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1.
Biochem Pharmacol ; : 116523, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251141

RESUMO

Thrombotic blockages within blood vessels give rise to critical cardiovascular disorders, including ischemic stroke, venous thromboembolism, and myocardial infarction. The current approach to the therapy of thrombolysis involves administering Plasminogen Activators (PA), but it is hindered by fast drug elimination, narrow treatment window, and the potential for bleeding complications. Leveraging nanomedicine to encapsulate and deliver PA offers a solution by improving the efficacy of therapy, safeguarding the medicine from proteinase biodegradation, and reducing unwanted effects in in vivo trials. In this review, we delve into the underlying venous as well as arterial thrombus pathophysiology and provide an overview of clinically approved PA used to address acute thrombotic conditions. We explore the existing challenges and potential directions within recent pivotal research on a variety of targeted nanocarriers, such as lipid, polymeric, inorganic, and biological carriers, designed for precise delivery of PA to specific sites. We also discuss the promising role of microbubbles and ultrasound-assisted Sono thrombolysis, which have exhibited enhanced thrombolysis in clinical studies. Furthermore, our review delves into approaches for the strategic development of nano-based carriers tailored for targeting thrombolytic action and efficient encapsulation of PA, considering the intricate interaction in biology systems as well as nanomaterials. In conclusion, the field of nanomedicine offers a valuable method for the exact and effective therapy of severe thrombus conditions, presenting a pathway toward improved patient outcomes and reduced complications.

2.
Mayo Clin Proc ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39254624
4.
ChemSusChem ; : e202401381, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113132

RESUMO

In this work, four saddled Pd(II) porphyrins were developed as photocatalyst for N-dealkylation of triethyl Rhodamine (TER) under visible light, and their catalytic ability was found to be negatively related to the out-of-plane of their macrocycles. Two important relationships involving the metalloporphyrins as catalyst were revealed: (1) a photoexcitative semiconductor effect between the 4dx2-ᵧ2(Pd) and a2u(π) orbitals of Pd(II) porphyrin on the dealkylation. (2) a domino process from strap length, ring geometry, core deformation, d-π gap variation, to photocatalytic activity. Two revelations imply a unidirectional electron transfer route from axial ligand, to central metal, to porphyrin ring based on photoexcitation and guide the design and development of complex photocatalysts, and their revelation is attributed to the acquisition of a series of Pd(II) porphyrins with continuous ring distortion. The findings help to understand the photocatalytic single electron transfer (SET)-first mechanism based on metallic complex.

5.
J Nanobiotechnology ; 22(1): 470, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118029

RESUMO

Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.


Assuntos
Isquemia , Espermatozoides , Trombose , Animais , Masculino , Camundongos , Isquemia/terapia , Espermatozoides/efeitos dos fármacos , Trombose/tratamento farmacológico , Terapia Trombolítica/métodos , Hipertermia Induzida/métodos , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Fibrinolíticos/química , Humanos , Camundongos Endogâmicos C57BL
6.
Biomed Pharmacother ; 178: 117270, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39126773

