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1.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37816138

RESUMO

Immune evasion and metabolism reprogramming have been regarded as two vital hallmarks of the mechanism of carcinogenesis. Thus, targeting the immune microenvironment and the reprogrammed metabolic processes will aid in developing novel anti-cancer drugs. In recent decades, herbal medicine has been widely utilized to treat cancer through the modulation of the immune microenvironment and reprogrammed metabolic processes. However, labor-based herbal ingredient screening is time consuming, laborious and costly. Luckily, some computational approaches have been proposed to screen candidates for drug discovery rapidly. Yet, it has been challenging to develop methods to screen drug candidates exclusively targeting specific pathways, especially for herbal ingredients which exert anti-cancer effects by multiple targets, multiple pathways and synergistic ways. Meanwhile, currently employed approaches cannot quantify the contribution of the specific pathway to the overall curative effect of herbal ingredients. Hence, to address this problem, this study proposes a new computational framework to infer the contribution of the immune microenvironment and metabolic reprogramming (COIMMR) in herbal ingredients against human cancer and specifically screen herbal ingredients targeting the immune microenvironment and metabolic reprogramming. Finally, COIMMR was applied to identify isoliquiritigenin that specifically regulates the T cells in stomach adenocarcinoma and cephaelin hydrochloride that specifically targets metabolic reprogramming in low-grade glioma. The in silico results were further verified using in vitro experiments. Taken together, our approach opens new possibilities for repositioning drugs targeting immune and metabolic dysfunction in human cancer and provides new insights for drug development in other diseases. COIMMR is available at https://github.com/LYN2323/COIMMR.


Assuntos
Antineoplásicos , Neoplasias , Plantas Medicinais , Humanos , Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Linfócitos T , Medicina Herbária , Microambiente Tumoral
2.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36719094

RESUMO

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Perfilação da Expressão Gênica , Transcriptoma
3.
Med Res Rev ; 44(2): 812-832, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38009264

RESUMO

As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle "undruggable" targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.


Assuntos
Quimera de Direcionamento de Proteólise , Humanos , Cinética , Mutação
4.
J Cell Mol Med ; 28(3): e18058, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38098246

RESUMO

Ionizing radiation (IR)-induced intestinal injury is usually accompanied by high lethality. Intestinal stem cells (ISCs) are critical and responsible for the regeneration of the damaged intestine. Astragalus polysaccharide (APS), one of the main active ingredients of Astragalus membranaceus (AM), has a variety of biological functions. This study was aimed to investigate the potential effects of APS on IR-induced intestine injury via promoting the regeneration of ISCs. We have established models of IR-induced intestinal injury and our results showed that APS played great radioprotective effects on the intestine. APS improved the survival rate of irradiated mice, reversed the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts, the number of ISCs and the expression of intestinal tight junction-related proteins after IR. Moreover, APS promoted the cell viability while inhibited the apoptosis of MODE-K. Through organoid experiments, we found that APS promoted the regeneration of ISCs. Remarkably, the results of network pharmacology, RNA sequencing and RT-PCR assays showed that APS significantly upregulated the HIF-1 signalling pathway, and HIF-1 inhibitor destroyed the radioprotection of APS. Our findings suggested that APS promotes the regeneration of ISCs through HIF-1 signalling pathway, and it may be an effective radioprotective agent for IR-induced intestinal injury.


Assuntos
Astrágalo , Transdução de Sinais , Camundongos , Animais , Polissacarídeos/farmacologia , Intestinos , Células-Tronco
5.
Anal Chem ; 96(40): 15888-15897, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39311834

RESUMO

The identification of molecules within complex mixtures is a major bottleneck in natural products (NPs) research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as the main tool for the high-throughput characterization of NPs. The large amount of data sets by LC-MS/MS presents a challenge for data processing and interpretation, and the LC-MS/MS molecular network (MN) is one of the most prominent tools for analyzing large MS/MS data sets, widely used for rapid classification, identification, and structural speculation of unknown compounds. However, the existence of a large number of redundant nodes leads to false-positive results. To solve this problem, we proposed the in-depth analysis of MN. In this study, in-depth analysis of MN of five NPs representing the common structures of saponin, steroid, flavonoid, alkaloid, and phenolic acid revealed the presence of redundant nodes (including other adducts, isotope, and in-source fragmentation) in addition to the normal nodes, which can lead to false-positive identification results. Additionally, the reasons for different redundant nodes are discussed and experimentally verified, and it was found that the impact of redundant nodes can be mitigated by optimizing the experimental conditions and employing Feature-Based Molecular Networking. Furthermore, Ion Identity Molecular Networking can rapidly discover and screen redundant nodes, simplifying the in-depth analysis of MN and improving the network connectivity of structurally related molecules. Finally, a combination formulation of 7 NPs is used as an example to provide a guide for in-depth analysis of MN for comprehensive characterization of complex systems. This study highlights the importance of an in-depth analysis of MN for better understanding and utilization of MS/MS data in complex systems to reduce the false-positive rate of identification by screening and filtering redundant nodes.


