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1.
Exp Cell Res ; 442(2): 114222, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39214329

RESUMEN

Targeting ferroptosis, a type of cell death elicited by Fe2+ and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na2SeO3) than that of non-TNBC MCF-7 cells. Na2SeO3 significantly elevated the level of L-ROS, MDA and Fe2+, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na2SeO3 in MDA-MB-231 cells. Notably, Na2SeO3-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na2SeO3-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.

2.
Mar Drugs ; 22(4)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38667800

RESUMEN

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Poríferos , Terpenos , Humanos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Poríferos/química , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Terpenos/farmacología , Terpenos/aislamiento & purificación , Terpenos/química , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células HCT116 , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vimentina/metabolismo , Línea Celular Tumoral , China
3.
J Appl Clin Med Phys ; 24(11): e14097, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37438966

RESUMEN

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.


Asunto(s)
Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Femenino , Humanos , Vejiga Urinaria/diagnóstico por imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Tomografía Computarizada por Rayos X , Radioterapia de Intensidad Modulada/métodos , Órganos en Riesgo
4.
Cladistics ; 38(3): 374-391, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34818432

RESUMEN

The sequential breakup of the supercontinent Pangaea since the Middle Jurassic is one of the crucial factors that has driven the biogeographical patterns of terrestrial biotas. Despite decades of effort searching for concordant patterns between diversification and continental fragmentation among taxonomic groups, increasing evidence has revealed more complex and idiosyncratic scenarios resulting from a mixture of vicariance, dispersal and extinction. Aquatic insects with discreet ecological requirements, low vagility and disjunct distributions represent a valuable model for testing biogeographical hypotheses by reconstructing their distribution patterns and temporal divergences. Insects of the order Megaloptera have exclusively aquatic larvae, their adults have low vagility, and the group has a highly disjunct geographical distribution. Here we present a comprehensive phylogeny of Megaloptera based on a large-scale mitochondrial genome sequencing of 99 species representing >90% of the world genera from all major biogeographical regions. Molecular dating suggests that the deep divergence within Megaloptera pre-dates the breakup of Pangaea. Subsequently, the intergeneric divergences within Corydalinae (dobsonflies), Chauliodinae (fishflies) and Sialidae (alderflies) might have been driven by both vicariance and dispersal correlated with the shifting continent during the Cretaceous, but with strikingly different and incongruent biogeographical signals. The austral distribution of many corydalids appears to be a result of colonization from Eurasia through southward dispersal across Europe and Africa during the Cretaceous, whereas a nearly contemporaneous dispersal via northward rafting of Gondwanan landmasses may account for the colonization of extant Eurasian alderflies from the south.


Asunto(s)
Genoma Mitocondrial , Holometabola , Animales , Genoma Mitocondrial/genética , Holometabola/genética , Insectos/genética , Mitocondrias/genética , Filogenia
5.
Immunol Invest ; 51(2): 316-330, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33161796

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease. Tumor necrosis factor ligand superfamily member 4 (TNFSF4) is an inflammatory factor that has been discussed in different inflammatory diseases and cancers. However, relationship between TNFSF4 and SLE is limited. MATERIAL AND METHODS: The present case-control study recruited 400 SLE patients and 600 healthy controls from Southern Chinese Han origin. Plasma levels of TNFSF4 were tested by enzyme linked-immunosorbent assay, and association of rs2205960, rs704840, rs844648, rs3850641 and rs17568 polymorphisms in TNFSF4 gene with SLE risk was evaluated by TaqMan assay according to genotyping. RESULTS: Plasma levels of TNFSF4 were significantly higher in SLE patients than that in healthy controls (390.87 (189.10-906.01) versus 132. 70 (81.27-195.58) pg/ml, P < 0.001). Increased levels of TNFSF4 were positively related to SLE disease activity score, optic nerve injury, leukopenia, and hypocompleminemia. Genotype TT+TG, allele T of rs2205960, genotype GG+GT of rs704840, genotype AA of rs844648 and rs17568 were significantly related to SLE risk (all P < 0.05). Moreover, polymorphism rs844648 was related to SLE patients with clinical feature rash either for genotype AA or allele A. CONCLUSION: TNFSF4 was elevated in SLE patients and may associate with SLE susceptibility in Southern Chinese Han population.


