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1.
Biochem Pharmacol ; 223: 116138, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494062

RESUMO

Central nervous system lymphoma (CNSL) is a type of hematological tumor. Treatment of CNSL is difficult due to the existence of the blood-brain barrier (BBB). Here, we used exosomes (Exos), a type of extracellular vesicle, and iRGD to construct a new drug carrier system and use it to load doxorubicin (DOX). The results of in vitro and in vivo experiments showed that the iRGD-Exo-DOX system can efficiently and securely transport DOX through the BBB and target tumor cells. The results suggest that iRGD-Exo-DOX may cross the BBB through brain microvascular endothelial cell-mediated endocytosis. Together, our study indicates an impactful treatment of central nervous system tumors.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Barreira Hematoencefálica , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Linhagem Celular Tumoral
3.
BMC Ophthalmol ; 24(1): 53, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308223

RESUMO

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.


Assuntos
Extração de Catarata , Traumatismos Oculares , Cápsula do Cristalino , Doenças do Cristalino , Facoemulsificação , Humanos , Feminino , Pessoa de Meia-Idade , Citocinas , Implante de Lente Intraocular/efeitos adversos , Doenças do Cristalino/diagnóstico , Doenças do Cristalino/etiologia , Doenças do Cristalino/cirurgia , Cápsula do Cristalino/cirurgia , Cápsula do Cristalino/patologia , Extração de Catarata/efeitos adversos , Facoemulsificação/efeitos adversos , Traumatismos Oculares/complicações , Complicações Pós-Operatórias/cirurgia
4.
Ann Hematol ; 103(4): 1181-1185, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294534

RESUMO

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Hibridização in Situ Fluorescente , Tretinoína/uso terapêutico , Receptor alfa de Ácido Retinoico/genética , Proteínas de Transporte/genética , Translocação Genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
5.
Front Immunol ; 14: 1267950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143751

RESUMO

Objective: To explore the role of Krüppel-like factor 14 (KLF14) and its underlying mechanism(s) of action in cell-cycle regulation in cervical cancer. Methods: Lentiviral infection was used to construct KLF14, KLF14 zinc-finger structural mutations, and empty vector controls in SiHa and HeLa cervical cancer cells. The effect of KLF14 on cervical cancer cell cycle was detected by flow cytometry. The effect of KLF14 on the expression of cyclin-dependent kinase 2 (CDK2), cyclin A2 (CCNA2), and MAPK signalling pathway-related molecules was detected by fluorescence quantitative RT-PCR (qRT-PCR) and western blot. Cervical cancer cells were treated with JNK-pathway inhibitors/agonists before we assessed changes in the cell cycle and the expression of the CDK2, CCNA2, and p-JNK/JNK. Subcutaneous xenograft studies to explore the effects of KLF14 on cervical cancer cell proliferation in vivo, and western blotting was implemented to measure the expression of CCNA2, CDK2, and the activation levels of the MAPK-signaling pathway proteins in tumours. Results: The proportion of cells in the S phase was increased in the KLF14-overexpressing group compared with the control group (P<0.001); CDK2, CCNA2, and p-JNK/JNK expression levels were elevated in the KLF14-overexpressing group relative to the control group (all P<0.05). When JNK-pathway activation was inhibited/promoted, the proportion of cells in the S phase was reduced/increased (P<0.05) and CDK2 and CCNA2 expression levels were reduced/decreased, respectively (all P<0.05). Vivo experiments revealed that KLF14 inhibited cervical cancer cell proliferation (P<0.01) and that p-JNK/JNK, CDK2, and CCNA2 expression levels were augmented in tumours in the overexpression group (P<0.01). Conclusion: KLF14 induced S-phase arrest in cervical cancer cells and inhibited the proliferation of cervical cancer cells in vivo; the induction of S-phase arrest was related to its zinc-finger structure. KLF14 also activated the JNK pathway to induce S-phase arrest and promote the expression of CDK2 and CCNA2. In summary, KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells.


