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1.
J Ethnopharmacol ; 336: 118754, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39208999

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.


Asunto(s)
Neoplasias Colorrectales , Sinergismo Farmacológico , Estrés del Retículo Endoplásmico , Oxaliplatino , Especies Reactivas de Oxígeno , Saponinas , Triterpenos , Animales , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células HCT116 , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Oxaliplatino/farmacología , Especies Reactivas de Oxígeno/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
2.
J Biol Chem ; : 107874, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39395805

RESUMEN

Elucidating the intricate molecular mechanisms of Alzheimer's disease (AD) requires a multidimensional analysis incorporating various omics data. In this study, we employed transcriptome and proteome profiling of AppNL-G-F, a human APP knock-in model of amyloidosis, at the early and mid-stages of amyloid-beta (Aß) pathology to delineate the impacts of Aß deposition on brain cells. By contrasting AppNL-G-F mice with TREM2 (Triggering receptor expressed on myeloid cells 2) knockout models, our study further investigates the role of TREM2, a well-known AD risk gene, in influencing microglial responses to Aß pathology. Our results highlight altered microglial states as a central feature of Aß pathology, characterized by the significant upregulation of microglia-specific genes related to immune responses such as complement system and antigen presentation, and catabolic pathways such as phagosome formation and lysosome biogenesis. The absence of TREM2 markedly diminishes the induction of these genes, impairs Aß clearance, and exacerbates dystrophic neurite formation. Importantly, TREM2 is required for the microglial engagement with Aß plaques and the formation of compact Aß plaque cores. Furthermore, this study reveals substantial disruptions in energy metabolism and protein synthesis, signaling a shift from anabolism to catabolism in response to Aß deposition. This metabolic alteration, coupled with a decrease in synaptic protein abundance, occurs independently of TREM2, suggesting the direct effects of Aß deposition on synaptic integrity and plasticity. In summary, our findings demonstrate altered microglial states and metabolic disruption following Aß deposition, offering mechanistic insights into Aß pathology and highlighting the potential of targeting these pathways in AD therapy.

3.
Nanotechnology ; 35(50)2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39312908

RESUMEN

We experimentally demonstrate the coherent random laser emission by combining CdSe/ZnS colloidal quantum dots with hollow optical fiber. Through the localized surface plasmon resonance induced by Ag nanoparticles (NPs), well-distinguished discrete spikes are observed from the Ag modified hollow fiber loaded with CdSe/ZnS QDs solution. In addition, coherent random laser action with low threshold is also realized in the hollow optical fiber filled with high packing-density CdSe/ZnS QDs even if the Ag NPs is not introduced. The self-assembled clusters of CdSe/ZnS QDs serve as the optical gain media as well as the strong scattering centers. The angle measurement experiments show that the directional emission of random laser can be adjusted by using different pumping manners. This facile, inexpensive, low pump threshold random laser could be widely used in photonic devices and display imaging.

4.
Sci Rep ; 14(1): 19067, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154127

RESUMEN

Building extraction aims to extract building pixels from remote sensing imagery, which plays a significant role in urban planning, dynamic urban monitoring, and many other applications. UNet3+ is widely applied in building extraction from remote sensing images. However, it still faces issues such as low segmentation accuracy, imprecise boundary delineation, and the complexity of network models. Therefore, based on the UNet3+ model, this paper proposes a 3D Joint Attention (3DJA) module that effectively enhances the correlation between local and global features, obtaining more accurate object semantic information and enhancing feature representation. The 3DJA module models semantic interdependence in the vertical and horizontal dimensions to obtain feature map spatial encoding information, as well as in the channel dimensions to increase the correlation between dependent channel graphs. In addition, a bottleneck module is constructed to reduce the number of network parameters and improve model training efficiency. Many experiments are conducted on publicly accessible WHU,INRIA and Massachusetts building dataset, and the benchmarks, BOMSC-Net, CVNet, SCA-Net, SPCL-Net, ACMFNet, MFCF-Net models are selected for comparison with the 3DJA-UNet3+ model proposed in this paper. The experimental results show that 3DJA-UNet3+ achieves competitive results in three evaluation indicators: overall accuracy, mean intersection over union, and F1-score. The code will be available at https://github.com/EnjiLi/3DJA-UNet3Plus .

