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1.
Phytomedicine ; 130: 155671, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38763005

RESUMO

BACKGROUND: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. PURPOSE: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. METHODS: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. RESULTS: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of ß-amyloid, reduced the content and abnormal accumulation of the toxic Aß1-42 protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. CONCLUSION: PRG promoted ß-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.

2.
Biomater Adv ; 161: 213888, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38759305

RESUMO

Short carbon fiber (SCF) reinforced polymer composites are expected to possess outstanding biotribological and mechanical properties in certain direction, while the non-oriented SCF weakens its reinforcing effect in the matrix. In this work, high-oriented SCF was achieved during nozzle extrusion, and then SCF reinforced polyether-ether-ketone (PEEK) composites were fabricated by fused deposition modeling (FDM). The concrete orientation process of SCF was theoretically simulated, and significant shear stress difference was generated at both ends of SCF. As a result, the SCF was distributed in the matrix in a hierarchical structure, containing surface layer I, II and core layer. Moreover, the SCF was oriented highly along the printing direction and demonstrated a more competitive orientation distribution compared to other studies. The SCF/PEEK composites showed a considerable improvement in wear resistance by 44 % due to self-lubricating and load-bearing capability of SCF. Besides, it demonstrated enhancements in Brinell hardness, compressive and impact strength by 48.52 %, 16.42 % and 53.64 %, respectively. In addition, SCF/PEEK composites also showed good cytocompatibility. The findings gained herein are useful for developing the high-oriented SCF reinforced polymer composites with superior biotribological and mechanical properties for artificial joints.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124351, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692109

RESUMO

Epidermal growth factor receptor (EGFR) plays a pivotal role in the initiation and progression of gliomas. In particular, in glioblastoma, EGFR amplification emerges as a catalyst for invasion, proliferation, and resistance to radiotherapy and chemotherapy. Current approaches are not capable of providing rapid diagnostic results of molecular pathology. In this study, we propose a terahertz spectroscopic approach for predicting the EGFR amplification status of gliomas for the first time. A machine learning model was constructed using the terahertz response of the measured glioma tissues, including the absorption coefficient, refractive index, and dielectric loss tangent. The novelty of our model is the integration of three classical base classifiers, i.e., support vector machine, random forest, and extreme gradient boosting. The ensemble learning method combines the advantages of various base classifiers, this model has more generalization ability. The effectiveness of the proposed method was validated by applying an individual test set. The optimal performance of the integrated algorithm was verified with an area under the curve (AUC) maximum of 85.8 %. This signifies a significant stride toward more effective and rapid diagnostic tools for guiding postoperative therapy in gliomas.


Assuntos
Receptores ErbB , Glioma , Espectroscopia Terahertz , Humanos , Glioma/genética , Glioma/patologia , Glioma/diagnóstico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Espectroscopia Terahertz/métodos , Aprendizado de Máquina , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Amplificação de Genes , Algoritmos , Máquina de Vetores de Suporte
4.
J Immunother Cancer ; 12(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749537

RESUMO

BACKGROUND: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC. METHODS: Cytosolic dsRNA level and its sensors were evaluated via cell-based assays (co-culture assay, confocal microscopy, pharmacological inhibition and immunofluorescent staining) and in vivo experiments. Biopsies and surgical tissues from patients with CRC who received preoperative chemoradiotherapy (neoCRT) were collected for multiplex cytokine assays, immunohistochemical analysis and SNP genotyping. We also generated a cancer-specific adenovirus-associated virus (AAV)-IFNß1 construct to evaluate its therapeutic efficacy in combination with RT, and the immune profiles were analyzed by flow cytometry and RNA-seq. RESULTS: Our studies revealed that RT stimulates the autonomous release of dsRNA from cancer cells to activate TLR3-mediated IFN-I signatures to facilitate antitumor immune responses. Patients harboring a dysfunctional TLR3 variant had reduced serum levels of IFN-I-related cytokines and intratumoral CD8+ immune cells and shorter disease-free survival following neoCRT treatment. The engineered cancer-targeted construct AAV-IFNß1 significantly improved the response to RT, leading to systematic eradication of distant tumors and prolonged survival in defective TLR3 preclinical models. CONCLUSION: Our results support that increasing cancer-intrinsic IFNß1 expression is an immunotherapeutic strategy that enhances the RT-induced antitumor immune response in locally patients with advanced CRC with dysfunctional TLR3.


