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1.
J Colloid Interface Sci ; 669: 228-235, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38713961

RESUMO

The development of heterogeneous supported nanocatalysts with a high kinetics combined with low cost is off importance but remains still challenged for hydrazine hydrate served as a promising hydrogen storage material. Herein, by virtue of surficial functional groups, ultrafine NiRh NPs were monodispersed on the two-dimensional V2C surface via a conventional wet chemical co-reduction. The optimized NiRh/V2C system demonstrates an excellent catalytic performance toward selectively catalyzing dehydrogenation of hydrazine hydrate, affording 100% H2 selectivity with the turnover frequency (TOF) value of 987.5 h-1 at 323 K. Such an enhancement is mainly attributed to synergistic effect of nanosystem, which will optimize local surface energy and promote electron transfer in NiRh/V2C system, thereby improving the kinetic selectivity of catalytic hydrazine hydrate decomposition. This work has provided a facile strategy for developing nanocatalysts with high kinetics that could enable huge industrial applications in the future.

2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(1): 135-144, 2024 Jan 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38615175

RESUMO

Advance care planning (ACP) is designed to ensure that patients lacking autonomous decision-making capacity receive medical services in accordance with their expectations and preferences. Individuals with advanced cancer are a crucial target for ACP implementation. However, the current practice of ACP in this group in China is suboptimal, demanding high-quality implementation evidence to strengthen ACP in the clinical practice of patients with advanced cancer. The existing literature can be summarized into 27 pieces of evidence across 7 dimensions, including initiation time, intervention content, intervention providers, intervention modalities, communication skills, outcome indicators, and environmental support. The aforementioned evidence could provide crucial support for improving ACP implementation for patients with advanced cancer. Subsequent research efforts should integrate patient preferences and explore the most suitable implementation strategies for ACP in the Chinese population with advanced cancer, considering diverse aspects such as traditional culture, ACP education and training, legislative support, and healthcare system refinement.


Assuntos
Planejamento Antecipado de Cuidados , Neoplasias , Humanos , Povo Asiático , China , Cognição , Neoplasias/terapia
3.
Chin J Nat Med ; 22(3): 212-223, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38553189

RESUMO

Cyathulae Radix, a traditional Chinese medicine and a common vegetable, boasts a history spanning millennia. It enhances bone density, boosts metabolism, and effectively alleviates osteoporosis-induced pain. Despite its historical use, the molecular mechanisms behind Cyathulae Radix's impact on osteoporosis remain unexplored. In this study, we investigated the effects and mechanisms of Cyathulae Radix ethanol extract (CEE) in inhibiting osteoporosis and osteoclastogenesis. Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks. Micro-computed tomography (micro-CT) assessed histomorphometric parameters, bone tissue staining observed distal femur histomorphology, and three-point bending tests evaluated tibia mechanical properties. Enzyme-linked immunosorbent assay (ELISA) measured serum estradiol (E2), receptor activator for nuclear factor B ligand (RANKL), and osteoprotegerin (OPG) levels. Osteoclastogenesis-related markers were analyzed via Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase (TRAP) staining, qRT-PCR, and WB assay. Compared with the ovariectomy (OVX) group, CEE treatment enhanced trabecular bone density, maximal load-bearing capacity, and various histomorphometric parameters. Serum E2 and OPG levels significantly increased, while Receptor activator of nuclear factor-κB (RANK) decreased in the CEE group. CEE downregulated matrix metallopeptidase 9 (MMP-9), Cathepsin K (CTSK), and TRAP gene and protein expression. In bone marrow macrophages (BMMs), CEE reduced mature osteoclasts, bone resorption pit areas, and MMP-9, CTSK, and TRAP expression during osteoclast differentiation. Compared with DMSO treatment, CEE markedly inhibited RANK, TNF receptor associated factor 6 (TRAF6), Proto-oncogene c-Fos (c-Fos), Nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expressions, and Extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), NF-kappa B-p65 (p65) phosphorylation in osteoclasts. In conclusion, CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis, potentially through modulating the Estrogen Receptor (ER)/RANK/NFATc1 signaling pathway.


