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1.
Int J Biol Macromol ; 268(Pt 2): 131999, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697416

RESUMO

In this paper, effects of preheating-induced denaturation of proteins and oleosomes on protein structure and soymilk quality were studied. The protein in soybeans baked at 55 °C (B-55) and 85 °C (B-85) showed an increase of ß-sheet content by 3.2 % and a decrease of α-helix content by 3.3 %, indicating that proteins were gradually unfolded while oleosomes remained intact. The protein resisted thermal denaturation during secondary heating, and soymilks were stable as reflected by a small d3,2 (0.4 µm). However, raw soymilk from soybeans baked at 115 °C (B-115), steamed for 1 min (ST-1) and 5 min (ST-5) presented oleosomes destruction and lipids aggregates. The proteins were coated around the oil aggregates. The ß-turn content from soybeans steamed for 10 min (ST-10) increased by 9.5 %, with a dense network where the OBs were tightly wrapped, indicating the serious protein denaturation. As a result, the soymilks B-115 or steamed ones were unstable as evidenced by the serious protein aggregation and larger d3,2 (5.65-12.48 µm). Furthermore, the soymilks were graininess and the protein digestion was delayed due to the formation of insoluble protein aggregates. The flavor and early-stage lipid digestion of soymilk from steamed soybeans was improved owing to lipid release.

2.
J Pharm Sci ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38750935

RESUMO

Characterization and understanding of protein higher order structure (HOS) is essential at all stages of biologics development. Here, two folding variants of a bispecific monoclonal antibody, the correctly folded form and an alternative configuration with reduced potency, were characterized by several HOS characterization techniques. Specifically, differential scanning calorimetry (DSC), circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), Raman and Raman optical activity (ROA) spectroscopy were used together to elucidate the impacts of disulfide bond scrambling in the fused scFv domains on the structure and thermal stability of the antibody. This study illustrates the importance of selecting appropriate biophysical characterization techniques based on the nature and magnitude of the HOS change.

3.
Chem Biol Interact ; 395: 111016, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670420

RESUMO

Acute kidney injury (AKI) is a common and serious global health problem with high risks of mortality and the development of chronic kidney diseases. Leonurine is a unique bioactive component from Leonurus japonicus Houtt. and exerts antioxidant, antiapoptotic or anti-inflammatory properties. This study aimed to explore the benefits of leonurine on AKI and the possible mechanisms involved, with a particular foc on the regulation of ferroptosis and endoplasmic reticulum (ER) stress. Our results showed that leonurine exhibited prominent protective effects against AKI, as evidenced by the amelioration of histopathological alterations and reduction of renal dysfunction. In addition, leonurine significantly suppressed ferroptosis in AKI both in vivo and in vitro by effectively restoring ultrastructural abnormalities in mitochondria, decreasing ASCL4 and 4-HNE levels, scavenging reactive oxygen species (ROS), as well as increasing GPX4 and GSH levels. In parallel, leonurine also markedly mitigated ER stress via down-regulating PERK, eIF-2α, ATF4, CHOP and CHAC1. Further studies suggested that ER stress was closely involved in erastin-induced ferroptosis, and leonurine protected tubular epithelial cells in vitro by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway. Mechanistically, ATF4 silencing in vitro regulated CHOP and ACSL4 expressions, ultimately weakening both ER stress and ferroptosis. Notably, analyses of single-cell RNA sequencing data revealed that ATF4, CHOP and ASCL4 in renal tubular cells were all abnormally upregulated in patients with AKI compared to healthy controls, suggesting their contributions to the pathogenesis of AKI. Altogether, these findings suggest that leonurine alleviates AKI by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway, thus providing novel mechanisms for AKI treatment.


