline, both groups showed improved BCTQ and cross-sectional area at all follow-up assessments (p<0.05). The short-axis group was not more effective except significant improvements in BCTQ-severity and BCTQ-function 1 month post-injection compared to the long-axis group (p = 0.031 and p = 0.023, respectively). Conclusions: Both short- and long-axis hydrodissection were effective for patients with mild-to-moderate CTS and the short-axis approach was not more effective than long-axis injection. Further studies with larger sample sizes, multiple injections, and larger injection volume are encouraged in the future.

2.
Oxid Med Cell Longev ; 2021: 8905578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512872

RESUMO

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress contribute to postischemic myocardial damage, but the upstream regulatory mechanisms have not been identified. In this study, we analyzed the role of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) in the regulation of mitochondrial function and ER stress in hypoxic cardiomyocytes. Our results show that MKP-1 overexpression sustains viability and reduces hypoxia-induced apoptosis among H9C2 cardiomyocytes. MKP-1 overexpression attenuates ER stress and expression of ER stress genes and improves mitochondrial function in hypoxia-treated H9C2 cells. MKP-1 overexpression also increases ATP production and mitochondrial respiration and attenuates mitochondrial oxidative damage in hypoxic cardiomyocytes. Moreover, our results demonstrate that ERK and JNK are the downstream signaling targets of MKP-1 and that MKP-1 overexpression activates ERK, while it inhibits JNK. Inhibition of ERK reduces the ability of MKP-1 to preserve mitochondrial function and ER homeostasis in hypoxic cardiomyocytes. These results show that MKP-1 plays an essential role in the regulation of mitochondrial function and ER stress in hypoxic H9C2 cardiomyocytes through normalization of the ERK pathway and suggest that MKP-1 may serve as a novel target for the treatment of postischemic myocardial injury.

3.
Adv Sci (Weinh) ; : e2100974, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514747

RESUMO

Fibroblast growth factor receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates FGF signaling. Various FGFR2 alterations are detected in breast cancer, yet it remains unclear if activation of FGFR2 signaling initiates tumor formation. In an attempt to answer this question, a mouse model berrying an activation mutation of FGFR2 (FGFR2-S252W) in the mammary gland is generated. It is found that FGF/FGFR2 signaling drives the development of triple-negative breast cancer accompanied by epithelial-mesenchymal transition that is regulated by FGFR2-STAT3 signaling. It is demonstrated that FGFR2 suppresses BRCA1 via the ERK-YY1 axis and promotes tumor progression. BRCA1 knockout in the mammary gland of the FGFR2-S252W mice significantly accelerated tumorigenesis. It is also shown that FGFR2 positively regulates PD-L1 and that a combination of FGFR2 inhibition and immune checkpoint blockade kills cancer cells. These data suggest that the mouse models mimic human breast cancers and can be used to identify actionable therapeutic targets.

4.
Reproduction ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34486978

RESUMO

There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages were compared between 25-30 day old and mature female mice. We found the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. This study should shed light on human adolescent pregnancy.

5.
Org Biomol Chem ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34476428

RESUMO

An exquisite metal-free cascade cyclization reaction of 2-acylbenzoic acids with amines was developed, which provided a powerful method for the one-pot synthesis of diverse isoindoloisoquinoline and benzoindolizinoindole derivatives. This protocol avoided the use of metal catalysts, proceeded with high efficiency and had broad substrate scope. These resulting products could be transformed into tertiary amines under the reduction of LiAlH4/AlCl3, followed by the Hofmann elimination offering lots of nitrogen-containing nine-membered ring compounds in excellent yields. All synthesized products containing fused N-polycyclic skeletons were difficult to be constructed using traditional methods and they have a wide range of applications in the pharmaceutical area.

6.
J Healthc Eng ; 2021: 3051578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476046

RESUMO

Supraspinatus tendon injury is a common clinical shoulder joint disease and is one of the most common causes of shoulder pain and dysfunction. Supraspinatus tendon injury will lead to articular cartilage injury and degeneration, then cause joint disease, seriously affect the quality of life of patients, and bring a huge burden to the family and society. This paper mainly studies and evaluates the application value of special signs of shoulder joint and indirect MR imaging in the diagnosis of supraspinatus tendon injury. Through a series of special examinations for the diagnosis of supraspinatus tendon injury in 90 patients, including zero degree abduction resistance test, arm drop test, Jobe test, Neer sign, and Hawkins sign, all patients in the study underwent indirect magnetic resonance imaging of the shoulder joint. Finally, arthroscopic examination results were used as the "gold standard" to evaluate and analyze the diagnosis. The results showed that among the special signs, the specificity of the falling-arm test was the highest (72.2%) in the diagnosis of full-thickness supraspinatus tendon injury. Hawkins sign had the highest sensitivity (84.0%). In the diagnosis of partial supraspinatus tendon injury, the specificity of the Jobe test was the highest, which was 66.6%. The Neer sign had the highest sensitivity of 50.0%. In the diagnosis of full-thickness supraspinatus tendon injury, there was no significant difference in sensitivity between indirect MRI and Hawkins sign, but the diagnostic specificity of indirect MRI was higher than that of special sign examination. In the diagnosis of partial supraspinatus tendon injury, the sensitivity and specificity of indirect MR imaging are higher than those of special sign examination.