Assuntos
Neoplasias Colorretais , Interferon Tipo I , Interferon beta , RNA de Cadeia Dupla , Humanos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/imunologia , Interferon beta/metabolismo , Camundongos , Animais , Interferon Tipo I/metabolismo , Transdução de Sinais , Feminino , Masculino
5.
Med Phys ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801337

RESUMO

BACKGROUND: Accurate and noninvasive assessment of split renal dysfunction is crucial, while there is lack of corresponding method clinically. PURPOSE: To investigate the feasibility of using diffusion-weighted imaging (DWI)-based radiomics models to evaluate split renal dysfunction. METHODS: We enrolled patients with impaired and normal renal function undergoing renal DWI examination. Glomerular filtration rate (GFR, mL/min) was measured using 99mTc-DTPA scintigraphy, which is reference standard of GFR measurement. The kidneys were classified into normal (GFR ≥40), mildly impaired (20≤ GFR < 40), moderately impaired (10≤ GFR < 20), and severely impaired (GFR < 10) renal function groups. Optimized subsets of radiomics features were selected from renal DWI images and radiomics scores (Rad-score) calculated to discriminate groups with different renal function. The radiomics model (Rad-score based) was developed in a training cohort and validated in a test cohort. Evaluations were conducted on the discrimination, calibration, and clinical application of the method. RESULTS: The final analysis included 330 kidneys. Logistic regression was used to develop three radiomics models, model A, B, and C, which were used to distinguish normal from impaired, mild from moderate, and moderate from severe renal function, respectively. The area under the curve of the three models were 0.822, 0.704, and 0.887 in the training cohort and 0.843, 0.717, and 0.897 in the test cohort, respectively, indicating efficient discrimination performance. CONCLUSIONS: DWI-based radiomics models have potential for evaluating split renal dysfunction and discriminating between normal and impaired renal function groups and their subgroups.

6.
Sleep Med ; 119: 379-388, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38761607

RESUMO

BACKGROUND: Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture. METHODS: PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks). RESULTS: Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS. CONCLUSIONS: This meta-analysis demonstrated that DAs significantly affect sleep parameters.

7.
Nano Lett ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775216

RESUMO

Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.

8.
Heliyon ; 10(9): e30131, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707430

RESUMO

Utilizing city-level data from China, the paper employs a spatial econometric analysis to investigate the impact of fiscal decentralization on urban pollution. Empirical evidence indicates: (1) In the context of the emphasis of ecological civilization construction in China, an increase of fiscal autonomy for local governments is conducive to mitigating urban pollution intensity. Specifically, fiscal decentralization in one city not only promotes a reduction in local pollution intensity but alleviates environmental pollution problems in adjacent cities through spatial spillover effects. (2) Industrial structure upgrading and green technology progress become crucial measures for local governments to realize pollution reduction targets through fiscal expenditure. (3) Heterogeneity analysis reveals that the positive significance of decentralization is most prominent in the eastern China, while local governments with fiscal autonomy in central region tend to transfer pollution to neighboring cities. (4) There is a threshold characteristic for fiscal decentralization to promote a reduction in urban pollution intensity, and its marginal effect becomes more significant accompanied by continuous introduction of sophisticated foreign direct investment. Finally, the paper summarizes the potential significance of fiscal decentralization among Chinese local governments against the background of "Chinese-style decentralization" and proposes corresponding policy recommendations.

9.
Int J Med Robot ; 20(3): e2635, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733580

RESUMO

BACKGROUND: Rotational alignment in total knee arthroplasty (TKA) is a crucial technical point that needs attention. We conducted a retrospective study to investigate whether a new robot-assisted TKA (RA-TKA) could improve the accuracy of rotational alignment and whether rotational alignment affects postoperative pain and functional evaluation of the knee. METHODS: A total of 136 consecutive patients who underwent TKA were included in this study. Half of the patients underwent RA-TKA and the other half underwent conventional TKA (CON-TKA) by the same group of surgeons. Collect the relevant parameters. RESULTS: The postoperative femoral rotation angle (FRA) was -0.72 ± 2.59° in the robot-assisted group and 1.13 ± 2.73° in the conventional group, and were statistically significantly different (p < 0.001). CONCLUSION: This study provides preliminary evidence that the RA-TKA provides more precise control of FRA than CON-TKA, and verifies that tibial rotation angle and combined rotation angle affect postoperative knee pain and functional evaluation.


