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1.
Lasers Med Sci ; 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34365550

RESUMO

Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15-110 months). D-PDT was performed with 633-nm red light at 80 m W/cm2 after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p < 0.001). D-PDT is a safe, cosmetic and effective treatment that could be a new candidate therapeutic for NMSC.

2.
Adv Sci (Weinh) ; 8(17): e2004850, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34240584

RESUMO

Elevated Wnt/ß-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pß-cateninThr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates ß-catenin at Thr40 to block its Ser33 phosphorylation by GSK3ß. Thus, MST4 mediates an active process that prevents ß-catenin from binding to and being degraded by ß-TrCP, leading to accumulation and full activation of ß-catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4T178E mutation with constitutive kinase activity or ß-cateninT40D mutation mimicking MST4-mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4-pß-cateninThr40 axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for ß-catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC.

3.
Angew Chem Int Ed Engl ; 60(40): 21905-21910, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34322970

RESUMO

In solid tumors, tumor invasion and metastasis account for 90 % of cancer-related deaths. Cell migration is steered by the lamellipodia formed at the leading edge. These lamellipodia can drive the cell body forward by its mechanical deformation regulated by cofilin. Inhibiting cofilin activity can cause significant defects in directional lamellipodia formation and the locomotory capacity of cell invasion, thus contributing to antimetastatic treatment. Herein, a near infrared light (NIR)-controlled nanoscale proton supplier was designed with upconversion nanoparticles (UCNPs) as a core coated in MIL-88B for interior photoacids loading; this photoacids loading can boost H+ transients in cells, which converts the cofilin to an inactive form. Strikingly, inactive cofilin loses the ability to mediate lamellipodia deformation for cell migration. Additionally, the iron, which serves as a catalyticaly active center in MIL-88B, initiates an enhanced Fenton reaction due to the increased H+ in the tumor, ultimately achieving intensive chemodynamic therapy (CDT). This work provides new insight into H+ transients in cells, which not only regulates cofilin protonation for antimetastatic treatment but also improves chemodynamic therapy.

4.
Environ Int ; 155: 106682, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34120005

RESUMO

There are global concerns about dietary exposure to metal(loid)s in foods. However, little is known about the relative contribution of rice versus fish to multiple metal(loid) exposure for the general population, especially in Asia where rice and fish are major food sources. We compared relative contributions of rice and fish consumption to multi-metal(loid) exposure on the city-scale (Nanjing) and province-scale in China. The effects of ingestion rate, metal(loid) level, and bioaccessibility were examined to calculate modeled risk from Cu, Zn, total As (TAs), inorganic As (iAs), Se, Cd, Pb, and methylmercury (MeHg). Metal(loid) levels in rice and fish samples collected from Nanjing City were generally low, except iAs. Metal(loid) bioaccessibilities in fish were higher than those in rice, except Se. Calculated carcinogenic risks induced by iAs intake (indicated by increased lifetime cancer risk, ILCR) were above the acceptable level (1 0 -4) in Nanjing City (median: 3 × 10-4 for female and 4 × 10-4 for male) and nine provinces (1.4 × 10-4 to 5.9 × 10-4) in China. Rice consumption accounted for 85.0% to 99.8% of carcinogenic risk. The non-carcinogenic hazard quotients (HQ) for single metals and hazard index (HI) for multi-metal exposure were < 1 in all cases, indicating of their slight non-carcinogen health effects associated. In Guangdong and Jiangsu provinces, results showed that rice and fish intake contributed similarly to the HI (i.e., 42.6% vs 57.4% in Guangdong and 54.6% vs 45.4% in Jiangsu). Sensitivity analysis indicated that carcinogenic risk was most sensitive to rice ingestion rate and rice iAs levels, while non-carcinogenic hazard (i.e., HQ and HI) was most sensitive to ingestion rate of fish and rice, and Cu concentration in rice. Our results suggest that rice is more important than fish for human dietary metal(loid) exposure risk in China, and carcinogenic risk from iAs exposure in rice requires particular attention.


