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OBJECTIVE: Proprionibacterium acnes (P. acnes)-induced inflammatory responses, proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris (AV). P. acnes was found to enhance the production of interleukin-8 (IL-8) by keratinocytes. This study aimed to investigate the role of IL-8 in P. acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism. METHODS: The P. acnes-stimulated HaCaT cell (a human keratinocyte cell line) model was established. Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1 (CXCR1) and C-X-C motif chemokine receptor 2 (CXCR2) on HaCaT cells. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-20-deoxyuridine (EdU) assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P. acnes, the IL-8 neutralizing antibody, the CXCR2 antagonist (SB225002), or the CXCR1/CXCR2 antagonist (G31P). Western blotting, nuclear and cytoplasmic separation, CCK-8 assay, and EdU assay were employed to determine the downstream pathway of CXCR2 after P. acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist, the protein kinase B (AKT) antagonist (AZD5363), or the constitutively active forkhead box O1 (FOXO1) mutant. Finally, autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine (3-MA). RESULTS: The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P. acnes stimulation. The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P. acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling. In brief, IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis. Subsequently, phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P. acnes-induced keratinocytes. CONCLUSION: This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P. acnes-induced keratinocytes, suggesting a potential therapeutic target for AV.
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BACKGROUND: The survival of critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) is highly dependent on their nutritional status. OBJECTIVES: The prognostic nutritional index (PNI) is an indicator used to assess nutritional status and is calculated as: PNI = (serum albumin in g/dL) × 10 + (total lymphocyte count in/mm3) × 0.005. In this retrospective study, we investigated the correlation between this index and clinical outcomes in critically ill patients with AKI receiving CRRT. METHODS: We analyzed data from 2076 critically ill patients admitted to the intensive care unit at Changhua Christian Hospital, a tertiary hospital in central Taiwan, between January 1, 2010, and April 30, 2021. All these patients met the inclusion criteria of the study. The relationship between PNI and renal replacement therapy-free survival (RRTFS) and mortality was examined using logistic regression models, Cox proportional hazard models, and propensity score matching. High utilization rate of parenteral nutrition (PN) was observed in our study. Subgroup analysis was performed to explore the interaction effect between PNI and PN on mortality. RESULTS: Patients with higher PNI levels exhibited a greater likelihood of achieving RRTFS, with an adjusted odds ratio of 2.43 (95% confidence interval [CI]: 1.98-2.97, p-value < 0.001). Additionally, these patients demonstrated higher survival rates, with an adjusted hazard ratio of 0.84 (95% CI: 0.72-0.98) for 28-day mortality and 0.80 (95% CI: 0.69-0.92) for 90-day mortality (all p-values < 0.05), compared to those in the low PNI group. While a high utilization rate of parenteral nutrition (PN) was observed, with 78.86% of CRRT patients receiving PN, subgroup analysis showed that high PNI had an independent protective effect on mortality outcomes in AKI patients receiving CRRT, regardless of their PN status. CONCLUSIONS: PNI can serve as an easy, simple, and efficient measure of lymphocytes and albumin levels to predict RRTFS and mortality in AKI patients with require CRRT.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Enfermedad Crítica , Evaluación Nutricional , Estado Nutricional , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Lesión Renal Aguda/terapia , Lesión Renal Aguda/mortalidad , Taiwán/epidemiología , Pronóstico , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Nutrición Parenteral/estadística & datos numéricosRESUMEN
