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1.
Proc Natl Acad Sci U S A ; 120(24): e2219649120, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37276408

RESUMEN

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.


Asunto(s)
Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Folistatina/genética , Folistatina/metabolismo , Tipificación del Cuerpo/genética , Factor de Crecimiento Transformador beta/metabolismo , Regulación del Desarrollo de la Expresión Génica
2.
Small ; : e2401147, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770990

RESUMEN

Cuproptosis, a recently discovered copper-dependent cell death, presents significant potential for the development of copper-based nanoparticles to induce cuproptosis in cancer therapy. Herein, a unique ternary heterojunction, denoted as HACT, composed of core-shell Au@Cu2O nanocubes with surface-deposited Titanium Dioxide quantum dots and modified with hyaluronic acid is introduced. Compared to core-shell AC NCs, the TiO2/Au@Cu2O exhibits improved energy structure optimization, successfully separating electron-hole pairs for redox use. This optimization results in a more rapid generation of singlet oxygen and hydroxyl radicals triggering oxidative stress under ultrasound radiation. Furthermore, the HACT NCs initiate cuproptosis by Fenton-like reaction and acidic environment, leading to the sequential release of cupric and cuprous ions. This accumulation of copper induces the aggregation of lipoylated proteins and reduces iron-sulfur proteins, ultimately initiating cuproptosis. More importantly, HACT NCs show a tendency to selectively target cancer cells, thereby granting them a degree of biosecurity. This report introduces a ternary heterojunction capable of triggering both cuproptosis and oxidative stress-related combination therapy in a stimulus-responsive manner. It can energize efforts to develop effective melanoma treatment strategies using Cu-based nanoparticles through rational design.

3.
Cancer Immunol Immunother ; 72(7): 2151-2168, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36828964

RESUMEN

The metabolic stress present in the tumor microenvironment of many cancers can attenuate T cell antitumor activity, which is intrinsically controlled by the mitochondrial plasticity, dynamics, metabolism, and biogenesis within these T cells. Previous studies have reported that the complement C1q binding protein (C1QBP), a mitochondrial protein, is responsible for maintenance of mitochondrial fitness in tumor cells; however, its role in T cell mitochondrial function, particularly in the context of an antitumor response, remains unclear. Here, we show that C1QBP is indispensable for T cell antitumor immunity by maintaining mitochondrial integrity and homeostasis. This effect holds even when only one allele of C1qbp is functional. Further analysis of C1QBP in the context of chimeric antigen receptor (CAR) T cell therapy against the murine B16 melanoma model confirmed the cell-intrinsic role of C1QBP in regulating the antitumor functions of CAR T cells. Mechanistically, we found that C1qbp knocking down impacted mitochondrial biogenesis via the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha signaling pathway, as well as mitochondrial morphology via the phosphorylation of mitochondrial dynamics protein dynamin-related protein 1. In summary, our study provides a novel mitochondrial target to potentiate the plasticity and metabolic fitness of mitochondria within T cells, thus improving the immunotherapeutic potential of these T cells against tumors.


Asunto(s)
Mitocondrias , Proteínas Mitocondriales , Linfocitos T , Microambiente Tumoral , Animales , Ratones , Humanos , Xenoinjertos , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos T/metabolismo , Técnicas de Silenciamiento del Gen , Mitocondrias/metabolismo , Transducción de Señal , Inmunoterapia Adoptiva
4.
Small ; 19(32): e2300976, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37066742