Assuntos
Fatores de Transcrição Kruppel-Like , Sistema de Sinalização das MAP Quinases , Neoplasias do Colo do Útero , Feminino , Humanos , Proliferação de Células , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/metabolismo , Zinco/farmacologia , Animais
6.
Chem Commun (Camb) ; 59(95): 14169-14172, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37955572

RESUMO

A Zinc phthalocyanine-based (ZnPc-PA) polymeric micelle around 70 nm and with dual-modal PTT/PDT functions for non-antibiotic bacteria eradication was developed. It showed an excellent bacterial killing efficiency of 95.2% and 96.7% in vitro against Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, respectively. Furthermore, the in vivo experiments proved its great potential for implant-associated infection (IAI).


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Micelas , Polímeros/farmacologia , Biofilmes , Antibacterianos/farmacologia
7.
Sci Rep ; 13(1): 20265, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985810

RESUMO

Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.


Assuntos
Agaricales , Polyporales , Triterpenos , Triterpenos/química , Carpóforos/química , Agaricales/química
8.
Front Plant Sci ; 14: 1265018, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841630

RESUMO

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, 'Tunisia' and 'Qingpi', throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit > flower > leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds.

9.
Int J Mol Sci ; 24(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37445735

RESUMO

Sichuan is the China's leading producer of loquat, with the largest cultivation area and yield ranked first in China. Loquat is a seasonal fruit highly appreciated by consumers; however, the fruit is prone to browning and lignification after harvest, affecting its storage quality. The effects of L-Cysteine (L-Cys, 0.01, 0.05, 0.1, 0.2%) and γ-aminobutyric acid (GABA, 0.025, 0.05, 0.075, 0.1%) on the sensory quality and antioxidant activity of loquat fruit during cold storage at 4 °C for 35 days and simulated shelf life for 5 days were investigated. The results showed that after 40 days of storage, compared with the control, 0.05% L-Cys and 0.05% GABA treatment of 'Zaozhong No. 6' loquat fruit effectively reduced the weight loss rate, browning index, decay index, respiratory rate, firmness, and lignin content and slowed the decreases in total soluble solids, soluble sugar, titratable acidityand vitamin C contents. The application of 0.05% L-Cys and 0.05% GABA significantly increased the contents of total phenols, total flavonoids, flavanols, and carotenoids; delayed the increase of relative electric conductivity, MDA, POD, and PPO activities; and significantly enhanced the activities of SOD and CAT, DPPH free radical scavenging ability, and FRAP, thereby improving antioxidant capacity. In summary, 0.05% L-Cys and 0.05% GABA treatment promotes the quality of loquat fruit after 40 days of storage, and significantly enhances antioxidant capacity, thus delaying senescence after harvest.


Assuntos
Antioxidantes , Eriobotrya , Antioxidantes/farmacologia , Antioxidantes/análise , Cisteína/análise , Eriobotrya/química , Frutas/química , Ácido gama-Aminobutírico/farmacologia
10.
Am J Surg ; 226(4): 531-541, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37451939

RESUMO

BACKGROUND: There is still controversy surrounding routine ilioinguinal neurectomy in open tension-free inguinal hernia repair. METHOD: PubMed, Cochrane Library and EMBASE databases were searched for randomized controlled trials of ilioinguinal neurectomy in open tension-free inguinal hernia repair. Revman 5.3 software was used for meta-analysis. RESULT: Meta-analysis revealed that the incidence of severe pain on the first postoperative day was lower in the ilioinguinal neurectomy group (ING) than in the ilioinguinal nerve preservation group (INPG) [P < 0.0001]. The incidence of no pain in the first month postoperatively [P = 0.0004], the incidence of no pain in the sixth months postoperatively [P < 0.00001], and the numbness incidence in the first month postoperatively [P = 0.001] in the ING was higher than that in the INPG. There was no significant difference in the incidence of severe pain in the first month postoperatively [P = 0.20], the numbness incidence in the sixth postoperative month [P = 0.05], the hypoesthesia incidence in the first [P = 0.15] and sixth [P = 0.85] postoperative months between the two groups. CONCLUSION: Ilioinguinal neurectomy in open tension-free inguinal hernia repair can better prevent postoperative pain.