The chemical constituents of Schizonepetae Spica were qualitatively analyzed by UHPLC-Q-TOF-MS/MS. An Agilent poroshell 120 SB-C_(18) column(3.0 mm×100 mm, 2.7 µm) was used for gradient elution with 0.1% formic acid water(A)-acetonitrile(B) solution as mobile phase at the flow rate of 0.4 mL·min~(-1) and column temperature of 45 â. The data were collected by scanning in positive and negative ion modes, and the compounds were identified by comparison of reference materials and PeakView software. Ninety-seven compounds were identified from Schizonepetae Spica, including 28 flavonoids, 23 phenolic acids, 23 fatty acids, 15 terpenoids, and 8 other compounds. The UHPLC-Q-TOF-MS/MS method established in this study can identify the chemical components of Schizonepetae Spica rapidly, accurately, and comprehensively, and provide a basis for the basic study of pharmacodynamic substances of Schizonepetae Spica.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , TerpenosRESUMEN
BACKGROUND: Heart failure (HF), a common cardiovascular condition, is characterized by significant morbidity and mortality. While traditional Chinese medicine (TCM) is often used as a complementary approach in HF management, systematic evaluations of its impact on clinical outcomes, TCM syndrome scores, and B-type natriuretic peptide (BNP) levels are lacking. This study fills this gap through a comprehensive analysis of randomized controlled trials (RCTs) focusing on TCM for HF treatment. It encompasses an assessment of methodological quality, a meta-analysis, and an evaluation of evidence quality based on established standards. The results offer crucial insights into the potential advantages and constraints of TCM in HF management. AIM: To systematically analyze the effects of TCM on the clinical comprehensive outcomes, TCM syndrome scores, and BNP levels in patients with HF and evaluated the quality of evidence for these trials. METHODS: RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Science and Technology Journal, and PubMed. Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool, and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software. Finally, the quality of evidence was rated according to the GRADE criteria. RESULTS: A total of 1098 RCTs were initially retrieved. After screening, 16 RCTs were finally included in our study, which were published between 2020 and 2023. These RCTs involved 1660 HF patients, including 832 in the TCM group [TCM combined with conventional Western medicine (CMW) treatment] and 828 in the CWM group (CWM treatment). The course of treatments varied from 1 wk to 3 months. TCM syndrome differentiation was analyzed in 11 of the included RCTs. In all included RCTs, outcome indicators included comprehensive clinical outcomes, TCM syndrome scores, and BNP levels. The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes [risk ratio = -0.54; 95% confidence interval (CI) = -0.61, -0.47; P < 0.00001], TCM syndrome scores [weighted mean difference (WMD) = -142.07; 95%CI = -147.56, -136.57; P < 0.00001], and BNP levels (WMD = -142.07; 95%CI = -147.56, -136.57; P < 0.00001). According to the GRADE criteria, RCTs where "TCM improves clinical comprehensive outcomes" were rated as low-quality evidence, and RCTs where "TCM reduces TCM syndrome scores" or "TCM decreases BNP levels" were rated as medium-quality evidence. CONCLUSION: TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients. Given the low and medium quality of the included RCTs, the application of these results should be cautious.
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Hiptagestenopterum K.Tan & M.X.Ren, a new species of Hiptage collected from a deep valley close to the Nujiang Gorge, northwest of Yunnan Province, China, is described and illustrated based on molecular and morphological data. The new species was found isolated in an entrenched valley of the Laowo River, a tributary of the Nujiang River, at the northern edge of the distribution range of the genus. H.stenopterum shares some morphological similarities with the narrowly endemic H.incurvatum and H.lushuiensis. However, H.stenopterum is easily distinguished by its oblanceolate lateral wing of winged mericarp, 10 to 12 calyx glands, and branchlets densely rusty tomentose. The new species status is also supported by molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS), which showed distinct systematic boundaries from the most morphologically similar species, H.incurvatum and their morphological relatives, H.lushuiensis.
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Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.
