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1.
Front Nutr ; 11: 1375053, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257607

RESUMEN

Background: Systemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients. Design: From August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used. Results: The prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p < 0.001). A positive association was observed between higher SII and the risk of malnutrition in both before and after adjustment models compared to the first quartile (Q3 vs. Q1, OR = 1.27, 95%CI: 1.15-1.40; Q4 vs. Q1, OR = 1.83, 95%CI: 1.67-2.00). However, a significant reduction in prevalence was observed when SII was in the second quartile (Q2 vs. Q1, OR < 1), as indicated by a restricted cubic spline with a U trend (p for nonlinear <0.001). According to the CONUT score, the prevalence of individuals with normal nutritional status decreased with increasing SII, while the occurrence of three different degrees of malnutrition generally increased. The Kappa value between the two diagnostic methods was 0.23, and the merged data observed an area under the ROC curve of 0.73 (95%CI: 0.714-0.742). Conclusion: The U-shaped association between SII and the prevalence of malnutrition was observed. Both lower and higher SII levels (either continuous or categorical variable) were significantly associated with an increased risk of malnutrition.

2.
Respir Res ; 25(1): 294, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095732

RESUMEN

BACKGROUND: Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis. METHODS: The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets. RESULTS: A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein-protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways. CONCLUSION: This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.


Asunto(s)
Bronquitis Crónica , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Bronquitis Crónica/tratamiento farmacológico , Bronquitis Crónica/metabolismo , Bronquitis Crónica/genética , Farmacología en Red/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Simulación del Acoplamiento Molecular/métodos , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales
3.
Asia Pac J Clin Nutr ; 33(4): 581-588, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39209368

RESUMEN

BACKGROUND AND OBJECTIVES: The current study aimed to explore the effect of nutritional prehabilitation on the clinical prognosis of elderly patients undergoing abdominal cancer surgery. METHODS AND STUDY DESIGN: A retrospective study was conducted, where participants were divided into two groups based on whether they received oral nutritional supplementation at the first outpatient visit. The nutritional prehabilitation group (n=41) adopted a nutritional prehabilitation mode (a standard energy intake of 25-30 kcal/kg· d was recommended). While the control group (n=55) received routine care. All patients underwent laparoscopic surgery according to the National Comprehensive Cancer Network (NCCN) guidelines. Changes in nutritional status, complications, psychological status, symptoms, hospitalization days, and expenditures were compared between the two groups. RESULTS: Both groups of patients experienced weight loss. However, the decline in body weight in the prehabilitation group was less than that in the control group (-1.88 vs. -2.56 kg, p < 0.001). In the comparison of nutritional prehabilitation group and control group, significant improvements were observed in the Hospital Anxiety Scale scores (5 vs. 5, p = 0.01) and MD Anderson Symptom Inventory scores (3 vs. 0, p < 0.001) respectively. The infection rate in the nutritional prehabilitation group was lower than that in the control group (17.1% vs. 36.4%, p = 0.04). Additionally, patients in the nutritional prehabilitation group had significantly fewer hospitalization days at discharge (14.3 vs. 17.1 days, p = 0.03). CONCLUSIONS: In elderly patients undergoing abdominal cancer surgery, a nutritional prehabilitation model may help maintain better physical and mental status, reduce infection rates, and shorten hospitalization days.


Asunto(s)
Suplementos Dietéticos , Neoplasias Gastrointestinales , Estado Nutricional , Cuidados Preoperatorios , Humanos , Estudios Retrospectivos , Anciano , Masculino , Femenino , Cuidados Preoperatorios/métodos , Neoplasias Gastrointestinales/cirugía , Anciano de 80 o más Años
4.
Theranostics ; 14(7): 2915-2933, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773976

RESUMEN

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.


Asunto(s)
Inmunoterapia , Terapia Neoadyuvante , Piroptosis , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Masculino , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Multiómica
5.
Biochem Biophys Res Commun ; 719: 150084, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38733742

RESUMEN

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.


