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1.
Transl Oncol ; 46: 102011, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823257

RESUMO

Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation. Moreover, FUT6 expression is regulated by rs10409772 shown in the luciferase essays, a single nucleotide polymorphism in the promoter of FUT6. Our study suggests that elevated expression of FUT6 promotes PKA/CREB signaling, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased FUT6 expression.

2.
Cancer Med ; 13(9): e7085, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716637

RESUMO

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.


Assuntos
Terapia por Exercício , Fadiga , Qualidade de Vida , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/psicologia , Masculino , Feminino , Fadiga/etiologia , Fadiga/terapia , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Idoso , Resultado do Tratamento , Adulto
3.
World J Urol ; 42(1): 330, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753035

RESUMO

PURPOSE: To compare the safety and efficacy of needle-perc-assisted endoscopic surgery (NAES) and retrograde intrarenal surgery (RIRS) for the treatment of 1- to 2-cm lower-pole stones (LPS) in patients with complex infundibulopelvic anatomy. METHODS: Between June 2020 and July 2022, 32 patients with 1- to 2-cm LPS and unfavorable lower-pole anatomy for flexible ureteroscopy were treated with NAES. The outcomes of these patients were compared with patients who underwent RIRS using matched-pair analysis (1:1 scenario). The matching parameters such as age, gender, body mass index, stone size, hardness, and pelvicalyceal anatomy characteristics including infundibular pelvic angle, infundibular length, and width were recorded. Data were analyzed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test. RESULTS: The two groups had similar baseline characteristics and lower-pole anatomy. The stone burden was comparable between both groups. NASE achieved a significantly better initial stone-free rate (SFR) than RIRS (87.5% vs 62.5%, p = 0.04). The auxiliary rates for the NAES and RIRS groups were 12.5% and 31.3%, respectively (p = 0.13). Finally, the SFR after 1 month follow-up period was still higher for the NAES group than RIRS group (93.8% versus 81.3%), but the difference was not statistically significant (p = 0.26). Concerning the operation duration, overall complication rates, and postoperative hospital stay, there were no differences between two groups. CONCLUSION: Compared to RIRS for treating 1- to 2-cm LPS in patients with unfavorable infundibulopelvic anatomy for flexible ureteroscopy, NAES was safe and effective with higher SFR and similar complication rate.


Assuntos
Cálculos Renais , Pelve Renal , Ureteroscopia , Humanos , Feminino , Masculino , Cálculos Renais/cirurgia , Pessoa de Meia-Idade , Análise por Pareamento , Pelve Renal/cirurgia , Ureteroscopia/métodos , Adulto , Resultado do Tratamento , Estudos Retrospectivos , Agulhas , Idoso , Rim/cirurgia , Rim/anatomia & histologia , Procedimentos Cirúrgicos Urológicos/métodos
4.
BMC Med ; 22(1): 199, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755585

RESUMO

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.


Assuntos
Antígeno B7-H1 , Biomarcadores Tumorais , Quimioterapia de Manutenção , Neoplasias Ovarianas , Ftalazinas , Piperazinas , Humanos , Feminino , Ftalazinas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Piperazinas/uso terapêutico , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Quimioterapia de Manutenção/métodos , Idoso , Adulto , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Proteína BRCA2/genética , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Recombinação Homóloga
5.
Diabetes Obes Metab ; 26(6): 2176-2187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38419419

RESUMO

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.


Assuntos
Tamanho Corporal , Doenças Cardiovasculares , Resistência à Insulina , Síndrome Metabólica , Obesidade , Humanos , Masculino , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , China/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Idoso , Neoplasias/epidemiologia , Estudos de Coortes , Seguimentos , População do Leste Asiático
6.
Hand Surg Rehabil ; 43(1): 101629, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185368

