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1.
Nucleic Acids Res ; 52(D1): D607-D621, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37757861

RESUMEN

Liquid biopsy has emerged as a promising non-invasive approach for detecting, monitoring diseases, and predicting their recurrence. However, the effective utilization of liquid biopsy data to identify reliable biomarkers for various cancers and other diseases requires further exploration. Here, we present cfOmics, a web-accessible database (https://cfomics.ncRNAlab.org/) that integrates comprehensive multi-omics liquid biopsy data, including cfDNA, cfRNA based on next-generation sequencing, and proteome, metabolome based on mass-spectrometry data. As the first multi-omics database in the field, cfOmics encompasses a total of 17 distinct data types and 13 specimen variations across 69 disease conditions, with a collection of 11345 samples. Moreover, cfOmics includes reported potential biomarkers for reference. To facilitate effective analysis and visualization of multi-omics data, cfOmics offers powerful functionalities to its users. These functionalities include browsing, profile visualization, the Integrative Genomic Viewer, and correlation analysis, all centered around genes, microbes, or end-motifs. The primary objective of cfOmics is to assist researchers in the field of liquid biopsy by providing comprehensive multi-omics data. This enables them to explore cell-free data and extract profound insights that can significantly impact disease diagnosis, treatment monitoring, and management.


Asunto(s)
Biomarcadores , Bases de Datos Factuales , Enfermedad , Multiómica , Neoplasias , Humanos , Biomarcadores/análisis , Genómica/métodos , Neoplasias/química , Neoplasias/genética , Enfermedad/genética
2.
Plant J ; 118(5): 1358-1371, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38341799

RESUMEN

Watercore is a common physiological disease of Rosaceae plants, such as apples (Malus domestica), usually occurring during fruit ripening. Apple fruit with watercore symptoms is prone to browning and rotting, thus losing commercial viability. Sorbitol and calcium ions are considered key factors affecting watercore occurrence in apples. However, the mechanism by which they affect the occurrence of watercore remains unclear. Here, we identified that the transcription factor MdWRKY9 directly binds to the promoter of MdSOT2, positively regulates the transcription of MdSOT2, increases sorbitol content in fruit, and promotes watercore occurrence. Additionally, MdCRF4 can directly bind to MdWRKY9 and MdSOT2 promoters, positively regulating their expression. Since calcium ions can induce the ubiquitination and degradation of the transcription factor MdCRF4, they can inhibit the transcription of MdWRKY9 and MdSOT2 by degrading MdCRF4, thereby reducing the sorbitol content in fruit and inhibiting the occurrence of fruit watercore disease. Our data sheds light on how calcium ions mitigate watercore in fruit, providing molecular-level insights to enhance fruit quality artificially.


Asunto(s)
Calcio , Frutas , Regulación de la Expresión Génica de las Plantas , Malus , Proteínas de Plantas , Sorbitol , Factores de Transcripción , Malus/genética , Malus/metabolismo , Frutas/genética , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Calcio/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Sorbitol/metabolismo , Regiones Promotoras Genéticas/genética
3.
Cell Mol Life Sci ; 81(1): 249, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836877

RESUMEN

Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs.


Asunto(s)
Legionella pneumophila , Fagosomas , Proteínas SNARE , Ubiquitinación , Proteínas de Unión al GTP rab , Legionella pneumophila/metabolismo , Humanos , Fagosomas/metabolismo , Fagosomas/microbiología , Proteínas SNARE/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Animales , Proteínas Qa-SNARE/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Vacuolas/metabolismo , Vacuolas/microbiología , Células HEK293 , Ratones , Proteínas de Unión a GTP rab7/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Retículo Endoplásmico/metabolismo
4.
Cancer ; 130(4): 553-562, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-38044705