Asunto(s)
Antígeno Carcinoembrionario , Neoplasias Colorrectales , Nanopartículas , Antígeno Carcinoembrionario/metabolismo , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Nanopartículas/química , Humanos , Animales , Línea Celular Tumoral , Imagen Óptica/métodos , Ratones , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Ratones Endogámicos BALB C , Colorantes Fluorescentes/química
6.
ACS Omega ; 9(15): 17491-17505, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38645376

RESUMEN

Geological bodies are important sources of greenhouse gas (GHG) emissions. Organic-rich oil shale in sedimentary basins is a good gas source rock, the GHG in which will be released into the atmosphere during crushing to affect climate change. Quantitative calculations of GHG emissions during oil shale crushing were carried out on oil shales from the Yaojie (YJ) and Fushun (FS) mining areas in China. Organic geochemistry, X-ray diffraction, and pore structure analysis experiments, as well as the relationship between storage time and GHG emissions, were analyzed to investigate the main controlling factors of GHG release in different types of oil shales. The results showed that the CH4 and CO2 released from the YJ oil shale were 0.002-0.145 mL/g and 0.011-0.054 mL/g, respectively; the CH4 and CO2 released from the FS oil shale were 0.0001-0.0008 mL/g and 0.002-0.045 mL/g, respectively. Residual CH4 release was closely related to total organic carbon (TOC) and maturity: the CH4 released from the organic-rich and mature YJ oil shale was much higher than that of the FS oil shale, which is relatively organic-lean and immature. The control factors of the released CO2 vary in different regions: CO2 released from the YJ oil shale was somewhat affected by the TOC, while that released from the FS oil shale was mainly controlled by carbonate minerals and their contributing pores. The results of pore structure and organic maceral analyses indicated that both organic and inorganic pores of the YJ oil shale are occupied by asphaltenes, forming a key gas preservation mechanism of residual CH4 and CO2 as solutes dissolved in asphaltenes. In addition, CO2 has a greater absorptive capacity than CH4 and is therefore more difficult to release during the same crushing time. As oil shale is stored for longer periods, residual CH4 will be preferentially released to the atmosphere, while residual CO2 will be released in large quantities during crushing.

7.
PLoS One ; 19(2): e0294426, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38315679

RESUMEN

The MADS-box gene family controls plant flowering and floral organ development; therefore, it is particularly important in ornamental plants. To investigate the genes associated with the MADS-box family in Clematis courtoisii, we performed full-length transcriptome sequencing on C. courtoisii using the PacBio Sequel third-generation sequencing platform, as no reference genome data was available. A total of 12.38 Gb of data, containing 9,476,585 subreads and 50,439 Unigenes were obtained. According to functional annotation, a total of 37,923 Unigenes (75.18% of the total) were assigned with functional annotations, and 50 Unigenes were identified as MADS-box related genes. Subsequently, we employed hmmerscan to perform protein sequence similarity search for the translated Unigene sequences and successfully identified 19 Unigenes associated with the MADS-box gene family, including MIKC*(1) and MIKCC (18) genes. Furthermore, within the MIKCC group, six subclasses can be further distinguished.


Asunto(s)
Clematis , Clematis/genética , Transcriptoma , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Genes de Plantas , Familia de Multigenes , Plantas/genética , Filogenia , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Plants (Basel) ; 13(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276772

RESUMEN

BACKGROUND: The yellow-leaf gl1 mutant of Lagerstroemia indica exhibits an altered phenylpropanoid metabolism pathway compared to wild-type (WT). However, details on the metabolites associated with leaf color variation, including color-specific metabolites with bioactive constituents, are not fully understood. METHODS: Chemical and metabolomics approaches were used to compare metabolite composition and antioxidant capacity between the gl1 mutant and WT leaves. RESULTS: The mutant exhibited an irregular xylem structure with a significantly lower phenolic polymer lignin content and higher soluble phenolic compounds. Untargeted metabolomics analysis identified phenolic compounds, particularly lignans, as key differential metabolites between gl1 and WT, with a significant increase in the mutant. The neolignan derivative balanophonin-4-O-D-glu was identified as a characteristic metabolite in the gl1 mutant. The soluble phenolic compounds of the gl1 mutant exhibited higher FRAP, ABTS, DPPH, and hydroxyl radical scavenging activity than in WT. Correlation analysis showed a positive relationship between antioxidant capacity and phenolic compounds in L. indica. CONCLUSIONS: Metabolites associated with leaf color variation in the L. indica yellow-leaf gl1 mutant demonstrated high antioxidant capacity, particularly in scavenging hydroxyl radicals.

9.
J Nutr Biochem ; 123: 109512, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37907171

RESUMEN

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity.