RESUMO

PURPOSE: Spasticity management in finger flexors (flexor digitorum profundus and superficialis and flexor pollicis longus) is a challenge. Recent studies demonstrated the short- and long-term efficacy of selective and hyperselective neurectomy for the spastic upper limb. However, hyperselective neurectomy of flexor digitorum profundus and flexor digitorum superficialis branches was incomplete, without impairing their muscular body and function. This cadaveric study describes a novel medial approach in the forearm, to reach all the muscular branches: flexor digitorum superficialis and profundus and flexor pollicis longus. MATERIAL AND METHODS: Fourteen cadaveric fresh frozen upper limbs were used. The feasibility of the medial surgical approach was studied, as well as the number, length and point of emergence of the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis. RESULTS: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, in all cases. A Martin Gruber communicating branch was found in 7 cases out of 14. CONCLUSION: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerve to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, without extensive transmuscular dissection of the pronator teres or flexor digitorum superficialis muscles. This approach opens the way for selective neurectomy of the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis muscles. LEVEL OF EVIDENCE: IV.


Assuntos
Antebraço , Músculo Esquelético , Humanos , Antebraço/cirurgia , Antebraço/inervação , Mãos , Denervação , Espasticidade Muscular/cirurgia , Cadáver
7.
Clin Transl Med ; 13(12): e1514, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38115701

RESUMO

BACKGROUND: IGH::DUX4 is frequently observed in 4% B-cell acute lymphoblastic leukaemia patients. Regarding the IGH::DUX4-driven transactivation and alternative splicing, which are the main reasons behind this acute leukaemia outbreak, it remains unclear how transcriptional cofactors contribute to this oncogenic process. Further investigation is required to elucidate their specific role in leukaemogenesis. METHODS: In order to investigate the cofactors of IGH::DUX4, integrated mining of Chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing of leukaemia cells and patient samples were conducted. Furthermore, to elucidate the synergistic interaction between transcription factor 12 (TCF12) and IGH::DUX4, knockdown and knockout experiment, mammalian two-hybridisation assay, co-immunoprecipitation and in situ proximity ligation assays were carried out. Additionally, to further investigate the direct interaction between TCF12 and IGH::DUX4, AI-based structural simulations were utilised. Finally, to validate the synergistic role of TCF12 in promoting IGH::DUX4 leukaemia, cell proliferation, apoptosis and drug sensitivity experiments were performed. RESULTS: In this study, we observed that the IGH::DUX4 target gene TCF12 might be an important cofactor/helper for this oncogenic driver. The co-expression of IGH::DUX4 and TCF12 resulted in enhanced DUX4-driven transactivation. Supportively, knockdown and knockout of TCF12 significantly reduced expression of IGH::DUX4-driven target genes in leukaemia REH (a precursor B-cell leukaemia cell line) and NALM-6 cells (a precursor B-cell leukaemia cell line). Consistently, in TCF12 knockout cells, the expression of structure-based TCF12 mutant, but not wild-type TCF12, failed to restore the TCF12-IGH::DUX4 crosstalk and the synergistic transactivation. More importantly, the breakdown in TCF12-IGH::DUX4 cooperation impaired IGH::DUX4-driven leukaemia cell survival, caused sensitivity to the chemotherapy. CONCLUSIONS: Altogether, these results helped to define a previously unrecognised TCF12-mediated positive self-feedback regulatory mechanism in IGH::DUX4 leukaemia, which holds the potential to function as a pivotal drug target for the management of this particular form of leukaemia. HIGHLIGHTS: Transcription factor 12 (TCF12) is a new novel cofactor in IGH::DUX4 transcriptional complexes/machinery. TCF12 mediates a positive self-feedback regulatory mechanism in IGH::DUX4-driven oncogenic transaction. IGH::DUX4-TCF12 structure/cooperation might represent a potent target/direction in future drug design against B-cell acute lymphoblastic leukaemia.