Assuntos
Produtos Biológicos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Produtos Biológicos/química , Produtos Biológicos/análise , Cromatografia Líquida/métodos , Flavonoides/química , Flavonoides/análise , Alcaloides/análise , Alcaloides/química , Saponinas/química , Saponinas/análise
6.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35794722

RESUMO

Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.


Assuntos
Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Descoberta de Drogas/métodos , Retroalimentação
7.
Chemistry ; : e202402607, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215487

RESUMO

Functional group interconversion is of great significance in organic synthesis. However, aerobic cleavage of C=N bonds to access carbonyl compounds still suffered from some limitations such as harsh reaction conditions, stoichiometric oxidants, poor substrate scope and use of toxic reagents. Herein, we report a catalyst-free and photo-induced aerobic cleavage of C=N bonds to afford diverse carbonyl compounds using oxygen from air as green oxidant. This mild methodology permits N-tosylhydrazones converted into the corresponding carbonyl compounds including ketones, aldehydes and carboxylic acids, showing broad functional group tolerance and compatibility. Moreover, the gram-scale reaction and post-modification of complicated molecules proved the applicability and efficiency of this strategy. Finally, a plausible mechanism was proposed based on spectroscopic investigations and detailed mechanistic studies.

8.
J Org Chem ; 89(9): 6180-6192, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38632865

RESUMO

The photochemistry of noncovalent interactions to promote organic transformations is an emerging approach to providing fresh opportunities in synthetic chemistry. Generally, the external substance is necessary to add as an interaction partner, thereby sacrificing the atom economy of the reaction. Herein, we describe a catalyst-free and noncovalent interaction-mediated strategy to access the olefination of N-tosylhydrazones using acetone as a solvent and an interaction partner. This protocol also features broad substrate scope, excellent functional group compatibility, and mild reaction conditions without transition metals. Moreover, the gram-scale synthesis of olefins and the generation of pharmaceutical intermediates highlighted its practical applicability. Lastly, mechanistic studies indicate that the reaction was initiated via noncovalent interactions between acetone and N-tosylhydrazone anion, which is also supported by density functional theory calculations.

9.
Macromol Rapid Commun ; 45(15): e2400162, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38719215

RESUMO

Light irradiation is an external stimulus, rapidly developed in switchable atom transfer radical polymerization (ATRP) via photo-activation methods in recent years. Herein, a photo-deactivation strategy is introduced to regulate ATRP with the assistance of photoswitchable hexaarylbiimidozole (HABI). Under visible light irradiation and in the presence of HABI, ATRP is greatly decelerated or quenched depending on the concentration of HABI. Interestingly, with visible light off, ATRP can proceed smoothly and follow a first-order kinetics. Moreover, photo-switchable ATRP alternatively with light off and on is demonstrated. Besides, the mechanism of photo-deactivation ATRP involving radical quenching is proposed in the presence of HABI.


Assuntos
Luz , Processos Fotoquímicos , Polimerização , Estrutura Molecular , Cinética , Polímeros/química , Radicais Livres/química
10.
Macromol Rapid Commun ; 45(18): e2400206, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39101672

RESUMO

In recent years, the fully oxygen-tolerant reversible deactivation radical polymerization (RDRP) has become a highly researched area. In this contribution, a new and minimalist method is successfully employed to accomplish fully oxygen-tolerant reversible addition-fragmentation chain transfer (RAFT) polymerization using bis(trithiocarbonate) disulfides (BisTTC) as an iniferter agent, where the released sulfur-centered trithiocarbonate (TTC) radical can initiate monomer. Furthermore, polymerization kinetics revealed the typical "living" features of this polymerization system. More importantly, by high-throughput screening, it is found that dodecyl-substituted TTC is responsible for the fully oxygen-tolerant RAFT polymerization though trithiocarbonate radical initiation and R radical deoxygenation. It is believed that trithiocarbonate radical initiation strategy provides a powerful and minimalist tool for fully oxygen-tolerant RDRPs.