Asunto(s)
Dieta Alta en Grasa , Leptina , Animales , Masculino , Ratones , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Quimiocina CX3CL1/metabolismo , Dieta Alta en Grasa/efectos adversos , Hipotálamo/metabolismo , Leptina/metabolismo , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/genética
10.
World J Gastrointest Surg ; 15(11): 2553-2563, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38111756

RESUMEN

BACKGROUND: Although the location of proximal cancer of the remnant stomach is the same as that of primary proximal cancer of the stomach, its clinical characteristics and prognosis are still controversial. AIM: To evaluate the clinicopathological features and prognosis factors of gastric stump cancer (GSC) and primary proximal gastric cancer (PGC). METHODS: From January, 2005 to December, 2016, 178 patients with GSC and 957 cases with PGC who received surgical treatment were enrolled. Patients in both groups underwent 1:1 propensity score matching analysis, and both clinical and pathological data were systematically collected for statistical purposes. Quality of life was evaluated by the C30 and STO22 scale between GSC-malignant (GSC following gastric cancer) and GSC-benign (GSC following benign lesions of the stomach). RESULTS: One hundred and fifty-two pairs were successfully matched after propensity score matching analysis. Of the 15 demographic and pathological variables collected, the analysis further revealed that the number of lymph nodes and positive lymph nodes were different prognostic and clinicopathological factors between PGC and GSC. Univariate and multivariate analyses showed that gender, differentiation degree and tumor-node-metastasis stage were independent risk factors for patients with GSC. Gender, vascular invasion, differentiation degree, depth of infiltration, positive lymph nodes, and tumor-node-metastasis stage were independent risk factors for patients with PGC. The 5-year overall survival and cancer-specific survival of patients with GSC were significantly lower than those in the PGC group, the scores for overall quality of life in the GSC-malignant group were lower than the GSC-benign, and the differences were statistically significant. CONCLUSION: The differences in clinicopathological characteristics between GSC and PGC were clarified, and PGC had a better prognosis than GSC.

11.
Front Microbiol ; 14: 1289682, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38149276

RESUMEN

The unprecedented public health and economic impact of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been met with an equally unprecedented scientific response. Sensitive point-of-care methods to detect SARS-CoV-2 antigens in clinical specimens are urgently required for the rapid screening of individuals with viral infection. Here, we developed an upconversion nanoparticle-based lateral flow immunochromatographic assay (UCNP-LFIA) for the high-sensitivity detection of SARS-CoV-2 nucleocapsid (N) protein. A pair of rabbit SARS-CoV-2 N-specific monoclonal antibodies was conjugated to UCNPs, and the prepared UCNPs were then deposited into the LFIA test strips for detecting and capturing the N protein. Under the test conditions, the limit of detection (LOD) of UCNP-LFIA for the N protein was 3.59 pg/mL, with a linear range of 0.01-100 ng/mL. Compared with that of the current colloidal gold-based LFIA strips, the LOD of the UCNP-LFIA-based method was increased by 100-fold. The antigen recovery rate of the developed method in the simulated pharyngeal swab samples ranged from 91.1 to 117.3%. Furthermore, compared with the reverse transcription-polymerase chain reaction, the developed UCNP-LFIA method showed a sensitivity of 94.73% for 19 patients with COVID-19. Thus, the newly established platform could serve as a promising and convenient fluorescent immunological sensing approach for the efficient screening and diagnosis of COVID-19.

12.
Asia Pac J Clin Nutr ; 32(3): 356-361, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37789656

RESUMEN

BACKGROUND AND OBJECTIVES: Lack of professional and accurate diagnosis of malnutrition led to a reduction in Diagnosis Related Group (DRG) payment and a decrease in Case-Mix Index (CMI). The aim of this study was to explore the effects of adding a proper nutritional diagnosis and modifying complication groups on DRG payment and CMI. METHODS AND STUDY DESIGN: Retrospective analysis was performed on patients ad-mitted to the hospital from January to June 2022 who had received a nutritional assessment. Patients were diagnosed as well-nourished, mild malnutrition, moderate malnutrition or severe malnutrition according to patient-generated subjective global assessment (PG-SGA) scores within 24 hours of admission. CMI and DRG hospital internal control standards were recalculated and compared with the original values. RESULTS: A total of 254 patients were enrolled, including 40 patients with mild malnutrition, 74 patients with moderate malnutrition and 122 patients with severe malnutrition. Of all subjects, 111 changed complication groups. The median of the DRG hospital internal control standard (12006.09 vs. 13797.19, p=0.01) and the median of CMI (0.91 vs. 1.04, p=0.026) were significantly higher than those before the diagnostic change. In patients with inflammatory bowel disease (IBD), the CMI value, hospital control standard of DRG, and the classification of DRG were significantly different from those before diagnosis revision (p<0.001). CONCLUSIONS: Fully identification and correct coding of malnutrition cases are conducive for hospitals to receive appropriate DRG compensation, and further contribute to the improvement of medical quality and the economic sustain-ability of hospitals.