RESUMO

The blood supply in the retina ensures photoreceptor function and maintains regular vision. Leber's hereditary optic neuropathy (LHON), caused by the mitochondrial DNA mutations that deteriorate complex I activity, is characterized by progressive vision loss. Although some reports indicated retinal vasculature abnormalities as one of the comorbidities in LHON, the paracrine influence of LHON-affected retinal ganglion cells (RGCs) on vascular endothelial cell physiology remains unclear. To address this, we established an in vitro model of mitochondrial complex I deficiency using induced pluripotent stem cell-derived RGCs (iPSC-RGCs) treated with a mitochondrial complex I inhibitor rotenone (Rot) to recapitulate LHON pathologies. The secretomes from Rot-treated iPSC-RGCs (Rot-iPSC-RGCs) were collected, and their treatment effect on human umbilical vein endothelial cells (HUVECs) was studied. Rot induced LHON-like characteristics in iPSC-RGCs, including decreased mitochondrial complex I activity and membrane potential, and increased mitochondrial reactive oxygen species (ROS) and apoptosis, leading to mitochondrial dysfunction. When HUVECs were exposed to conditioned media (CM) from Rot-iPSC-RGCs, the angiogenesis of HUVECs was suppressed compared to those treated with CM from control iPSC-RGCs (Ctrl-iPSC-RGCs). Angiogenesis-related proteins were altered in the secretomes from Rot-iPSC-RGC-derived CM, particularly angiopoietin, MMP-9, uPA, collagen XVIII, and VEGF were reduced. Notably, GeneMANIA analysis indicated that VEGFA emerged as the pivotal angiogenesis-related protein among the identified proteins secreted by health iPSC-RGCs but reduced in the secretomes from Rot-iPSC-RGCs. Quantitative real-time PCR and western blots confirmed the reduction of VEGFA at both transcription and translation levels, respectively. Our study reveals that Rot-iPSC-RGCs establish a microenvironment to diminish the angiogenic potential of vascular cells nearby, shedding light on the paracrine regulation of LHON-affected RGCs on retinal vasculature.


Assuntos
Células Endoteliais da Veia Umbilical Humana , Células-Tronco Pluripotentes Induzidas , Atrofia Óptica Hereditária de Leber , Células Ganglionares da Retina , Humanos , Atrofia Óptica Hereditária de Leber/metabolismo , Atrofia Óptica Hereditária de Leber/patologia , Atrofia Óptica Hereditária de Leber/genética , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Rotenona/farmacologia , Meios de Cultivo Condicionados/farmacologia , Apoptose/efeitos dos fármacos , Complexo I de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Angiogênese
7.
Colloids Surf B Biointerfaces ; 243: 114054, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39079188

RESUMO

Creating a versatile and remotely self-assembling biocomposite for delivering therapeutics to alleviate inflammatory diseases poses significant challenges. This study introduces a novel biocomposite, created through cold-atmosphere plasma treatment, that combines fucoidan (Fu) and neutrophil lysate (Nu) to mediate the self-assembly of diferuloylmethane (DIF) and iron oxide (IO) nanoclusters, termed DIF-Nu/Fu-IO NC. This biocomposite forms a phototherapeutic and magnetically-driven in situ gel with open-porous architecture loaded with DIF, offering non-invasive theranostic capabilities for treating inflammatory diseases. It demonstrates efficacy in both an intraarticular zymosan-induced rheumatoid arthritis animal model and an intranasal LPS-induced inflammatory lung model. Upon administration, near-infrared (NIR) irradiation and magnet application significantly improved the condition of the animals with rheumatoid arthritis and lung inflammation. This breakthrough heralds a new paradigm in bioinspired, versatile, theranostic, self-assembling biocomposites for addressing clinical inflammatory diseases.


Assuntos
Neutrófilos , Polissacarídeos , Animais , Polissacarídeos/química , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Camundongos , Compostos Férricos/química , Furocumarinas/química , Furocumarinas/farmacologia , Artrite Reumatoide/terapia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Inflamação/tratamento farmacológico , Gases em Plasma/química , Fototerapia/métodos , Géis/química , Humanos , Tamanho da Partícula , Propriedades de Superfície
8.
Int Nurs Rev ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957073

