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1.
BMC Musculoskelet Disord ; 25(1): 290, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622692

RESUMO

BACKGROUND: The proximal femoral nail anti-rotation (PFNA) with cement enhancement enhances the anchorage ability of internal fixation in elderly with osteoporotic intertrochanteric fracture. However, whether it is superior to hemiarthroplasty is still controversial. The present study aimed to determine which treatment has better clinical outcomes among older patients. METHODS: We retrospectively analyzed 102 elderly patients with osteoporosis who developed intertrochanteric fractures and underwent PFNA combined with cement-enhanced internal fixation (n = 52, CE group), and hemiarthroplasty (n = 50, HA group) from September 2012 to October 2018. All the intertrochanteric fractures were classified according to the AO/OTA classification. Additionally, the operative time, intraoperative blood loss, intraoperative and postoperative blood transfusion rates, postoperative weight-bearing time, hospitalization time, Barthel Index of Activities Daily Living, Harris score of hip function, visual analog (VAS) pain score, and postoperative complications were compared between the two groups. RESULTS: The CE group had significantly shorter operative time, lesser intraoperative blood loss, lower blood transfusion rate, and longer postoperative weight-bearing time than the HA group. The CE group had lower Barthel's Index of Activities of Daily Living, lower Harris' score, and higher VAS scores in the first and third months after surgery than the HA group, but no difference was observed between the two groups from 6 months to 12 months. There was no significant difference in the total post-operative complications between the two groups. CONCLUSION: The use of PFNA combined with a cement-enhanced internal fixation technique led to shorter operative time and lesser intraoperative blood loss and trauma in elderly patients as compared to HA.


Assuntos
Fixação Intramedular de Fraturas , Hemiartroplastia , Fraturas do Quadril , Humanos , Idoso , Estudos Retrospectivos , Pinos Ortopédicos , Hemiartroplastia/efeitos adversos , Hemiartroplastia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Atividades Cotidianas , Resultado do Tratamento , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Cimentos Ósseos/uso terapêutico , Complicações Pós-Operatórias/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos
2.
J Am Chem Soc ; 146(15): 10767-10775, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38591723

RESUMO

Atomically precise superatomic copper nanoclusters (Cu NCs) have been the subject of immense interest for their intriguing structures and diverse properties; nonetheless, the variable oxidation state of copper ions and complex solvation effects in wet synthesis systems pose significant challenges for comprehending their synthesis and crystallization mechanism. Herein, we present a solvent-mediated approach for the synthesis of two Cu NCs, namely, superatomic Cu26 and pure-Cu(I) Cu16. They initially formed as a hetero-phase and then separated as a homo-phase via modulating binary solvent composition. In situ UV/vis absorption and electrospray ionization mass spectra revealed that the solvent-mediated assembly was determined to be the underlying mechanism of hetero/homo-phase crystallization. Cu26 is a 2-electron superatom with a kernel-shell structure that includes a [Cu20Se12]4- shell and [Cu6]4+ kernel, containing two 1S jellium electrons. Conversely, Cu16 is a pure-Cu(I) Cu/Se nanocluster that features a [Cu16Se6]4+ core protected by extra dimercaptomaleonitrile ligands. Remarkably, Cu26 exhibits unique near-infrared phosphorescence (NIR PH) at 933 nm due to the presence of a superatomic kernel-related charge transfer state (3MM(Cu)CT). Overall, this work not only showcases the hetero/homo-phase crystallization of Cu NCs driven by a solvent-mediated assembly mechanism but also enables the rare occurrence of NIR PH within the 2-electron copper superatom family.