Assuntos
Metais Pesados , Oryza , Poluentes do Solo , Animais , China , Monitoramento Ambiental , Feminino , Humanos , Masculino , Metais Pesados/análise , Medição de Risco , Poluentes do Solo/análise , População Urbana
5.
Adv Sci (Weinh) ; 8(11): e2002548, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34105274

RESUMO

Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.

6.
Angew Chem Int Ed Engl ; 60(28): 15472-15481, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33964189

RESUMO

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2 - ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2 - , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Imidazóis/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Zeolitas/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidazóis/química , Masculino , Estruturas Metalorgânicas/química , Estresse Nitrosativo/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Raios X , Zeolitas/química
8.
Front Public Health ; 9: 630620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692982

RESUMO

The outbreak of coronavirus disease-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma. A self-administered online questionnaire was distributed to melanoma patients through social media. Demographic and clinical data, and pandemic-related impacts (unemployment and income loss) were collected. HRQoL was determined by the Functional Assessment of Cancer Therapy-General (FACT-G) and its disease-specific module (the melanoma subscale, MS). A total of 135 patients with melanoma completed the study. The mean age of the patients was 55.8 ± 14.2 years, 48.1% (65/135) were male, and 17.04% (34/135) were unemployed since the epidemic. Unemployment of the patients and their family members and income loss were significantly associated with a lower FACT-G score, while the MS score was associated with the unemployment of the patients' family members. Our findings suggested that unemployment is associated with impaired HRQoL in melanoma patients during the COVID-19 epidemic.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , COVID-19/economia , COVID-19/psicologia , Melanoma/economia , Melanoma/psicologia , Qualidade de Vida/psicologia , Desemprego/psicologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Desemprego/estatística & dados numéricos
9.
Adv Mater ; 33(17): e2100472, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33759262

RESUMO

Intracellular catalytic reactions can tailor tumor cell plasticity toward high-efficiency treatments, but the application is hindered by the low efficiency of intracellular catalysis. Here, a magneto-electronic approach is developed for efficient intracellular catalysis by inducing eddy currents of FePt-FeC heterostructures in mild alternating magnetic fields (frequency of f = 96 kHz and amplitude of B ≤ 70 mT). Finite element simulation shows a high density of induced charges gathering at the interface of FePt-FeC heterostructure in the alternating magnetic field. As a result, the concentration of an essential coenzyme-ß-nicotinamide adenine dinucleotide-in cancer cells is significantly reduced by the enhanced catalytic hydrogenation reaction of FePt-FeC heterostructures under alternating magnetic stimulation, leading to over 80% of senescent cancer cells-a vulnerable phenotype that facilitates further treatment. It is further demonstrated that senescent cancer cells can be efficiently killed by the chemodynamic therapy based on the enhanced Fenton-like reaction. By promoting intracellular catalytic reactions in tumors, this approach may enable precise catalytic tumor treatment.

10.
Angew Chem Int Ed Engl ; 60(16): 8905-8912, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33527642

RESUMO

The local electron density of an atom is one key factor that determines its chemical properties. Regulating electron density can promote the atom's reactivity and so reduce the reaction activation energy, which is highly desired in many chemical applications. Herein, we report an intra-crystalline electron lever strategy, which can regulate the electron density of reaction centre atoms via manipulating ambient lattice states, for Fenton activity improvement. Typically, with the assistance of ultrasound, the Mn4+ -O-Fe3+ bond in BiFe0.97 Mn0.03 O3 perovskite nanocrystals can drive valence electrons and free electrons to accumulate on Fe atoms by a polarization electric field originated from the designed lattice strain. The increase of electron density significantly improves the catalytic activity of Fe, decreasing the activation energy of BiFe0.97 Mn0.03 O3 -mediated Fenton reaction by 52.55 %, and increasing the . OH yield by 9.21-fold. This study provides a new way to understand the sono-Fenton chemistry, and the increased . OH production enables a highly effective chemodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Compostos de Cálcio/química , Elétrons , Nanopartículas/química , Neoplasias/tratamento farmacológico , Óxidos/química , Terapia Fototérmica , Titânio/química , Antineoplásicos/química , Compostos de Cálcio/metabolismo , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Neoplasias/metabolismo , Óxidos/metabolismo , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Titânio/metabolismo
11.
Chem Rev ; 121(4): 1981-2019, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33492935