Assuntos
Hérnia Inguinal , Humanos , Hérnia Inguinal/cirurgia , Hérnia Inguinal/complicações , Hipestesia/complicações , Hipestesia/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/cirurgia , Denervação/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Herniorrafia/efeitos adversos
11.
PLoS Pathog ; 19(5): e1011051, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37195999

RESUMO

Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of vδ2+ γδ T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses. Trial Registration: ClinicalTrials.gov NCT01994525.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , Humanos , Animais , Malária Falciparum/prevenção & controle , Plasmodium falciparum/genética , Vacinação , Interferons , Imunidade , Esporozoítos
12.
Inflamm Res ; 72(5): 933-945, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36997814

RESUMO

BACKGROUND: Curcumin is a diketone compound extracted from the rhizomes of some plants in the Zingiberaceae and Araceae family. It possesses a variety of biological activities, including antioxidant, anti-inflammatory and anti-cancer properties. However, the cellular and molecular antipruritic mechanisms of curcumin remain to be explored. OBJECTIVE: Our objective was to study the role of curcumin in pruritus and determine whether its antipruritic effect is related to MrgprB2 receptor. METHODS: The effect of curcumin on pruritus in mice was examined by scratching behavior test. The antipruritic mechanism of curcumin was explored by using transgenic mice (MrgprB2-/- mice, MrgprB2CreTd/tomato mice), histological analysis, western blot and immunofluorescence. In addition, the relationship between curcumin and MrgprB2/X2 receptor was studied in vitro by using calcium imaging, plasmid transfection and molecular docking RESULTS: In the current study, we found that curcumin had obvious antipruritic effect. Its antipruritic effect was related to the regulation of MrgprB2 receptor activation and mast cells tryptase release. In vitro, mouse peritoneal mast cells activated by compound 48/80 could be inhibited by curcumin. In addition, curcumin was also found to suppress the calcium flux in MrgprX2 or MrgprB2-overexpression HEK cells induced by compound 48/80, substance P, and PAMP 9-20, displaying the specific relation with the MrgprB2/X2 receptor. Moreover, molecular docking results showed that curcumin had affinity to MrgprX2 protein. CONCLUSIONS: Overall, these results indicated that curcumin has the potential to treat pruritus induced by mast cell MrgprB2 receptor.


Assuntos
Curcumina , Mastócitos , Camundongos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Cálcio/metabolismo , Antipruriginosos/metabolismo , Antipruriginosos/farmacologia , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Prurido/tratamento farmacológico , Prurido/metabolismo , Prurido/patologia , Degranulação Celular , Camundongos Endogâmicos C57BL
13.
Apoptosis ; 28(7-8): 997-1011, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37000316

RESUMO

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomes carrying microRNAs (miRNAs) have promising therapeutic potential in various disorders, including premature ovarian failure (POF). Previous evidence has revealed the low plasma level of miR-22-3p in POF patients. Nevertheless, exosomal miR-22-3p specific functions underlying POF progression are unclarified. METHODS: A cisplatin induced POF mouse model and in vitro murine ovarian granulosa cell (mOGC) model were established. Exosomes derived from miR-22-3p-overexpressed hUCMSCs (Exos-miR-22-3p) were isolated. CCK-8 assay and flow cytometry were utilized for measuring mOGC cell viability and apoptosis. RT-qPCR and western blotting were utilized for determining RNA and protein levels. The binding ability between exosomal miR-22-3p and Kruppel-like factor 6 (KLF6) was verified using luciferase reporter assay. Hematoxylin-eosin staining, ELISA, and TUNEL staining were performed for examining the alteration of ovarian function in POF mice. RESULTS: Exos-miR-22-3p enhanced mOGC viability and attenuated mOGC apoptosis under cisplatin treatment. miR-22-3p targeted KLF6 in mOGCs. Overexpressing KLF6 reversed the above effects of Exos-miR-22-3p. Exos-miR-22-3p ameliorated cisplatin-triggered ovarian injury in POF mice. Exos-miR-22-3p repressed ATF4-ATF3-CHOP pathway in POF mice and cisplatin-treated mOGCs. CONCLUSION: Exosomal miR-22-3p from hUCMSCs alleviates OGC apoptosis and improves ovarian function in POF mouse models by targeting KLF6 and ATF4-ATF3-CHOP pathway.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Insuficiência Ovariana Primária , Feminino , Humanos , Camundongos , Animais , Insuficiência Ovariana Primária/metabolismo , Cisplatino/farmacologia , Exossomos/genética , Exossomos/metabolismo , Fator 6 Semelhante a Kruppel/metabolismo , Apoptose , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Células da Granulosa/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/farmacologia , Fator 4 Ativador da Transcrição/metabolismo
14.
Adv Clin Exp Med ; 32(8): 865-872, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36753377