Asunto(s)
Desnutrición , Humanos , Estudios Retrospectivos , Desnutrición/diagnóstico , Desnutrición/epidemiología , Desnutrición/etiología , Hospitalización , Grupos Diagnósticos Relacionados , Evaluación Nutricional , Estado Nutricional
13.
J Med Chem ; 66(17): 11965-11984, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37597216

RESUMEN

A series of heterocyclic ring-fused derivatives of 20(S)-protopanaxadiol (PPD) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Among these compounds, 33 (SH491, IC50 = 11.8 nM) showed the highest potency with 100% inhibition at 0.1 µM and 44.4% inhibition at an even lower concentration of 0.01 µM, which was much more potent than the lead compound PPD (IC50 = 10.3 µM). Cytotoxicity tests indicated that the inhibitory effect of these compounds on RANKL-induced osteoclast differentiation was not due to their cytotoxicity. Interestingly, SH491 also exhibited a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. Mechanistic studies revealed that SH491 inhibits the expression of osteoclastogenesis-related marker genes and proteins, including TRAP, CTSK, MMP-9, and ATPase v0d2. In vivo, SH491 could dramatically decrease the ovariectomy-induced osteoclast activity and relieve osteoporosis obviously. Thus, these PPD derivatives could be served as promising leads for the development of novel antiosteoporosis agents.


Asunto(s)
Adenosina Trifosfatasas , Osteoporosis , Femenino , Humanos , Osteoclastos , Osteogénesis , Osteoporosis/tratamiento farmacológico
14.
Support Care Cancer ; 31(6): 341, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37195367

RESUMEN

OBJECTIVE: To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. METHODS: EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. RESULTS: The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). CONCLUSIONS: EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..


Asunto(s)
Neoplasias Esofágicas , Estado Nutricional , Humanos , Estudios Retrospectivos , Nutrición Enteral/métodos , Intubación Gastrointestinal/efectos adversos , Intubación Gastrointestinal/métodos , Neoplasias Esofágicas/terapia , Quimioradioterapia/efectos adversos
16.
Adv Sci (Weinh) ; 10(15): e2207417, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36998102

RESUMEN

The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype-related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG-3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in-house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPSLow is characterized as immune-activated, and IPSHigh is immune-silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPSLow and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti-PD-1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC.


Asunto(s)
Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Inmunofenotipificación , Pronóstico , Inmunoterapia , Microambiente Tumoral
17.
Medicine (Baltimore) ; 102(12): e33335, 2023 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-36961192

RESUMEN

BACKGROUND: This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy. METHODS: A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann-Whitney U and chi-square tests. RESULTS: The ALB and Hb levels of the patients in the control group decreased significantly [ALB: -2.6 (-5.6, 0), P = .01; Hb: -12.0 (-27.0, -2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004). CONCLUSION: Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.


Asunto(s)
Proteína C-Reactiva , Neoplasias Esofágicas , Humanos , Apoyo Nutricional , Estado Nutricional , Neoplasias Esofágicas/terapia , Quimioradioterapia/efectos adversos
18.
J Plant Physiol ; 280: 153886, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36493670

RESUMEN

Photooxidation is the major physiological performance of the Lagerstroemia indica chlorosis mutant gl1 under field conditions. The mechanisms of the progressive symptoms of oxidative damage from the lower older leaves to the upper mature leaves are complicated and still unclear. The aim of this work was to investigate the physiological mechanisms of oxidative stress from the perspective of the photosynthetic metabolites. The phytosynthetic metabolites of gl1 mutant changed significantly compared to wild type (WT) L. indica, such as by increasing phenolics, decreasing soluble sugar, protein and ascorbate, and redistributing antioxidant enzyme activities. The co-accumulation of phenolics and guaiacol-POD in gl1 mutant promote the removal of H2O2, as well the increase of phenoxyl radicals levels. Furthermore, the ion balance was significantly disturbed and Fe accumulated the most among these fluctuating nutrients in the leaves of gl1 mutant. The accumulated Fe was found neither in the chloroplasts nor in the cell wall of the leaves and became unshielded Fe, which favors the Fenton/Haber-Weiss reaction and stabilizes the phenoxyl radicals in metal complexation. The results suggested that the increase of phenolics and Fe accumulation were obviously involved in oxidative damage of gl1 mutant.