Assuntos
Artroplastia do Joelho , Fêmur , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Rotação , Fêmur/cirurgia , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Amplitude de Movimento Articular , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Resultado do Tratamento
10.
World J Gastrointest Surg ; 16(4): 1109-1120, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38690052

RESUMO

BACKGROUND: The incidence of gastric cancer has significantly increased in recent years. Surgical resection is the main treatment, but the method of digestive tract reconstruction after gastric cancer surgery remains controversial. In the current study, we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after surgery. To this end, we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction (DTR) and esophageal jejunum Roux-en-Y reconstruction (RY). AIM: To explore the application effect of DTR in total laparoscopic radical total gastrectomy (TLTG) and evaluate its safety and efficacy. METHODS: We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January 2023. Among them, 35 cases were treated with DTR, and the remaining 42 cases were treated with traditional RY. After 1:1 propensity score matching, the cases were grouped into 31 cases per group, with evenly distributed data. The clinical characteristics and short- and long-term clinical outcomes of the two groups were statistically analyzed. RESULTS: The two groups showed no significant differences in basic data, intraoperative blood loss, number of lymph node dissections, first defecation time after operation, postoperative hospital stay, postoperative complications, and laboratory examination results on the 1st, 3rd, and 5th days after operation. The operation time of the DTR group was longer than that of the RY group [(307.58 ± 65.14) min vs (272.45 ± 62.09) min, P = 0.016], but the first intake of liquid food in the DTR group was shorter than that in the RY group [(4.45 ± 1.18) d vs (6.0 ± 5.18) d, P = 0.028]. The incidence of reflux heartburn (Visick grade) and postoperative gallbladder disease in the DTR group was lower than that in the RY group (P = 0.033 and P = 0.038). Although there was no significant difference in body weight, hemoglobin, prealbumin, and albumin between the two groups at 1,3 and 6 months after surgery, the diet of patients in the DTR group was better than that in the RY group (P = 0.031). CONCLUSION: The clinical effect of DTR in TLTG is better than that of RY, indicating that it is a more valuable digestive tract reconstruction method in laparoscopic gastric cancer surgery.

11.
ACS Biomater Sci Eng ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722972

RESUMO

It still remains challenging to design multifunctional therapeutic reagents for effective cancer therapy under a unique tumor microenvironment including insufficient endogenous H2O2 and O2, low pH, and a high concentration of glutathione (GSH). In this work, a CO-based phototherapeutic system triggered by photogenerated holes, which consisted of ionic liquid (IL), the CO prodrug Mn2(CO)10, and iridium(III) porphyrin (IrPor) modified carbonized ZIF-8-doped graphitic carbon nitride nanocomposite (IL/ZCN@Ir(CO)), was designed for cascade hypoxic tumors. Upon light irradiation, the photogenerated holes on IL/ZCN@Ir(CO) oxidize water into H2O2, which subsequently induces Mn2(CO)10 to release CO. Meanwhile, IrPor can convert H2O2 to hydroxyl radical (•OH) and subsequent singlet oxygen (1O2), which further triggers CO release. Moreover, the degraded MnO2 shows activity for glutathione (GSH) depletion and mimics peroxidase, leading to GSH reduction and •OH production in tumors. Thus, this strategy can in situ release high concentrations of CO and reactive oxygen species (ROS) and deplete GSH to efficiently induce cell apoptosis under hypoxic conditions, which has a high inhibiting effect on the growth of tumors, offering an attractive strategy to amplify CO and ROS generation to meet therapeutic requirements in cancer treatment.

14.
Cancer Immunol Immunother ; 73(5): 92, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564022

RESUMO

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.


Assuntos
Camptotecina/análogos & derivados , Neoplasias Colorretais , Inibidores da Topoisomerase I , Humanos , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Neoplasias Colorretais/terapia , Citosol , Microambiente Tumoral
15.
World J Gastrointest Oncol ; 16(4): 1668-1675, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660638

RESUMO

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

16.
Biol Pharm Bull ; 47(4): 827-839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599826

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.