Assuntos
Oxigênio , Polimerização , Oxigênio/química , Radicais Livres/química , Enxofre/química , Cinética , Estrutura Molecular , Polímeros/química , Dissulfetos/química , Tionas
11.
J Nanobiotechnology ; 22(1): 227, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711078

RESUMO

BACKGROUND: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. RESULTS: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. CONCLUSIONS: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.


Assuntos
Chlorella , Portadores de Fármacos , Fotossíntese , Animais , Camundongos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Terapia Combinada , Fotoquimioterapia/métodos , Neoplasias/terapia , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Feminino
12.
Clin Exp Pharmacol Physiol ; 51(7): e13873, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815994

RESUMO

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.


Assuntos
Eritromicina , Glicogênio , Fadiga Muscular , Músculo Esquelético , Orosomucoide , Resistência Física , Animais , Eritromicina/farmacologia , Eritromicina/análogos & derivados , Camundongos , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Glicogênio/metabolismo , Orosomucoide/metabolismo , Resistência Física/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
13.
J Biopharm Stat ; 34(5): 737-752, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38812413

RESUMO

The failure rates of phase 3 trials are high. Incorrect sample size due to uncertainty of effect size could be a critical contributing factor. Adaptive sequential design (ASD), which may include one or more sample size re-estimations (SSR), has been a popular approach for dealing with such uncertainties. The operating characteristics (OCs) of ASD, including the unconditional power and mean sample size, can be substantially affected by many factors, including the planned sample size, the interim analysis schedule and choice of critical boundaries and rules for interim analysis. We propose a systematic, comprehensive strategy which uses iterative simulations to investigate the operating characteristics of adaptive designs and help achieve adequate unconditional power and cost-effective mean sample size if the effect size is in a pre-identified range.


Assuntos
Simulação por Computador , Projetos de Pesquisa , Humanos , Tamanho da Amostra , Projetos de Pesquisa/estatística & dados numéricos , Modelos Estatísticos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/métodos , Interpretação Estatística de Dados
14.
J Biopharm Stat ; : 1-15, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619921

RESUMO

Single-arm phase II trials are very common in oncology. A fixed sample trial may lack sufficient power if the true efficacy is less than the assumed one. Adaptive designs have been proposed in the literature. We propose a Simon's design based, adaptive sequential design. Simon's design is the most used fixed sample design for single-arm phase II oncology trials. A prominent feature of Simon's design is that it minimizes the sample size when there is no clinically meaningful efficacy. We identify Simon's trial as a special group sequential design. Established methods for sample size re-estimation (SSR) can be readily applied to Simon's design. Simulations show that simply adding SSR to Simon's design may still not provide desirable power. We propose some expansions to Simon's design. The expanded design with SSR can provide even more power.

15.
Eur Arch Otorhinolaryngol ; 281(5): 2327-2332, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38057488

RESUMO

OBJECTIVE: We compared the signal intensity ratio (SIR) of the cochlear basal turn between Meniere's disease and healthy controls to investigate potential damage of the blood-labyrinth barrier in Meniere's disease. METHODS: Thirty patients diagnosed with unilateral definite Meniere's disease and 24 healthy controls were enrolled. 3D-FLAIR scan was conducted to assess the grades of endolymphatic hydrops in Meniere's patients while measuring the SIR of cochlear basal turns in both groups. The differences of bilateral SIR between Meniere's disease and healthy control were compared, and the correlation between the SIR on affected ear in Meniere's disease and the grades of cochlear and vestibular hydrops were analyzed. RESULTS: SIR of affected ear in Meniere's disease exhibited significant increase compared to that of unaffected ear. No significant difference was observed in SIR between the two ears in the healthy control. Furthermore, the SIR of unaffected side in Meniere's disease was higher than that of both ears in healthy controls. The SIR in affected ear of Meniere's disease exhibited positive correlation with hydrops in both cochlea and vestibula. CONCLUSION: The permeability of blood-labyrinth barrier is increased in Meniere's disease, in combination with the typical criteria of Meniere's disease it may be a good biological marker. Destruction of blood-labyrinth barrier may be one of the causes of endolymphatic hydrops in Meniere's disease.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Vestíbulo do Labirinto , Humanos , Doença de Meniere/complicações , Doença de Meniere/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hidropisia Endolinfática/diagnóstico por imagem , Vestíbulo do Labirinto/diagnóstico por imagem , Edema
16.
Ren Fail ; 46(1): 2301041, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38425055