RESUMEN

BACKGROUND: In the general population, individuals with minoritized sexual orientation and gender identity have a higher burden of chronic health conditions than heterosexual individuals. However, the extent to which sexual orientation is associated with excess burden of chronic conditions in adolescent and young adult cancer survivors (AYACS) is unknown. METHODS: Lesbian, gay, and bisexual (LGB) AYACSs, LGB individuals without a history of cancer, and heterosexual AYACSs were identified by self-reported data from the cross-sectional National Health Interview Survey (2013-2020). Socioeconomic factors and the prevalence of chronic health conditions were compared between groups using χ2 tests. Logistic regression methods were used to determine the odds of chronic conditions by socioeconomic factors within and between survivor and comparison groups. RESULTS: One hundred seventy LGB cancer survivors, 1700 LGB individuals without a history of cancer, and 1700 heterosexual cancer survivors were included. Compared with heterosexual survivors, LGB survivors were less likely to be married (p = .001) and more likely to have never been married (p < .001). LGB survivors were more likely to have incomes between 100% and 200% of the federal poverty level than LGB individuals without a history of cancer (p = .012) and heterosexual survivors (p = .021) and were less likely to report incomes >200% the federal poverty level. LGB survivors had higher odds of chronic health conditions than LGB individuals without a history of cancer (odds ratio, 2.45; p < .001) and heterosexual survivors (odds ratio, 2.16; p = .003). CONCLUSIONS: LGB AYACSs are at increased risk of having chronic health conditions compared with both LGB individuals without a history of cancer and heterosexual AYACSs.


Asunto(s)
Neoplasias , Minorías Sexuales y de Género , Humanos , Adolescente , Adulto Joven , Femenino , Masculino , Estudios Transversales , Identidad de Género , Bisexualidad , Conducta Sexual , Sobrevivientes , Enfermedad Crónica , Neoplasias/epidemiología
5.
Cancer ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39257218

RESUMEN

BACKGROUND: The objective of this study was to evaluate the efficacy of an in-person, small-group mammography video discussion (SMVD) intervention on mammography uptake among nonadherent Chinese American immigrant women. METHODS: Women (N = 956) were randomized into either an SMVD group, where Chinese-speaking community health workers (CHWs) used an effective, culturally appropriate video to discuss mammography, or a video-only group, which viewed the cultural video sent by mail. Outcomes were mammography uptake at 6 months and 21 months postintervention. RESULTS: Women in both groups increased mammography uptake, and an outcome analysis revealed no group differences (adjusted odds ratio [AOR], 1.18; 95% confidence interval [CI], .68-2.06). Overall, 61.2% of the SMVD group and 55.3% of the video-only group had at least one mammogram during the 21-month follow-up period. When considering attendance to the SMVD, SMVD attendees had higher mammography uptake than the video-only group (AOR, 1.51; 95% CI, 1.19-1.92), and SMVD nonattendees had lower mammography uptake than the video-only group (AOR, .33; 95% CI, .22-.50). CONCLUSIONS: Both intervention strategies were associated with increased mammography uptake. The authors observed that the increase in use was greater among women who participated in the SMVD session compared with those who viewed the cultural video only. Future research may explore a virtual SMVD intervention for higher session attendance and increased mammography uptake (ClinicalTrials.gov identifier NCT01292200).

6.
Cancer ; 130(17): 3011-3022, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38676935

RESUMEN

BACKGROUND: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population. METHODS: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate the odds of psychological distress by cancer status after adjusting for covariates. Interactions between variables and cancer status were investigated. RESULTS: The study included 334 Black survivors of AYA cancer and 3340 Black controls. Compared to controls, survivors were more likely to report moderate/severe distress (odds ratio [OR], 1.64; p < .001), use mental health care (OR, 1.53; p = .027), report an inability to afford mental health care (OR, 3.82; p < .001), and use medication for anxiety and/or depression (OR, 2.16; p = .001). Forty-one percent of survivors reported moderate/severe distress, and only 15% used mental health care. Among survivors, ages 18-39 years (vs. 40-64 years) and current smoking (vs. never smoking) were associated with the presence of moderate/severe distress. Among survivors with distress, high poverty status was associated with reduced utilization of mental health care. CONCLUSIONS: A cancer diagnosis for a Black AYA is associated with greater psychological distress within an already vulnerable population.


Asunto(s)
Negro o Afroamericano , Supervivientes de Cáncer , Distrés Psicológico , Humanos , Femenino , Masculino , Adulto Joven , Adolescente , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Neoplasias/psicología , Neoplasias/terapia , Neoplasias/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Estrés Psicológico/epidemiología , Servicios de Salud Mental/estadística & datos numéricos
7.
Ann Surg ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145635