Asunto(s)
Anemia Hipocrómica , Ferroptosis , Lagerstroemia , Lagerstroemia/genética , Lagerstroemia/metabolismo , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo , Antioxidantes/metabolismo , Anemia Hipocrómica/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo
19.
Lipids Health Dis ; 21(1): 102, 2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36242019

RESUMEN

BACKGROUND: Visceral obesity is associated with cancer incidence and prognosis. Altered lipid profiles are frequently seen in visceral obese patients. The blood test of lipid profiles is more convenient and has no radical side effects than computed tomography (CT), which is presently the most accurate way to measure visceral fat area. This article aims to investigate the associations between lipid profiles and visceral obesity in gastrointestinal cancer patients. METHODS: In total, 399 patients newly diagnosed with gastrointestinal cancer were enrolled in this observational study. Lipid profiles were obtained from blood samples, and visceral fat mass area (VFA) was measured by CT. VFA ≥ 100 cm2 was considered visceral obesity. The area under the receiver operating characteristic curve (AUROC) was utilized to evaluate the prognostic powers of lipid parameters for viscerally obese gastrointestinal cancer patients. RESULTS: Patients who had visceral obesity had higher triglyceride (TG) levels (1.20 ± 0.60 vs. 0.87 ± 0.57 mmo/L, P < 0.001), total cholesterol (TC) levels (3.57 ± 0.84 vs. 3.40 ± 0.82, P = 0.044), and low-density lipoprotein (LDL-C) levels (2.08 ± 0.66 vs. 1.94 ± 0.66, P = 0.047) and lower high-density lipoprotein (HDL-C) levels (0.88 ± 0.24 vs. 1.00 ± 0.26, P < 0.001) than those in the normal group. TG was positively correlated with VFA (r = 0.299, P < 0.001), while HDL-C was inversely correlated with VFA (r = -0.237, P < 0.001). TG and HDL-C had predictive capacity for visceral obesity at cutoff levels of 0.92 mmol/L (AUROC 0.700, 95% CI, 0.653-0.745, P < 0.001) and 0.98 mmol/L (AUROC 0.700, 95% CI, 0.585-0.682, P < 0.001), respectively. TG > 0.92 mmol/L with HDL-C < 0.98 mmol/L was linked with an increased risk of visceral obesity (OR = 4.068, 95% CI, 2.338-7.079, P < 0.001). CONCLUSIONS: Lipid profiles were significantly correlated with VFA. Gastrointestinal cancer patients with TG > 0.92 mmol/L and HDL-C < 0.98 mmol/L were at elevated risk of visceral obesity in the Chinese population. Identifying visceral obesity and taking proper actions in gastrointestinal cancers are helpful for overall tumor prognosis.


Asunto(s)
Neoplasias Gastrointestinales , Obesidad Abdominal , HDL-Colesterol , LDL-Colesterol , Estudios Transversales , Neoplasias Gastrointestinales/complicaciones , Humanos , Lipoproteínas HDL , Obesidad/complicaciones , Obesidad Abdominal/complicaciones , Triglicéridos
20.
Curr Oncol ; 29(10): 6947-6955, 2022 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-36290823

RESUMEN

Head and neck cancer (HNC) sufferers usually encounter arduous nutritional problems when they are receiving antineoplastic therapy. Consequently, the presence of anxiety and depression is commonly observed in this population. This study aimed to explore the physical and psychological influence of nutritional counseling in patients with HNC. Patients receiving concurrent chemo-radiotherapy were randomly assigned to the nutritional counseling group (n = 32, 52.45%) and the control group (n = 29, 47.54%) according to their treatment patterns. In the nutritional counseling group, registered dietitians provided face-to-face counseling during the antineoplastic treatment course at least every two weeks. Nutrient intake amount, relevant nutritional indexes, quality of life, and the degree of anxiety and depression were compared between the two groups. We observed a decrease in the calorie and protein intake amount in both groups, while the decrease in the control group is even worse. The weight loss is more obvious in the control group. The HADS scores in the intervention group were significantly lower than that in the control group (p < 0.05). The Karnofsky Performance Status (KPS) scores in the intervention group were significantly higher than that in the control group (p < 0.05). The level of serum total protein, serum albumin, transferrin, and the thickness of the triceps skin fold decreased less in the intervention group (p < 0.05). Our findings suggest that nutrition counseling is essential for the maintenance of calorie and protein intake in HNC suffers, which contributes to an improvement in the physical and psychological states. The impacts observed in this pilot study warrant further exploration in a larger prospective trial.


Asunto(s)
Antineoplásicos , Neoplasias de Cabeza y Cuello , Humanos , Proyectos Piloto , Calidad de Vida , Estudios Prospectivos , Consejo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Proteínas Sanguíneas , Transferrinas , Albúminas
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