Assuntos
Fator 4 Ativador da Transcrição , Injúria Renal Aguda , Estresse do Retículo Endoplasmático , Ferroptose , Ácido Gálico , Transdução de Sinais , Fator de Transcrição CHOP , Ferroptose/efeitos dos fármacos , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Fator 4 Ativador da Transcrição/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Animais , Fator de Transcrição CHOP/metabolismo , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Espécies Reativas de Oxigênio/metabolismo , Substâncias Protetoras/farmacologia
4.
Environ Int ; 186: 108656, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38621321

RESUMO

Cadmium (Cd) is an accumulative toxic metal which poses a serious threat to human health, even in trace amounts. One of the most important steps in the pathophysiology of lung cancer (LC) is the epithelial-mesenchymal transition (EMT). In this investigation, a cell malignant transformation model was established by exposing human bronchial epithelial cells (16HBE) to a low dose of Cd for 30 weeks, after which a highly expressed circular RNA (circ_000999) was identified. Cd-induced EMT was clearly observed in rat lungs and 16HBE cells, which was further enhanced following circ_000999-overexpression. Furthermore, upregulated EIF4A3 interacted with the parental gene AGTPBP1 to promote high expression of circ_000999. Subsequent experiments confirmed that circ_000999 could regulate the EMT process by competitively binding miR-205-5p and inhibiting its activity, consequently upregulating expression of zinc finger E-box binding protein 1 (ZEB1). Importantly, the circ_000999 expression level in LC tissues was significantly increased, exhibiting a strong correlation with EMT indicators. Overall, these findings provide a new objective and research direction for reversing lung EMT and subsequent treatment and prevention of LC.


Assuntos
Cádmio , Transição Epitelial-Mesenquimal , MicroRNAs , RNA Circular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Animais , Humanos , Ratos , Cádmio/toxicidade , Transformação Celular Neoplásica , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Masculino
5.
Sci Total Environ ; 929: 172584, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641101

RESUMO

Salinization and sodication have become an important abiotic stress affecting soil fertility and crop production in the western of the Songnen Plain in Northeast China. And rice cultivation is considered as one of the most effective biological methods to reclaim saline-sodic soils and ensure food security. However, it is difficult to select the optimal measures to regulate rice growth for increasing yield, because the independent and comprehensive influences of the soil limitation factors on rice yield are not quantitatively evaluated. In this study, the hierarchical partitioning (HP) and the structural equation model (SEM) were used to quantitatively evaluate the influences of salinization parameters, salt ion concentrations and soil nutrients to identify the dominant limitation factors and obstacle mechanism for rice yield. The results showed that soil pH was the key index in salinization parameters, [CO32- + HCO3-] was the key index in salt ion concentrations and available nitrogen (AN) was the key index in soil nutrients to impact rice yield, which independent influences reached 53.7 %, 45.4 % (negative) and 53.2 % (positive), respectively. Soil pH was determined by [CO32- + HCO3-], and the negative effect of alkali stress on rice yield mainly caused by [CO32- + HCO3-] was greater than that of salt stress mainly caused by [Na+] in saline-sodic paddy fields. Among the soil chemical factors, soil pH and AN were the most important explanatory variables of rice yield in saline-sodic paddy fields, which standardized total effects were - 0.32 and 0.40, respectively. Furthermore, the AN showed a more significant negative correlation with soil pH and a higher yield-increasing potential in severe saline-sodic soils (9 ≤ pH < 10) than that in moderate saline-sodic soils (8 ≤ pH < 9). Therefore, decreasing [CO32- + HCO3-] and increasing the content of AN are key to improve rice yield in saline-sodic paddy fields.