5.
Lab Med ; 55(5): 615-619, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-38581097

RESUMEN

BACKGROUND: Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. METHODS: A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. RESULTS: Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. CONCLUSION: Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.


Asunto(s)
Hemoglobinas Anormales , Heterocigoto , Humanos , Hemoglobinas Anormales/genética , China , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Talasemia alfa/sangre , Masculino , Femenino , Adulto , Cromatografía Líquida de Alta Presión , Electroforesis Capilar , Índices de Eritrocitos
6.
Development ; 151(8)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577841

RESUMEN

Enteroendocrine cells (EECs) are crucial for sensing ingested nutrients and regulating feeding behavior. How gut microbiota regulate the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis demonstrates that commensal microbiota colonization significantly increases the expression of many genes associated with mitochondrial function. Using new methods to image EEC cytoplasmic and mitochondrial Ca2+ activity in live zebrafish, our data revealed that it is dynamically regulated during the EEC development process. Mature EECs display an increased mitochondrial-to-cytoplasmic Ca2+ ratio. Mitochondria are evenly distributed in the cytoplasm of immature EECs. As EECs mature, their mitochondria are highly localized at the basal membrane where EEC vesicle secretion occurs. Conventionalized (CV) EECs, but not germ-free (GF) EECs, exhibit spontaneous low-amplitude Ca2+ fluctuation. The mitochondrial-to-cytoplasmic Ca2+ ratio is significantly higher in CV EECs. Nutrient stimulants, such as fatty acid, increase cytoplasmic Ca2+ in a subset of EECs and promote a sustained mitochondrial Ca2+ and ATP increase. However, the nutrient-induced EEC mitochondrial activation is nearly abolished in GF zebrafish. Together, our study reveals that commensal microbiota are crucial in supporting EEC mitochondrial function and maturation.


Asunto(s)
Calcio , Células Enteroendocrinas , Microbioma Gastrointestinal , Mitocondrias , Pez Cebra , Animales , Pez Cebra/microbiología , Células Enteroendocrinas/metabolismo , Mitocondrias/metabolismo , Microbioma Gastrointestinal/fisiología , Calcio/metabolismo , Nutrientes/metabolismo , Adenosina Trifosfato/metabolismo
7.
J Cachexia Sarcopenia Muscle ; 15(3): 1094-1107, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38526005