Assuntos
Leucemia de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Animais , Humanos , Retroalimentação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Linhagem Celular , Carcinogênese/genética , Mamíferos
8.
Orthop Traumatol Surg Res ; : 103721, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37866508

RESUMO

OBJECTIVE: High median nerve injuries can lead to poor distal recovery, especially poor functioning of median innervated thenar muscles involved in thumb opposition and palmar abduction. The palmaris brevis (PB) is a small subcutaneous muscle innervated by ulnar nerve. Innervation of the PB is in most of cases provided by the ulnar digital nerve to the little finger. The purpose of this study is to assess the feasibility of transferring the PB motor branch (PBMB) to the median nerve thenar motor branch (TMB), in order to allow for early restoration of thumb palmar abduction and opposition, through a preliminary cadaveric study. METHODS: Twenty-five cadaver upper limbs were dissected under magnification. The length of the PBMB and TMB, and their origin were recorded. Nerve transfer from PBMB to TMB was conducted, and evaluated on 2 parameters: surgical feasibility, and distance from the coaptation site to the recipient nerve muscle entry point. The PBMB and TMB were harvested, fixated in formalin, then embedded in paraffin. They were sectioned transversely, and stained with a combination of hematoxylin-eosin and Luxol fast blue. Myelinated axons were counted in each specimen and the donor-to-recipient axon ratio was recorded. RESULTS: The PBMB was constant and originated from the ulnar digital nerve of the little finger in all cases. The transfer from PBMB to TMB was feasible in all cases. Mean myelinated axon counts of PBMB and TMB were 253±142 and 356±198, respectively (p=0.06). The donor-to-recipient axon ratio was 1:1.41. The mean distance from coaptation of the PBMB to the recipient thenar muscles was 23.1±3.0mm. CONCLUSIONS: Based on our results, PBMB to TMB transfer is feasible. The PBMB has the advantage over other distal nerve transfer donors to be constant and superficial, allowing for an easier harvest. Moreover, this procedure does not sacrifice any intrinsic function of the hand, and the proximity of the PBMB with the carpal tunnel allows for a single incision procedure. Therefore, early restoration of the median innervated thenar muscles may be feasible by the PBMB to TMB transfer in cases of high median nerve lesions. LEVEL OF EVIDENCE: IV.

9.
World J Urol ; 41(11): 3121-3127, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37750960

RESUMO

PURPOSE: The goal of this study is to compare traditional percutaneous nephrolithotomy (PCNL) and needle-perc-assisted endoscopic surgery (NAES) in the treatment of complicated solitary kidney stones via a single-center randomized controlled prospective study. METHODS: A total of patients with complex (Guy's score II-IV) solitary kidney stones between July 2019 to June 2022 were enrolled in the study. Participants were stratified into two groups: needle-perc-assisted endoscopic surgery group (group A) and traditional PCNL group (group B). All procedures were finished by X-ray free technique. The clinical characteristics and outcomes were analyzed. RESULTS: A total of 90 (44 in Group A and 46 in Group B) patients were finally included in our study. There were no statistically differences in terms of gender, age, body mass index (BMI), stone burden between two groups. The mean operative duration of Group A was significant higher than group B (95.1 ± 21.4 min vs 72.5 ± 29.5 min, p=0.02). The 1-month stone-free rate (SFR) was significant higher in Group A than B (90.9% vs 73.9%, p=0.03). A less hemoglobin drop (p=0.01), shorter postoperative in-hospital day (p=0.04), and lower severe complication (Clavien-Dindo III and above) rates (p=0.03) were observed in Group A. CONCLUSION: For patients with solitary kidney stones, NAES technique provides a higher one-session SFR, a better renal function recovery and compared with traditional PCNL.


Assuntos
Cálculos Renais , Nefrostomia Percutânea , Rim Único , Humanos , Estudos Prospectivos , Nefrostomia Percutânea/métodos , Estudos Retrospectivos , Cálculos Renais/complicações , Cálculos Renais/cirurgia , Resultado do Tratamento
10.
Hum Cell ; 36(6): 2214-2227, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37535222

RESUMO

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.