3.
Angew Chem Int Ed Engl ; : e202403464, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581155

RESUMO

Herein, two atomically precise silver nanoclusters, Ag54 and Ag33, directed by inner anion templates (CrO42- and/or Cl-), are initially isolated as a mixed phase from identical reactants across a wide temperature range (20-80 °C). Interestingly, fine-tuning the reaction temperature can realize pure phase synthesis of the two nanoclusters; that is, a metastable Ag54 is kinetically formed at a low temperature (20 °C), whereas such a system is steered towards a thermodynamically stable Ag33 at a relatively high temperature (80 °C). Electrospray ionization mass spectrometry illustrates that the stability of Ag33 is superior to that of Ag54, which is further supported by density functional theory calculations. Importantly, the difference in structural stability can influence the pathway of 1,4-bis(pyrid-4-yl)benzene induced transformation reaction starting from Ag54 and Ag33. The former undergoes a dramatic breakage-reorganization process to form an Ag31 dimer (Ag31), while the same product can be also achieved from the latter following a noninvasive ligand exchange process. Both the Ag54 and Ag33 have the potential for further remote laser ignition applications. This work not only demonstrates how temperature controls the isolation of a specific phase, but also sheds light on the structural transformation pathway of nanoclusters with different stability.

4.
Ann Surg ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557792

RESUMO

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

5.
Sci Rep ; 14(1): 9461, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658587

RESUMO

Average windward area is an important index for calculating the trajectory, velocity attenuation and terminal effect of explosive fragments. In order to solve the problems that existing theoretical method cannot calculate windward area of irregular fragment and experiment method is not convenient for automatic calculation and has low accuracy, a Monte Carlo subdivision projection simulation algorithm is proposed. The average windward area of arbitrary shaped fragments can be obtained with coordinate translation, random rotation, plane projection, convex-hull triangulation, concave boundary searching and sorting with maximum edge length constraint, subdivision area calculation, and averaging by thousands of cycles. Results show that projection area obtained by the subdivision projection algorithm is basically the same as that obtained by software method of computer aided design. Moreover, the maximum calculation error of the algorithm is less than 7%, and its accuracy is much higher than that of the equivalent ellipsoid method. The average windward area calculated by the Monte Carlo subdivision projection simulation algorithm is consistent with theoretical formula for prefabricated fragments, and the error is less than 3%. The convergence and accuracy of the Monte Carlo subdivision projection algorithm are better than those of the icosahedral uniform orientation method.

6.
Oncol Rep ; 51(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38606513

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Currently, the predominant clinical treatment is the combination of surgical resection with concurrent radiotherapy and chemotherapy, using temozolomide (TMZ) as the primary chemotherapy drug. Lidocaine, a widely used amide­based local anesthetic, has been found to have a significant anticancer effect. It has been reported that aberrant hepatocyte growth factor (HGF)/mesenchymal­epithelial transition factor (MET) signaling plays a role in the progression of brain tumors. However, it remains unclear whether lidocaine can regulate the MET pathway in GBM. In the present study, the clinical importance of the HGF/MET pathway was analyzed using bioinformatics. By establishing TMZ­resistant cell lines, the impact of combined treatment with lidocaine and TMZ was investigated. Additionally, the effects of lidocaine on cellular function were also examined and confirmed using knockdown techniques. The current findings revealed that the HGF/MET pathway played a key role in brain cancer, and its activation in GBM was associated with increased malignancy and poorer patient outcomes. Elevated HGF levels and activation of its receptor were found to be associated with TMZ resistance in GBM cells. Lidocaine effectively suppressed the HGF/MET pathway, thereby restoring TMZ sensitivity in TMZ­resistant cells. Furthermore, lidocaine also inhibited cell migration. Overall, these results indicated that inhibiting the HGF/MET pathway using lidocaine can enhance the sensitivity of GBM cells to TMZ and reduce cell migration, providing a potential basis for developing novel therapeutic strategies for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Transdução de Sinais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Movimento Celular , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos Alquilantes/farmacologia
7.
Front Cell Infect Microbiol ; 14: 1322119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638825

RESUMO

Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.


Assuntos
Cistite , Infecções por Escherichia coli , Doenças do Sistema Imunitário , Infecções Urinárias , Escherichia coli Uropatogênica , Feminino , Camundongos , Animais , Bexiga Urinária/microbiologia , NF-kappa B , Levofloxacino/farmacologia , Galectina 3 , Interleucina-6 , Receptor 4 Toll-Like , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia
8.
J Asian Nat Prod Res ; : 1-10, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594843