RESUMEN

BACKGROUND: Sarcopenia is a potential risk factor for adverse outcomes in haematopoietic cell transplantation (HSCT) recipients. We aimed to explore longitudinal body changes in muscle and adipose mass and their prognostic value in allogeneic HSCT-treated severe aplastic anaemia (SAA) patients. METHODS: We retrospectively analysed consecutive SAA patients who underwent allogeneic HSCT between January 2017 and March 2022. Measurements of pectoral muscle and corresponding subcutaneous fat mass were obtained via chest computed tomography at baseline and at 1 month, 3 months, 6 months, and 12 months following HSCT. Sarcopenia was defined as pectoral muscle index (PMI) lower than the sex-specific median at baseline. Changes in body composition over time were evaluated by generalized estimating equations. Cox regression models were used to investigate prognostic factors affecting overall survival (OS) and failure-free survival (FFS). A nomogram was constructed from the Cox regression model for OS. RESULTS: We included 298 adult SAA patients (including 129 females and 169 males) with a median age of 31 years [interquartile range (IQR), 24-39 years] at baseline. Sarcopenia was present in 148 (148/298, 50%) patients at baseline, 218 (218/285, 76%) patients post-1 month, 209 (209/262, 80%) patients post-3 month, 169 (169/218, 78%) patients post-6 month, and 129 (129/181, 71%) patients post-12 month. A significant decrease in pectoral muscle mass was observed in SAA patients from the time of transplant to 1 year after HSCT, and the greatest reduction occurred in post 1-3 months (P < 0.001). The sarcopenia group exhibited significantly lower 5-year OS (90.6% vs. 100%, log-rank P = 0.039) and 5-year FFS (89.2% vs. 100%, log-rank P = 0.021) than the nonsarcopenia group at baseline. Sarcopenia at baseline (hazard ratio, HR, 6.344; 95% confidence interval, CI: 1.570-25.538; P = 0.01; and HR, 3.275; 95% CI: 1.159-9.252; P = 0.025, respectively) and the delta value of the PMI at 6 months post-transplantation (ΔPMI6) (HR, 0.531; 95% CI: 0.374-0.756; P < 0.001; and HR, 0.666; 95% CI: 0.505-0.879; P = 0.004, respectively) were demonstrated to be independent prognostic factors for OS and FFS in SAA patients undergoing HSCT, and were used to construct the nomogram. The C-index of the nomogram was 0.75, and the calibration plot showed good agreement between the predictions made by the nomogram and actual observations. CONCLUSIONS: Sarcopenia persists in SAA patients from the time of transplant to the 1-year follow-up after HSCT. Both sarcopenia at baseline and at 6 months following HSCT are associated with poor clinical outcomes, especially in patients with persistent muscle mass loss up to 6 months after transplantation.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Sarcopenia , Humanos , Sarcopenia/etiología , Masculino , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Anemia Aplásica/terapia , Anemia Aplásica/complicaciones , Adulto , Estudios Retrospectivos , Adulto Joven , Trasplante Homólogo , Pronóstico , Sobrevivientes , Persona de Mediana Edad
8.
bioRxiv ; 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37961164

RESUMEN

The enteroendocrine cells (EECs) in the intestine are crucial for sensing ingested nutrients and regulating feeding behavior. The means by which gut microbiota regulates the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis of the EECs from germ-free (GF) and conventionalized (CV) zebrafish revealed that commensal microbiota colonization significantly increased the expression of many genes that are associated with mitochondrial function. Using in vivo imaging and 3D automated cell tracking approach, we developed new methods to image and analyze the EECs' cytoplasmic and mitochondrial calcium activity at cellular resolution in live zebrafish. Our data revealed that during the development, shortly after gut microbiota colonization, EECs briefly increased cytoplasm and mitochondrial Ca2+, a phenomenon we referred to as "EEC awakening". Following the EEC awakening, cytoplasmic Ca2+ levels but not mitochondrial Ca2+ level in the EECs decreased, resulting in a consistent increase in the mitochondrial-to-cytoplasmic Ca2+ ratio. The increased mitochondrial-to-cytoplasmic Ca2+ ratio is associated with the EEC maturation process. In immature EECs, we further discovered that their mitochondria are evenly distributed in the cytoplasm. When EECs mature, their mitochondria are highly localized in the basal lateral membrane where EEC vesicle secretion occurs. Furthermore, CV EECs, but not GF EECs, exhibit spontaneous low-amplitude calcium fluctuation. The mitochondrial-to-cytoplasm Ca2+ ratio is significantly higher in CV EECs. When stimulating the CV zebrafish with nutrients like fatty acids, nutrient stimulants increase cytoplasmic Ca2+ in a subset of EECs and promote a sustained mitochondrial Ca2+ increase. However, the nutrient induced EEC mitochondrial activation is nearly abolished in GF zebrafish. Together, our study reveals that commensal microbiota are critical in supporting EEC mitochondrial function and maturation. Selectively manipulating gut microbial signals to alter EEC mitochondrial function will provide new opportunities to change gut-brain nutrient sensing efficiency and feeding behavior.