Asunto(s)
Lupus Eritematoso Sistémico , Ligando OX40 , Alelos , Estudios de Casos y Controles , China/epidemiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lupus Eritematoso Sistémico/genética , Ligando OX40/genética , Polimorfismo de Nucleótido Simple
6.
Luminescence ; 37(4): 672-680, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35142028

RESUMEN

The LiLa(MoO4 )2 :Sm3+ and LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphors were prepared using the citric-acid-fueled combustion method and the influence of concentrations of Bi3+ dopant on LiLa(MoO4 )2 :Sm3+ red luminescence was investigated. The LiLa(MoO4 )2 :Sm3+ and LiLa(MoO4 )2 :Sm3+ ,Bi3+ samples matched well with the scheelite structure and I41 /a space group and did not detect structural changes. Under an excitation of 403 nm, the prepared LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor was excited and produced orange-red emission. When compared with the LiLa(MoO4 )2 :Sm3+ phosphor, the LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor exhibited enhanced fluorescence intensity because the Bi3+ dopant ions are doped as a sensitizer. The optimal doping concentrations of Sm3+ and Bi3+ were 5 and 1 mol%, respectively. Furthermore, the energy transfer from Bi3+ to Sm3+ is effective (3 P1 → 4 K11/2 ). Subsequently, the electrons in an unstable excited state were transferred to a stable ground state (4 G5/2 → 6 H5/2 , 6 H7/2 , 6 H9/2 ). The Commission Internationale de L'Eclairage (CIE) chromaticity coordinates of the optimized LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor were situated in the orange-red region. The luminescence of the LiLa(MoO4 )2 :Sm3+ ,Bi3+ phosphor generated under near-ultraviolet (UV) irradiation could be used to produce a warm white light, indicating its possible applications in white light-emitting diodes.

7.
Int J Med Sci ; 18(2): 325-334, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390801

RESUMEN

Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism. Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment. Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited. Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/genética , Endopeptidasas/genética , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Caspasa 3/genética , Biología Computacional , Regulación hacia Abajo , Doxorrubicina/uso terapéutico , Endopeptidasas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Células MCF-7 , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética
8.
Neural Plast ; 2021: 6682275, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688340

RESUMEN

Chronic pain is considered an economic burden on society as it often results in disability, job loss, and early retirement. Opioids are the most common analgesics prescribed for the management of moderate to severe pain. However, chronic exposure to these drugs can result in opioid tolerance and opioid-induced hyperalgesia. On pain modulation strategies, exploiting the multitarget drugs with the ability of the superadditive or synergistic interactions attracts more attention. In the present report, we have reviewed the analgesic effects of different dopamine receptors, particularly D1 and D2 receptors, in different regions of the central nervous system, including the spinal cord, striatum, nucleus accumbens (NAc), and periaqueductal gray (PAG). According to the evidence, these regions are not only involved in pain modulation but also express a high density of DA receptors. The findings can be categorized as follows: (1) D2-like receptors may exert a higher analgesic potency, but D1-like receptors act in different manners across several mechanisms in the mentioned regions; (2) in the spinal cord and striatum, antinociception of DA is mainly mediated by D2-like receptors, while in the NAc and PAG, both D1- and D2-like receptors are involved as analgesic targets; and (3) D2-like receptor agonists can act as adjuvants of µ-opioid receptor agonists to potentiate analgesic effects and provide a better approach to pain relief.


Asunto(s)
Dolor/tratamiento farmacológico , Dolor/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Receptores de Dopamina D2/agonistas , Analgésicos/farmacología , Animales , Tolerancia a Medicamentos/fisiología , Humanos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiopatología , Dimensión del Dolor/métodos , Sustancia Gris Periacueductal/metabolismo , Receptores Opioides mu/efectos de los fármacos , Receptores Opioides mu/metabolismo
9.
Mol Ther ; 24(8): 1358-68, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26961408

RESUMEN

Hepatocellular carcinoma (HCC) is a hypervascular cancer without effective treatment. Here we report that polypeptide of NC1 domain of type VIII collagen (Vastatin) is an endogenous polypeptide expressed in normal liver tissue but lost in the liver of most HCC patients (73.1%). Its expression level is negatively associated with tumor size (P = 0.035) and metastasis (P = 0.016) in HCC patients. To evaluate its potential use as a therapeutic, we constructed a recombinant adeno-associated virus carrying Vastatin (rAAV-Vastatin) to treat HCC in an orthotopic Buffalo rat model. rAAV-Vastatin treatment significantly prolonged the median survival, inhibited tumor growth, and completely prevented metastasis in HCC-bearing rats by decreasing microvessel density and increasing tumor necrosis. No detectable toxicity in nontumor-bearing mice was observed. To investigate its molecular mechanisms, we performed DNA microarray, western blotting assays, and bioinformatic analysis to determine its effect on global gene expression patterns and signal transduction pathways. Our results indicated that rAAV-Vastatin significantly reduced the expressions of Pck1, JAG2, and c-Fos, thus inhibiting the cellular metabolism, Notch and AP-1 signaling pathways, respectively. Hence, we demonstrated for the first time that Vastatin is a novel, safe, and effective antiangiogenic therapeutic and a potential biomarker for HCC.