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COVID-19 , Medicamentos Herbarios Chinos , Humanos , Cromatografía Líquida de Alta Presión , Simulación del Acoplamiento Molecular , Farmacología en Red , Medicina Tradicional China , Espectrometría de MasasRESUMEN
This study used both the element occurrence form analysis and the chronic health risk assessment method to investigate the accumulation characteristics of heavy metals in the soil-crop system and the health risk assessment of agricultural products in northeastern Yunnan, which is a typical area of Southwest China where heavy metals are enriched in soil. Based on the study of 1137 groups of agricultural products and corresponding root soils, the results showed that the soil cadmium (Cd) and lead (Pb) in the lead-zinc ore concentration area were higher than the risk-intervention values of the "Soil Environmental Quality Risk control standard for soil contamination of agricultural land" (GB 15618-2018), whereas the soil Cd in the other parent material areas was within the screening-intervention buffer zone, and Pb was below the minimum risk-screening value. According to the National Food Safety Standard of China (GB 2762-2017), the heavy metal Cd in potatoes and soybeans in the area seriously exceeded the standard, the heavy metal Pb in tartary buckwheat and walnut exceeded the limit value, and the exceeding rate of heavy metal Cd in crops from these parent material areas showed: clastic rock>basalt>lead-zinc ore>carbonate ≈ Quaternary sedimentary>sand (mud) rock. According to the U.S. Environmental Protection Agency's assessment method for the chronic health risk of heavy metal intake by humans, the grains and potatoes, staple foods, and fruits had low chronic health risks of heavy metal intake. Agricultural products from the parent material area of clastic rock, sand (mud) rock, Quaternary sedimentary, and lead-zinc ore concentration showed health risks; with the change in soil physical and chemical properties and the increase in the types of edible crops, the risk will gradually increase. Based on this research, it is urgent to carry out real-time monitoring of agricultural products in the area.
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Metales Pesados , Contaminantes del Suelo , Humanos , Suelo/química , Cadmio/análisis , Arena , Plomo/análisis , China , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Zinc , Medición de Riesgo , Productos Agrícolas/química , Monitoreo del AmbienteAsunto(s)
Bacteriemia/patología , Chryseobacterium/patogenicidad , Úlcera de la Córnea/patología , Infecciones por Flavobacteriaceae/patología , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Bacteriemia/cirugía , Chryseobacterium/efectos de los fármacos , Chryseobacterium/enzimología , Chryseobacterium/crecimiento & desarrollo , Conjuntiva/efectos de los fármacos , Conjuntiva/microbiología , Conjuntiva/patología , Conjuntiva/cirugía , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/cirugía , Farmacorresistencia Bacteriana Múltiple , Femenino , Infecciones por Flavobacteriaceae/diagnóstico , Infecciones por Flavobacteriaceae/microbiología , Infecciones por Flavobacteriaceae/cirugía , Humanos , Colgajos Quirúrgicos/microbiología , Colgajos Quirúrgicos/patología , Insuficiencia del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Far-upstream element (FUSE)-binding protein 2 (FBP2) was a member of single-stranded DNA-binding protein family; it played an important role in regulating transcription and post-transcription and is involved in the regulation of C-MYC gene expression in liver tumors. However, the role of FBP2 in breast cancer and its mechanism has not been studied yet. Here, we discovered that FBP2 was up-regulated in breast cancer tissues and breast cancer cell lines. Moreover, immunohistochemistry analysis demonstrated that up-regulated FBP2 was highly associated with tumor grade, Ki-67, and poor prognosis, which was an independent prognostic factor for survival of breast cancer patients. At the cellular level, we found that FBP2 was correlated with cell cycle progression by accelerating G1/S transition, and knockdown of FBP2 could weaken cell proliferation, anchorage-independent cell growth, while enhancing the sensitivity of breast cancer cells to doxorubicin. More importantly, we found that activation of PI3K/AKT pathway could phosphorylate FBP2, and then make FBP2 shuttle from cytoplasm into the nucleus, which was the main mechanism of breast cancer cell proliferation and drug resistance. Taken together, our findings supported the notion that FBP2 might via PI3K/AKT pathway influence breast cancer progression and drug resistance, which might provide a new target for the design of anti-cancer drugs for breast cancer patients.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Proteínas de Unión al ARN/metabolismo , Transactivadores/metabolismo , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or ß (ERα/ß) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. METHODS: We assessed the association between EGFR mutations as well as ERα/ß expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. RESULTS: We found that the cytosolic but not the nuclear expression of ERß was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERß. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. CONCLUSION: Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERß in cytosol.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Línea Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Quinazolinas/administración & dosificación , Tamoxifeno/administración & dosificaciónRESUMEN
Adenylate cyclase-associated protein 1 (CAP1) is a conserved protein that was found to be up-regulated in breast cancer and related to the migration of breast cancer. We verified its roles in breast cancer specimens and cell lines. In our results, 71 of 100 specimens of breast cancer showed high levels of CAP1 by immunohistochemistry. Associated with statistical analysis, we saw that CAP1 was related to the grade of breast cancer. In MDA-MB-231, the expression of CAP1 was the highest and by knocking down the expression of CAP1 in MDA-MB-231, its ability for proliferating and migrating apparently decreased and induced changes in morphology, which were related to the arrangement of F-actin. Therefore, CAP1 might be a potential molecular targeted therapy for surgery and immune treatment.