7.
Shanghai Kou Qiang Yi Xue ; 30(3): 247-252, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476439

RESUMO

PURPOSE: To investigate the effects of different hypoxic concentrations on biological characteristics of human dental pulp stem cells in vitro. METHODS: Impacted mandibular third molars were extracted from healthy individuals, and the dental pulp stem cells were cultured by tissue block enzyme digestion. Cells cultured under the conditions of 3%, 5% and 21% oxygen concentration for 7 days were set as 3% hypoxia group, 5% hypoxia group, and 21% nomoxia group, respectively. Flow cytometry was used to detect cell surface markers, cell cycle and apoptosis. Cell proliferation was measured by CCK-8 method. Transwell chamber assay was used to detect migration ability. Statistical analysis was completed by SPSS 20.0 software package. RESULTS: The expression rates of CD44, CD29 and D73 of the subculture cells were 97.25%, 99.36% and 99.60%, respectively. The proliferation ability of dental pulp stem cells was the strongest in 5% hypoxia group, and weakest in 3% hypoxia group, with significant difference(P<0.05). The apoptosis rate had no significant difference among various concentrations of oxygen(P>0.05). Compared with 21% nomoxia group, the proportion of dental pulp stem cells in G1 phase was significantly lower than that in 3% hypoxia group and 5% hypoxia group(P<0.05), and cell in S phase was significantly higher than that in 3% hypoxia group and 5% hypoxia group(P<0.05). The migration ability was the strongest in 3% hypoxia group, and weakest in 21% nomoxia group, with significant difference(P<0.05). CONCLUSIONS: Different concentrations of hypoxia have great influence on the morphology, proliferation, migration and cell cycle of human dental pulp stem cells in vitro with little impact on cell apoptosis.


Assuntos
Polpa Dentária , Células-Tronco , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Hipóxia
8.
Anim Genet ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494299

RESUMO

Improvement of ewe reproduction is considerable by appropriately increasing litter size and sustaining non-seasonal breeding. However, their genetic makeups have not been entirely elucidated. Genome-wide analyses of 821 individuals were performed by combining three genomic approaches (genome-wide association study, XP-nSL, and runs of homozygosity). Consequently, 35 candidate genes including three domestication genes (TSHR, GTF2A1, and KITLG) were identified. Other than the FecB mutation at BMPR1B, we described a significant association of a missense mutation rs406686139 at seasonal lambing-associated TSHR gene with litter size. Some promising novel genes may be relevant for sheep reproduction by multitude biological processes, such as FETUB functioning in fertilization, HNRNPA1 in oogenesis, DCUN1D1 in spermatogenesis, and HRG in fertility outcome. The present study suggests that improvement of ewe reproduction is attributed to selective breeding, and casts light on the genetic basis and improvement of sheep reproduction.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120332, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34488001

RESUMO

Based on the thiourea quenching of the chemiluminescence of Tb3+/ prulifloxacin (PUFX) sensitized KMnO4-Na2SO3 system, a convenient and rapid chemiluminescence method for the determination of thiourea was proposed. The reaction between KMnO4 and Na2SO3 brought only weak chemiluminescence, but the chemiluminescence increased sharply in the presence of sensitizer Tb3+/ PUFX. Addition of thiourea can prevent the reaction between KMnO4 and Na2SO3, thus the chemiluminescence intensity was significantly decreased. Under the optimum conditions, the calibration graphs for thiourea were linear in the range of 1.0 × 10-7 to 4.0 × 10-5 mol•L-1. The limit of detection was 6.4 × 10-8 mol•L-1. The method was applied satisfactorily to the determination of thiourea in tap water, lake water and rice noodles and the spiked recoveries were between 104.7 ~ 113.4%. The possible mechanism of sensitization and quenching was also proposed.