11.
Trials ; 24(1): 542, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37592299

RESUMO

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/cirurgia , Estudos Prospectivos , Qualidade de Vida , Laparoscopia/efeitos adversos , Histerectomia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
12.
Adv Sci (Weinh) ; 10(26): e2302425, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37431681

RESUMO

Aldolase A (ALDOA), a crucial glycolytic enzyme, is often aberrantly expressed in various types of cancer. Although ALDOA has been reported to play additional roles beyond its conventional enzymatic role, its nonmetabolic function and underlying mechanism in cancer progression remain elusive. Here, it is shown that ALDOA promotes liver cancer growth and metastasis by accelerating mRNA translation independent of its catalytic activity. Mechanistically, ALDOA interacted with insulin- like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to facilitate its binding to m6 A-modified eIF4G mRNA, thereby increasing eIF4G protein levels and subsequently enhancing overall protein biosynthesis in cells. Importantly, administration of GalNAc-conjugated siRNA targeting ALDOA effectively slows the tumor growth of orthotopic xenografts. Collectively, these findings uncover a previously unappreciated nonmetabolic function of ALDOA in modulating mRNA translation and highlight the potential of specifically targeting ALDOA as a prospective therapeutic strategy in liver cancer.


Assuntos
Frutose-Bifosfato Aldolase , Neoplasias Hepáticas , Humanos , Frutose-Bifosfato Aldolase/genética , Fator de Iniciação Eucariótico 4G , Linhagem Celular Tumoral , Neoplasias Hepáticas/genética , RNA Interferente Pequeno/metabolismo
13.
Mol Metab ; 75: 101766, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37406987

RESUMO

Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Humanos , NF-kappa B/metabolismo , Diabetes Mellitus Tipo 2/complicações , Neoplasias Colorretais/metabolismo , Transdução de Sinais
14.
Cell Death Dis ; 14(6): 351, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291119

RESUMO

In addition to the classical role as a serum effector system of innate immunity, accumulating evidence suggests that intracellular complement components have indispensable functions in immune defense, T cell homeostasis, and tumor cell proliferation and metastasis. Here, we revealed that complement component 3 (C3) is remarkably upregulated in paclitaxel (PTX)-resistant non-small cell lung cancer (NSCLC) cells and that knockdown of C3 promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy. Ectopic C3 decreased PTX-induced apoptosis and induced resistance to PTX treatment in original NSCLC cells. Interestingly, C3b, the activated fragment of C3, was found to translocate into the nucleus and physically associate with the HDAC1/2-containing SIN3A complex to repress the expression of GADD45A, which plays an important role in cell growth inhibition and apoptosis induction. Importantly, C3 downregulated GADD45A by enhancing the binding of the SIN3A complex with the promoter of GADD45A, thus decreasing the H3Ac level to compress chromatin around the GADD45A locus. Subsequently, ectopic GADD45A promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy, and insufficiency of GADD45A in original cancer cells induced resistance to PTX treatment. These findings identify a previously unknown nucleus location and oncogenic property for C3 in chemotherapy and provide a potential therapeutic opportunity to overcome PTX resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Paclitaxel , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Complemento C3b , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Histona Desacetilase 1/genética
15.
Nat Aging ; 3(7): 813-828, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37277640

RESUMO

Regulatory T (Treg) cells modulate several aging-related liver diseases. However, the molecular mechanisms regulating Treg function in this context are unknown. Here we identified a long noncoding RNA, Altre (aging liver Treg-expressed non-protein-coding RNA), which was specifically expressed in the nucleus of Treg cells and increased with aging. Treg-specific deletion of Altre did not affect Treg homeostasis and function in young mice but caused Treg metabolic dysfunction, inflammatory liver microenvironment, liver fibrosis and liver cancer in aged mice. Depletion of Altre reduced Treg mitochondrial integrity and respiratory capacity, and induced reactive oxygen species accumulation, thus increasing intrahepatic Treg apoptosis in aged mice. Moreover, lipidomic analysis identified a specific lipid species driving Treg aging and apoptosis in the aging liver microenvironment. Mechanistically, Altre interacts with Yin Yang 1 to orchestrate its occupation on chromatin, thereby regulating the expression of a group of mitochondrial genes, and maintaining optimal mitochondrial function and Treg fitness in the liver of aged mice. In conclusion, the Treg-specific nuclear long noncoding RNA Altre maintains the immune-metabolic homeostasis of the aged liver through Yin Yang 1-regulated optimal mitochondrial function and the Treg-sustained liver immune microenvironment. Thus, Altre is a potential therapeutic target for the treatment of liver diseases affecting older adults.


