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1.
Biomed Pharmacother ; 174: 116543, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608523

RESUMO

In recent years, there has been an increasing number of related studies on exosomes. Most studies have focused on exosomes derived from mammals, confirming the important role that exosomes play in cell communication. Plants, as a natural ingredient, plant-derived exosomes have been confirmed to have similar structures and functions to mammalian-derived exosomes. Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such as miRNA, mRNA, protein, and lipids obtained from plant cells, that can participate in intercellular communication and mediate transboundary communication, have high bioavailability and low immunogenicity, are relatively safe, and have been shown to play an important role in maintaining cell homeostasis and preventing, and treating a variety of diseases. In this review, we describe the biogenesis, isolation and purification methods, structural composition, stability, safety, function of PELNs and challenges. The functions of PELNs in anti-inflammatory, antioxidant, antitumor and drug delivery are mainly described, and the status of research on exosome nanoparticles of Chinese herbal medicines is outlined. Overall, we summarized the importance of PELNs and the latest research results in this field and provided a theoretical basis for the future research and clinical application of PELNs.

2.
Med Biol Eng Comput ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558351

RESUMO

Unplanned readmission after primary total knee arthroplasty (TKA) costs an average of US $39,000 per episode and negatively impacts patient outcomes. Although predictive machine learning (ML) models show promise for risk stratification in specific populations, existing studies do not address model generalizability. This study aimed to establish the generalizability of previous institutionally developed ML models to predict 30-day readmission following primary TKA using a national database. Data from 424,354 patients from the ACS-NSQIP database was used to develop and validate four ML models to predict 30-day readmission risk after primary TKA. Individual model performance was assessed and compared based on discrimination, accuracy, calibration, and clinical utility. Length of stay (> 2.5 days), body mass index (BMI) (> 33.21 kg/m2), and operation time (> 93 min) were important determinants of 30-day readmission. All ML models demonstrated equally good accuracy, calibration, and discriminatory ability (Brier score, ANN = RF = HGB = NEPLR = 0.03; ANN, slope = 0.90, intercept = - 0.11; RF, slope = 0.93, intercept = - 0.12; HGB, slope = 0.90, intercept = - 0.12; NEPLR, slope = 0.77, intercept = 0.01; AUCANN = AUCRF = AUCHGB = AUCNEPLR = 0.78). This study validates the generalizability of four previously developed ML algorithms in predicting readmission risk in patients undergoing TKA and offers surgeons an opportunity to reduce readmissions by optimizing discharge planning, BMI, and surgical efficiency.

3.
J Transl Med ; 22(1): 283, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491378

RESUMO

The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Hipóxia/genética , Glicólise/genética , Proliferação de Células/genética , Linhagem Celular Tumoral
4.
Microb Cell Fact ; 23(1): 93, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539193

RESUMO

Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways.


Assuntos
Fusarium , Fusarium/genética , Fusarium/metabolismo , Fungos/metabolismo , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Biologia Computacional , Família Multigênica , Vias Biossintéticas/genética
5.
Phytomedicine ; 127: 155476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430586

RESUMO

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.


Assuntos
Encefalite por Herpes Simples , Herpes Simples , Herpesvirus Humano 1 , Animais , Camundongos , Humanos , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/diagnóstico , Antivirais/farmacologia , Antivirais/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Herpes Simples/tratamento farmacológico
6.
J Exp Bot ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38452221