10.
J Colloid Interface Sci ; 606(Pt 2): 1435-1444, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34492478

RESUMO

Improving the selectivity of photocatalysis and reducing the generation of toxic by-products are the two key challenges for the development of highly efficient and stable photocatalysts. In this work, it was revealed that Zn-Ti-layered double hydroxide (ZT-LDH) photocatalyst, which generated less intermediates, showed better toluene degradation efficiency (removal ratio, 75.2%) and stability, compared with P25 (removal ratio, 10.9%). During the photocatalytic toluene degradation, benzaldehyde and benzoic acid were the main intermediates existed in the gas phase and on the surface of the catalyst, respectively. By combining experiments with theoretical calculation, it was found that the hydrogen atoms on the hydroxyl groups in the LDH would selectively attract the oxygen atoms in the carbon-oxygen double bond of the two major intermediates, facilitating their adsorption and activation on ZT-LDH. Besides, the surface electronic structure of ZT-LDH was demonstrated to facilitate the ring-opening reaction of the two major intermediates, eventually maintaining high activity and stability. This work could provide new molecular perspectives for understanding the photocatalytic reactions in VOCs degradation and developing efficient and stable photocatalysts.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34507817

RESUMO

OBJECTIVE: Calcified aortic valvular disease is known as an inflammation-related process related to force. The purpose of this study was to determine whether micromechanical force could induce valve calcification of porcine valvular interstitial cells and to examine the role of integrin αvß3 in valvular calcification by using a novel method: magnetic twisting cytometry. METHODS: Porcine valvular interstitial cells were cultured in vitro, and micromechanical force was applied to porcine valvular interstitial cells using magnetic twisting cytometry. Changes in calcification-related factors osteopontin and RUNX2 were detected. By using the calcification medium, the optimal magnetic twisting cytometry parameters for inducing valvular interstitial cell calcification were determined, and a magnetic twisting cytometry calcification promotion model was established. The role of αvß3 in calcification was studied by using αvß3 antagonists to block the function of αvß3. RESULTS: Reverse transcription polymerase chain reaction assays showed that the expression of osteopontin was enhanced 30 minutes after 25G-1Hz 5 minutes of stimulation. Western blotting assays showed that the expression of osteopontin and RUNX2 was upregulated 24 hours after 25G-1Hz 5 minutes of stimulation. The optimal magnetic twisting cytometry parameter for inducing porcine valvular interstitial cell calcification was 25G-2Hz for 10 minutes. The expression of osteopontin and RUNX2 decreased significantly after the addition of αvß3 antagonist. Clinically, patients with bicuspid aortic valves had high expression of RUNX2 and ß3 in the aortic valve, and ß3 significantly correlated with RUNX2. CONCLUSIONS: By using magnetic twisting cytometry, we established a porcine valvular interstitial cell calcification model by micromechanical force stimulation and obtained the optimal parameters. Integrin αvß3 plays a key role in the aortic valve calcification process.

12.
J Am Chem Soc ; 143(35): 14046-14052, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34437800

RESUMO

A new and general method to functionalize the C(sp3)-C(sp2) bond of alkyl and alkene linkages has been developed, leading to the dealkenylative generation of carbon-centered radicals that can be intercepted to undergo Ni-catalyzed C(sp3)-C(sp2) cross-coupling. This one-pot protocol leverages the easily procured alkene feedstocks for organic synthesis with excellent functional group compatibility without the need for a photoredox catalyst.

13.
J Am Chem Soc ; 143(36): 14438-14444, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34464528

RESUMO

Azoles are important motifs in medicinal chemistry, and elaboration of their structures via direct N-H/C-H coupling could have broad utility in drug discovery. The ambident reactivity of many azoles, however, presents significant selectivity challenges. Here, we report a copper-catalyzed method that achieves site-selective cross-coupling of pyrazoles and other N-H heterocycles with substrates bearing (hetero)benzylic C-H bonds. Excellent N-site selectivity is achieved, with the preferred site controlled by the identity of co-catalytic additives. This cross-coupling strategy features broad scope for both the N-H heterocycle and benzylic C-H coupling partners, enabling application of this method to complex molecule synthesis and medicinal chemistry.