RESUMO

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

9.
Hepatobiliary Surg Nutr ; 13(2): 198-213, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617471

RESUMO

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

10.
J Am Chem Soc ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622809

RESUMO

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

11.
Biomed Environ Sci ; 37(3): 233-241, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582988

RESUMO

Objective: Hypertriglyceridemic waist (HW), hypertriglyceridemic waist-to-height ratio (HWHtR), and waist-to-hip ratio (WHR) have been shown to be indicators of cardiometabolic risk factors. However, it is not clear which indicator is more suitable for children and adolescents. We aimed to investigate the relationship between HW, HWHtR, WHR, and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods: This was a national cross-sectional study. Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China. Demographics, physical activity, dietary intake, and family history of chronic diseases were obtained through questionnaires. ANOVA, χ 2 and logistic regression analysis was conducted. Results: A significant sex difference was observed for HWHtR and WHR, but not for HW phenotype. The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents (HW: OR = 12.22, 95% CI: 9.54-15.67; HWHtR: OR = 9.70, 95% CI: 6.93-13.58). Compared with the HW and HWHtR phenotypes, the association between risk of cardiometabolic health risk factors (CHRF) clustering and high WHR was much weaker and not significant (WHR: OR = 1.14, 95% CI: 0.97-1.34). Conclusion: Compared with HWHtR and WHR, the HW phenotype is a more convenient indicator withhigher applicability to screen children and adolescents for cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares , Cintura Hipertrigliceridêmica , Criança , Humanos , Masculino , Feminino , Adolescente , Cintura Hipertrigliceridêmica/complicações , Cintura Hipertrigliceridêmica/epidemiologia , Relação Cintura-Quadril , Fatores de Risco Cardiometabólico , Fatores de Risco , Estudos Transversais , Análise por Conglomerados , Razão Cintura-Estatura , China/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Circunferência da Cintura , Índice de Massa Corporal
12.
Shanghai Kou Qiang Yi Xue ; 33(1): 90-96, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583032

RESUMO

PURPOSE: To observe the long-term clinical effect of implants retained complete overdentures with Locator attachments. METHODS: A total of 48 patients with edentulous jaws treated with implants retained complete overdentures with Locator attachments were selected from the Outpatient Department of Peking University School and Hospital of Stomatology from 2016 to 2017. Among them, 21 patients underwent double-maxillary complete overdentures restoration and 27 patients underwent single-maxillary restoration. A total of 230 implants were implanted. The clinical observation indicators included the implant survival rate, peri-implant mucosal bleeding on probing(BOP), the change in the vertical height of alveolar bone absorption around the implants, overdenture base fracture rate, artificial tooth fall off and fracture rate and other complications. The change of the locator attachment retention force of the implant-supported overdentures was evaluated. SPSS 13.0 software package was used for data analysis. RESULTS: During the five-years clinical observation period, 5 implants fell off, 1 narrow dimeter implant in the anterior zone was broken, and 12 implants were lost to follow-up. The implant survival rate was 97.25%. One year after the restoration therapy finished, peri-implant mucosal bleeding on probing (BOP+) was detected in 48 (21.4%) implants. The average BI was 0.21±0.42, which was higher in the anterior zone than that in the posterior zone. The vertical alveolar bone absorption height around the implants was (0.21±0.35) mm, 2 implants-supported complete overdenture bases were broken. After 5 years of restoration, 163(76.89%) implants had peri-implant mucosal bleeding on probing(BOP+). The average BI was 1.00±0.70, and the vertical alveolar bone absorption height around the implants was (0.58±0.85) mm. There was no significant difference between males and females. There was no significant difference in the peri-implant mucosal bleeding index and the alveolar bone vertical absorption height between the anterior zone and the posterior zone(P>0.05). The mean BI of peri-implant mucosa and the vertical absorption height of peri-implant alveolar bone were significantly different between the 1-year observation period and the 5-year observation period respectively(P<0.01). There were 17(26.15%) cases with overdenture bases fracture, and the fracture rate of artificial teeth was 16.92%. Most of them occurred in the midline area of the anterior zone and the location of the overdenture base on the locator attachments. The average first replacement time of the locator attachment nylon retainer washer was 34.2±10.3 months. CONCLUSIONS: Implants retained complete overdentures with Locator attachments are effective in long term clinical observation. Complications are mainly found in peri-implant mucosal bleeding on probing and vertical alveolar bone absorption, and tended to increase gradually over time. The fracture of the implant retains complete overdenture bases and the fall off or fracture of the artificial teeth are the second serious complications. Overdenture base with metal frame at the location of the Locator abutment and the midline of the anterior area should be strengthened, and narrow diameter implants should be avoided as far as possible in the anterior zone.


