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1.
Front Oncol ; 14: 1395202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39314626

RESUMEN

Purposes: To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Methods: Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. Results: There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Conclusion: Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively.

2.
Int J Mol Sci ; 25(17)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39273495

RESUMEN

Plants encounter numerous adversities during growth, necessitating the identification of common stress activators to bolster their resistance. However, the current understanding of these activators' mechanisms remains limited. This study identified three anti-stress activators applicable to apple trees, all of which elevate plant proline content to enhance resistance against various adversities. The results showed that the application of these sugar substitutes increased apple proline content by two to three times compared to the untreated group. Even at a lower concentration, these activators triggered plant stress resistance without compromising apple fruit quality. Therefore, these three sugar substitutes can be exogenously sprayed on apple trees to augment proline content and fortify stress resistance. Given their effectiveness and low production cost, these activators possess significant application value. Since they have been widely used in the food industry, they hold potential for broader application in plants, fostering apple industry development.


Asunto(s)
Malus , Prolina , Estrés Fisiológico , Azúcares , Malus/metabolismo , Malus/fisiología , Prolina/metabolismo , Azúcares/metabolismo , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas
3.
J Clin Pediatr Dent ; 48(5): 174-182, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39275835

RESUMEN

This study aims to retrospectively evaluate the differences in dental treatments rendered in general anesthesia (GA) for patients who did or did not receive application of silver diamine fluoride (SDF) prior to GA. 1559 patients (≤6 years) who completed treatment with GA for caries at University of California San Francisco (UCSF) between 2015 and 2019 were included in the study. At baseline patients' electronic health record was reviewed to collect planned treatment, complete dental treatment and demographics. Patients were identified as SDF group (N = 335, 21.49%) or comparison (N = 1224, 78.51%). Dental treatments rendered were compared between the SDF and comparison group with multi-variable regression, including variables for demographics and clinical findings at baseline. The initial analysis identified variations in gender, age, dental pain, pulp involvement, and initial treatment plans between the SDF and comparison groups at baseline. In an unadjusted analysis, the SDF group displayed a statistically significant increase in the number of crown procedures but a notable decrease in the number of pulp therapy and extraction treatments completed (p < 0.05). An adjusted multivariable model affirmed the inverse relationship between SDF application and completion of pulp therapy and extractions at the time of GA (p < 0.05). No significant association was identified with the total number of crowns needed and SDF. The model further indicated a positive correlation between the total count of pulp therapy and extractions completed with patient age and the wait-time for GA. In conclusion, pre-GA application of SDF to carious primary teeth is negatively correlated with completed pulp therapy and extraction. SDF application prior to dental treatment with GA may be a valuable tool to reduce invasive dental procedures in GA.


Asunto(s)
Anestesia General , Caries Dental , Fluoruros Tópicos , Compuestos de Amonio Cuaternario , Compuestos de Plata , Humanos , Fluoruros Tópicos/uso terapéutico , Compuestos de Plata/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Caries Dental/prevención & control , Compuestos de Amonio Cuaternario/uso terapéutico , Preescolar , Niño , Cariostáticos/uso terapéutico , Anestesia Dental/métodos , Extracción Dental , Coronas
4.
Rev Cardiovasc Med ; 25(7): 238, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139427

RESUMEN

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

5.
Cancer Med ; 13(10): e7290, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38770646

RESUMEN

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.


Asunto(s)
Neoplasias de las Paratiroides , Paratiroidectomía , Humanos , Paratiroidectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/patología , Estudios Retrospectivos , Adenoma/cirugía , Adenoma/patología , Endoscopía/métodos , Resultado del Tratamiento , Adulto , Hiperparatiroidismo Primario/cirugía , Anciano , Puntaje de Propensión , Tempo Operativo
6.
Microorganisms ; 12(3)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38543519

RESUMEN

Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in Streptococcus mutans, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the liaS and liaR genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of lmrB in S. mutans contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope's stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of S. mutans.