RESUMO

INTRODUCTION: Hypertension and rising serum uric acid (sUA) played a pivotal role in the development of Chronic Kidney Disease (CKD). This study investigates the interactive effect of sUA and hypertension on CKD and identifies the optimal threshold of sUA among individuals with and without hypertension in the Chinese community population. MATERIALS AND METHODS: The study included 4180 individuals aged 45-85 years, derived from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015. Additionally, a hospital-based study enrolled subjects in the Department of Nephrology at Zhongshan Hospital, China from January 1, 2019, to December 31, 2021. The interaction effect analysis were used to assess the impact of sUA and hypertension on CKD. We also compared the distribution of sUA and the CKD risk in community populations, distinguishing between those with and without hypertension. For the hospital-based population, kidney injury was marked by a KIM-1 positive area. RESULTS: Our results indicate a higher prevalence of CKD in the community population with hypertension (10.2% vs. 3.9%, p < .001). A significant additive synergistic effects of the sUA and hypertension on the CKD risk were found. When the sUA level was < 4.55 mg/dL in the hypertensive population and < 5.58 mg/dL in the non-hypertensive population, the risk of CKD was comparable (p = .809). In the propensity score matched (PSM) population, the result remained roughly constant. CONCLUSION: Therefore, even moderate levels of sUA was associated with a higher risk of CKD in middle-aged hypertensive patients, who warrant stricter sUA control.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Pessoa de Meia-Idade , Humanos , Ácido Úrico , Estudos Longitudinais , Fatores de Risco , Estudos Transversais , Hipertensão/complicações
17.
J Sci Food Agric ; 104(7): 3992-4003, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323719

RESUMO

BACKGROUND: Resveratrol (Res) is promising food functional factor with favorable antioxidant and anti-inflammatory properties, although its poor water solubility and low bioavailability limit extensive application. Therefore, in combination with another promising polysaccharide (Mesona chinensis polysaccharides, MCP), Res-loaded food nanocarriers (ResNPs) were developed to increase its water solubility, bioactivity and targeting properties. ResNPs were then applied to alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis. RESULTS: Resveratrol can be well encapsulated in MCP-based nanoparticles in an amorphous state, improving its water solubility. ResNPs showed pH-response controlled release behavior in the gastrointestinal tract and increased the enrichment of Res in the colon. In vivo experiments of ResNPs against DSS-induced ulcerative colitis (UC) revealed that ResNPs significantly improved UC symptoms, modulated intestinal inflammation and down-regulated oxidative stress levels compared to free Res. ResNPs also play an positive role with respect to inhibiting the mitogen-activated protein kinase pathway and promoting the expression of tight junction proteins. In addition, ResNPs improved the species composition and relative abundance of intestinal flora in UC mice, which effectively regulated the balance of intestinal flora and promoted the production of short-chain fatty acids. CONCLUSION: These results suggest that MCP-based nanoparticles can effectively improve the solubility of resveratrol and enhance its in vivo bioactivity. Moreover, the present study also provides a new strategy for the prevention and treatment of UC with food polyphenol. © 2024 Society of Chemical Industry.


Assuntos
Colite Ulcerativa , Colite , Nanopartículas , Zeína , Camundongos , Animais , Resveratrol/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Nanopartículas/química , Concentração de Íons de Hidrogênio , Água/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo
18.
Clin Otolaryngol ; 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39428356

RESUMO

OBJECTIVE: The aim of this investigation was to explore the potential correlation between the signal intensity ratio (SIR) at the internal auditory canal (IAC) fundus and hearing impairment in Meniere's disease (MD), thereby providing a foundation to further understand the mechanisms underlying hearing loss. DESIGN: Fifty patients diagnosed with unilateral definite MD were enrolled in the study. 3D-FLAIR MRI was conducted 4 h after intravenous administration of gadobutrol to determine the SIR of the bilateral IAC fundus. The difference in the SIR of the IAC fundus between the affected and unaffected sides was assessed, followed by an analysis of its correlation with low-, middle-, and high-tone hearing thresholds. Correlation analysis was also conducted between the degree of endolymphatic hydrops (EH) in the vestibule and cochlea and the SIR on the affected side. RESULTS: The degree of EH in MD can be clearly visualised using 3D-FLAIR MRI. The SIR on the affected side was significantly higher than that on the unaffected side (p = 0.000). Furthermore, a positive correlation was observed between the SIR at the affected and low (r = 0.692, p = 0.000), middle (r = 0.615, p = 0.000) and high-tone (r = 0.440, p = 0.001) hearing thresholds, while the SIR showed no significant correlation with cochlear (r = 0.315, p = 0.088) or vestibular hydrops (r = 0.215, p = 0.244). CONCLUSION: The IAC fundus barrier may be damaged in patients with MD, representing one of the factors affecting the level of hearing.