RESUMO

BACKGROUND: Refractory abdominal wounds are commonly complicated by surgical site infections, which prolong hospital stays and increase medical costs. There is little clinical data on the use of allogeneic platelet gel (PG) therapy for refractory infected wounds. OBJECTIVES: This study aimed to evaluate the efficacy and safety of allogeneic PGs in the treatment of refractory abdominal wounds. MATERIAL AND METHODS: A prospective single-center study was performed in a national abdominal trauma referral center between June 2019 and June 2021. A total of 11 patients with refractory abdominal wounds were treated with allogeneic PGs after the failure of standard medical treatments. The PGs were derived from platelets collected from healthy donors using apheresis, and each PG was tested for platelet count, transfusion-related diseases, aerobic and anaerobic bacteria, and growth factor concentration. Clinical efficacy was evaluated by assessing the wound surface and observing the condition of the wound, including wound area and percentage of granulation. RESULTS: The median age of the patients was 37 years (1st quartile, 3rd quartile (Q1, Q3): 31-55 years), median (Q1, Q3) hemoglobin level was 95 g/L (78-120 g/L) and median (Q1, Q3) serum albumin level was 39.9 g/L (34.9-42.7 g/L). The PG platelet count was 976.5 ±174.9×109/L. Results of transfusion-associated contagion tests for aerobic and anaerobic bacteria were negative. Growth factor contents (pg/mL) were: for transforming growth factor beta 1 (TGF-ß1); 2542.39 ±430.60, for platelet-derived growth factor BB (PDGF-BB); 23230.03 ±4236.14 and FOR vascular endothelial growth factor (VEGF); 91.41 ±23.31. The rate of wound healing was 100%, and the median (Q1, Q3) healing time was 30 days (18-40 days). The follow-up period was 5-27 months, during which no recurrence of the wounds was found. CONCLUSIONS: The present study demonstrated that allogeneic PGs are a safe and effective treatment for refractory abdominal wounds.


Assuntos
Plaquetas , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Fator A de Crescimento do Endotélio Vascular , Estudos Prospectivos , Cicatrização
15.
Cell Mol Immunol ; 20(3): 277-291, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36631557

RESUMO

Upon recognition of foreign antigens, naïve B cells undergo rapid activation, growth, and proliferation. How B-cell growth and proliferation are coupled with activation remains poorly understood. Combining CRISPR/Cas9-mediated functional analysis and mouse genetics approaches, we found that Dhx33, an activation-induced RNA helicase, plays a critical role in coupling B-cell activation with growth and proliferation. Mutant mice with B-cell-specific deletion of Dhx33 exhibited impaired B-cell development, germinal center reactions, plasma cell differentiation, and antibody production. Dhx33-deficient B cells appeared normal in the steady state and early stage of activation but were retarded in growth and proliferation. Mechanistically, Dhx33 played an indispensable role in activation-induced upregulation of ribosomal DNA (rDNA) transcription. In the absence of Dhx33, activated B cells were compromised in their ability to ramp up 47S ribosomal RNA (rRNA) production and ribosome biogenesis, resulting in nucleolar stress, p53 accumulation, and cellular death. Our findings demonstrate an essential role for Dhx33 in coupling B-cell activation with growth and proliferation and suggest that Dhx33 inhibition is a potential therapy for lymphoma and antibody-mediated autoimmune diseases.