RESUMO

BACKGROUND: Rotating-shift nurses are susceptible to sleep disorders due to numerous factors, such as their biological clock, emotions, and age. At present, a lack of research exists on whether chronotype and shift type jointly influence the sleep quality of nurses. AIM: To verify whether chronotype is a moderator variable of the relationship between shift type and sleep quality in nurses in order to provide empirical evidence for future mental and physical health improvement. METHOD: Clinical rotating-shift nurses at a medical center in northern Taiwan were recruited as participants between November 1, 2023, and December 13, 2023. All of the nurses were working a monthly rotating shift schedule. Hierarchical multiple regression analysis was employed to investigate whether the influence of shift type on sleep quality in nurses varied with chronotype. The STROBE checklist was used for reporting this study. RESULTS: The participants were 255 rotating-shift nurses in this study. Hierarchical multiple regression results revealed that rotating-shift nurses who were older (B = 0.19, p = 0.029), had greater physical fatigue (B = 0.27, p = 0.016), and had more negative emotions (B = 0.17, p = 0.011) suffered from poorer sleep quality. After controlling the above factors, we further found that chronotype indeed had moderating effects on the influence of shift type on sleep quality (B = -1.83, p = 0.049). CONCLUSIONS: This study demonstrates that early- and intermediate-type nurses are more suitable for working the day and evening shifts, whereas late-type nurses are more suitable for working the night shift. IMPLICATION FOR NURSING AND HEALTH POLICY: Coordinating chronotype with shift type will ensure that shift schedules better match the biological clocks of nurses; such individual considerations could help to improve their sleep quality.

10.
Cells ; 13(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38786072

RESUMO

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, we identified several AR-regulated genes involved in the maturation of spermatogenesis, including chromodomain Y-like protein (CDYL) and transition proteins 1 (TNP-1), that were significantly decreased in ARKO mouse testes. AR and CDYL were found to co-localize and interact in Sertoli cells. The AR-CDYL complex bound to the promoter regions of TNP1 and modulated their transcriptional activity. CDYL acts as a co-regulator of AR transactivation, and its expression is decreased in the Sertoli cells of human testes from patients with azoospermia. The androgen receptor-chromodomain Y-like protein axis plays a crucial role in regulating a network of genes essential for spermatogenesis in Sertoli cells. Disruption of this AR-CDYL regulatory axis may contribute to spermatogenic failure. These findings provide insights into novel molecular mechanisms targeting the AR-CDYL signaling pathway, which may have implications for developing new therapeutic strategies for male infertility.


Assuntos
Receptores Androgênicos , Células de Sertoli , Transdução de Sinais , Espermatogênese , Animais , Humanos , Masculino , Camundongos , Azoospermia/metabolismo , Azoospermia/genética , Azoospermia/patologia , Proteínas de Homeodomínio , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Células de Sertoli/metabolismo , Espermatogênese/genética , Fatores de Transcrição
11.
Eur J Pharmacol ; 977: 176676, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38815787

RESUMO

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.


Assuntos
Apoptose , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Fibrose , Flavanonas , Obstrução Ureteral , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Obstrução Ureteral/complicações , Obstrução Ureteral/patologia , Obstrução Ureteral/tratamento farmacológico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Apoptose/efeitos dos fármacos , Masculino , Camundongos , Linhagem Celular , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Fator de Crescimento Transformador beta/metabolismo , Ratos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Camundongos Endogâmicos C57BL
12.
Arthroscopy ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719177

RESUMO

PURPOSE: To evaluate the effectiveness of marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (scaffold) in treating focal osteochondral lesions of the knee. METHODS: In total, 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the scaffold group or the MS group. International Knee Documentation Committee subjective score, the Knee Injury Osteoarthritis Outcome Score, and magnetic resonance imaging (MRI) were assessed preoperatively and at 1 and 2 years after operation to compare treatment outcomes. Biopsy and second-look arthroscopy were performed at 1 year postoperatively for consenting patients. RESULTS: There were 27 patients (mean age 31.33 ± 10.95 years) in the scaffold group, and 27 patients (31.74 ± 11.44) in the MS group. The scaffold group and the MS group both included 23 patients with lesions ≤12.5 × 12.5 mm2 mm in size. In addition, each group had 4 patients with lesions between than 12.5 × 12.5 mm2 and ≤12.5 × 25 mm2. Both interventions achieved significant improvement in clinical outcome scores at 2 years. The scaffold group had greater International Knee Documentation Committee score than the MS group at 2 years (93.85 ± 9.55 vs 92.11 ± 9.84) and in the Symptoms/Stiffness and Sport/Recreation subscales of Knee Injury Osteoarthritis Outcome Score at 2 years (96.57 ± 5.97 vs 93.57 ± 6.52, P < .05) and (90.2 ± 17.76 vs 82.8 ± 16.08, P < .05). CONCLUSIONS: The use of biphasic scaffold loaded with autologous cartilage in treating focal osteochondral lesions demonstrates superior clinical outcomes and better cartilage refill on magnetic resonance imaging at the 2-year follow-up compared to marrow stimulation. LEVEL OF EVIDENCE: Level I, Randomized controlled trial.