6.
Transl Cancer Res ; 13(2): 952-974, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482442

RESUMO

Background: Wilms' tumor 1 associated protein (WTAP) is an essential component of the m6A methyltransferase complex. The research on WTAP has been continuously developed and promoted in recent years. It is needed to make systematic specific bibliometric and database analyses on WTAP, to identify the cooperation and impact of authors, countries, institutions and journals, to evaluate the knowledge base and find the hotspot trends, and to detect the emerging topics regarding WTAP research. Methods: The related articles and reviews of WTAP in the Web of Science Core Collection from January 1999 to June 2022 were retrieved, and CiteSpace and VOSviewer were used to perform bibliometric and knowledge-map analyses. Multiple databases were used to explore the expression level of WTAP in pan-cancers and its correlation with prognosis and immune infiltration. Results: In recent years, the number of publications on WTAP research has increased rapidly. Among the journals publishing WTAP research, Frontiers in Cell and Developmental Biology had the most papers, while Nature papers were most cited. The country with the highest number of publications on WTAP was China, and China Medical University was the institution with the most publications. The most prominent author was Haruo Sugiyama from Japan. Four main aspects of WTAP research included m6A modification, tumor association, cancer therapy, and regulatory mechanisms. The research frontiers and hotspots were m6A modification, methyltransferase, demethylation, tumor microenvironment (TME), and immunotherapy. Bioinformatics analysis showed that the expression of WTAP was up-regulated in a variety of tumors and closely related to TME and survival prognosis. Conclusions: From the bibliometric and database analyses on the researches on WTAP, it is suggested that up-regulated WTAP in cancers may promote cancer progression by mediating abnormal m6A modifications to reshape the TME, thereby affecting the survival prognosis of the patients. The information would provide helpful references for scholars focusing on WTAP and provide new insights for WTAP as a prognostic evaluation and immunotherapy for tumors in the future.

7.
bioRxiv ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38464057

RESUMO

Poor neurodevelopment is often observed with congenital heart disease (CHD), especially with mutations in chromatin modifiers. Here analysis of mice with hypoplastic left heart syndrome (HLHS) arising from mutations in Sin3A associated chromatin modifier Sap130 , and adhesion protein Pcdha9, revealed neurodevelopmental and neurobehavioral deficits reminiscent of those in HLHS patients. Microcephaly was associated with impaired cortical neurogenesis, mitotic block, and increased apoptosis. Transcriptional profiling indicated dysregulated neurogenesis by REST, altered CREB signaling regulating memory and synaptic plasticity, and impaired neurovascular coupling modulating cerebral blood flow. Many neurodevelopmental/neurobehavioral disease pathways were recovered, including autism and cognitive impairment. These same pathways emerged from genome-wide DNA methylation and Sap130 chromatin immunoprecipitation sequencing analyses, suggesting epigenetic perturbation. Mice with Pcdha9 mutation or forebrain-specific Sap130 deletion without CHD showed learning/memory deficits and autism-like behavior. These novel findings provide mechanistic insights indicating the adverse neurodevelopment in HLHS may involve cell autonomous/nonautonomous defects and epigenetic dysregulation and suggest new avenues for therapy.

8.
J Med Syst ; 48(1): 35, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530526

RESUMO

This retrospective study assessed the effectiveness and impact of implementing a Modified Early Warning System (MEWS) and Rapid Response Team (RRT) for inpatients admitted to the general ward (GW) of a medical center. This study included all inpatients who stayed in GWs from Jan. 2017 to Feb. 2022. We divided inpatients into GWnon-MEWS and GWMEWS groups according to MEWS and RRT implementation in Aug. 2019. The primary outcome, unexpected deterioration, was defined by unplanned admission to intensive care units. We defined the detection performance and effectiveness of MEWS according to if a warning occurred within 24 h before the unplanned ICU admission. There were 129,039 inpatients included in this study, comprising 58,106 GWnon-MEWS and 71,023 GWMEWS. The numbers of inpatients who underwent an unplanned ICU admission in GWnon-MEWS and GWMEWS were 488 (.84%) and 468 (.66%), respectively, indicating that the implementation significantly reduced unexpected deterioration (p < .0001). Besides, 1,551,525 times MEWS assessments were executed for the GWMEWS. The sensitivity, specificity, positive predicted value, and negative predicted value of the MEWS were 29.9%, 98.7%, 7.09%, and 99.76%, respectively. A total of 1,568 warning signs accurately occurred within the 24 h before an unplanned ICU admission. Among them, 428 (27.3%) met the criteria for automatically calling RRT, and 1,140 signs necessitated the nursing staff to decide if they needed to call RRT. Implementing MEWS and RRT increases nursing staff's monitoring and interventions and reduces unplanned ICU admissions.