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Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Movimiento Celular/genética , Proliferación Celular , Proteínas del Citoesqueleto/genética , Proteínas de Ciclo Celular/biosíntesis , Línea Celular Tumoral , Proteínas del Citoesqueleto/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Terapia Molecular DirigidaRESUMEN
OBJECTIVE: To investigate the clinical value of the expression of glucose regulated protein 78 (GRP78) for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma ( GC) . METHODS: A cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival (DFS). RESULTS: The positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis (all P < 0.05), not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was (53.6 ± 0.9) months and (38.3 ± 0.8) months, respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS in GRP78-negative and-positive patients treated with taxane-containing chemotherapy was (58.6 ± 2.6) months and (49.1 ± 2.7) months, respectively, but the difference was statistically not significant (P = 0.111). In contrast, in the subset of GRP78-negative and- positive patients treated with taxane-containing regimens, the DFS was (45.5 ± 1.9) months and (35.1 ± 2.2) months, respectively, showing a significant difference (P = 0.038). In the group of patients with positive GRP78 expression, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05). CONCLUSIONS: The results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.
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Adenocarcinoma/metabolismo , Proteínas de Choque Térmico/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Chaperón BiP del Retículo Endoplásmico , Femenino , Gastrectomía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Taxoides/administración & dosificaciónRESUMEN
This paper introduces a pathological information network and image analysis system designed by ourselves. The system offers an efficient means for modern medical diagnosis and treatment, teaching, research and management in the department of pathology.
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Diagnóstico por Imagen , Servicios de Información , Patología Clínica/métodos , Diseño de Software , Sistemas de Información Radiológica , Análisis de SistemasRESUMEN
OBJECTIVE: To reclassify retrospectively 370 cases of malignant lymphomas. METHODS: According to the WHO new classification, the clinical features and pathology as well as immunophenotype of 370 lymphomas were analysed. RESULTS: In the 370 lymphomas, there were 359 non-Hodgkin's lymphomas (NHL) (97.03%) and 11 Hodgkin's lymphomas (HL) (2.97%). Of the 359 NHL, 246 were B-cell lymphomas (68.52%), 108 T-cell lymphomas (30.08%), 1 each histiocytic lymphoma and follicular dendritic cell sarcoma, and 3 NK cell lymphomas. The extranodal lymphomas were 196 cases (54.6%) and the nodal lymphomas 163 cases (45.4%). The incidence of NHL categories were in proper order as follows: diffuse large B cell lymphoma (173 cases, 48.2%) > peripheral T cell lymphoma (54 cases, 15.0%) > mucosa associated lymphoid tissue (MALT) lymphoma (31 cases, 8.6%) > NK/T cell lymphoma (25 cases, 7.0%) > follicular lymphoma (21 cases, 5.8%) > anaplastic large cell lymphoma (12 cases, 3.3%). CONCLUSION: The results suggested that the study of malignant lymphomas with WHO new classification have important clinical significance.