9.
Clin Lab ; 69(10)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37844042

RESUMEN

BACKGROUND: Hemoglobin (Hb) J-Cubujuqui is a rare Hb variant, and reports about it are very limited. There are no descriptions that it affects the results of glycated Hb. METHODS: In this study, we describe a rare variant discovered during newborn screening. Both high-performance liquid chromatography (HPLC) and capillary electrophoresis for hemoglobin analysis displayed abnormal peaks. The Hb variant was confirmed by Sanger sequencing. RESULTS: The pedigree study shows the variant was inherited from the newborn's father. His fasting blood glucose (FBG) level was 5.5 mmol/L. HbA1c measured by HPLC was falsely low in her father (2.41%), whereas that measured by immunoassay was normal (5.11%). Sanger sequencing revealed a heterozygous mutation (CGT˃AGT) at amino acid position 141 of the α1 gene, corresponding to Hb J-Cubujuqui [α1 141(HC3) Arg→Ser (CGT˃AGT); HBA1:c.424C˃A (or HBA2)]. CONCLUSIONS: This is the first report that Hb J-Cubujuqui interferes with the measurement of HbA1cand prompts clinicians to pay attention to the accuracy of glycated Hb results.


Asunto(s)
Hemoglobina J , Hemoglobinas Anormales , Humanos , Femenino , Recién Nacido , Hemoglobina J/análisis , Hemoglobina J/genética , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/análisis , Mutación , Hemoglobina Glucada/genética , Electroforesis Capilar , Cromatografía Líquida de Alta Presión
10.
Medicine (Baltimore) ; 102(42): e34512, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37861497

RESUMEN

Tripterygium wilfordii hook (TWH) has been used to treat Behcet's disease (BD) but its underlying mechanism remains unclear. This study aims to explore the mechanism of TWH on BD using network pharmacology and molecular docking. The bioactive constituents of TWH and their corresponding target genes were extracted from the Traditional Chinese Medicine systems pharmacology database and analysis platform. BD target genes were obtained by searching the DisGeNet and GeneCards databases. Gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were conducted to elucidate the function of overlapping genes between TWH and BD target genes. A protein-protein interaction network was constructed using Cytoscape and STRING platforms, and the core target genes were identified from the overlapping genes. Finally, molecular docking was used to assess the binding affinity between the core targets and TWH bioactive constituents. We identified 25 intersection genes related to both TWH and BD and 27 bioactive ingredients of TWH. Through analysis of protein-protein interaction network, 6 core targets (TNF, IFNG, prostaglandin-endoperoxide synthase 2, NOS2, VCAM-1, and interleukin-2) were screened out. Enrichment analysis demonstrated that the antioxidant properties of TWH constituents might play a significant role in their therapeutic effects. Molecular docking revealed high binding affinity between the bioactive constituents of TWH, such as kaempferol, triptolide, 5, 8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin, and their corresponding target genes, suggesting the potential of TWH to treat BD. Our investigation clarified the active components, therapeutic targets of BD in the treatment of TWH and provided a theoretical foundation for further researches.


Asunto(s)
Síndrome de Behçet , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Tripterygium , Síndrome de Behçet/tratamiento farmacológico , Cumarinas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China
11.
Eur J Pharmacol ; 957: 175986, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37598924

RESUMEN

Colorectal cancer (CRC) is the third most common cancer, and is one of the leading causes of cancer-related death worldwide. At the time of diagnosis, about 20% of patients with CRC present metastatic disease. Regorafenib, an oral multi-kinase inhibitor, has been demonstrated the efficacy and tolerability in patients with metastatic CRC. Oxaliplatin is a frontline treatment regimen for CRC, and combination treatments with oxaliplatin and other chemotherapeutic agents exert superior therapeutic effects. However, side effects and drug resistance limited their further clinical application. Here, we found that combined treatment with regorafenib and oxaliplatin synergistically enhanced anti-tumor activities in CRC by activating reactive oxygen species (ROS) mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 signaling pathways. Regorafenib promoted ROS production by suppressing the expression of selenoprotein S (SELENOS). Knocking down SELENOS sensitized ROS-mediated anti-tumor effects of regorafenib in CRC cells. Furthermore, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with regorafenib and oxaliplatin. This study provided solid experimental evidences for the combined treatment with regorafenib and oxaliplatin in CRC.