RESUMEN

OBJECTIVE: To assess the effectiveness of optimized ex-vivo liver resection and autotransplantation (ELRA) for treating liver malignancies. SUMMARY BACKGROUND DATA: ELRA is a promising surgery for radical resection of conventionally unresectable tumors, despite the disappointing long-term prognosis during its' developmental stages. A recent multicenter study reported 5-year overall and disease-free survival rates (OS, DFS) of 28% and 20.8%, respectively. METHODS: We retrospectively analyzed data of patients who underwent ELRA for advanced liver cancers between 2009 and 2022. We applied ELRA via our novel surgical indication classification system where the surgical risk with curative intent for advanced liver malignancy was controllable using the ex-vivo approach. The ELRA was optimized for determinacy, predictability, and controllability via the precision liver surgery paradigm (PLS). RESULTS: Thirty-seven cases with liver malignancies were enrolled. The operative time and anhepatic phase duration were 649.6±200.0 and 261.2±74.5 min, respectively, while the intraoperative blood loss was 1902±1192 mL. Negative resection margins were achieved in all patients, and the 90-day morbidity at Clavien-Dindo IIIa/IIIb and mortality rates were 27.0% and 24.3%. Post-ELRA 1-, 3-, and 5-year actual OS rates were 62.2%, 37.8%, and 35.1%, respectively, and 1-, 3-, and 5-year actual DFS were 43.2%, 24.3%, and 18.9%, respectively. CONCLUSIONS: Long-term outcomes of ELRA under the PLS for advanced liver malignancy were favorable. Appropriate criteria for disease selection & surgical indications and optimized procedures together can improve surgical treatment and patient prognosis.

8.
Oncologist ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180465

RESUMEN

BACKGROUND: Arm symptoms commonly endure in post-breast cancer period and persist into long-term survivorship. However, a knowledge gap existed regarding the interactions among these symptoms. This study aimed to construct symptom networks and visualize the interrelationships among arm symptoms in breast cancer survivors (BCS) both with and without lymphedema (LE). PATIENTS AND METHODS: We conducted a secondary analysis of 3 cross-sectional studies. All participants underwent arm circumference measurements and symptom assessment. We analyzed 17 symptoms with a prevalence >15%, identifying clusters and covariates through exploratory factor and linear regression analysis. Contemporaneous networks were constructed with centrality indices calculated. Network comparison tests were performed. RESULTS: 1116 cases without missing data were analyzed, revealing a 29.84% prevalence of LE. Axillary lymph node dissection [ALND] (vs sentinel lymph node biopsy [SLNB]), longer post-surgery duration, and radiotherapy significantly impacted overall symptom severity (P < .001). "Lymphatic Stasis," "Nerve Injury," and "Movement Limitation" symptom clusters were identified. Core symptoms varied: tightness for total sample network, firmness for non-LE network, and tightness for LE network. LE survivors reported more prevalent and severe arm symptoms with stronger network connections than non-LE group (P = .010). No significant differences were observed among different subgroups of covariates (P > .05). Network structures were significantly different between ALND and SLNB groups. CONCLUSION: Our study revealed arm symptoms pattern and interrelationships in BCS. Targeting core symptoms in assessment and intervention might be efficient for arm symptoms management. Future research is warranted to construct dynamic symptom networks in longitudinal data and investigate causal relationships among symptoms.

9.
Biochem Biophys Res Commun ; 725: 150232, 2024 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897042

RESUMEN

Molecular processes are orchestrated by various proteins that promote early endosomes to become late endosomes and eventually fuse with lysosomes, guaranteeing the degradation of the content. Rab7, which is localized to late endosomes, is one of the most well-known GTPases. ORP1L is recruited by Rab7 to facilitate the fusion of late endosomes and lysosomes. Here, we present the structure of GDP-bound Rab7 Q67L with ORP1L. Structural analysis, supported by biochemical and ITC binding experiments, not only provides structural insight into the interactions between the ORP1L ANK domain and Rab7 but also suggests that the GTPase activity of Rab7 does not interfere with its ORP1L-binding capacity.


Asunto(s)
Guanosina Difosfato , Unión Proteica , Proteínas de Unión al GTP rab , Proteínas de Unión a GTP rab7 , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión a GTP rab7/metabolismo , Guanosina Difosfato/metabolismo , Guanosina Difosfato/química , Humanos , Modelos Moleculares , Receptores de Esteroides/metabolismo , Receptores de Esteroides/química , Conformación Proteica , Sitios de Unión
10.
Small ; 20(29): e2309038, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38456768

RESUMEN

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.