13.
Comput Struct Biotechnol J ; 24: 322-333, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38690549

RESUMO

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

14.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612685

RESUMO

Endometriosis is a complex gynecological disease that affects more than 10% of women in their reproductive years. While surgery can provide temporary relief from women's pain, symptoms often return in as many as 75% of cases within two years. Previous literature has contributed to theories about the development of endometriosis; however, the exact pathogenesis and etiology remain elusive. We conducted a preliminary investigation into the influence of primary endometrial cells (ECs) on the development and progression of endometriosis. In vitro studies, they were involved in inducing Lipopolysaccharide (LPS) in rat-isolated primary endometrial cells, which resulted in increased nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) mRNA gene expression (quantitative polymerase chain reaction analysis, qPCR) and protein expression (western blot analysis). Additionally, in vivo studies utilized autogenic and allogeneic transplantations (rat to rat) to investigate endometriosis-like lesion cyst size, body weight, protein levels (immunohistochemistry), and mRNA gene expression. These studies demonstrated that estrogen upregulates the gene and protein regulation of cytoskeletal (CK)-18, transforming growth factor-ß (TGF-ß), VEGF, and tumor necrosis factor (TNF)-α, particularly in the peritoneum. These findings may influence cell proliferation, angiogenesis, fibrosis, and inflammation markers. Consequently, this could exacerbate the occurrence and progression of endometriosis.


Assuntos
Endometriose , Feminino , Humanos , Animais , Ratos , Fator A de Crescimento do Endotélio Vascular/genética , Proliferação de Células , Citoesqueleto , RNA Mensageiro
15.
Ying Yong Sheng Tai Xue Bao ; 35(3): 827-836, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646771

RESUMO

The proportion and area of ratoon rice planting in China have been substantially increased, due to continuous improvement of rice breeding methods and consecutive innovation of cultivation technology, which has developed into one of rice planting modes with significant production efficiency. Combining the experience in research and practice, from the perspective of crop physiology and ecology, we reviewed the current situation and prospects of high-yielding formation and physiological mechanisms of ratoon rice. We focused on four key aspects: screening and breeding of ratoon rice cultivars and the classification; suitable stubble height for mechanically harvested ratoon rice, as well as water and fertilizer management; dry matter production and allocation in ratoon rice and the relationship with yield formation; regenerative activity and vigor of ratoon rice roots and their relationship with rhizosphere micro-ecological characteristics. As for the extending of mechanized low-cut stubbles ratoon rice technique, we should properly regulate the rhizosphere system, coordinate rhizosphere nutrient supply, germination of axillary buds, and tillering regeneration, to achieve the target of "four-high-one-low", that is high regeneration coefficient, high number of regeneration panicle, high harvest index, high yield, high quality, low-carbon and safe, aiming to improve the sustainability of ratoon rice industry.


Assuntos
Oryza , Oryza/crescimento & desenvolvimento , China , Produção Agrícola/métodos , Rizosfera , Melhoramento Vegetal , Agricultura/métodos , Fertilizantes , Raízes de Plantas/crescimento & desenvolvimento
16.
J Periodontol ; 95(8): 764-777, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38523602

RESUMO

BACKGROUND: This study aimed to investigate the contribution of myeloid differentiation primary-response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis-induced experimental periodontitis. METHODS: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate-resistant acid phosphatase (TRAP), the receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age- and sex-matched homozygous littermates (wild-type [WT, Myd88+/+] and Myd88-/- on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. RESULTS: P. gingivalis-infected Myd88-/- mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88-/- CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL-10 and IL-17a expressions in gingival tissue at D14-D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88-/- mice. The Myd88-/- mice exhibited characteristic increases in gram-positive species and species having probiotic properties, while gram-negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88-/- mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection. CONCLUSIONS: MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis-induced experimental periodontitis.