7.
Hematology ; 29(1): 2304488, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38299685

RESUMEN

OBJECTIVE: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment. METHODS: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment. RESULTS: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance. CONCLUSION: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Médula Ósea/patología , Densidad Microvascular , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Resistencia a Antineoplásicos/genética
9.
NPJ Biofilms Microbiomes ; 10(1): 3, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233485

RESUMEN

Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.


Asunto(s)
Bacteriocinas , Nisina , Enfermedad del Hígado Graso no Alcohólico , Enfermedades Periodontales , Ratones , Humanos , Animales , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Nisina/farmacología , Nisina/metabolismo , Disbiosis , Enfermedades Periodontales/microbiología , Porphyromonas gingivalis/metabolismo , Inflamación/complicaciones , Estrés Oxidativo
10.
Neuroimage ; 285: 120497, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38142755

RESUMEN

Major depressive disorder (MDD) is a serious and heterogeneous psychiatric disorder that needs accurate diagnosis. Resting-state functional MRI (rsfMRI), which captures multiple perspectives on brain structure, function, and connectivity, is increasingly applied in the diagnosis and pathological research of MDD. Different machine learning algorithms are then developed to exploit the rich information in rsfMRI and discriminate MDD patients from normal controls. Despite recent advances reported, the MDD discrimination accuracy has room for further improvement. The generalizability and interpretability of the discrimination method are not sufficiently addressed either. Here, we propose a machine learning method (MFMC) for MDD discrimination by concatenating multiple features and stacking multiple classifiers. MFMC is tested on the REST-meta-MDD data set that contains 2428 subjects collected from 25 different sites. MFMC yields 96.9% MDD discrimination accuracy, demonstrating a significant improvement over existing methods. In addition, the generalizability of MFMC is validated by the good performance when the training and testing subjects are from independent sites. The use of XGBoost as the meta classifier allows us to probe the decision process of MFMC. We identify 13 feature values related to 9 brain regions including the posterior cingulate gyrus, superior frontal gyrus orbital part, and angular gyrus, which contribute most to the classification and also demonstrate significant differences at the group level. The use of these 13 feature values alone can reach 87% of MFMC's full performance when taking all feature values. These features may serve as clinically useful diagnostic and prognostic biomarkers for MDD in the future.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo , Aprendizaje Automático
11.
MedComm (2020) ; 4(5): e365, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37701532

RESUMEN

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

12.
Org Lett ; 25(31): 5735-5739, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37526228

RESUMEN

Herein, we describe a gram-scale synthesis of alstoscholarinoid B, a rearranged triterpenoid with potent antihyperuricemic bioactivity. This synthesis was inspired by the biogenetic hypothesis and achieved in seven steps from oleanolic acid with an overall yield of 51%.

13.
Cancer Med ; 12(16): 16846-16858, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37395126

RESUMEN

BACKGROUND: Limited attempts have been made in trans-areola single-site endoscopic thyroidectomy (TASSET) due to technical challenges and the lengthy time for proficiency. This study aimed to define the learning curve of TASSET and to describe improvements in operative performance over time. METHODS: Based on 222 consecutive TASSET procedures, the learning curve was established according to the operation time by using cumulative sum analysis (CUSUM). The end-point of learning curve was defined as the number of cases necessitated to reach the initial surgical proficiency stage. The demographic information, surgical and oncological outcomes, surgical stress, and postoperative complications were also analyzed. RESULTS: There were 70 cases of simple lobectomy for benign nodules and 152 cases of lobectomy with central neck dissection (CND) for malignancy. The mean operative time was 106.54 ± 38.07 min (range: 46-274 min). The learning curve identified two phases: the skill acquisition phase (Case 1-Case 41) and the proficiency phase (Case 42-Case 222). There were no significant differences in demographic information, drainage amount and duration, oncological outcomes, and postoperative complications between the two phases (p > 0.05). Both operation time and postoperative hospitalization decreased significantly in Phase 2 (154.63 ± 52.21 vs. 95.64 ± 22.96 min, p < 0.001; 4.12 ± 0.93 vs. 3.65 ± 0.63 days, p < 0.001). Additionally, the mean variations of surgical stress factors (C-reactive protein and erythrocyte sedimentation rate) decreased significantly as the phase progress. The case number required for proficiency phase in benign and malignant tumor were 18 and 33, respectively, and lymph node resection posed a significant impact on the endpoint of the learning curve (p < 0.001). Meanwhile, the size of nodule showed no significant impact (p = 0.622). For right-handed surgeons, 16 cases and 25 cases were required for technical competence in left-sided and right-sided lesions, respectively, and no significant difference reached (p = 0.266). CONCLUSIONS: TASSET has demonstrated safe and technically feasible with comparable oncological outcomes. Experience of 41 cases was required for surgical competence and proficiency. The initial learning stage could be more quickly adopted by high-volume thyroid surgeons with standardized procedures.