Asunto(s)
Macrófagos , Células Supresoras de Origen Mieloide , Osteosarcoma , Péptidos , Microambiente Tumoral , Zeolitas , Animales , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Osteosarcoma/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/terapia , Microambiente Tumoral/efectos de los fármacos , Péptidos/química , Zeolitas/química , Ratones , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/metabolismo , Línea Celular Tumoral , Aminopiridinas/química , Aminopiridinas/farmacología , Nanopartículas/química , Pirroles/química , Pirroles/farmacología , Terapia de Inmunosupresión , Sistemas de Liberación de Medicamentos , Humanos
11.
Ann Surg Oncol ; 31(1): 284-302, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37725224

RESUMEN

BACKGROUND: Identification of risk factors facilitates the prevention of breast cancer-related lymphedema (BCRL). Several published systematic reviews have already addressed the risk factors for BCRL. This study aimed to systematically identify potential risk factors for BCRL and evaluate the quality of evidence. METHODS: The study followed methodologic guidance from the Joanna Briggs Institute, and the Cochrane Handbook. The following electronic databases were systematically searched from inception to 15 November 2022: PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, SinoMed, Wanfang, JBI Database, Cochrane Database, ProQuest, and PROSPERO. Two authors independently screened studies, extracted data, and assessed methodologic quality using AMSTAR2, risk of bias using ROBIS, and evidence quality using GRADE. The study evaluated overlap, assessed the small-study effect, and calculated the I2 statistic and Egger's P value as needed. RESULTS: The study included 14 publications comprising 10 meta-analyses and 4 systematic reviews. The authors identified 39 factors and 30 unique meta-analyses. In the study, 13 innate personal trait-related risk factors, such as higher body mass index (BMI) and axillary lymph nodes dissection, showed statistically significant associations with BCRL incidence. Breast reconstruction was found to be a protective factor. The methodologic quality was low or critically low. The majority of the systematic reviews and/or meta-analyses were rated as having a high risk of bias. Evidence quality was low for 22 associations and moderate for 8 associations. CONCLUSIONS: The currently identified risk factors for BCRL all are innate personal trait-related factors. Future well-designed studies and robust meta-analyses are needed to explore potential associations between behavioral-, interpersonal-, and environmental-related factors and BCRL, as well as the role of genetic variations and pathophysiologic factors.


Asunto(s)
Linfedema del Cáncer de Mama , Neoplasias de la Mama , Linfedema , Femenino , Humanos , Linfedema del Cáncer de Mama/etiología , Neoplasias de la Mama/complicaciones , Escisión del Ganglio Linfático/efectos adversos , Linfedema/etiología , Linfedema/patología , Factores de Riesgo , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
12.
Ann Surg Oncol ; 31(10): 6611-6622, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38958801

RESUMEN

BACKGROUND: Upper limb lymphedema (ULL) is a common and deliberating complication for breast cancer survivors (BCSs). Breast cancer survivors with ULL reported a wide range of symptoms. However, little is known about symptom patterns and interrelationships among them. This study was designed to explore symptom clusters and construct symptom networks of ULL-related symptoms among BCSs and to identify the core symptoms. METHODS: This study is a secondary data analysis using datasets from three cross-sectional studies of BCSs in China. A total of 341 participants with maximum interlimb circumference ≥2 cm and complete responses in Part I of the Breast Cancer and Lymphedema Symptom Experience Index were included. Symptom clusters were identified through principal component analysis, and multiple linear regression analysis was employed to explore factors associated with severity of overall ULL-related symptoms. A contemporaneous network with 20 frequently reported symptoms were constructed after controlling for covariates. RESULTS: Three symptom clusters, including lymph stasis symptom cluster, nerve symptom cluster, and movement limitation symptom cluster, were identified. Postsurgery time, axillary lymph node dissection, and radiotherapy were associated with the severity of ULL-related symptoms. Tightness (rs = 1.379; rscov = 1.097), tingling (rs = 1.264; rscov = 0.925), and firmness (rs = 1.170; rscov = 0.923) were the most central symptoms in both networks with and without covariates. CONCLUSIONS: Breast cancer survivors with ULL experienced severe symptom burden. Tightness, tingling, and firmness were core symptoms of ULL among BCSs. Our findings demonstrated that the assessment and targeted intervention of specific core symptoms might help to relive effectively the burden of ULL-related symptom among BCSs.