14.
J Transl Med ; 19(1): 334, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362383

RESUMO

BACKGROUND: Although the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer. METHODS: The expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan-Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer. RESULTS: DDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells. CONCLUSION: DDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais , Neoplasias da Mama/genética , RNA Helicases DEAD-box/genética , Feminino , Humanos , Prognóstico , Proteômica , Células-Tronco
15.
Sci Adv ; 7(34)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34407939

RESUMO

Numerous animal studies have demonstrated that fear acquisition and expression rely on the coordinated activity of medial prefrontal cortex (mPFC) and amygdala and that theta oscillations support interregional communication within the fear network. However, it remains unclear whether these results can be generalized to fear learning in humans. We addressed this question using intracranial electroencephalography recordings in 13 patients with epilepsy during a fear conditioning paradigm. We observed increased power and inter-regional synchronization of amygdala and mPFC in theta (4 to 8 hertz) oscillations for conditioned stimulus (CS+) versus CS-. Analysis of information flow revealed that the dorsal mPFC (dmPFC) led amygdala activity in theta oscillations. Last, a computational model showed that trial-by-trial changes in amygdala theta oscillations predicted the model-based associability (i.e., learning rate). This study provides compelling evidence that theta oscillations within and between amygdala, ventral mPFC, and dmPFC constitute a general mechanism of fear learning across species.

16.
J Cell Sci ; 134(2)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34432034

RESUMO

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1, also known as TP53BP1). The results provide evidence that α-TAT1 and Ac-α-Tub inhibit the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT and why the decrease in α-TAT1 and Ac-α-Tub promotes silicosis fibrosis. This article has an associated First Person interview with the first authors of the paper.


Assuntos
Transição Epitelial-Mesenquimal , Tubulina (Proteína) , Acetilação , Dano ao DNA , Transição Epitelial-Mesenquimal/genética , Humanos , Processamento de Proteína Pós-Traducional , Dióxido de Silício/toxicidade , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
17.
J Healthc Eng ; 2021: 7865155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457222

RESUMO

Aim: To study the diagnostic effect of hip fracture in the elderly. In this paper, a total of 100 elderly patients with hip fracture from January 2020 to May 2021 were selected for X-ray and CT examination after admission. The operation was taken as the final criteria for determining hip fracture type, and the diagnosis of hip fracture by CT three-dimensional reconstruction was analyzed and studied. The results showed that the diagnostic rate of CT 3D reconstruction for various types of hip fracture in the elderly was higher than that of CT plain scan and X-ray (P < 0.05). For the diagnosis of intra-articular small bone fragments, the rate of missed diagnosis was 2% (2/100) with CT 3D reconstruction, 10% (10/100) with conventional CT scan, and 20% (20/100) with X-ray. The rate of misdiagnosis was 5.0% (5/100) with CT 3D reconstruction. Routine CT scan was 15% (15/100), X-ray was 30% (30/100), and CT 3D reconstruction was significantly lower than other examinations (P < 0.05). Conclusion: CT 3D reconstruction has high accuracy in the diagnosis of various types of hip fractures in the elderly.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34463419

RESUMO

Shape complementarity is a biological craft for precisely binding substrates at protein-protein interfaces. An analogy to such a function can be drawn conceptually for crystalline porous solids; yet the manifested entities are rare in reticular chemistry. The bottleneck-shaped pores carved out of a metal-organic framework, Zn(MIBA) 2 (aka. MAF-stu-13), can perfectly accommodate benzene molecules. Remarkably, its framework adapts to the optimal guest binding-the enhanced host-guest interactions in the neck in turn minimize the guest-guest repulsion in the pore to the extent it turns into attraction-as demonstrated by the combined X-ray structural and DFT computational studies. This adaptive material can be used for liquid-phase production of ultrahigh-purity (≥ 99%) cyclohexane, achieving a balance between uptake capacity and separation selectivity and surpassing the performances of other porous and nonporous crystals reported recently (e.g. product purity 99.4% vs. 97.5% to date).

19.
J Healthc Eng ; 2021: 9596518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422250

RESUMO

Aim: To study the application value of ankle fracture classification and diagnosis. In this paper, the clinical data of 100 cases of ankle fracture patients admitted from May 2020 to May 2021 were analyzed by CT 3D reconstruction. All patients received surgical treatment and underwent spiral CT 3D reconstruction and X-ray examination before surgery. The results showed that 20 cases (20.00%) of the 100 cases were PER, 24 cases (24%) of the 100 cases were PAB, 31 cases (31%) of the 100 cases were SER, and 25 cases (25%) of the 100 cases were SAB, respectively. Conclusion: The diagnostic accuracy of CT 3D reconstruction for different types of ankle fracture is higher than that of X-ray, and the differences are statistically significant (P < 0.05). CT 3D reconstruction is applied in the early diagnosis of ankle fracture, which can accurately detect the classification of patients. It has important clinical application value and can be used as the first choice for the early classification diagnosis of ankle fracture.

20.
Metallomics ; 13(9)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34402906

RESUMO

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

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