Assuntos
Reabsorção Óssea , Osteoporose , Feminino , Camundongos , Animais , Humanos , Osteoclastos/metabolismo , Microtomografia por Raio-X , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Osteoporose/tratamento farmacológico , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Diferenciação Celular , NF-kappa B/genética , NF-kappa B/metabolismo , Ovariectomia
4.
BMJ Open ; 13(10): e072905, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37802627

RESUMO

INTRODUCTION: Health education, as a crucial strategic measure of disease prevention and control in the 21st century, has become an important part of healthcare. As the main deliverers of patient health education, nursing personnel's patient health education competence (PHEC) has received much attention. Instruments for assessing the PHEC of nursing personnel have been developed internationally, but there is a lack of systematic reviews and evaluations of the psychometric properties of these instruments. To effectively select appropriate PHEC assessment instruments in specific contexts, a systematic and comprehensive review and evaluation of these measurement instruments are needed. The goal of this systematic review is to systematically evaluate the psychometric properties of existing PHEC instruments. METHODS AND ANALYSIS: In this study, eight databases will be searched between 1 March 2023 and 31 2023 to retrieve studies that include instrument(s) measuring the PHEC of nursing personnel. Two researchers will independently perform literature screening, data extraction and literature evaluation. In case of disagreement, a third researcher will be involved in the resolution. The measurement properties of PHEC assessment instruments will be systematically reviewed based on the consensus-based standards for the selection of health measurement instruments (COMSIN) methodology and guideline. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. We will share the findings from the study at national and/or international conferences and in a peer-reviewed journal in the fields of health education and/or patient education. PROSPERO REGISTRATION NUMBER: CRD42023393293.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem , Humanos , Revisões Sistemáticas como Assunto , Atenção à Saúde , Psicometria , Literatura de Revisão como Assunto
5.
Biomater Adv ; 154: 213649, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37820459

RESUMO

The use of nanoparticle (NP) delivery systems in cancer treatment has received significant interest, however use of such systems in delivery of cytotoxic chemotherapy agents can be limited by low encapsulation efficiency and burst release of the cytotoxin, as well issues with throughput and reproducibility during the fabrication of drug-loaded NPs. In this study, we used a hydrodynamic flow-focusing microfluidic system to successfully produce poly(lactic-co-glycolic acid) (PLGA) NPs. The physico-chemical properties of PLGA NPs were controlled by changing the manufacturing parameters, such as flow rate ratio, total flow rate, PLGA and surfactant concentration. The NAMPT inhibitor-polymer conjugate, hydroxyl-FK866-PLGA, was synthesized and used to fabricate hydroxyl-FK866-PLGA NPs for the formulation of localized delivery systems able to release low doses of cytotoxins and enhance the efficacy of NAMPT inhibitors. Hydroxyl-FK866-PLGA NPs were prepared with optimized fabrication parameters, having average Z-size of 128 ± 8 nm (PDI < 0.2), ζ-potential of -14.8 ± 5.3 mV and high encapsulation efficiency (98.6 ± 5.8 %). The pH-dependent release of hydroxyl-FK866 was monitored over time in conditions mimicking the normal (pH 7.4) and inflamed/tumor (pH 6.4) microenvironments, observing a sustained release pattern (over two months) without any initial burst release. Finally, toxicity of hydroxyl-FK866-PLGA NPs were tested in selected human cell lines, the human leukemia monocytic cell line (THP-1), and the human triple negative breast cancer cell line (MDA-MB-231). Our work suggests that microfluidic systems are a promising technology for a rapid and efficient manufacturing of PLGA-based NPs for the controlled release of cytotoxins. Moreover, the use of drug-polymer conjugates is an effective approach for the manufacturing of polymeric NPs enabling high encapsulation efficiency and a prolonged and sustained pH-dependent drug release.