Asunto(s)
Neoplasias del Colon , Animales , Ratones , Humanos , Oxaliplatino/farmacología , Especies Reactivas de Oxígeno , Neoplasias del Colon/tratamiento farmacológico , Muerte Celular , Estrés Oxidativo , Modelos Animales de Enfermedad
12.
Chem Commun (Camb) ; 59(35): 5217-5220, 2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37014626

RESUMEN

Herein, we describe an efficient method involving the synthesis of diverse quinoxalines using the DMSO/tBuONa/O2 system as a single-electron oxidant to form α-imino radicals and nitrogen radicals for the direct construction of C-N bonds. This methodology provides a novel approach to form α-imino radicals with good reactivity.

13.
Neoplasia ; 39: 100897, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36940556

RESUMEN

Lung cancer is one of the most commonly diagnosed cancers worldwide. Although cisplatin-based chemotherapy regimens serve a pivotal role in non-small cell lung cancer (NSCLC) treatment, drug resistance and serious side effects limited its further clinical application. Regorafenib, a small-molecule multi-kinase inhibitor, was demonstrated to have promising anti-tumor activity in various solid tumors. In the present study, we found that regorafenib markedly enhanced cisplatin-induced cytotoxicity in lung cancer cells by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ER Stress), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Regorafenib increased ROS generation by promoting NADPH oxidase 5 (NOX5) expression, and knocking down NOX5 attenuated ROS-mediated cytotoxicity of regorafenib in lung cancer cells. Additionally, mice xenograft model validated that synergistic anti-tumor effects of combined treatment with regorafenib and cisplatin. Our results suggested that combination therapy with regorafenib and cisplatin may serve as a potential therapeutic strategy for some NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , NADPH Oxidasa 5/farmacología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Línea Celular Tumoral , Estrés del Retículo Endoplásmico
14.
Sensors (Basel) ; 23(3)2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36772110

RESUMEN

Detecting irregular or arbitrary shape text in natural scene images is a challenging task that has recently attracted considerable attention from research communities. However, limited by the CNN receptive field, these methods cannot directly capture relations between distant component regions by local convolutional operators. In this paper, we propose a novel method that can effectively and robustly detect irregular text in natural scene images. First, we employ a fully convolutional network architecture based on VGG16_BN to generate text components via the estimated character center points, which can ensure a high text component detection recall rate and fewer noncharacter text components. Second, text line grouping is treated as a problem of inferring the adjacency relations of text components with a graph convolution network (GCN). Finally, to evaluate our algorithm, we compare it with other existing algorithms by performing experiments on three public datasets: ICDAR2013, CTW-1500 and MSRA-TD500. The results show that the proposed method handles irregular scene text well and that it achieves promising results on these three public datasets.

15.
Dermatol Ther ; 35(12): e15910, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36208443

RESUMEN

Ustekinumab (brand name Stelara®) is a human interleukin-12 and -23 antagonist and has been indicated for the treatments of moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. This review aims to synthesize and interpret the literature evaluating the off-label uses of ustekinumab. We performed searches in PubMed and ClinicalTrials.gov for clinical trials, observational studies, case series, and case reports evaluating label uses of ustekinumab. Studies evaluated the efficacy of ustekinumab for the following conditions: other types of psoriasis (expect plaque psoriasis and psoriatic arthritis), pityriasis rubra pilaris, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, et al. Based on the available literature, ustekinumab appears to be a potential treatment choice for many other diseases. However, more clinical trials data are needed to adequately assess the safety and efficacy of ustekinumab for the treatment of these conditions.