RESUMEN

Piezoelectric material-mediated sonodynamic therapy (SDT) has received considerable research interest in cancer therapy. However, the simple applications of conventional piezoelectric materials do not realize the full potential of piezoelectric materials in medicine. Therefore, the energy band structure of a piezoelectric material is modulated in this study to meet the actual requirement for cancer treatment. Herein, an elaborate PEGylated piezoelectric solid solution 0.7BiFeO3 -0.3BaTiO3 nanoparticles (P-BF-BT NPs) is synthesized, and the resultant particles achieve excellent piezoelectric properties and their band structure is tuned via band engineering. The tuned band structure of P-BF-BT NPs is energetically favorable for the synchronous production of superoxide radicals (•O2 - ) and oxygen (O2 ) self-supply via water splitting by the piezoelectric effect. Besides, the P-BF-BT NPs can initiate the Fenton reaction to generate hydroxyl radical (•OH), and thus, chemodynamic therapy (CDT) can be augmented by ultrasound. Detailed in vitro and in vivo research has verified the promising effects of multimodal imaging-guided P-BF-BT NP-mediated synergistic SDT/CDT by the piezo-Fenton process in hypoxic tumor elimination, accompanied by high therapeutic biosafety. The current demonstrates a novel strategy for designing and synthesizing "custom-made" piezoelectric materials for cancer therapy in the future.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Ingeniería , Radical Hidroxilo , Hipoxia , Oxígeno , Línea Celular Tumoral , Neoplasias/terapia , Peróxido de Hidrógeno
5.
Anal Biochem ; 661: 114985, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36414087

RESUMEN

Wearable and flexible sensors are playing increasing roles in health monitoring (like physiological electrical signals and components of biofluids). Therein, sweat as a carrier of informative biomarkers would attract great attention for health status identification. However, most wearable biosensors have a short lifetime with complex fabrication processes and expensive costs, which would largely limit the application scene to some extent. Here, we developed a state-of-the-art flexible and integrated sensor patch with screen-printing technology for in-situ and real-time monitoring of electrolyte balance and skin state. The screen-printed sensor patch was easily fabricated, highly reproducible, disposable and relatively stable, which was extremely for sweat sensors with low cost. The state of art sensors on the patch of Na+, pH, skin impedance and temperature all showed excellent performance with high linearity (coefficient of determinations (R2) are 0.998, 0.994, 0.998 and 0.997, respectively). Besides, the detection ranges of Na+ and pH sensors are wide enough for sweat analysis of 10-100 mM and 2-8, respectively. The proposed device provides a new strategy for real-time sweat analysis, preventing dehydration and skin state monitoring during exercise.

6.
Skin Res Technol ; 29(11): e13520, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38009022

RESUMEN

In the presence of diseases transmitted through respiratory droplets and direct contact, healthcare workers (HCWs) necessitate the use of personal protective equipment (PPE). For optimal safety, PPE should securely conform to the skin during extended wear. However, conventional PPE often lacks adequate air permeability and hygroscopicity, trapping heat and moisture emitted by the body within the enclosure. Such a hot and humid internal environment can induce skin damage, such as erythema, rash, pruritus, and itching among others, leading to microbial growth on the skin surface, the production of inflammatory mediators at the wound site and an increased risk of infection. This review strives to comprehensively elucidate the fundamental mechanisms triggering adverse skin reactions and their resultant manifestations. Furthermore, we explore recent advancements aimed at inhibiting these mechanisms to effectively mitigate the occurrence of skin lesions.


Asunto(s)
Invenciones , Enfermedades de la Piel , Humanos , Equipo de Protección Personal , Piel , Prurito
7.
Ecotoxicol Environ Saf ; 267: 115636, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37918331