RESUMO

Since the first connection between Fenton chemistry and biomedicine, numerous studies have been presented in this field. Comprehensive presentation of the guidance from Fenton chemistry and a summary of its representative applications in cancer therapy would help us understand and promote the further development of this field. This comprehensive review first supplies basic information regarding Fenton chemistry, including Fenton reactions and Fenton-like reactions. Subsequently, the current progress of Fenton chemistry is discussed, with some corresponding representative examples presented. Furthermore, the current strategies for further optimizing the performance of chemodynamic therapy guided by Fenton chemistry are highlighted. Most importantly, future perspectives on the combination of biomedicine with Fenton chemistry or a wider range of catalytic chemistry approaches are presented. We hope that this review will attract positive attention in the chemistry, materials science, and biomedicine fields and further tighten their connections.


Assuntos
Compostos Férricos/química , Compostos Ferrosos/química , Peróxido de Hidrogênio/química , Ferro/química , Animais , Catálise , Humanos , Radical Hidroxila/química , Nanoestruturas/química , Neoplasias/metabolismo , Neoplasias/terapia , Oxirredução
12.
Adv Healthc Mater ; 10(5): e2000912, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32691929

RESUMO

Understanding the detailed tumor microenvironment (TME) is essential to achieve effective treatment of tumor, because TME has an extremely profound influence on the occurrence, development, invasion, and metastasis of tumor. It is of great significance to realize accurate diagnosis of the TME by using functional computed tomography (CT) contrast nanoagents (FCTNAs). Here, an overview of FCTNAs that respond to the overexpressed receptors, acidic microenvironment, overexpressed glutathione and enzymes, and hypoxia in tumor is provided, and also prospects the advance of novel spectral CT technique to detect the TME precisely. Utilizing FCTNAs is expected to achieve accurate monitoring of the TME and further provide guidance for the effective personalized tumor treatment in clinic.


Assuntos
Nanopartículas , Neoplasias , Meios de Contraste , Humanos , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Microambiente Tumoral
16.
Sci Adv ; 6(39)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32978153

RESUMO

Traumatic spinal cord injury (SCI) is caused by external physical impacts and can induce complex cascade events, sometimes converging to paralysis. Existing clinical drugs to traumatic SCI have limited therapeutic efficacy because of either the poor blood-spinal cord barrier (BSCB) permeability or a single function. Here, we suggest a "pleiotropic messenger" strategy based on near-infrared (NIR)-triggered on-demand NO release at the lesion area for traumatic SCI recovery via the concurrent neuroregeneration and neuroprotection processing. This NO delivery system was constructed as upconversion nanoparticle (UCNP) core coated by zeolitic imidazolate framework-8 (ZIF-8) with NO donor (CysNO). This combined strategy substantial promotes the repair of SCI in vertebrates, ascribable to the pleiotropic effects of NO including the suppression of gliosis and inflammation, the promotion of neuroregeneration, and the protection of neurons from apoptosis, which opens intriguing perspectives not only in nerve repair but also in neurological research and tissue engineering.

17.
ACS Nano ; 14(10): 13391-13405, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32931252

RESUMO

Implant-related infections (IRIs) are a serious complication after orthopedic surgery, especially when a biofilm develops and establishes physical and chemical barriers protecting bacteria from antibiotics and the hosts local immune system. Effectively eliminating biofilms is essential but difficult, as it requires not only breaking the physical barrier but also changing the chemical barrier that induces an immunosuppressive microenvironment. Herein, tailored to a biofilm microenvironment (BME), we proposed a space-selective chemodynamic therapy (CDT) strategy to combat IRIs using metastable CuFe5O8 nanocubes (NCs) as smart Fenton-like reaction catalysts whose activity can be regulated by pH and H2O2 concentration. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by CuFe5O8 NCs, thereby disrupting the rigid biofilm. Outside the biofilm with relatively higher pH and lower H2O2 concentration, lower levels of generated •OH effectively reversed the immunosuppressive microenvironment by inducing pro-inflammatory macrophage polarization. Biofilm fragments and exposed bacteria were then persistently eliminated through the collaboration of pro-inflammatory immunity and •OH. The spatially selective activation of CDT and synergistic immunomodulation exerted excellent effects on the treatment of IRIs in vitro and in vivo. The anti-infection strategy is expected to provide a method to conquer IRIs.