Asunto(s)
Artritis Psoriásica , Pitiriasis Rubra Pilaris , Psoriasis , Humanos , Ustekinumab/efectos adversos , Artritis Psoriásica/tratamiento farmacológico , Uso Fuera de lo Indicado , Psoriasis/tratamiento farmacológico , Pitiriasis Rubra Pilaris/tratamiento farmacológico
16.
BMC Med Genomics ; 15(1): 172, 2022 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-35932013

RESUMEN

BACKGROUND: Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. METHODS: In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. RESULTS: The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. CONCLUSIONS: The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.


Asunto(s)
Síndrome del Nevo Basocelular , Carcinoma Basocelular , Neoplasias Cutáneas , Síndrome del Nevo Basocelular/genética , Síndrome del Nevo Basocelular/metabolismo , Síndrome del Nevo Basocelular/patología , Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Proteínas Hedgehog/genética , Humanos , Mutación , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología
17.
Hemoglobin ; 46(3): 187-190, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35616292

RESUMEN

We report a novel ß chain hemoglobin (Hb) variant found in a Chinese family. A high level of Hb F was observed on capillary electrophoresis (CE). However, high performance liquid chromatography (HPLC) showed a high level of Hb A2. DNA sequencing revealed a single base substitution (T>G) at codon 96 of exon 2 of the ß-globin gene. This alters the normally encoded leucine to arginine [ß96(FG3)Leu→Arg; HBB: c.290T>G] that we propose to name Hb Laibin for the region of origin of the proband. The pedigree study showed that it was inherited from his mother.


Asunto(s)
Hemoglobinas Anormales , Arginina/genética , China , Codón , Hemoglobinas Anormales/genética , Humanos , Leucina/genética , Mutación , Globinas beta/genética
18.
J Food Biochem ; 46(6): e13802, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34041771

RESUMEN

Ophiopogonis Radix is a kind of traditional Chinese medicine as well as a type of functional food. Because Ophiopogonis Radix grows in the ground, it is often damaged by worms during planting or broken when people try to dig them out, which leads to the containments of spoiled products of different proportion in Ophiopogonis Radix. Volatile organic compounds (VOCs) in Ophiopogonis Radix, which involves spoiled products in different proportions, were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Finally, a total of 87 VOCs were discovered after analysis, and 14 of them were chose to established characteristic fingerprints. Twelve of the 14 characteristic compounds were be recognized by a built-in database. The results showed that the content of hexanol, ethanol, methanol, (E)-2-hexenal, and hexanal was in inverse proportion with the containing of spoiled products, so they may be characteristic VOCs of fresh Ophiopogonis Radix,; and the content of 3-methy-1-butanol, furfural, 5-methylfural, phenylacetaldehyde, 2-methylbutanoic acid, 2-butanone, and 2-acetylfuran are proportional to the containing of spoiled products, so they may be the characteristic of VOCs of spoiled Ophiopogonis Radix. The signal peak intensities of the 14 characteristic VOCs were used as the variables of principal component analysis (PCA). The result shows that the fresh Ophiopogonis Radix and the spoiled Ophiopogonis Radix could be clearly differentiated, and the different proportions of spoiled products were grouped into separate categories, respectively. The larger the proportion of spoiled products, the greater the difference between the sample and fresh Ophiopogonis Radix. PRACTICAL APPLICATIONS: Ophiopogonis Radix is a kind of commonly used traditional Chinese medicine and functional food. In the actual use of Ophiopogonis Radix, the damage caused by worms during planting and the breakage during being dug out often lead to Ophiopogonis Radix containing spoiled products in the market. The existence of spoiled products greatly affects the quality and safety of Ophiopogonis Radix. Due to the difference in flavor between fresh Ophiopogonis Radix and spoiled products, the present study used HS-GC-IMS method to analyze the VOCs in fresh Ophiopogonis Radix and Ophiopogonis Radix containing spoiled products of different proportions and screened out the characteristic VOCs of fresh Ophiopogonis Radix and spoiled Ophiopogonis Radix. The results provide scientific basis for quality control of Ophiopogonis Radix.