Assuntos
Perda do Osso Alveolar , Disbiose , Gengiva , Fator 88 de Diferenciação Mieloide , Periodontite , Porphyromonas gingivalis , Linfócitos T Reguladores , Células Th17 , Animais , Masculino , Camundongos , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/imunologia , Diferenciação Celular , Disbiose/imunologia , Gengiva/microbiologia , Gengiva/imunologia , Inflamação/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota , Osteoprotegerina/análise , Periodontite/microbiologia , Periodontite/imunologia , Ligante RANK , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Microtomografia por Raio-X/métodos
17.
J Adv Res ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38548265

RESUMO

INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

18.
Aging (Albany NY) ; 16(3): 2679-2701, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305803

RESUMO

Renal cell carcinoma (RCC) is the predominant form of malignant kidney cancer. Sunitinib, a primary treatment for advanced, inoperable, recurrent, or metastatic RCC, has shown effectiveness in some patients but is increasingly limited by drug resistance. Recently identified cuproptosis, a copper-ion-dependent form of programmed cell death, holds promise in combating cancer, particularly drug-resistant types. However, its effectiveness in treating drug resistant RCC remains to be determined. Exploring cuproptosis's regulatory mechanisms could enhance RCC treatment strategies. Our analysis of data from the GEO and TCGA databases showed that the cuproptosis-related gene DBT is markedly under expressed in RCC tissues, correlating with worse prognosis and disease progression. In our study, we investigated copper CRGs in ccRCC, noting substantial expression differences, particularly in advanced-stage tumors. We established a connection between CRG expression levels and patient survival, positioning CRGs as potential therapeutic targets for ccRCC. In drug resistant RCC cases, we found distinct expression patterns for DBT and GLS CRGs, linked to treatment resistance. Our experiments demonstrated that increasing DBT expression significantly reduces RCC cell growth and spread, underscoring its potential as a therapeutic target. This research sheds new light on the role of CRGs in ccRCC and their impact on drug resistance.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Ácido Tióctico/análogos & derivados , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Cobre , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Apoptose
19.
BMC Pulm Med ; 24(1): 59, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281038

RESUMO

BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Teoria de Enfermagem , Estudos Retrospectivos , Estudos de Casos e Controles , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Qualidade de Vida
20.
Luminescence ; 39(2): e4667, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38178733

RESUMO

Ciprofloxacin (CIP) is a widely used broad-spectrum antibiotic and has been associated with various side effects, making its accurate detection crucial for patient safety, drug quality compliance, and environmental and food safety. This study presents the development of a ternary nucleotide-lanthanide coordination nanoprobe, GMP-Tb-BDC (GMP: guanosine 5'-monophosphate, BDC: 2-amino-1,4-benzenedicarboxylic acid), for the sensitive and ratiometric detection of CIP. The GMP-Tb-BDC nanoprobe was constructed by incorporating the blue-emissive ligand BDC into the Tb/GMP coordination polymers. Upon the addition of CIP, the fluorescence of terbium ion (Tb3+ ) was significantly enhanced due to the coordination and fluorescence sensitization properties of CIP, while the emission of the BDC ligand remained unchanged. The nanoprobe demonstrated good linearity in the concentration range of 0-10 µM CIP. By leveraging mobile phone software to analyze the color signals, rapid on-site analysis of CIP was achieved. Furthermore, the nanoprobe exhibited accurate analysis of CIP in actual drug and milk samples. This study showcases the potential of the GMP-Tb-BDC nanoprobe for practical applications in CIP detection.


Assuntos
Elementos da Série dos Lantanídeos , Humanos , Ciprofloxacina , Nucleotídeos , Ligantes , Térbio , Guanosina Monofosfato
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