Assuntos
Hepatopatias , RNA Longo não Codificante , Animais , Camundongos , Envelhecimento/genética , Homeostase/genética , Hepatopatias/metabolismo , RNA Longo não Codificante/genética , Linfócitos T Reguladores
16.
ACS Appl Mater Interfaces ; 15(22): 26682-26690, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37226043

RESUMO

Aerogels, due to their unique interconnected 3D networks, and large number of air-filled pores, extend the structural characteristics and physicochemical properties of the nanoscale to the macro level. However, aerogels made from a single component can hardly meet the needs of multifunctional energy harvesting/supply situations. Here, a BaTiO3-based hybrid aerogel (BTO HA) with 3D network structure was prepared. When the BTO HA is used as the electrode of triboelectric nanogenerator (BTO HA-TENG), high electrical output performances were obtained, which is due to the synergistic effect of solid-solid contact electrifications between the two electrification layers, the gas-solid contact electrifications between the inner surface of BTO HA and the air filled in the aerogel pores, and the piezoelectricity of the doped BaTiO3 nanoparticles. The BTO HA-TENG exhibited excellent fatigue resistance and structural stability after 12,000 cycles of alternatively contact/separation tests, and it can not only provide stable power supply for commercial capacitors, drive small mobile electronic devices but also can be used as a self-powered sensor to monitor human motion signals. Compared with traditional TENGs depending on surface charge transfer, the BTO HA-TENG exhibited its unique advantage that it can generate and transfer triboelectric charges by 3D volume, which boost TENGs' electrical output performances.

17.
World J Urol ; 41(6): 1653-1658, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37052640

RESUMO

PURPOSE: The goal of this study is to evaluate the efficacy and safety of modified triangular double-J (DJ) stent in 1-2 cm renal or ureter calculi after retrograde intrarenal surgery (RIRS) via a randomized, controlled clinical study. METHODS: A total of 196 patients with 1-2 cm renal or ureter calculi who were performed RIRS and received 7Fr modified triangular DJ stents (100 cases) or 6Fr normal DJ stents (96 cases). All operations were performed by experienced surgeons. The clinical characteristics and outcomes were analyzed. RESULTS: There were no significant differences between two groups in terms of age, gender, BMI, location, hydronephrosis, urea WBC, urea RBC, BUN, Cr, laser emission time, operation time, Hb loss, postoperative BUN, postoperative Cr. Patients who received modified triangular DJ stents were shown to have higher stone-free rate (p = 0.038), but lower general health (p = 0.004). CONCLUSION: The modified triangular 7Fr DJ stents were more efficient for patients underwent RIRS than 6Fr normal DJ stents.


Assuntos
Cálculos Renais , Ureter , Ureterolitíase , Humanos , Ureter/cirurgia , Cálculos Renais/cirurgia , Qualidade de Vida , Rim/cirurgia , Stents , Resultado do Tratamento
18.
Heliyon ; 9(2): e13317, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36825174