Assuntos
Portadores de Fármacos , Nanopartículas , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Ácido Poliglicólico/química , Microfluídica , Reprodutibilidade dos Testes , Citotoxinas , Nanopartículas/química
6.
Eur J Med Chem ; 260: 115769, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683363

RESUMO

Acute lung injury (ALI) is a life-threatening disease with limited therapeutic options available in clinic. Development of novel strategies and drugs for anti-ALI therapy are urgently needed. In this study, a facile synthesis of 21 icetexane diterpenes and derivatives with widely-varied oxidation states, particularly the taxamairins that are otherwise challenging to access, were developed from the readily available carnosic acid. Further explorations of their biological implications led to the identification of taxamairin B (6) as a potent anti-inflammatory agent by decreasing the gene expressions of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), as well as mitigating NO and ROS production, within LPS-induced RAW264.7 cells. Taxamairin B (6, 25 mg/kg) also exerted significant protective effects against in LPS-induced ALI in mice. Mechanistic insights drawn from the transcriptomic analysis revealed that taxamairin B (6) down-regulated the PI3K-AKT pathway, along with the suppression of the nuclear translocation of NF-κB. This study not only paves a new pathway to taxamairins, but also provides novel drug leads for the development of anti-inflammatory agents with unique mode of actions.


Assuntos
Lesão Pulmonar Aguda , Diterpenos , Animais , Camundongos , NF-kappa B , Lipopolissacarídeos/farmacologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Diterpenos/farmacologia , Macrófagos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico
7.
Support Care Cancer ; 31(10): 573, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698687

RESUMO

PURPOSE: The aim of this study was to identify symptom clusters in breast cancer patients undergoing adjuvant chemotherapy. METHODS: A prospective longitudinal study was conducted. And a sample of 620 breast cancer patients receiving adjuvant chemotherapy was recruited using convenience sampling from May 20, 2020, to March 31, 2021. Data were collected eight times: the first chemotherapy cycle (T1) to the eighth cycle of chemotherapy (T8). Exploratory factor analysis was used to explore the composition of symptom clusters. RESULTS: Symptoms with an incidence of less than 20% were deleted and the remaining symptoms were included in the factor analysis. Three common factors were extracted in T1, including gastrointestinal symptom cluster, emotional and psychological symptom cluster, and menopausal symptom cluster. Five common factors were extracted from T2 to T7, including gastrointestinal symptom cluster, emotional and psychological symptom cluster, neurological symptom cluster, menopausal symptom cluster, and self-image disorder symptom cluster. Four common factors were extracted at T8, including gastrointestinal symptom cluster, emotional and psychological symptom cluster, neurological symptom cluster, and menopausal symptom cluster. CONCLUSION: Breast cancer patients undergoing adjuvant chemotherapy experience multiple symptoms and different symptom clusters in different chemotherapy cycles. It is a benefit for health care providers to better understand and care for breast cancer patients. It will also help such women to manage concurrent symptoms ahead to promote their quality of life.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Estudos Longitudinais , Síndrome , Estudos Prospectivos , Qualidade de Vida
8.
Sci Rep ; 13(1): 14706, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679587

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-ß1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-ß but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.


Assuntos
Fibrose Pulmonar Idiopática , Lignanas , Animais , Camundongos , PPAR gama , Lignanas/farmacologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Bleomicina/efeitos adversos
9.
Artigo em Inglês | MEDLINE | ID: mdl-37353313

RESUMO

BACKGROUND AND OBJECTIVE: An in-depth understanding of what constitutes a good death among patients with cancer is vital to providing patient-centred palliative care. This review aimed to synthesise evidence on the perceptions of a good death among patients with cancer. METHODS: This systematic review involved a synthesis of qualitative data. A three-step process suggested by the Joanna Briggs Institute was used to synthesise the data. RESULTS: A total of 1432 records were identified, and five articles met the inclusion criteria. Seven synthesised findings emerged: (1) being aware of cancer, (2) pain and symptom management, (3) dying well, (4) being remembered after death, (5) individual perspectives of a good death, (6) individual behaviours leading to a good death, and (7) culture and religions. A structural framework was developed to elicit two layers that could be regarded as determinants of a good death. One layer suggested how multiple external issues impact a good death, whereas the other layer involves patients' internal attributes that shape their experiences of a good death. The elements in the two layers were inter-related to exert a crossover effect on good death in specific cultural and religious contexts. CONCLUSION: A good death is a process initiated from the time of awareness of cancer and extends beyond demise. Holistic approaches encompassing the management of physical and psychological distress along with psychosocial behavioural interventions to enhance patients' positive perspectives and behaviours are recommended to improve their quality of life and death.