Assuntos
Equipe de Respostas Rápidas de Hospitais , Quartos de Pacientes , Humanos , Estudos Retrospectivos , Pacientes Internados , Hospitalização , Unidades de Terapia Intensiva , Mortalidade Hospitalar
9.
Am J Infect Control ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460730

RESUMO

BACKGROUND: To evaluate the economic loss of hospital-acquired infections (HAIs) among tumor patients so as to help policymakers to allocate health care resources and address the issue. METHODS: We conducted a retrospective, 1:1 matched case-control study in a large region cancer hospital between January 1 and December 31, 2022. The economic burden was estimated as the median of the 1:1 pair differences of various hospitalization fees and hospital length of stay (LOS). RESULTS: In this study of 329 matched pairs, the patients with HAIs incurred higher hospitalization cost (ie, $16,927) and experienced longer hospital LOS (ie, 22 days), compared to the non-HAI groups. The extra hospitalization cost and the prolonged hospital LOS caused by HAIs were $4,919 and 9 days, respectively. Accordingly, the direct nonmedical economic loss attributable to HAI was approximately $478 to 835 per case. Furthermore, the increment of hospitalization costs varied by sites of infection, types of tumors, and stratum of age. CONCLUSIONS: HAIs lead to the increment of direct economic burden and hospital LOS in tumor patients. Our findings highlight the importance of implementing effective infection control measures in hospitals to reduce the financial burden on tumor patients.

10.
Geriatr Nurs ; 56: 138-147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38342002

RESUMO

Patients with moderate to severe COPD frequently experience dyspnea, which causes these patients to acquire a fear of dyspnea and a fear of activity. This study developed a cognitive intervention combined with active cycle of breathing technique (ACBT) intervention program based on the fear-avoidance model, with the goal of evaluating the program's effectiveness in improving dyspnea-related kinesiophobia in patients with moderate to severe COPD. This study had a total of 106 participants. For 8 weeks, the intervention group (N=53) received cognitive combined with ACBT, while the control group (N=53) received standard care. The findings of the four times the dyspnea belief questionnaire were collected indicated that the combined intervention had a better impact on reducing dyspnea-related kinesiophobia than did routine nursing (P<0.05), and the impact persisted even after the intervention. Additionally, it may enhance dyspnea and quality of life, increase exercise capacity, and lower the BODE index.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Qualidade de Vida , Cinesiofobia , Dispneia , Cognição
11.
J Hazard Mater ; 469: 133828, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38412643

RESUMO

According to the World Health Organization, chronic obstructive pulmonary disease (COPD) was one of the top ten causes of death worldwide in 2019. The ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) provides a useful indicator for the diagnosis of COPD. Existing data have demonstrated that cadmium (Cd) exposure is associated with COPD. However, data concerning the incidence and progression of cadmium-induced COPD is inconsistent. To explore the relationship between cadmium exposure and the risk of COPD in humans, through January 12, 2023, we conducted a thorough search of the PubMed, Cochrane, Web of Science, Embase and Scopus databases for relevant material. In this study, a meta-analysis was conducted to evaluate the association between cadmium and COPD. This meta-analysis indicated that exposure to cadmium (per 1 µg/L increase) was associated with reduced FEV1/FVC (% change = -47.54%, 95% CI: -54.99% to -40.09%). Subgroup analysis showed that the combined effect estimates were significantly higher in the COPD patient group (% change = -54.66%, 95% CI: -83.32% to -26.00%) than in the general population (% change = -52.11%, 95%CI: -60.53% to -43.70%). Therefore, we conclude that cadmium exposure is associated with reduced FEV1/FVC, which suggests a risk for COPD.