Asunto(s)
Pezones , Tiroidectomía , Humanos , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Curva de Aprendizaje , Endoscopía/efectos adversos , Endoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
14.
Anal Biochem ; 672: 115179, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37150424

RESUMEN

The development of heat-induced antigen retrieval technologies with Tris-EDTA buffer has dramatically improved immunostaining of specific antigens for routine immunohistochemical detection (Krenacs et al., 2010) [1]. However, little evidence exists on whether heat-Induced antigen retrieval utilizing Tris-EDTA buffer can strip western blot (WB) membranes and allow sequential reprobing. Here, we serendipitously discover that ∼95 °C Tris-EDTA buffer with 0.01% Tween 20 could repeatedly strip the Nitrocellulose membranes (NC). After electroblotting, NC blots were soaked into Tris-EDTA stripping buffer (∼95 °C, 10-25min) and we could perform at least five rounds (the following antibodies used: Vinculin, Atg7, Caspase-3, UBA5, JNK and ERK1/2) stripping in sequential chemiluminescent detections. The NC membranes also show clear western signals and background without losing transferred proteins during the reprobing process of WB. Hence, this study report additional new roles of the heat-Induced antigen retrieval Tris-EDTA buffer with 0.01% Tween 20. The method is simpler, more affordable and harmless for the nitrocellulose paper, which will be helpful for effective reprobing in western blotting applications.


Asunto(s)
Calor , Trometamina , Colodión , Ácido Edético , Polisorbatos , Antígenos , Western Blotting
15.
Future Microbiol ; 18: 225-233, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37097048

RESUMEN

Streptococcus mutans is one of the major cariogenic pathogens in the oral cavity. The dlt operon is responsible for the process of D-alanylation of lipoteichoic acid and is related to the virulence of S. mutans. The dlt operon contributes to the adhesion, biofilm formation, stress response, interspecies competitiveness and autolysis of S. mutans. In addition, we have summarized the possible regulatory networks of the dlt operon. This review highlights the significant role of the dlt operon in S. mutans and provides new ideas for ecological caries prevention.


What is this summary about? Dental caries is a common oral disease that destroys teeth. Streptococcus mutans is the major pathogen of dental caries and its cariogenic virulence factors depend on the ability of biofilm formation, acid production and tolerance, stress response, and interspecific competitiveness. The dlt operon is responsible for the process of D-alanylation of lipoteichoic acid and is related to the virulence of Gram-positive bacteria. To understand the role of the dlt operon in S. mutans, this review summarized this based on previous studies. What were the results? The dlt operon can regulate the D-alanylation of lipoteichoic acid to affect the cell surface charge of S. mutans. The change in characteristics of the cell wall will affect the physiological functions of S. mutans, such as adhesion, biofilm formation, stress response, autolysis and interspecies competitiveness. However, the regulatory mechanism of the dlt operon is still unclear and needs further study. What do the results of the study mean? This review highlights the significant role of the dlt operon in S. mutans, which will increase the understanding of the cariogenic mechanism of S. mutans and provide new ideas for ecological caries prevention, such as the development of antibacterial agents targeting the dlt operon.