Asunto(s)
Inhibidores de la Angiogénesis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Colágeno Tipo VIII/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Adulto , Anciano , Inhibidores de la Angiogénesis/metabolismo , Animales , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Colágeno Tipo VIII/metabolismo , Dependovirus/genética , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Femenino , Expresión Génica , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana Edad , Necrosis , Clasificación del Tumor , Metástasis de la Neoplasia , Neovascularización Patológica/genética , Ratas , Receptores Notch/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , Transducción Genética , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
10.
J Cell Mol Med ; 19(4): 760-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25639535

RESUMEN

MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy.


Asunto(s)
Apoptosis/genética , Neoplasias de la Mama/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Factor de Transcripción Sp1/genética , Regiones no Traducidas 3'/genética , Biomarcadores de Tumor/genética , Western Blotting , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Estimación de Kaplan-Meier , Células MCF-7 , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción Sp1/metabolismo
11.
J Cell Mol Med ; 18(5): 811-23, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24628949

RESUMEN

Docetaxel is commonly used as an effective chemotherapeutic drug for gastric cancer patients recently. With the increasing emergence of docetaxel resistance nowadays, identification of suitable biomarkers for predicting chemosensitivity to docetaxel may be a key role for improving therapeutic effects for gastric cancer patients. In this study, we investigated the correlation between the expression of transcription factor forkhead box protein M1 (FOXM1) and chemotherapy response to docetaxel in gastric cancer, the possible mechanism for which was further explored. As a result, FOXM1 overexpression was shown to mediate resistance to docetaxel in gastric cancers. It altered microtubule dynamics to protect tumour cells from docetaxel-induced apoptosis. Mechanistic investigations revealed that tubulin-destabilizing protein Stathmin, which mediated docetaxel resistance in FOXM1-silenced gastric cancer cells, is a direct down-stream target of FOXM1, whereas another microtubule dynamics protein mitotic centromere-associated kinesin (MCAK), shown to be related to docetaxel resistance in gastric cancer cells, is not associated with FOXM1 expression significantly. These results were further provided by immunohistochemical analysis, indicating that FOXM1 and Stathmin expression levels were correlated in 103 post-operational gastric cancer specimens. Moreover, when we attenuated FOXM1 expression with FOXM1 inhibitor thiostrepton, docetaxel resistance in gastric cancers was found to be reversed, simultaneously with the down-regulation of FOXM1 and Stathmin. Therefore, FOXM1 can be a useful marker for predicting and monitoring docetaxel response. Through the inhibition of FOXM1, docetaxel resistance can be reversed, and thus FOXM1 could be a new therapeutic target in docetaxel-resistant gastric cancer.


Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Estatmina/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Taxoides/uso terapéutico , Regulación hacia Arriba/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Docetaxel , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/genética , Gastrectomía , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Humanos , Cinesinas/metabolismo , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Análisis Multivariante , Fenotipo , Pronóstico , Regiones Promotoras Genéticas/genética , Modelos de Riesgos Proporcionales , Estatmina/metabolismo , Neoplasias Gástricas/cirugía , Taxoides/farmacología , Tioestreptona/farmacología , Tioestreptona/uso terapéutico , Regulación hacia Arriba/efectos de los fármacos
12.
bioRxiv ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38895208

RESUMEN

A defined number of hematopoietic stem cell (HSC) clones are born during development and expand to form the pool of adult stem cells. An intricate balance between self-renewal and differentiation of these HSCs supports hematopoiesis for life. HSC fate is determined by complex transcription factor networks that drive cell-type specific gene programs. The transcription factor RUNX1 is required for definitive hematopoiesis, and mutations in Runx1 have been shown to reduce clonal diversity. The RUNX1 cofactor, CBFý, stabilizes RUNX1 binding to DNA, and disruption of their interaction alters downstream gene expression. Chemical screening for modulators of Runx1 and HSC expansion in zebrafish led us to identify a new mechanism for the RUNX1 inhibitor, Ro5-3335. We found that Ro5-3335 increased HSC divisions in zebrafish, and animals transplanted with Ro5-3335 treated cells had enhanced chimerism compared to untreated cells. Using human CD34+ cells, we show that Ro5-3335 remodels the RUNX1 transcription complex by binding to ELF1, independent of CBFý. This allows specific expression of cell cycle and hematopoietic genes that enhance HSC self-renewal and prevent differentiation. Furthermore, we provide the first evidence to show that it is possible to pharmacologically increase the number of stem cell clones in vivo , revealing a previously unknown mechanism for enhancing clonal diversity. Our studies have revealed a mechanism by which binding partners of RUNX1 determine cell fate, with ELF transcription factors guiding cell division. This information could lead to treatments that enhance clonal diversity for blood diseases.