Assuntos
Implantes Dentários , Arcada Edêntula , Masculino , Feminino , Humanos , Revestimento de Dentadura , Prótese Dentária Fixada por Implante/efeitos adversos , Retenção de Dentadura , Mandíbula/cirurgia , Implantes Dentários/efeitos adversos
13.
J Cell Biol ; 223(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38558238

RESUMO

Plants often adapt to adverse or stress conditions via differential growth. The trans-Golgi network (TGN) has been implicated in stress responses, but it is not clear in what capacity it mediates adaptive growth decisions. In this study, we assess the role of the TGN in stress responses by exploring the previously identified interactome of the Transport Protein Particle II (TRAPPII) complex required for TGN structure and function. We identified physical and genetic interactions between AtTRAPPII and shaggy-like kinases (GSK3/AtSKs) and provided in vitro and in vivo evidence that the TRAPPII phosphostatus mediates adaptive responses to abiotic cues. AtSKs are multifunctional kinases that integrate a broad range of signals. Similarly, the AtTRAPPII interactome is vast and considerably enriched in signaling components. An AtSK-TRAPPII interaction would integrate all levels of cellular organization and instruct the TGN, a central and highly discriminate cellular hub, as to how to mobilize and allocate resources to optimize growth and survival under limiting or adverse conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Fosforilação , Transporte Proteico , Rede trans-Golgi/metabolismo , Proteínas de Transporte/metabolismo
14.
J Ethnopharmacol ; : 118223, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642624

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique,molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

15.
Exp Ther Med ; 27(4): 169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476917

RESUMO

As the global population ages, the prevalence of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease and stroke continues to increase. Therefore, it is necessary to develop preventive and therapeutic methods against neuroinflammatory diseases. Lipofundin is a lipid emulsion commonly used in clinical anesthetic solvents and nutritional supplements. Lipid emulsions have been shown to possess anti-inflammatory properties. However, the potential beneficial effect of lipofundin against neuroinflammation requires elucidation. In the present study, two cell models were used to investigate the efficacy of lipofundin against neuroinflammation. In the first model, BV2 mouse microglial cells were treated with lipopolysaccharide (LPS) to induce nitric oxide (NO) production as a model of neuroinflammation. In the second model, HMC3 human microglial were activated by LPS, and changes in the secretion of factors associated with inflammation were analyzed using Luminex xMAP® technology. Griess assay results revealed that lipofundin significantly prevented and treated LPS-induced NO production. An anti-neuroinflammatory effect was also observed in HMC3 cells, where lipofundin exhibited excellent preventive and therapeutic properties by reducing the LPS-induced expression and secretion of interleukin-1ß. Notably, lipofundin also promoted the secretion of certain growth factors, suggesting a potential neuroprotective effect. These results demonstrate that, in addition to its role as a solvent for drugs and nutritional support, lipofundin may also have beneficial effects in alleviating the progression of neuroinflammation. These findings may serve as an important reference for future translational medicine applications.