RESUMO

Low temperatures affect flower development in rose (Rosa hybrida), increasing petaloid stamen number and reducing normal stamen number. We identified the low-temperature-responsive R2R3-MYB transcription factor RhMYB17, which is homologous to Arabidopsis (Arabidopsis thaliana) MYB17. RhMYB17 was upregulated at low temperatures, and RhMYB17 transcripts accumulated in floral buds. Transient silencing of RhMYB17 by virus-induced gene silencing decreased petaloid stamen number and increased normal stamen number. According to the ABCDE model of floral organ identity, class A genes contribute to sepal and petal formation. Transcription factor binding analysis identified RhMYB17 binding sites in the promoters of rose APETALA2 (RhAP2) and APETALA2-LIKE (RhAP2L). Yeast one-hybrid assays, dual-luciferase reporter assays, and electrophoretic mobility shift assays confirmed that RhMYB17 directly binds to the promoters of RhAP2 and RhAP2L, thereby activating their expression. RNA sequencing further demonstrated that RhMYB17 plays a pivotal role in regulating the expression of class A genes, and indirectly influences the expression of class C gene. This study reveals a novel mechanism for the homeotic transformation of floral organs in response to low temperatures.

7.
Cell Death Dis ; 15(2): 147, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360722

RESUMO

Tamoxifen (TAM) is the frontline therapy for estrogen receptor-positive (ER+) breast cancer in premenopausal women that interrupts ER signaling. As tumors with elevated heterogeneity, amounts of ER-negative (ER-) cells are present in ER+ breast cancer that cannot be directly killed by TAM. Despite complete remissions have been achieved in clinical practice, the mechanism underlying the elimination of ER- cells during TAM treatment remains an open issue. Herein, we deciphered the elimination of ER- cells in TAM treatment from the perspective of the bystander effect. Markable reductions were observed in tumorigenesis of ER- breast cancer cells by applying both supernatants from TAM-treated ER+ cells and a transwell co-culture system, validating the presence of a TAM-induced bystander effect. The major antitumor protein derived from ER+ cells, peptidyl-prolyl cis-trans isomerase B (PPIB), is the mediator of the TAM-induced bystander effect identified by quantitative proteomics. The attenuation of ER- cells was attributed to activated BiP/eIF2α/CHOP axis and promoted endoplasmic reticulum stress (ERS)-induced apoptosis, which can also be triggered by PPIB independently. Altogether, our study revealed a novel TAM-induced bystander effect in TAM treatment of ER+ breast cancer, raising the possibility of developing PPIB as a synergistic antitumor agent or even substitute endocrine therapy.


Assuntos
Neoplasias da Mama , Efeito Espectador , Peptidilprolil Isomerase , Tamoxifeno , Feminino , Humanos , Antineoplásicos Hormonais/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Isoenzimas , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
8.
BMC Immunol ; 25(1): 16, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347480

RESUMO

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.


Assuntos
Artemisininas , Síndrome de Sjogren , Camundongos , Animais , Camundongos Endogâmicos NOD , Interleucina-17 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Síndrome de Sjogren/tratamento farmacológico , Artemisininas/farmacologia , Artemisininas/uso terapêutico
9.
Mol Carcinog ; 63(5): 859-873, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353359

RESUMO

Breast cancer has become the most commonly diagnosed cancer. Heterogeneous nuclear ribonucleoprotein C (HNRNPC), a reader of N6-methyladenosine (m6A), has been observed to be upregulated in various types of cancer. Nevertheless, the role of HNRNPC in breast cancer and whether it is regulated by m6A modification deserve further investigation. The expression of HNRNPC in breast cancer was examined by quantitative real-time polymerase chain reaction and western blot analysis. RNA immunoprecipitation was performed to validate the binding relationships between HNRNPC and WD repeat domain 77 (WDR77). The effects of HNRNPC and m6A regulators on WDR77 were investigated by actinomycin D assay. The experiments in vivo were conducted in xenograft models. In this research, we found that HNRNPC was highly expressed in breast cancer, and played a crucial role in cell growth, especially in the luminal subtype. HNRNPC could combine and stabilize WDR77 mRNA. WDR77 successively drove the G1/S phase transition in the cell cycle and promoted cell proliferation. Notably, this regulation axis was closely tied to the m6A modification status of WDR77 mRNA. Overall, a critical regulatory mechanism was identified, as well as promising targets for potential treatment strategies for luminal breast cancer.