10.
Biosci Biotechnol Biochem ; 87(9): 960-971, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37291698

RESUMO

Inhibition of extensive osteoclastogenesis and bone resorption is considered a potential therapeutic target for the treatment of osteoporosis. Isobavachalcone (IBC) is derived from the traditional Chinese herb Psoralea corylifolia Linn. We showed that IBC dose-dependently suppressed receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis in bone marrow monocyte/macrophage (BMMs) and osteoclastic bone-resorption function without cytotoxicity at a dose of no more than 8 µmin vitro. Mechanistically, the results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) indicated that IBC inhibited the RANKL-induced degradation of IκBα and phosphorylation of nuclear factor kappa B (NF-κB) in BMMs, and subsequently downregulated the expression of osteoclastic-specific genes and osteoclastogenesis-related proteins. TRAP staining and qRT-PCR showed that IBC can inhibit osteoclast differentiation by down-regulating the expression of miR-193-3p on osteoclast differentiation. Overall, our findings suggest that IBC may serve as a promising compound for the treatment of osteoporosis and other metabolic bone diseases.


Assuntos
Reabsorção Óssea , MicroRNAs , Osteoporose , Humanos , NF-kappa B/metabolismo , Osteogênese , Ligante RANK/farmacologia , Ligante RANK/metabolismo , Transdução de Sinais , Osteoclastos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Osteoporose/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Fatores de Transcrição NFATC/metabolismo
11.
Adv Sci (Weinh) ; 10(16): e2207010, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37083240

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with high incidence rates of metastasis and cachexia. High circulating activin A, a homodimer of inhibin ßA subunits that are encoded by INHBA gene, predicts poor survival among PDAC patients. However, it still raises the question of whether activin A suppression renders favorable PDAC outcomes. Here, the authors demonstrate that activin A is abundantly detected in tumor and stromal cells on PDAC tissue microarray and mouse PDAC sections. In orthotopic male mice, activin A suppression, which is acquired by tumor-targeted Inhba siRNA using cholesterol-modified polymeric nanoparticles, retards tumor growth/metastasis and cachexia and improves survival when compared to scramble siRNA-treated group. Histologically, activin A suppression coincides with decreased expression of proliferation marker Ki67 but increased accumulation of α-SMAhigh fibroblasts and cytotoxic T cells in the tumors. In vitro data demonstrate that activin A promotes KPC cell proliferation and induces the downregulation of α-SMA and upregulation of IL-6 in pancreatic stellate cells (PSC) in the SMAD3-dependent mechanism. Moreover, conditioned media from activin A-stimulated PSC promoted KPC cell growth. Collectively, our data provide a mechanistic basis for tumor-promoting roles of activin A and support therapeutic potentials of tumor activin A suppression for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Masculino , Camundongos , Animais , Caquexia/etiologia , Linhagem Celular Tumoral , RNA Interferente Pequeno/genética
12.
Oncogene ; 42(16): 1308-1320, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36882523

RESUMO

Glioblastoma (GBM) is the most common malignant glioma, with a high recurrence rate and a poor prognosis. However, the molecular mechanism behind the malignant progression of GBM is still unclear. In the present study, through the tandem mass tag (TMT)-based quantitative proteomic analysis of clinical primary and recurrent glioma samples, we identified that aberrant E3 ligase MAEA was expressed in recurrent samples. The results of bioinformatics analysis showed that the high expression of MAEA was related to the recurrence and poor prognosis of glioma and GBM. Functional studies showed that MAEA could promote proliferation, invasion, stemness and temozolomide (TMZ) resistance. Mechanistically, the data indicated that MAEA targeted prolyl hydroxylase domain 3 (PHD3) K159 to promote its K48-linked polyubiquitination and degradation, thus enhancing the stability of HIF-1α, thereby promoting the stemness and TMZ resistance of GBM cells through upregulating CD133. The in vivo experiments further confirmed that knocking down MAEA could inhibit the growth of GBM xenograft tumors. In summary, MAEA enhances the expression of HIF-1α/CD133 through the degradation of PHD3 and promotes the malignant progression of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Glioblastoma/metabolismo , Recidiva Local de Neoplasia/metabolismo , Prolil Hidroxilases/metabolismo , Proteômica , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
13.
Front Cell Infect Microbiol ; 13: 1131218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968100