Assuntos
RNA Ribossômico , Animais , Camundongos , Ciclo Celular , Proliferação de Células , RNA Ribossômico/genética , Regulação para Cima
16.
Perfusion ; 38(6): 1260-1267, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35726366

RESUMO

OBJECTIVES: The aim of this research is to determine the optimum blood pressure (BP) control goal for hypertensive type B aortic dissection (TBAD) patients undergoing surgery. METHODS: Between January 2019 and April 2021, 259 hypertensive TBAD patients undergoing surgery were included in the research. 98 patients received intensive BP control with a target of systolic BP (SBP) < 120 mmHg, and 161 received standard BP control targeting SBP between 120 and 140 mmHg. Clinical data from two groups were compared. RESULTS: Patients who received intensive BP control experienced a significantly higher incidence of acute kidney injury (AKI) postoperatively (21/98, 21.4% vs 14/161, 8.7%, p = 0.004). The intensive group took more anti-hypertensive drugs per day compared with the standard group (1.9 vs 1.5, p < 0.001). Triple-drug combination treatment was more frequent in the intensive group (38.8% vs 14.3%, p < 0.001), as were angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB; 67.3% vs 44.7%, p 0.001), and thiazide-like diuretic (44.9% vs 18.0%, p < 0.001). CONCLUSIONS: Intensive BP control treatment increases the incidence of AKI and raises the utilization of the anti-hypertensive drug, but did not reduce the operative mortality and late mortality in TBAD patients undergoing surgical repair.


Assuntos
Injúria Renal Aguda , Dissecção Aórtica , Hipertensão , Humanos , Inibidores da Enzima Conversora de Angiotensina , Pressão Sanguínea , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/cirurgia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Resultado do Tratamento
17.
Cancer Med ; 12(4): 4486-4495, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053931

RESUMO

BACKGROUND: Homologous recombination deficiency (HRD) is a well-known biomarker which could predict poly-ADP ribose polymerase 1 (PARP) inhibitor and platinum drug response. As an aggressive cancer, small-cell lung cancer (SCLC) is sensitive to platinum drugs, but relapse occurs rapidly. Herein, we aim to illustrate the genomic alteration patterns of homologous recombination repair (HRR)-related genes in a Chinese SCLC cohort and further analyze the relationship among HRR gene mutations and known biomarkers of immune checkpoint inhibitor (ICI) response, including tumor mutation burden (TMB) and programmed cell death-ligand 1 (PD-L1) expression. METHODS: Next-generation sequencing (NGS)-based target capture sequencing of 543 cancer-related genes was performed to analyze the genomic profiles of 133 Chinese SCLC patients, and TMB was calculated. PD-L1 expression was evaluated in 90 out of 133 patients using the SP142 PD-L1 immunohistochemistry assay. RESULTS: Among the 133 patients with SCLC, 47 (35.3%) had HRR gene mutations. ATM (8.3%) was the most frequently mutated HRR gene in the cohort, followed by NBN (4.5%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (23.4%) and 4 (8.5%) patients, respectively. HRR gene mutations cooccurred with KMT2D gene mutations. There were several differences in genomic alterations between patients with HRR gene mutations (HRR-Mut) and without HRR mutations (HRR-WT). The results revealed that TP53 and RB1 were commonly mutated genes in both groups. Mutations in the KMT2D gene and genes in the RTK-RAS pathway occurred more frequently in the HRR-Mut group. Furthermore, we found that mutations in HRR genes were associated with high TMB (Wilcoxon, p = 0.048), but there was no correlation of HRR gene mutation status with PD-L1 expression. CONCLUSIONS: We exhaustively describe the genomic alteration profile of Chinese SCLC patients and provide further evidence that HRR gene mutations are prevalent in SCLC patients.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Platina , Antígeno B7-H1/genética , Recidiva Local de Neoplasia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Mutação , Biomarcadores Tumorais/genética , Recombinação Homóloga
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1834-1838, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476912

RESUMO

OBJECTIVE: To evaluate the effect of sonication, repeated freeze-thaw cycles, calcium salt solution and their combination on the content of related growth factors (GFs) released by platelet rich plasma (PRP). METHODS: Twenty PRPs from healthy blood donors were divided into 9 groups, including sonication group, freeze-thaw group, calcium gluconate group, calcium chloride group, sonication + calcium gluconate group, sonication + calcium chloride group, freeze-thaw + calcium gluconate group, freeze-thaw + calcium chloride group, and sonication + freeze-thaw group. After PRP activated by above 9 methods, the content of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) were detected by ELISA. RESULTS: The platelet concentration of the samples was (966.7±202.6)×109/L. The content of TGF-ß1 in sonication + freeze-thaw group was the highest, while the lowest was in freeze-thaw group. The content of VEGF in freeze-thaw + calcium chloride group was the highest, while the lowest was in calcium gluconate group. The content of PDGF-BB in sonication + freeze-thaw group was the highest, while the lowest was in calcium gluconate group. There was no significant differences in the three GFs between calcium gluconate group and calcium chloride group. CONCLUSION: Among the 9 activated methods of PRP, there is no difference between two calcium salt solutions. And the combination of repeated freeze-thaw cycles and sonication may be the best treatment method to promote PRP to release GFs, while calcium gluconate is the weakest way.