Assuntos
Adenina , Neoplasias da Mama , Ribonucleoproteínas Nucleares Heterogêneas Grupo C , Humanos , Feminino , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Neoplasias da Mama/genética , RNA Mensageiro/genética , Ciclo Celular/genética , Receptores de Estrogênio
10.
World J Clin Cases ; 12(2): 431-442, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313641

RESUMO

BACKGROUND: The relation between orthodontic treatment and temporomandibular disorders (TMDs) is under debate; the management of TMD during orthodontic treatment has always been a challenge. If TMD symptoms occur during orthodontic treatment, an immediate pause of orthodontic adjustments is recommended; the treatment can resume when the symptoms are managed and stabilized. CASE SUMMARY: This case report presents a patient (26-year-old, female) with angle class I, skeletal class II and TMDs. The treatment was a hybrid of clear aligners, fixed appliances and temporary anchorage devices (TADs). After 3 mo resting and treatment on her TMD, the patient's TMD symptom alleviated, but her anterior occlusion displayed deep overbite. Therefore, the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves. After the levelling, the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion. After careful examination of temporomandibular joints (TMJ) position, the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion. Eventually, the improved facial appearance and relatively stable occlusion were achieved. The 1-year follow-up records showed there was no obvious change in TMJ morphology, and her occlusion was stable. CONCLUSION: TMD screening and monitoring is of great clinical importance in the TMD susceptible patients. Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

11.
Life (Basel) ; 14(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38398718

RESUMO

Light is an indispensable factor in the healthy growth of living organisms, and alterations in the photoperiod can have consequences for body homeostasis. The eyestalk is a photosensitive organ that secretes various hormones to regulate the Chinese mitten crab (Eriocheir sinensis). However, the photoperiod-dependent eyestalk patterns of gene expression that may underlie changes in body homeostasis are unknown. In this study, we investigated the molecular mechanisms involved in eyestalk transcriptomic responses in E. sinensis under different photoperiod regimes on days 2, 4, and 6. The photoperiods tested were 12, 24, and 0 h light/day. In total, we obtained 110, 958, 348 clean datasets and detected 1809 differentially expressed genes (DEGs). Genes involved in the crustacean hyperglycemic hormone superfamily and juvenile hormones were observed, which play important roles in gonadal development, growth, and immunity in E. sinensis and may also be involved in photoperiod adaptation. In addition, the MAPK signaling pathway was the only signaling pathway identified in the continuous light group but was absent in the continuous darkness group. We suggest that the MAPK pathway is highly responsive to light input during the subjective night and insensitive to light during the middle of the subjective day. These results provide insight into the molecular mechanisms underlying the effects of photoperiod on the immune regulation of E. sinensis.

12.
J Clin Rheumatol ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38389137

RESUMO

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth (p <0.001), dry eyes (p <0.001), fatigue (p <0.001), arthralgia (p <0.001), and dental caries (p <0.001) and higher rates of anti-Sjögren syndrome A (p < 0.05), anti-Ro52 (p < 0.05), and anti-SSB (p < 0.05) positivity than their control groups, with prevalence increasing with disease duration (ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

13.
Sci Rep ; 14(1): 2519, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291067

RESUMO

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.


Assuntos
Face , Má Oclusão Classe III de Angle , Adulto , Humanos , Face/diagnóstico por imagem , Face/anatomia & histologia , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Nariz , Maxila/diagnóstico por imagem , Maxila/cirurgia , Lábio , Cefalometria/métodos , Imageamento Tridimensional/métodos
14.
J Am Chem Soc ; 145(50): 27248-27253, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38064654