Asunto(s)
Linfedema del Cáncer de Mama , Neoplasias de la Mama , Extremidad Superior , Humanos , Femenino , Persona de Mediana Edad , Extremidad Superior/patología , Estudios Transversales , Neoplasias de la Mama/patología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Linfedema del Cáncer de Mama/etiología , Estudios de Seguimiento , Supervivientes de Cáncer/estadística & datos numéricos , Pronóstico , Linfedema/etiología , Escisión del Ganglio Linfático/efectos adversos , Calidad de Vida , Adulto , China/epidemiología , Mastectomía/efectos adversos , Anciano
13.
Neuroendocrinology ; 114(8): 786-798, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38815558

RESUMEN

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.


Asunto(s)
Arginina Vasopresina , Factor Natriurético Atrial , Endolinfa , Mareo por Movimiento , Animales , Factor Natriurético Atrial/farmacología , Factor Natriurético Atrial/metabolismo , Factor Natriurético Atrial/administración & dosificación , Arginina Vasopresina/farmacología , Arginina Vasopresina/administración & dosificación , Arginina Vasopresina/metabolismo , Mareo por Movimiento/tratamiento farmacológico , Masculino , Endolinfa/efectos de los fármacos , Endolinfa/metabolismo , Oído Interno/efectos de los fármacos , Ratas Sprague-Dawley , Acuaporina 2/metabolismo , Ratas
14.
EMBO Rep ; 23(8): e53468, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35785414

RESUMEN

Androgen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the outcome of the disease. Using a proteomics approach, we identified the tripartite motif-containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate that TRIM33 facilitates AR chromatin binding to directly regulate a transcription program that promotes PCa progression. TRIM33 further stabilizes AR by protecting it from Skp2-mediated ubiquitination and proteasomal degradation. We also show that TRIM33 is essential for PCa tumor growth by avoiding cell-cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33-coactivated gene signature highly expressed in PCa tumors and predict disease recurrence. Overall, our results reveal that TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.


Asunto(s)
Neoplasias de la Próstata , Receptores Androgénicos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Recurrencia Local de Neoplasia/genética , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores Androgénicos/uso terapéutico , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
15.
Cell Biol Toxicol ; 40(1): 47, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869718

RESUMEN

Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.


Asunto(s)
Nefropatías Diabéticas , Transición Epitelial-Mesenquimal , Proteínas de Homeodominio , Túbulos Renales , ARN Largo no Codificante , Transición Epitelial-Mesenquimal/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Humanos , Ratones , Túbulos Renales/metabolismo , Túbulos Renales/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Masculino , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glucosa/metabolismo , Glucosa/farmacología , Fibrosis , Ratones Endogámicos C57BL , Femenino , Persona de Mediana Edad
16.
Bioorg Chem ; 153: 107902, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39461186

RESUMEN

Larotaxel (LTX) and SB-T-1214 (SBT), two new synthetic experimental toxoids, have shown broad-spectrum antitumor activity, especially against tumors that are resistant to other drugs. However, their poor solubility, membrane permeability, and first-pass effect limits their use in oral administration. We designed and synthesized two long-chain triglyceride-mimic prodrugs of LTX (LTXSSTG) and SBT (SBTSSTG), which are bridged by disulfide bonds and efficiently incorporated them into Self-nanoemulsifying drug delivery system (SNEDDS). These prodrugs can bypass hepatic metabolism by entering the blood through intestinal lymphatic transport, following a similar oral absorption pathway to dietary lipids. It was found that LTXSSTG and SBTSSTG significantly improved oral bioavailability (about 4.5-fold for LTX and 3.4-fold for SBT) compared to their solution forms. Moreover, with LTXSSTG and SBTSSTG incorporating reduction stimulus-responsive spacer were much more effective in suppressing tumor growth in vivo with eliminated adverse effects than solution form. To sum up, this strategy provides a new avenue to enhance oral delivery of new toxoids.