Assuntos
Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Humanos , Cádmio/toxicidade , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Volume Expiratório Forçado , Capacidade Vital
12.
Cell Rep ; 43(2): 113751, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38341855

RESUMO

The premetastatic niche (PMN) contributes to lung-specific metastatic tropism in osteosarcoma. However, the crosstalk between primary tumor cells and lung stromal cells is not clearly defined. Here, we dissect the composition of immune cells in the lung PMN and identify granulocytic myeloid-derived suppressor cell (gMDSC) infiltration as positively associated with immunosuppressive PMN formation and tumor cell colonization. Osteosarcoma-cell-derived extracellular vesicles (EVs) activate lung interstitial macrophages to initiate the influx of gMDSCs via secretion of the chemokine CXCL2. Proteomic profiling of EVs reveals that EV-packaged S100A11 stimulates the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in macrophages by interacting with USP9X. High level of S100A11 expression or circulating gMDSCs correlates with the presentation of lung metastasis and poor prognosis in osteosarcoma patients. In summary, we identify a key role of tumor-derived EVs in lung PMN formation, providing potential strategies for monitoring or preventing lung metastasis in osteosarcoma.


Assuntos
Neoplasias Ósseas , Vesículas Extracelulares , Neoplasias Pulmonares , Osteossarcoma , Humanos , Proteômica , Proteínas S100 , Ubiquitina Tiolesterase
13.
Zhongguo Zhong Yao Za Zhi ; 49(1): 151-161, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403348

RESUMO

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.


Assuntos
Injúria Renal Aguda , Ferroptose , Camundongos , Masculino , Animais , Cisplatino/efeitos adversos , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/genética , Glicogênio , Superóxido Dismutase , Ferro , 1-Acilglicerofosfocolina O-Aciltransferase
14.
Artigo em Inglês | MEDLINE | ID: mdl-38376127

RESUMO

OBJECTIVE: To investigate the efficacy of targeted scapular stabilization exercise in shoulder pain. DESIGN: This is an evaluator-blinded, multicenter, randomized controlled trial. The scapular stabilization exercise group (n = 45) received scapular stabilization exercise based on the type of scapular dyskinesis (SD) for 6 weeks; the conventional exercise group (n = 45) received pendulum, wall climbing and stick exercises for 6 weeks. Constant-Murley score (CMS), were numerical rating scale (NRS), range of motion (ROM), type of SD, lateral scapular sliding test (LSST), pectoralis minor index (PMI), scapular index (SI) and satisfaction were assessed at baseline, two, four, six-week treatment and a 6-week follow-up. RESULTS: After a 6-week intervention, the improvement of CMS was greater in the scapular stabilization exercise group than in the conventional exercise group, and improvement continued at the 6-week follow-up (F = 15.39, P < 0.001, Partial η2 = 0.17). The Results were also significant for NRS during activity, LSST, PMI, type of SD and satisfaction in favor of the scapular stabilization exercise group (P < 0.05). CONCLUSION: Targeted scapular stabilization exercise is an effective intervention program that might be applied to the rehabilitation of shoulder pain.

15.
BMC Cancer ; 24(1): 247, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388388

RESUMO

BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.


Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Neoplasias Ureterais/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Urológicas/cirurgia , Neoplasias Urológicas/patologia , Células Epiteliais/patologia , Carcinoma de Células Escamosas/cirurgia
16.
Cell Metab ; 36(3): 598-616.e9, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38401546

RESUMO

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Trombose , Humanos , Camundongos , Animais , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Colágeno/metabolismo , Plaquetas/metabolismo , COVID-19/metabolismo
17.
Eur J Oncol Nurs ; 69: 102535, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401347

RESUMO

OBJECTIVE: To verify and compare whether the digital stories could effectively improve the resilience, self-efficacy and quality of life of postoperative NSCLC patients. MATERIALS AND METHODS: A total of 90 participants at baseline were randomly assigned to two groups, 45 patients per group. The intervention group received the digital storytelling intervention which includes 4 videos on different topics: positive psychological quality, cultivating healthy living habits, establishing good social support, and insisting on scientific exercise, whereas the control group received only routine care. The resilience, self-efficacy, and quality of life were assessed at baseline (T0) (within 3 days before surgery), immediately after intervention (T1), one month after intervention (T2), and three months after intervention (T3). A linear mixed effects model was used to test the effects of the digital storytelling interventions on resilience, self-efficacy, and quality of life. RESULTS: The intervention group reported significantly greater improvements in resilience, self-efficacy, and quality of life (all P < 0.001) at follow-ups than the control group after controlling for age, gender, and education level as covariates. Moreover, the sensitivity analysis results are consistent with the per-protocol, that overall time × group interactions effects were significantly different in resilience, self-efficacy, and quality of life (all P < 0.001). CONCLUSION: The digital storytelling intervention based on lung cancer survivors' experience can effectively improve resilience, self-efficacy and quality of life in postoperative lung cancer patients. More comprehensive researches are needed to evaluate the longer-term impacts of the DST and its feasibility for those with more advanced cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Resiliência Psicológica , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Qualidade de Vida , Autoeficácia , Neoplasias Pulmonares/cirurgia
18.
Phytother Res ; 38(3): 1623-1650, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302697