RESUMO

SARS-CoV-2 is the virus that causes the global pandemic of COVID-19. The main protease (Mpro) of SARS-CoV-2 is essential for viral infection and is one of the major therapeutic targets for COVID-19. Here, we report the design, synthesis, and biological characterization of a novel heterobifunctional small molecule that could effectively induce the degradation of SARS-CoV-2 Mpro and its drug-resistant mutants in HEK 293T cells, thus demonstrating a new alternative strategy for intervening with proteins important for this novel coronavirus.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Inibidores de Proteases/química , Simulação de Acoplamento Molecular , Peptídeo Hidrolases
15.
Clin Transl Med ; 13(12): e1512, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38073586

RESUMO

As the most prominent RNA modification, N6-methyladenosine (m6 A) participates in the regulation of tumour initiation and progression. Circular RNAs (circRNAs) also play crucial roles in ubiquitous life processes. Whether circRNAs are required for m6 A regulation in renal cell carcinoma (RCC) remains unclear. Meta-analysis and bioinformatics identified that IGF2BP3 was upregulated in RCC and indicated a worse prognosis. IGF2BP3 significantly promoted RCC progression in vitro and in vivo. Mechanistically, circRARS bound to KH1-KH2 domains of IGF2BP3 to enhance m6 A modification recognition. A 12-nt sequence (GUCUUCCAGCAA) was proven to be the IGF2BP3-binding site of circRARS. Additionally, CAPN15, CD44, HMGA2, TNRC6A and ZMIZ2 were screened to be the target genes regulated by the IGF2BP3/circRARS complex in an m6 A-dependent manner. Stabiliser proteins, including HuR, Matrin3 and pAbPC1, were recruited by circRARS, thereby increasing the mRNA stability of the forementioned five target genes. Consequently, the IGF2BP3/circRARS complex facilitated the lipid accumulation of RCC cells and promoted sunitinib resistance via target genes. circRARS synergised with IGF2BP3 to facilitate m6 A recognition, thereby promoting RCC progression. Thus, IGF2BP3 could be a potential biomarker for RCC diagnosis and prognosis and a therapeutic target.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Calpaína , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica , Neoplasias Renais/genética , Proteínas Inibidoras de STAT Ativados , RNA Circular/genética
16.
Biosci Rep ; 43(12)2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38131305

RESUMO

The chemokine receptor CXCR4 has become an attractive therapeutic target for HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis. A wide variety of synthetic antagonists of CXCR4 have been developed and studied for a growing list of clinical applications. To compare the biological effects of different antagonists on CXCR4 functions and their common and/or distinctive molecular interactions with the receptor, we conducted head-to-head comparative cell-based biological and mutational analyses of the interactions with CXCR4 of eleven reported antagonists, including HC4319, DV3, DV1, DV1 dimer, V1, vMIP-II, CVX15, LY2510924, IT1t, AMD3100, and AMD11070 that were representative of different structural classes of D-peptides, L-peptide, natural chemokine, cyclic peptides, and small molecules. The results were rationalized by molecular modeling of CXCR4-antagonist interactions from which the common as well as different receptor binding sites of these antagonists were derived, revealing a number of important residues such as W94, D97, H113, D171, D262, and E288, mostly of negative charge. To further examine this finding, we designed and synthesized new antagonistic analogs by adding positively charged residues Arg to a D-peptide template to enhance the postulated charge-charge interactions. The newly designed analogs displayed significantly increased binding to CXCR4, which supports the notion that negatively charged residues of CXCR4 can engage in interactions with moieties of positive charge of the antagonistic ligands. The results from these mutational, modeling and new analog design studies shed new insight into the molecular mechanisms of different types of antagonists in recognizing CXCR4 and guide the development of new therapeutic agents.