13.
Org Lett ; 26(1): 12-17, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38127552

RESUMEN

A versatile Co(III)-catalyzed C6-selective C-H activation/pyridine migration of 2-pyridones with available propiolates as coupling partners was demonstrated. This method features high atom economy, excellent regioselectivity, and good functional group tolerance by employing an inexpensive Co(III) catalyst under mild reaction conditions. Moreover, gram-scale synthesis and late-stage modifications of pharmaceuticals were performed to prove the effectiveness of these synthetic approaches.

14.
Methods Mol Biol ; 2640: 445-452, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995612

RESUMEN

Uncovering the transcriptomic signatures of quiescent muscle stem cells elicits the regulatory networks on stem cell quiescence. However, the spatial clues of the transcripts are missing in the commonly used quantitative analysis such as qPCR and RNA-seq. Visualization of RNA transcripts using single-molecule in situ hybridization provides additional subcellular localization clues to understanding gene expression signatures. Here, we provide an optimized protocol of smFISH analysis on Fluorescence-Activated Cell Sorting isolated muscle stem cells to visualize low-abundance transcripts.


Asunto(s)
Perfilación de la Expresión Génica , Células Madre , Hibridación Fluorescente in Situ/métodos , ARN/genética , Músculos
15.
Sci Rep ; 13(1): 2111, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747075

RESUMEN

In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1ß and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.


Asunto(s)
Melatonina , Neuralgia , Ratas , Masculino , Animales , FN-kappa B/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Melatonina/farmacología , Melatonina/uso terapéutico , Proteína X Asociada a bcl-2 , Apoptosis , Antiinflamatorios/farmacología , Citocinas/metabolismo , Neuralgia/tratamiento farmacológico
16.
J Biomed Opt ; 28(6): 065005, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37334208

RESUMEN

Significance: Near-infrared (NIR) diffuse reflectance spectroscopy has been widely used for non-invasive glucose measurement in humans, as glucose can induce a significant and detectable optical signal change in tissue. However, the scattering-dominated glucose spectrum in the range of 1000 to 1700 nm is easily confused with many other scattering factors, such as particle density, particle size, and tissue refractive index. Aim: Our aim is to identify the subtle distinctions between glucose and these factors through theoretical analysis and experimental verification, in order to employ suitable methods for eliminating these interferences, thus increasing the accuracy of non-invasive glucose measurement. Approach: We present a theoretical analysis of the spectra of 1000 to 1700 nm for glucose and some scattering factors, which is then verified by an experiment on a 3% Intralipid solution. Results: We found that both the theoretical and experimental results show that the effective attenuation coefficient of glucose has distinct spectral characteristics, which are distinct from the spectra caused by particle density and refractive index, particularly in the range of 1400 to 1700 nm. Conclusions: Our findings can offer a theoretical foundation for eliminating these interferences in non-invasive glucose measurement, aiding mathematical methods to model appropriately and enhance the accuracy of glucose prediction.


Asunto(s)
Glucosa , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Pruebas Hematológicas , Tamaño de la Partícula , Dispersión de Radiación
17.
Org Lett ; 25(24): 4416-4421, 2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37306363

RESUMEN

A palladium-catalyzed olefination of meta-C-H bonds in arenes containing oxyamides using a nitrile template as the directing group has been established. The methodology exhibited high meta-selectivity and tolerated different functional groups such as benzyloxyamides and olefin substrates. The desired products were obtained in good yields. This approach enabled the modification of natural products and drugs and was also applicable on the gram-scale. Furthermore, the directing template was readily removed by selective cleavage of the amide bond or the O-N bond to obtain meta-functionalized hydroxylamines and benzyl alcohols. The proposed method holds great potential for the design of novel drugs.


Asunto(s)
Alquenos , Paladio , Paladio/química , Catálisis , Alquenos/química , Amidas , Alcoholes Bencílicos
18.
Acad Radiol ; 30 Suppl 2: S114-S126, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37003874

RESUMEN

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.


Asunto(s)
Neoplasias de la Mama , Ultrasonografía Mamaria , Femenino , Humanos , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Sensibilidad y Especificidad , Mamografía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , China/epidemiología
19.
Heliyon ; 9(4): e15051, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37012905

RESUMEN

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P < 0.001). The mediation model works well, The total indirect effect was 0.22 (95%CI = [0.17, 0.28]), and the direct effect was 0.16 (95%CI = [0.08, 0.24]). Limitations: This study used a self-assessment scale. Conclusions: Anxiety and depressive symptoms played a chain mediating role between sleep quality and suicide risk.

20.
Ther Adv Med Oncol ; 15: 17588359231187205, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484525

RESUMEN

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

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