RESUMO

Stem cells play a crucial role in re-establishing homeostasis in the body, and the search for mechanisms by which they interact with the host to exert their therapeutic effects remains a key question currently being addressed. Considering their significant regenerative/therapeutic potential, research on mesenchymal stem cells (MSCs) has experienced an unprecedented advance in recent years, becoming the focus of extensive works worldwide to develop cell-based approaches for a variety of diseases. Initial evidence for the effectiveness of MSCs therapy comes from the restoration of dynamic microenvironmental homeostasis and endogenous stem cell function in recipient tissues by systemically delivered MSCs. The specific mechanisms by which the effects are exerted remain to be investigated in depth. Importantly, the profound cell-host interplay leaves persistent therapeutic benefits that remain detectable long after the disappearance of transplanted MSCs. In this review, we summarize recent advances on the role of MSCs in multiple disease models, provide insights into the mechanisms by which MSCs interact with endogenous stem cells to exert therapeutic effects, and refine the interconnections between MSCs and cells fused to damaged sites or differentiated into functional cells early in therapy.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Diferenciação Celular/fisiologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-36674295

RESUMO

Intimate partner violence (IPV) is a major public health problem resulting in a significant impediment to equal participation, quality of life, and personal, social, and economic development. At present, a variety of screening instruments for IPV have emerged in developed countries, and some of them have been adapted to the language and culture of different countries, such as Hurt, Insult, Threaten, Scream (HITS) and the Abuse Assessment Screen (AAS). The selection of the most appropriate IPV screening instrument for the target population and context from among those instruments has become difficult for researchers when intending to start screening. Therefore, a systemic review of IPV screening instruments is needed. This protocol describes a COSMIN-based systematic review of the measurement properties of these instruments. The aims of the systematic review are to (1) evaluate the methodological quality of studies on the measurement properties including the validity, reliability, and internal consistency of these IPV screening instruments, and (2) provide suggestions for relevant researchers in their local context for using the IPV screening instruments.


Assuntos
Violência por Parceiro Íntimo , Programas de Rastreamento , Necessidades e Demandas de Serviços de Saúde , Programas de Rastreamento/instrumentação , Qualidade de Vida , Reprodutibilidade dos Testes , Revisões Sistemáticas como Assunto
15.
Biomater Adv ; 145: 213236, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36512927

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a five-year survival rate of around 10 %. CXCR4 and STAT3 display crucial effects on proliferation, metastasis, angiogenesis, and formation of immunosuppressive microenvironment in pancreatic tumors. Here, we have tested the hypothesis that conjugation of α-tocopherol (TOC) to a polycation (PAMD), synthesized from CXCR4-antagonist AMD3100, will improve delivery of therapeutic siRNA to silence STAT3 in PDAC tumors. PAMD-TOC/siSTAT3 nanoparticles showed superior anti-cancer and anti-migration performance compared to the parent PAMD/siSTAT3 nanoparticles in both murine and human PDAC cell lines. The biodistribution of the nanoparticles in orthotropic mouse KPC8060 and human PANC-1 models, indicated that tumor accumulation of PAMD-TOC/siRNA nanoparticles was improved greatly as compared to PAMD/siRNA nanoparticles. This improved cellular uptake, penetration, and tumor accumulation of PAMD-TOC/siSTAT3 nanoparticles, also contributed to the suppression of tumor growth, metastasis and improved survival. Overall, this study presents a prospective treatment strategy for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , RNA Interferente Pequeno/genética , Tocoferóis/farmacologia , Tocoferóis/uso terapêutico , Distribuição Tecidual , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Microambiente Tumoral
16.
Asia Pac J Oncol Nurs ; 10(1): 100168, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36578350