Assuntos
Peptídeos , Transdução de Sinais , Peptídeos/genética , Peptídeos/farmacologia , Peptídeos/química , Modelos Moleculares , Receptores de Quimiocinas , Receptores CXCR4/genética
17.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139341

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver-gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças Mitocondriais , Hepatopatia Gordurosa não Alcoólica , Humanos
18.
Heliyon ; 9(11): e21337, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37964859

RESUMO

Background: Patients with primary Sjögren's syndrome (pSS) take a higher risk of developing lymphoma, which is the most frequent cause of death in pSS. Based on this situation, the number of publications focusing on pSS-associated lymphoma has been growing. Nevertheless, the extent, range, and nature of available research in this field have not been systematically summarized. This study aimed to map the literature available on pSS-associated lymphoma and identify global hotspots and trends. Methods: Papers on pSS and lymphoma published from 1991 to 2022 were searched from the Web of Science Core Collection. Microsoft Excel, SPSS Statistics, VOSviewer, and CiteSpace software were used to analyze and visualize the quantity and citations of publications, and the global research hotspots and trends of pSS-associated lymphoma. Results: 629 publications from 50 countries/regions and 538 institutions were included in this study. From 1991 to 2022, the cumulative publications steadily increased. The USA ranked first in the number of publications (n = 118, 18.76 %), followed by Italy (n = 94, 14.94 %) and France (n = 73, 11.61 %). Udine University (n = 29) and Salvatore De Vita (n = 39) were the most prolific affiliation and author, respectively. Claudio Vitali was the most frequently cited author (n = 335). In total, the most frequently occurring keywords were clustered into four well-defined groups. The first group of keywords pointed to the clinical assessment and treatment of pSS-associated lymphoma. The second group highlighted the pathogenesis. The third group identified the predictors and prognosis of pSS-associated Lymphoma, while the fourth group focused on interstitial lung disease and pulmonary lymphoma in patients with pSS. Currently, the hot keywords include consensus, disease activity, and pathogenesis. Ultrasonography, mucosa-associated lymphoid tissue (MALT) lymphoma, and epidemiology are the emerging research trends in pSS-associated lymphoma. Conclusion: Research on pSS-associated lymphoma is burgeoning. Despite clinical assessment, treatment and pathogenesis, researchers also showed great interest in the predictors, prognosis, and pulmonary manifestations of pSS-associated lymphoma. Current research of pSS-associated lymphoma mainly focuses on consensus, disease activity, and pathogenesis, while the emerging research trends in pSS are pointing to ultrasonography, MALT lymphoma and epidemiology.

19.
Biomater Res ; 27(1): 121, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001505

RESUMO

Studies have reported on the significance of copper incorporated nanomaterials (CINMs) in cancer theranostics and tissue regeneration. Given their unique physicochemical properties and tunable nanostructures, CINMs are used in photothermal therapy (PTT) and photothermal-derived combination therapies. They have the potential to overcome the challenges of unsatisfactory efficacy of conventional therapies in an efficient and non-invasive manner. This review summarizes the recent advances in CINMs-based PTT in biomedicine. First, the classification and structure of CINMs are introduced. CINMs-based PTT combination therapy in tumors and PTT guided by multiple imaging modalities are then reviewed. Various representative designs of CINMs-based PTT in bone, skin and other organs are presented. Furthermore, the biosafety of CINMs is discussed. Finally, this analysis delves into the current challenges that researchers face and offers an optimistic outlook on the prospects of clinical translational research in this field. This review aims at elucidating on the applications of CINMs-based PTT and derived combination therapies in biomedicine to encourage future design and clinical translation.

20.
Molecules ; 28(20)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37894665

RESUMO

Selective dehydrogenative silylation is one of the most valuable tools for synthesizing organosilicon compounds. In this study, a regio- and stereoselective ruthenium-catalyzed dehydrogenative intermolecular silylation was firstly developed to access (E)-alkenyl silyl-ether derivatives and silyl-ether heterocycles with good functional group tolerance. Furthermore, two pathways for RuH2(CO)(PPh3)3/NBE-catalyzed dehydrogenative intermolecular silylation of alcohols and alkenes as well as intermolecular silylation of naphthol derivatives were investigated with H2SiEt2 as the hydrosilane reagent.

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