17.
Oral Oncol ; 152: 106755, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38547780

RESUMO

OBJECT: Previous studies suggest BRAFV600E mutation is a marker for poor prognosis in papillary thyroid cancer, however, its ability to further risk stratify papillary thyroid microcarcinoma (PTMC) remains controversial. We aimed to explore the association between BRAFV600E mutation and the clinicopathological features and recurrence in Chinese PTMC patients. METHODS: We retrospectively reviewed 2094 PTMC patients who underwent surgery and had a valid BRAFV600E mutation test result. Among them, 1292 patients had complete follow-up data. The mutation incidence was determined. Moreover, the clinicopathological characteristics, disease-free survival (DFS), and response to therapy distribution were compared between the mutation and non-mutation groups. RESULTS: BRAFV600E mutation was observed in 90.6 % of all patients and 89.2 % of patients with complete follow-up data. No significant difference was observed in lymph node metastases (LNM) number categories between the mutation and non-mutation groups among all patients (P = 0.329) and 1292 patients (P = 0.408). Neither the 3-year DFS (97.9 % vs. 98.0 %, P = 0.832) nor the response to therapy distribution (P > 0.05) indicated a significant difference between the mutation and non-mutation groups. The 3-year DFS differs among patients having different LNM number categories (99.8 % vs. 98.5 % vs. 77.3 %, P < 0.001). Multivariate analysis revealed that high-volume (over 5) LNM (Total thyroidectomy (TT): OR = 4.000, 95 % CI 2.390-6.694, P < 0.001; Unilateral thyroidectomy (UT): OR = 4.183, 95 % CI 1.565-11.190, P = 0.004), rather than BRAFV600E mutation (P > 0.05), was an independent risk factor of response to therapy. CONCLUSIONS: Our results suggested that BRAFV600E mutation could not accurately predict LNM or the recurrence of Chinese PTMC patients. Moreover, high-volume LNM is significantly associated with PTMC prognosis.

18.
mSystems ; 9(4): e0020624, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38514462

RESUMO

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.


Assuntos
Colite , Helicobacter pylori , Animais , Humanos , Camundongos , Proteínas de Bactérias/genética , Antígenos de Bactérias/genética , Helicobacter pylori/genética , Transcriptoma/genética , Precursores de RNA/metabolismo , Interações Hospedeiro-Patógeno/genética , Análise de Sequência de RNA , RNA Mensageiro/metabolismo , Citotoxinas/metabolismo
19.
Exp Appl Acarol ; 92(3): 403-421, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38489086

RESUMO

Spider mites (Acari: Tetranychidae) are polyphagous pests of economic importance in agriculture, among which the two-spotted spider mite Tetranychus urticae Koch has spread widely worldwide as an invasive species, posing a serious threat to fruit tree production in China, including Beijing. The hawthorn spider mite, Amphitetranychus viennensis Zacher, is also a worldwide pest of fruit trees and woody ornamental plants. The cassava mite, Tetranychus truncatus Ehara, is mainly found in Asian countries, including China, Korea and Japan, and mainly affects fruit trees and agricultural crops. These three species of spider mites are widespread and serious fruit tree pests in Beijing. Rapid and accurate identification of spider mites is essential for effective pest and plant quarantine in Beijing orchard fields. The identification of spider mite species is difficult due to their limited morphological characteristics. Although the identification of insect and mite species based on PCR and real-time polymerase chain reaction TaqMan is becoming increasingly common, DNA extraction is difficult, expensive and time-consuming due to the minute size of spider mites. Therefore, the objective of this study was to establish a direct multiplex PCR method for the simultaneous identification of three common species of spider mites in orchards, A. viennensis, T. truncatus and T. urticae, to provide technical support for the differentiation of spider mite species and phytosanitary measures in orchards in Beijing. Based on the mitochondrial cytochrome c oxidase subunit I (COI) of the two-spotted spider mite and the cassava mite and the 18S gene sequence of the hawthorn spider mite as the amplification target, three pairs of specific primers were designed, and the primer concentrations were optimized to establish a direct multiplex PCR system for the rapid and accurate discrimination of the three spider mites without the need for DNA extraction and purification. The method showed a high sensitivity of 0.047 ng for T. truncatus and T. urticae DNA and 0.0002 ng for A. viennensis. This method eliminates the DNA extraction and sequencing procedures of spider mite samples, offers a possibility for rapid monitoring of multiple spider mites in an integrated microarray laboratory system, reducing the time and cost of leaf mite identification and quarantine monitoring in the field.


Assuntos
Reação em Cadeia da Polimerase Multiplex , Tetranychidae , Animais , Tetranychidae/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Pequim , Complexo IV da Cadeia de Transporte de Elétrons/genética
20.
J Ethnopharmacol ; 328: 118097, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38531432

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.


Assuntos
Cistanche , Glucosídeos , Glucosídeos Iridoides , Fenóis , Polifenóis , Animais , Quimiometria , Peixe-Zebra , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Constipação Intestinal
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