RESUMO

Objective: This study aimed to examine the fidelity of intervention delivery and identify precursory factors contributing to the successful delivery and beneficial effects of family-oriented dignity therapy. Methods: This was a process evaluation with quantitative and qualitative methods alongside a randomized controlled trial from March to May 2019. Nonparametric statistics were used to analyze how participants' demographics (n â€‹= â€‹45 dyads) and process variables influenced the intervention effects. Fourteen patients, 11 family caregivers, and 11 nurses were interviewed to explore their perception of the intervention. Conventional content analysis was adopted to analyze the qualitative data. Results: The fidelity was achieved with minor deviations from the protocol. Higher educational level and higher income were significantly correlated with lower levels of existential distress (H â€‹= â€‹12.20, P â€‹= â€‹0.030) and higher spiritual well-being (H â€‹= â€‹-16.310, P â€‹= â€‹0.031), respectively. Higher levels of interest were significantly correlated with lower levels of existential distress (H â€‹= â€‹10.396, P â€‹= â€‹0.035) and peace of mind distress (H â€‹= â€‹-16.778, P â€‹= â€‹0.006) and higher levels of life meaning (H â€‹= â€‹-12.808, P â€‹= â€‹0.047). Patients who had higher response levels to the question were significantly correlated with lower levels of symptom distress (H â€‹= â€‹-13.879, P â€‹= â€‹0.035). Four major categories were identified from the interview data: (1) benefits of the intervention, (2) risks of the intervention, (3) factors that enhance successful dignity-conserving care, and (4) difficulties and barriers to the delivery of dignity-conserving care. Conclusions: Fidelity and precursory factors that enhance the beneficial effects of family-oriented dignity therapy were identified. Reinforcement strategies, such as using supplementary video, audio, and reading materials; developing a flexible approach to expressing feelings; and exploring lessons and achievements from various perspectives, are recommended for future research to enhance intervention effects. Trial registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900020806).

17.
Mol Pharm ; 19(12): 4631-4643, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36346968

RESUMO

Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Polímeros/uso terapêutico , Neoplasias Pancreáticas
18.
Am J Cancer Res ; 12(10): 4825-4839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381313

RESUMO

Glioblastoma (GBM) is the most frequently observed and aggressive type of high-grade malignant glioma. Temozolomide (TMZ) is the primary agent for GBM treatment. However, TMZ resistance remains a major challenge. In this study, we report that MDK is overexpressed in GBM, which leads to enhanced proliferation, apoptosis inhibition, increased invasion and TMZ resistance in GBM cells. It was also determined that MDK could significantly improve the stem-like properties of GBM cells. Mechanistically, MDK enhanced p-JNK through Notch1 and subsequently increased the expression of stemness markers, such as CD133 and Nanog, thereby promoting TMZ resistance. Finally, xenograft experiments and clinical sample analysis also demonstrated that MDK knockdown could significantly inhibit tumor growth in vivo, and the expression of MDK was positively correlated with Notch1, p-JNK and CD133. This study revealed that MDK induces TMZ resistance by improving the stem-like properties of GBM by upregulating the Notch1/p-JNK signaling pathway, which provides a possible target for therapeutic intervention of GBM, especially in TMZ-resistant GBM with high MDK expression.

19.
J Vis Exp ; (187)2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36279535

RESUMO

Extracellular vesicles (EVs) are heterogeneous membrane nanoparticles released by most cell types, and they are increasingly recognized as physiological regulators of organismal homeostasis and important indicators of pathologies; in the meantime, their immense potential to establish accessible and controllable disease therapeutics is emerging. Mesenchymal stem cells (MSCs) can release large amounts of EVs in culture, which have shown promise to jumpstart effective tissue regeneration and facilitate extensive therapeutic applications with good scalability and reproducibility. There is a growing demand for simple and effective protocols for collecting and applying MSC-EVs. Here, a detailed protocol is provided based on differential centrifugation to isolate and characterize representative EVs from cultured human MSCs, exosomes, and microvesicles for further applications. The adaptability of this method is shown for a series of downstream approaches, such as labeling, local transplantation, and systemic injection. The implementation of this procedure will address the need for simple and reliable MSC-EVs collection and application in translational research.