19.
Zhonghua Nan Ke Xue ; 30(6): 514-518, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-39212360

RESUMO

OBJECTIVE: To compare thulium laser enucleation of the prostate (ThuLEP) with plasma kinetic resection of the prostate (PKRP) in the treatment of BPH. METHODS: We retrospectively analyzed the medical records of 160 cases of BPH treated by ThuLEP (the observation group, n = 80) or PKRP (the control group, n = 80) in our hospital from January 2021 to December 2023. We recorded the operation time, bladder irrigation time, catheter retention time, hospitalization time, postoperative complications, and pre- and postoperative maximum urinary flow rate (Qmax), residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume, followed by comparison of the data obtained between the two groups of patients. RESULTS: Compared with the controls, the patients of the observation group showed significantly shorter operation time (ï¼»67.25 ± 7.24ï¼½ vs ï¼»60.10 ± 5.15ï¼½ min, P< 0.05), bladder irrigation time (ï¼»46.90 ± 10.77ï¼½ vs ï¼»43.24 ± 6.65ï¼½ h, P< 0.05), catheterization time (ï¼»5.60 ± 1.31ï¼½ vs ï¼»5.03 ± 1.24ï¼½ d, P< 0.05) and hospitalization time (ï¼»7.31 ± 2.00ï¼½ vs ï¼»6.55 ± 1.67ï¼½ d, P< 0.05), higher Qmax (ï¼»18.50 ± 1.24ï¼½ vs ï¼»20.68 ± 1.45ï¼½ ml/s, P< 0.05), lower PVR (ï¼»12.10 ± 3.53ï¼½ vs ï¼»10.82 ± 3.10ï¼½ ml, P< 0.05), PSA (ï¼»4.60 ± 0.78ï¼½ vs ï¼»3.38 ± 0.40ï¼½ µg/L, P< 0.05) and prostate volume (ï¼»25.35 ± 6.46ï¼½ vs ï¼»20.12 ± 5.13ï¼½ ml, P< 0.05) at 3 months after surgery, but no statistically significant difference in the total incidence of postoperative complications (7.50% ï¼»6/80ï¼½ vs 5.00% ï¼»4/80ï¼½, P > 0.05). CONCLUSION: ThuLEP, with its advantages of notable effect, short operation and hospitalization time, significant improvement of urinary flow dynamics and prostate function, deserves clinical promotion for the treatment of BPH.


Assuntos
Terapia a Laser , Hiperplasia Prostática , Túlio , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Estudos Retrospectivos , Terapia a Laser/métodos , Próstata/cirurgia , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento , Complicações Pós-Operatórias , Duração da Cirurgia , Idoso , Antígeno Prostático Específico/sangue
20.
J Am Chem Soc ; 145(1): 322-333, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36542493

RESUMO

Alternative antibacterial therapies refractory to existing mechanisms of antibiotic resistance are urgently needed. One such attractive therapy is to inhibit bacterial adhesion and colonization. Ser O-heptosylation (Ser O-Hep) on autotransporters of Gram-negative bacteria is a novel glycosylation and has been proven to be essential for bacterial colonization. Herein, we chemically synthesized glycopeptides containing this atypical glycan structure and an absolute C6 configuration through the assembly of Ser O-Hep building blocks. Using glycopeptides as haptens, we generated first-in-class poly- and monoclonal antibodies, termed Anti-SerHep1a and Anti-SerHep1b, that stereoselectively recognize Ser O-heptosylation (d/l-glycero) with high specificity in vitro and in vivo. Importantly, these antibodies effectively blocked diffusely adhering Escherichia coli 2787 adhesion to HeLa cells and in mice in a dose- and Ser O-Hep-dependent manner. Together, these antibodies represent not only useful tools for the discovery of unknown serine O-heptosylated proteins bearing various C6 chiral centers but also a novel class of antiadhesion therapeutic agents for the treatment of bacterial infection.


Assuntos
Anticorpos Monoclonais , Polissacarídeos , Humanos , Animais , Camundongos , Células HeLa , Glicosilação , Polissacarídeos/química , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Escherichia coli , Glicopeptídeos/química
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