Assuntos
Berberina , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Berberina/análogos & derivados , Estudos de Casos e Controles , Coptis chinensis , Neurônios Dopaminérgicos/metabolismo , Mutação , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rizoma
17.
Breast Cancer ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652345

RESUMO

BACKGROUND: Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis. METHODS: We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model. RESULTS: In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18-0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (Pinteraction = 0.006) as well as PR (Pinteraction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant. CONCLUSION: Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.

18.
Int J Biol Macromol ; 268(Pt 1): 131828, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663694

RESUMO

Combined medication has attracted increasing attention as an important treatment option for tumors due to the serious adverse effects of chemotherapy. In this study, as a new therapy strategy, a combination treatment of MDP (a polysaccharide from the rhizome of Menispermum dauricum DC.) with cyclophosphamide (CTX) was investigated. The results showed that combination treatment with MDP and CTX exerted a significantly synergistic anti-tumor effect in Lewis tumor-bearing mice, improved CTX-induced emaciation and hair loss, as well as increased the number of leukocytes, erythrocytes, hemoglobin, and platelets in the peripheral blood. In addition, compared with CTX alone, the thymus index and spleen index of the MDP + CTX group were increased, the number of CD3 + T cells, CD8 + T cells, white blood cells and B cells in spleen also increased significantly. MDP could also ameliorate the increase in liver and kidney index caused by CTX. In the Lewis lung cancer model, MDP showed a certain degree of anti-tumor effects, which may be related to its promotion of tumor-associated macrophages (TAMs) to M1 phenotype polarisation, enhancement of the number of T cells in tumor tissues and promotion of Th cells in tumor tissues to Th1 phenotype polarisation, thus alleviating the immunosuppressive microenvironment in tumor tissues. This study laid the foundation for the development of MDP as a polysaccharide drug for the treatment or adjuvant therapy of tumors and has important significance for the further clinical application of polysaccharides.


Assuntos
Ciclofosfamida , Polissacarídeos , Rizoma , Microambiente Tumoral , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Rizoma/química , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacologia , Masculino , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/patologia , Antineoplásicos/farmacologia , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Baço/imunologia
19.
Front Immunol ; 15: 1373371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686375

RESUMO

Background: Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP. Methods: We conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted. Results: A total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups. Conclusion: The CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.


Assuntos
Creatinina , Unidades de Terapia Intensiva , Pancreatite , Albumina Sérica , Humanos , Masculino , Pancreatite/mortalidade , Pancreatite/sangue , Pancreatite/diagnóstico , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Creatinina/sangue , Idoso , Prognóstico , Albumina Sérica/análise , Biomarcadores/sangue , Bases de Dados Factuais , Adulto
20.
In Vivo ; 38(3): 1229-1235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688617

RESUMO

BACKGROUND/AIM: Given the characteristics of Serratia marcescens (S. marcescens), this study aimed at investigating its presence in the hands and contact lens cases of orthokeratology wearers, along with the status of bacterial contamination. PATIENTS AND METHODS: The 39 patients received the questionnaires about the background of orthokeratology and hygiene habits. A total of 39 contact lens cases and 39 hand samples from the patients were collected at Show Chwan Memorial Hospital from June to August in 2020 and sent to National Chung Cheng University for DNA extraction and PCR identification. RESULTS: The results indicated a detection rate of 5.13% for S. marcescens in the contact lens cases and 12.82% in the hand samples. Additionally, 66.67% of contact lens case samples and 30.77% of hand samples found positive for 16s bacterial amplicons. The relationship between hand contamination and the duration of contact lens usage were revealed for both S. marcescens (p=0.021) and 16s bacterial amplicons (p=0.048). CONCLUSION: The results indicated that hand hygiene is more critical than focusing on contact lens hygiene when it comes to preventing S. marcescens infections. Nevertheless, both proper hand and contact lens hygiene practices can reduce the detection of bacterial eye pathogens, especially a common intestinal bacterium.


Assuntos
Infecções por Serratia , Serratia marcescens , Humanos , Serratia marcescens/isolamento & purificação , Serratia marcescens/genética , Masculino , Feminino , Infecções por Serratia/microbiologia , Infecções por Serratia/epidemiologia , Infecções por Serratia/diagnóstico , Procedimentos Ortoceratológicos/métodos , Lentes de Contato/microbiologia , Lentes de Contato/efeitos adversos , Criança , Adolescente , Higiene , Higiene das Mãos , Adulto , Mãos/microbiologia
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