Assuntos
Exossomos , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Reprodutibilidade dos Testes , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Células Cultivadas
20.
Acta bioeth ; 28(2): 269-279, oct. 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1402933

RESUMO

Abstract: Background: With the increasing number of internet users, it becomes feasible to identify individuals at high risk of suicide and then carry out online suicide prevention. At the same time, online suicide prevention volunteers may encounter moral distress, which requires more attention. Purpose: This study aimed to explore the experience of moral distress in online suicide prevention. Method: The study was carried out as a qualitative study following the method of phenomenology. 11 interviewers were recruited through the purposive sampling method. Data were collected through semi-structured, in-depth face-to-face interviews. Colaizzi's phenomenological framework was used for data analysis. Results: All participants reported they encountered moral distress during online suicide prevention. Four themes were condensed, including: "constraints from the surrounding," "be cruel to be kind," "baby spoiled by free milk," and "when face death and depression" Participants also described their emotional experiences and response when they encountered moral distress. Conclusion: Moral distress in the process of online suicide prevention exists. More attention should be paid to the moral distress and ethical issues in online suicide prevention as the internet gradually becomes a brand-new way to prevent suicide.


Resumen: Antecedentes: Con el creciente número de usuarios de Internet, es posible identificar a las personas con alto riesgo de suicidio y llevar a cabo la prevención del suicidio en línea. Al mismo tiempo, los voluntarios de esta prevención pueden encontrarse con angustia moral, lo que requiere más atención. Objetivo: Este estudio tiene como objetivo explorar la experiencia de la angustia moral en la prevención del suicidio en línea. Método: El estudio se llevó a cabo como un estudio cualitativo siguiendo el método de la fenomenología. Se reclutó a 11 entrevistadores mediante el método de muestreo intencional. Los datos se recogieron mediante entrevistas semiestructuradas y en profundidad, cara a cara. Se utilizó el marco fenomenológico de Colaizzi para el análisis de los datos. Resultados: Todos los participantes informaron que habían encontrado angustia moral durante la prevención del suicidio en línea. Se condensaron cuatro temas, a saber: "limitaciones del entorno", "ser cruel para ser amable", "bebé mimado por la leche gratis" y "cuando se enfrenta a la muerte y la depresión". Los participantes también describieron sus experiencias emocionales y su respuesta cuando se encontraron con la angustia moral. Conclusión: La angustia moral en este proceso existe. Hay que prestar más atención a la angustia moral y a las cuestiones éticas en la prevención del suicidio en línea, ya que Internet se convierte gradualmente en una nueva forma de prevenir el suicidio.


Resumo: Antecedentes: Com o crescente número de usuário de internet, torna-se viável identificar indivíduos com alto risco de suicídio e então conduzir prevenção de suicídio online. Ao mesmo tempo, voluntários de prevenção de suicídio online podem enfrentar stress moral, o qual requer mais atenção. Proposta: Esse estudo objetiva explorar a experiência de stress moral em prevenção de suicídio online. Método: O estudo foi conduzido como um estudo qualitativo seguindo o método da fenomenologia. Foram recrutados 11 entrevistados do método de amostragem intencional. Foram coletados dados através de entrevistas face a face, semiestruturadas e em profundidade. O referencial fenomenológico de Colaizzi foi utilizado para análise dos dados. Resultados: Todos os participantes relataram terem experimentado stress moral durante a prevenção de suicídio online. Quatro temas foram condensados: "limitações do ambiente", "ser cruel para ser gentil", "bebê mimado com leite gratuito" e "quando encarando a morte e a depressão". Os participantes também descreveram suas experiências emocionais e respostas quando enfrentaram stress moral. Conclusão: Stress moral no processo de prevenção de suicídio online existe. Mais atenção deve ser dada ao stress moral e aspectos éticos em prevenção de suicídio online na medida em que a internet se torna gradualmente uma maneira totalmente nova de prevenção de suicídio.


Assuntos
Humanos , Masculino , Feminino , Voluntários/psicologia , Internet , Angústia Psicológica , Prevenção do Suicídio , Entrevistas como Assunto , Pesquisa Qualitativa
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