Assuntos
Plasma Rico em Plaquetas , Fator de Crescimento Transformador beta1 , Humanos , Fator A de Crescimento do Endotélio Vascular , Gluconato de Cálcio , Cálcio , Cloreto de Cálcio , Becaplermina
19.
Clin Interv Aging ; 17: 1687-1695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467316

RESUMO

Purpose: A longer stent is associated with adverse events after percutaneous coronary intervention (PCI). However, little information is available on the relationship between stent length and periprocedural prognosis in patients with ST segment elevation myocardial infarction (STEMI). We aimed to assess the target vessel stent length influence on angiographic outcomes and in-hospital major adverse cardiovascular event (MACE) during primary PCI in patients with STEMI. Patients and Methods: This single-center retrospective observational study included 246 patients with STEMI admitted to the Zhejiang Provincial People's Hospital between January 2019 and December 2021, who underwent primary PCI and successful stent implantation. The exclusion criteria included left main lesion, multiple diseased vessel-stenting, bleeding disorders, contrast allergy, and incomplete data. Patients were divided into two groups based on the median stents length: group A (≤29 mm, n=125) and group B (>29mm, n=121). Periprocedural outcomes were slow flow/no-reflow (SF-NR) and in-hospital MACE, which included acute heart failure, malignant arrhythmia, cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, and urgent revascularization. Multivariate logistic analyses were used to explore the correlation between stent length and SF-NR. Results: A total of 246 patients (82.9% males) with a mean age of 59.9±12.6 years were included in the analysis. The incidence of SF-NR was significantly higher in group B than in group A (36.4% vs 23.2%, p=0.024). However, the in-hospital MACE incidence rate was similar between the two groups (7.2% vs 7.4%, p=0.943). Multivariate logistic regression analysis showed that stent length and diameter, and peak troponin I level were independent risk factors for SF-NR. Conclusion: Excessive stent length is an independent risk factor for SF-NR, without any significant influence on the risk of MACE during hospitalization.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Masculino , Humanos , Idoso , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , Hospitais
20.
BMC Cancer ; 22(1): 1145, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344947

RESUMO

BACKGROUND: Cervical cancer (CC) is a common gynecological malignancy worldwide. Some patients perform serious resistance after chemotherapy, and long-stranded non-coding RNA MEG3 is reported to be involved in the regulation of chemoresistance in many solid tumors. However, its involvement in cervical adenocarcinoma has not been reported. METHODS: Hela cell lines, cisplatin-resistant cell lines (Hela-CR) and nude mice were used in this study. After MEG3 was overexpressed or knocked down in cells by the lentivirus vector, cell growth was detected by the CCK-8 assay, and cell migration was evaluated using Transwell assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of MEG3, miR-21 and PTEN mRNA. Apoptosis was detected by flow cytometry. The targeting relationship between mRNAs was predicted and verified using dual-luciferase reporter gene experiments. Western blot was executed to examine Bax, cleaved-caspase 3, Bcl-2, PTEN and GAPDH expression. Cells were injected into the mice to form xenograft tumors to compare tumorigenesis capacity. RESULTS: We demonstrated that MEG3 was down-regulated in cervical cancer by analyzing the TCGA database. Moreover, knockdown of MEG3 promoted CC cell proliferation, migration and inhibited the apoptosis. These changes of CC cells were more pronounced under cisplatin treatment. Further studies showed that the MEG3/miR-21/PTEN axis affected cisplatin sensitivity in cervical cancer cells, and these results of recue assay were used to confirm this conclusion. CONCLUSIONS: MEG3 performing as ceRNA promotes cisplatin sensitivity in CC cells through the miR-21/PTEN axis.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Camundongos Nus , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Células HeLa , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Mensageiro , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
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