17.
Support Care Cancer ; 32(9): 585, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134915

RESUMEN

PURPOSE: Survivors of adolescent and young adult (AYA) cancer face significant psychological distress and encounter barriers accessing mental health care. However, limited research exists on psychological health among lesbian, gay, and bisexual (LGB) survivors of AYA cancer, particularly in comparison with heterosexual survivors and LGB individuals without a history of cancer. METHODS: Using the National Health Interview Survey (2013-2018), we identified LGB survivors of AYA cancer, LGB individuals without a history of cancer, and heterosexual survivors of AYA cancer. Sociodemographic, chronic health conditions, modifiable factors (such as smoking and alcohol use), and psychological outcomes were assessed using chi-square tests. Logistic regression models, adjusted for survey weights, evaluated the odds of psychological distress by cancer status after accounting for covariates. Interactions between variables and cancer status were explored. RESULTS: The study comprised 145 LGB survivors, 1450 LGB individuals without a history of cancer, and 1450 heterosexual survivors. Compared to heterosexual survivors, LGB survivors were more likely to report severe distress (aOR = 2.26, p = 0.021) and had higher odds of reporting a mental health care visit (aOR = 1.98, p = 0.003). Odds of severe distress (aOR = 1.36, p = 0.36) and reporting a mental health care visit (aOR = 1.27, p = 0.29) were similar between LGB survivors and LGB individuals without a history of cancer. While 47.8% of LGB survivors reported moderate/severe distress, only 29.7% reported a mental health care visit. CONCLUSION: A history of cancer during the AYA years is associated higher odds of severe psychological distress among LGB survivors compared to heterosexual survivors. However, many LGB survivors with psychological distress have not accessed mental health care.


Asunto(s)
Supervivientes de Cáncer , Distrés Psicológico , Minorías Sexuales y de Género , Humanos , Femenino , Masculino , Adulto Joven , Adolescente , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Minorías Sexuales y de Género/psicología , Minorías Sexuales y de Género/estadística & datos numéricos , Adulto , Neoplasias/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Servicios de Salud Mental/estadística & datos numéricos , Estrés Psicológico/epidemiología
18.
Environ Res ; 257: 119329, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38851372

RESUMEN

Conventional methods, such as freshwater dilution and ammonia stripping, have been widely employed for microalgae-based piggery wastewater (PW) treatment, but they cause high freshwater consumption and intensive ammonia loss, respectively. This present work developed a novel fast microbial nitrogen-assimilation technology by integrating nitrogen starvation, zeolite-based adsorption, pH control, and co-culture of microalgae-yeast for the PW treatment. Among them, the nitrogen starvation accelerated the nitrogen removal and shortened the treatment period, but it could not improve the tolerance level of microalgal cells to ammonia toxicity based on oxidative stress. Therefore, zeolite was added to reduce the initial total ammonia-nitrogen concentration to around 300 mg/L by ammonia adsorption. Slowly releasing ammonia at the later phase maintained the total ammonia-nitrogen concentration in the PW. However, the pH increase could cause lots of ammonia loss air and pollution and inhibit the desorption of ammonia from zeolite and the growth and metabolism of microalgae during the microalgae cultivation. Thus, the highest biomass yield (3.25 g/L) and nitrogen recovery ratio (40.31%) were achieved when the pH of PW was controlled at 6.0. After combining the co-cultivation of microalgae-yeast, the carbon-nitrogen co-assimilation and the alleviation of pH fluctuation further enhanced the nutrient removal and nitrogen migration to high-protein biomass. Consequently, the fast microbial nitrogen-assimilation technology can help update the industrial system for high-ammonia wastewater treatment by improving the treatment and nitrogen recovery rates.


Asunto(s)
Amoníaco , Microalgas , Nitrógeno , Aguas Residuales , Nitrógeno/metabolismo , Aguas Residuales/química , Aguas Residuales/microbiología , Amoníaco/metabolismo , Microalgas/metabolismo , Microalgas/crecimiento & desarrollo , Animales , Zeolitas/química , Eliminación de Residuos Líquidos/métodos , Porcinos , Contaminantes Químicos del Agua , Crianza de Animales Domésticos/métodos , Proteínas en la Dieta
19.
BMC Public Health ; 24(1): 1506, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840086

RESUMEN

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. METHODS: The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. DISCUSSION: Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. TRIAL REGISTRATION: NCT05057312.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Promoción de la Salud/métodos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Texas , Vacunación/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
BMC Public Health ; 24(1): 1736, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38944666

RESUMEN

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.


Asunto(s)
Ejercicio Físico , Rotura Prematura de Membranas Fetales , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Adulto , Rotura Prematura de Membranas Fetales/epidemiología , China , Estudios Prospectivos , Cohorte de Nacimiento , Adulto Joven , Encuestas y Cuestionarios , Factores de Riesgo , Estudios de Cohortes , Pueblos del Este de Asia
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