Assuntos
Peróxido de Hidrogênio , Radical Hidroxila , Biofilmes , Concentração de Íons de Hidrogênio
18.
Medicine (Baltimore) ; 99(39): e22252, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991421

RESUMO

A 31-year-old male patient with psoriasis received administration of traditional Chinese medicine (TCM) during a disease course of 14 years. He showed multiple keratoma together with squamous cell carcinoma (SCC) in left lower limbs. After admission, the conditions were stable after treatment, and received surgery for treating SCC. The skin defect was treated using full-thickness skin graft. The postoperative survival of the flap was satisfactory, and the conditions of psoriasis were well controlled. In this case, we presented the feasibility of graft in the donor site from a psoriatic lesion. Besides, we analyzed the possibility of SCC and keratinizing lesions.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Cutâneas/cirurgia , Transplante de Pele/métodos , Retalhos Cirúrgicos/transplante , Adulto , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Medicina Tradicional Chinesa , Psoríase/complicações , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia
19.
Photodiagnosis Photodyn Ther ; 31: 101944, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800966

RESUMO

Cystic acne of the scalp is relatively resistant to conventional treatment because of its thick wall and deep cavity. This study was conducted as a comparative analysis of clinical outcomes of single surgery and those of surgery combined with photodynamic therapy for cystic acne of the scalp. Ten patients were treated only with surgical incisions and drainage of pus and necrotic tissues, and another ten patients were treated with photodynamic therapy immediately after surgery, followed by two weekly cycles thereafter. The combination treatment group reported better outcomes than the single surgery group in terms of duration of wound healing, the number of dressing changes, pain score at the time of dressing change, and recurrence rate. Our study demonstrateds that the combination of surgery and photodynamic therapy may have pronounced effects on the treatment for cystic acne of the scalp.


Assuntos
Acne Vulgar , Fotoquimioterapia , Acne Vulgar/tratamento farmacológico , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Couro Cabeludo , Resultado do Tratamento , Cicatrização
20.
Biomaterials ; 258: 120257, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32798739

RESUMO

Currently, reactive oxygen species (ROS)-induced apoptosis systems have drawn increasing attention in cancer therapy, owing to their specific tumor inhibition ability and great biocompatibility. Herein, we developed a highly dispersed nano-enzyme based on the assembly of natural glucose oxidase (GOD) onto CoFe-layered double hydroxides (CoFe-LDHs) monolayer nanosheets. By virtue of the high dispersion of Fe3+ within the host layer, the CoFe-LDHs nanosheets exhibit a collaborative enhanced Fenton catalytic activity with a rate constant of 3.26 × 10-4 s-1, which is 1-3 orders of magnitude higher than other iron-containing Fenton reaction agents. Subsequently, with a massive H2O2 triggered by GOD, GOD/CoFe-LDHs nanohybrid converts a cascade of glucose into hydroxyl radicals under tumor acid conditions, which is validated by a high maximum velocity (Vmax = 2.23 × 10-6 M) and low Michaelis-Menten constant (KM = 5.40 mM). Through the intracellular catalytic Fenton reaction within the tumor environment, both in vitro and in vivo results demonstrate the excellent antitumor effect of GOD/CoFe-LDHs. Therefore, a self-supplied, ultra-efficient and sequential catalytic tumor-specific therapy has been achieved based on GOD/CoFe-LDHs nano-enzyme, which holds great promise in clinical cancer therapy with minimum side effects.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Catálise , Glucose Oxidase , Humanos , Hidróxidos , Neoplasias/tratamento farmacológico
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