Asunto(s)
Caries Dental , Streptococcus mutans , Humanos , Streptococcus mutans/genética , Virulencia/genética , Biopelículas , Boca , Operón
16.
Anal Biochem ; 665: 115070, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36736988

RESUMEN

Inactivation of horseradish peroxidase (HRP) treatment is a conventional preference to stripping for sequential detections of different proteins of chemiluminescent western blotting (WB). However, little evidence exists on whether other chemical substances treatment can affects the biological activity of HRP during stripping and re-probing of WB blots. Here, we successfully develop 20% crotonic acid (CA) as an alternative to stripping to inhibit HRP used for sequential chemiluminescent WB on polyvinylidene difluoride (PVDF) and Nitrocellulose (NC) membrane. Moreover, NC blots incubation in CA (40 °C, 30min) allow us to perform three round HRP inhibition in sequential detections without losing transferred proteins and damaging membrane. Hence, the method will help us save time and valuable samples without the need to rerun gels.


Asunto(s)
Crotonatos , Proteínas , Peroxidasa de Rábano Silvestre/química , Western Blotting
17.
Exp Hematol Oncol ; 12(1): 3, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36624542

RESUMEN

Breast cancer heterogeneity determines cancer progression, treatment effects, and prognosis. However, the precise mechanism for this heterogeneity remains unknown owing to its complexity. Here, we summarize the origins of breast cancer heterogeneity and its influence on disease progression, recurrence, and therapeutic resistance. We review the possible mechanisms of heterogeneity and the research methods used to analyze it. We also highlight the importance of cell interactions for the origins of breast cancer heterogeneity, which can be further categorized into cooperative and competitive interactions. Finally, we provide new insights into precise individual treatments based on heterogeneity.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39281806

RESUMEN

Background: Diabetic microvascular complications are the main causes of organ dysfunction and even death in diabetic patients. Our previous studies confirmed the beneficial effects of Yiqi Jiedu Huayu Decoction (YJHD) on diabetic cardiomyopathy and diabetic nephropathy. It is not clear whether YJHD can treat multiple diabetic microvascular complications including diabetic retinopathy, diabetic cardiomyopathy, and diabetic nephropathy through some common mechanisms. Methods: TCMSP, SymMap, STITCH, Swiss Target Prediction, and SEA databases were used to collect and analyze the components and targets of YJHD. GeneCards, DrugBank, DisGeNET, OMIM, and GEO databases were used to obtain target genes for diabetic retinopathy, diabetic cardiomyopathy, and diabetic nephropathy. The GO and KEGG enrichment analyses were performed on the DAVID and STRING platforms. Molecular docking was used to evaluate the binding sites and affinities of compounds and target proteins. Animal experiments were designed to validate the network pharmacology results. Results: Through network pharmacological analysis, oxidative stress, inflammatory response, and apoptosis were identified as key pathological phenotypes for the treatment of diabetic microvascular complications with YJHD. In addition, JNK, p38, and ERK1/2 were predicted as key targets of YJHD in regulating the abovementioned pathological phenotypes. The results of animal experiments showed that YJHD could ameliorate retinal pathological changes of diabetes rats. YJHD can inhibit oxidative stress and inflammation in heart and kidney of diabetic rats. Molecular docking showed strong binding between compounds and JNK, p38, and ERK1/2. Berlambine may play a key role in the treatment process and is considered as a promising regulator of MAPK protein family. The regulatory effects of YJHD on JNK, p38, and ERK1/2 were demonstrated in animal experiments. Conclusions: YJHD may play a therapeutic role in diabetic microvascular complications by regulating oxidative stress, inflammatory response, and apoptosis. The regulation of JNK, p38, and ERK1/2 phosphorylation may be the key to its therapeutic effect.

19.
Front Mol Biosci ; 9: 991308, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330220

RESUMEN

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers.

20.
J Clin Med ; 11(21)2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36362609

RESUMEN

Thyroid cancer (TC) is the most prevalent endocrine malignancy, with a rising incidence in the past decade [...].

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