RESUMO

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/ß-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Macroautofagia , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Autofagia , Proliferação de Células
19.
J Med Internet Res ; 26: e47134, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194260

RESUMO

BACKGROUND: Embodied conversational agents (ECAs) are computer-generated animated humanlike characters that interact with users through verbal and nonverbal behavioral cues. They are increasingly used in a range of fields, including health care. OBJECTIVE: This scoping review aims to identify the current practice in the development and evaluation of ECAs for chronic diseases. METHODS: We applied a methodological framework in this review. A total of 6 databases (ie, PubMed, Embase, CINAHL, ACM Digital Library, IEEE Xplore Digital Library, and Web of Science) were searched using a combination of terms related to ECAs and health in October 2023. Two independent reviewers selected the studies and extracted the data. This review followed the PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. RESULTS: The literature search found 6332 papers, of which 36 (0.57%) met the inclusion criteria. Among the 36 studies, 27 (75%) originated from the United States, and 28 (78%) were published from 2020 onward. The reported ECAs covered a wide range of chronic diseases, with a focus on cancers, atrial fibrillation, and type 2 diabetes, primarily to promote screening and self-management. Most ECAs were depicted as middle-aged women based on screenshots and communicated with users through voice and nonverbal behavior. The most frequently reported evaluation outcomes were acceptability and effectiveness. CONCLUSIONS: This scoping review provides valuable insights for technology developers and health care professionals regarding the development and implementation of ECAs. It emphasizes the importance of technological advances in the embodiment, personalized strategy, and communication modality and requires in-depth knowledge of user preferences regarding appearance, animation, and intervention content. Future studies should incorporate measures of cost, efficiency, and productivity to provide a comprehensive evaluation of the benefits of using ECAs in health care.


Assuntos
Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Voz , Pessoa de Meia-Idade , Humanos , Feminino , Comunicação , Doença Crônica
20.
BMJ Open ; 14(1): e071967, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191256

RESUMO

INTRODUCTION: Long head of biceps brachii tendinopathy (LHBT) is characterised by persistent pain and disability of shoulder joint, impairing patients' quality of life. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment, which promotes tissue regeneration and repair. However, ESWT has a side effect that often causes short-term pain and swelling in the treatment area. It is known that the effects of Kinesio taping (KT) on relieving swelling and pain. Due to insufficient clinical evidence from current limited studies, this randomised controlled study aims to explore the effects of ESWT combined with KT on upper limb function during individuals with LHBT. METHODS AND ANALYSIS: A 2×2 factorial design, double-blind, randomised controlled trial will be conducted. A total of 144 participants will be randomly allocated into one of four groups (KT+ESWT, KT+sham ESWT, sham KT+ESWT or sham KT+sham ESWT) to participate in a 4-week treatment programme. Measurements will be taken at pretreatment (baseline), immediately after treatment and 6 weeks after treatment. The primary endpoint will be the Constant-Murley score (CMS), the secondary endpoints will include the pain Numerical Rating Scale, range of motion, pressure pain threshold and soft tissue hardness of biceps, speed test and global rating of change. Repeated measures analysis of variance will be used to compare differences among the effects of different interventions. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. In addition to international conference reports, findings will be disseminated through international publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100051324.


Assuntos
Doenças Musculoesqueléticas , Qualidade de Vida , Humanos , China , Extremidade Superior , Método Duplo-Cego , Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
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