RESUMO

Objective: To explore the effectiveness, feasibility, and training effect of a highly simulated and adaptable laparoscopic training system in the advanced integrated two-stage laparoscopic simulation training course for surgical residents. Methods: This study prospectively took the surgical residents who received the advanced integrated two-stage laparoscopic simulation training course in our hospital from December 2019 to December 2021 as the research objects. In the stage one course, the trainees are randomly distributed into the dry simulation system group and Darwin laparoscopic training system group. The subjective assessment results of the trainees from the two groups are collected by questionnaires, and the simulation assessment results of the two groups are evaluated in a unified, objective, and standardized assessment form. The pre-course and post-course questionnaires were used to evaluate the feasibility and effectiveness of the Darwin system in the stage two course. Results: A total of 62 trainees completed the stage one and stage two courses. In the stage one course, the trainees were randomly distributed into the dry simulation trainer group (N = 19) and the Darwin group (N = 43). The results of the subjective assessment questionnaire showed that compared with the dry simulator group, the students in the Darwin group had higher subjective scores (P < 0.05). The objective assessment results for the 3 modules of "One Track Transfer", "One Tunnel Pass" and "High and Low Pillars" in the Darwin group were significantly better than those in the dry simulator group (P < 0.05). The trainees who received the stage two course completed the questionnaires before and after the course. The results showed that compared with pre-course evaluation, "basic theoretical knowledge of laparoscopy", "basic skills of laparoscopy", "laparoscopic suture technique" and "camera-holding technique" were significantly improved after training (P < 0.05). Conclusion: The highly simulated and adaptable laparoscopic training system is effective and feasible in the advanced integrated two-stage laparoscopic simulation training course for surgical residents.

19.
Ann Plast Surg ; 90(5S Suppl 2): S112-S119, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36752502

RESUMO

INTRODUCTION: The performance of a prosthetic breast augmentation through the axilla always makes the surgeon fear the possibility of damage to the breast lymphatic network. Indocyanine green is a fluorescent marker allowing the analysis of the lymphatic system. This anatomical work aims at demonstrating, thanks to the use of indocyanine green, whether the realization of a prosthetic breast augmentation by axillary way leads to lesions of the breast lymphatic network and also seeks to show the feasibility of detecting the axillary sentinel node after axillary breast augmentation. MATERIAL AND METHOD: This is an anatomical study. After injection of indocyanine green in the periareolar area, a prosthetic breast augmentation was performed through the axilla. At the end of the procedure, a change in the distribution of indocyanine green in the skin or its abnormal presence was sought: at the level of the skin incision, the prosthetic space, or in contact with the prosthesis itself. The presence of green in these situations was synonymous with a lesion of the lymphatic network. In the opposite case, we considered that the lymphatic system was respected. After sampling, an axillary lymph node we also looked for the presence of indocyanine green at its contact. RESULTS: We performed 22 breast injections. The lymphatic network could be demonstrated in 15 of them. Among these 15 injections, 12 (80%) were in favor of a preservation of the lymphatic network, whereas 3 (20%) evoked a lesion of the lymphatic network. In all subjects (100%), an axillary lymph node was found with the presence of indocyanine green within it. CONCLUSION: Our study is in favor of a preservation of the lymphatic network during a prosthetic breast augmentation by axillary way. Furthermore, with the collection of an axillary lymph node containing the dye from each subject, this work demonstrates the feasibility of axillary sentinel node detection with indocyanine green after axillary breast augmentation. Further work on live subjects and on a larger number of subjects would be necessary to confirm these results.


Assuntos
Implantes de Mama , Neoplasias da Mama , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Verde de Indocianina , Linfonodos/cirurgia , Corantes , Neoplasias da Mama/cirurgia , Axila/cirurgia , Excisão de Linfonodo
20.
Ann Plast Surg ; 90(5S Suppl 2): S203-S208, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36752518

RESUMO

ABSTRACT: The management of complex forearm injuries is challenging, not only because of the anatomical complexity of the region but also because of the dramatic functional consequences of these injuries. Preservation of the upper limb and restoration of hand function are the focus of the surgical management of these injuries. Decision making will consider several parameters such as the type of injury, the patient, the moment of reconstruction, the debridement, and the options available for reconstruction.A multidisciplinary approach joining plastic surgeons and orthopedic surgeons in a team effort is essential to achieve the best outcomes. On the basis of their experience, the authors conclude that the keystone in complex forearm injuries management is represented by a careful assessment of the lesions, an aggressive and early debridement, the prevention of complications such as infection and compartment syndrome, and an "as early as possible" reconstruction.


Assuntos
Traumatismos do Antebraço , Traumatismos da Mão , Humanos , Traumatismos do Antebraço/cirurgia , Antebraço/cirurgia , Traumatismos da Mão/cirurgia
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