Asunto(s)
Compuestos Orgánicos Volátiles , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Espectrometría de Movilidad Iónica/métodos , Raíces de Plantas/química , Compuestos Orgánicos Volátiles/análisis
19.
J Food Biochem ; 46(6): e13850, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34227128

RESUMEN

Ophiopogonis Radix can be divided into Zhemaidong (ZMD) and Chuanmaidong (CMD). The main planting areas of ZMD are Cixi City and Sanmen county. The quality and price of Ophiopogonis Radix from different producing areas are different. In this study, the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) method is used to rapidly identify ZMD and CMD. The method is also used to identify ZMD from Cixi and Sanmen by analyzing volatile organic compounds (VOCs). A total of 58 VOCs was obtained from ZMD samples with more abundant signals of which 41 were identified. The peak intensities of all VOCs in ZMD and CMD, Cixi and Sanmen data were averaged and then those VOCs whose peak intensities were distributed outside of mean ± 2 standard deviation (µ ± 2σ) were selected as characteristic markers. We selected 14 characteristic markers to establish the characteristic fingerprint of ZMD and CMD, among the 14 VOCs, ZMD contained more eucalyptus oil compounds than CMD, CMD contained more volatile aldehydes than ZMD. We selected 12 characteristic markers for the establishment of the characteristic fingerprint of ZMD from Cixi and Sanmen. The principal component analysis (PCA) results indicated that both ZMD and CMD or ZMD from Cixi and Sanmen could be effectively divided. The ZMD and CMD as well as ZMD from Cixi and Sanmen were evaluated by partial least squares regression-discriminants analysis (PLS-DA) resulting to be excellent chemical descriptors for sample discrimination. One hundred percent classification rates for both PLS-DA calibration and prediction models were obtained. These results provided a reference for the traceability of species and origin and market standard of Ophiopogonis Radix. PRACTICAL APPLICATIONS: Ophiopogonis Radix can be divided into Zhejiang Ophiopogonis Radix (ZMD) and Sichuan Ophiopogonis Radix (CMD). As far as ZMD is concerned, its producing areas mainly include the traditional planting areas (Cixi City) and new growth areas (Sanmen county). In this paper, the HS-GC-IMS method was adopted to analyze VOCs in Ophiopogonis Radix from different producing areas and then we screen out the respective characteristic VOCs of ZMD and CMD as well as ZMD from Cixi and Sanmen. These characteristic VOCs can effectively identify ZMD and CMD as well as ZMD from Cixi City and Sanmen country to provide a scientific basis for the origin identification of Ophiopogonis Radix.


Asunto(s)
Medicamentos Herbarios Chinos , Compuestos Orgánicos Volátiles , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Movilidad Iónica , Raíces de Plantas/química , Compuestos Orgánicos Volátiles/análisis
20.
Development ; 148(21)2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34758081

RESUMEN

The developmental programs that build and sustain animal forms also encode the capacity to sense and adapt to the microbial world within which they evolved. This is abundantly apparent in the development of the digestive tract, which typically harbors the densest microbial communities of the body. Here, we review studies in human, mouse, zebrafish and Drosophila that are revealing how the microbiota impacts the development of the gut and its communication with the nervous system, highlighting important implications for human and animal health.


Asunto(s)
Eje Cerebro-Intestino/fisiología , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/crecimiento & desarrollo , Animales , Linaje de la Célula , Sistema Nervioso Entérico/citología , Sistema Nervioso Entérico/crecimiento & desarrollo , Sistema Nervioso Entérico/fisiología , Motilidad Gastrointestinal , Tracto Gastrointestinal/inervación , Tracto Gastrointestinal/microbiología , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/crecimiento & desarrollo , Neuronas/citología , Neuronas/fisiología
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