RESUMEN

Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors of the skin, occurring primarily in the elderly population. CSCC is the second most common nonmelanoma skin malignancy in humans. The development of cutaneous squamous cell carcinoma is closely linked to environmental factors. Microplastics, as a new pollutant, are currently being intensively studied for their potential health effects. However, the effect of microplastics on skin cancer is not yet known and is an important scientific question that needs to be addressed. To this end, in the current study, two skin squamous cell carcinoma cell lines (SCL-1 and A431) were utilized to investigate the effects of microplastics on skin cancer, and cell behavior experiments showed that microplastics were internalized into the skin squamous cell carcinoma cell line in a time- and dose-dependent manner. Further experiments showed that microplastics promoted the proliferation of skin cancer cells by MTT, flow cytometry, laser confocal microscopy, Western blotting and other experimental techniques. Mechanistic studies showed that microplastics could lead to increased mitochondrial ROS in skin cancer cells, which in turn caused a change in mitochondrial membrane potential, thus opening mPTP, which in turn caused the release of mt-DNA from mitochondria into the cytoplasm, thus activating NLRP3 and ultimately causing skin cancer cell proliferation. We further evaluated the effect of microplastics on HaCaT cells in a normal skin cell model and showed that microplastics caused damage to normal skin cells through NLRP3-mediated inflammation and scorch death. The current study suggests that microplastics, as a new contaminant, may promote tumor cell proliferation while causing damage to normal skin.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Anciano , Humanos , Neoplasias Cutáneas/inducido químicamente , Microplásticos/toxicidad , Plásticos , Proteína con Dominio Pirina 3 de la Familia NLR , Proliferación Celular
8.
Mol Cancer ; 21(1): 194, 2022 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-36209106

RESUMEN

Chimeric antigen receptor T (CAR-T) cells therapy has revolutionized the treatment paradigms for hematological malignancies, with multi-line therapy-refractory patients achieving durable complete remissions (CR) and relatively high objective response rate (ORR). So far, many CAR-T products, such as Kymriah, Yescarta and Tecartus, have been developed and got the unprecedented results. However, some patients may relapse afterwards, driving intense investigations into promoting the development of novel strategies to overcome resistance and mechanisms of relapse. Notable technical progress, such as nanobodies and CRISPR-Case9, has also taken place to ensure CAR-T cell therapy fully satisfies its medical potential. In this review, we outline the basic principles for the development and manufacturing processes of CAR-T cell therapy, summarize the similarities and differences in efficacy of different products as well as their corresponding clinical results, and discuss CAR-T immunotherapy combined with other clinical effects of drug therapy.


Asunto(s)
Neoplasias Hematológicas , Receptores Quiméricos de Antígenos , Anticuerpos de Dominio Único , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Inmunoterapia Adoptiva/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptores de Antígenos de Linfocitos T/genética , Receptores Quiméricos de Antígenos/genética
9.
Mol Cancer ; 21(1): 163, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35974338

RESUMEN

Gastrointestinal cancer is the most common human malignancy characterized by high lethality and poor prognosis. Emerging evidences indicate that N6-methyladenosine (m6A), the most abundant post-transcriptional modification in eukaryotes, exerts important roles in regulating mRNA metabolism including stability, decay, splicing, transport, and translation. As the key component of the m6A methyltransferase complex, methyltransferase-like 14 (METTL14) catalyzes m6A methylation on mRNA or non-coding RNA to regulate gene expression and cell phenotypes. Dysregulation of METTL14 was deemed to be involved in various aspects of gastrointestinal cancer, such as tumorigenesis, progression, chemoresistance, and metastasis. Plenty of findings have opened up new avenues for exploring the therapeutic potential of gastrointestinal cancer targeting METTL14. In this review, we systematically summarize the recent advances regarding the biological functions of METTL14 in gastrointestinal cancer, discuss its potential clinical applications and propose the research forecast.


Asunto(s)
Neoplasias Gastrointestinales , Metiltransferasas , Neoplasias Gastrointestinales/genética , Humanos , Metilación , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN/metabolismo , ARN Mensajero/metabolismo
10.
Cancer Sci ; 113(3): 875-890, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34978120

RESUMEN

T cells survival, proliferation, and anti-tumor response are closely linked to their mitochondrial health. Complement C1q binding protein (C1QBP) promotes mitochondrial fitness through regulation of mitochondrial metabolism and morphology. However, whether C1QBP regulates T cell survival, proliferation, and anti-tumor immune function remains unclear. Our data demonstrated that C1QBP knockdown induced the accumulation of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential to impair T cell mitochondrial fitness. At the same time, C1QBP insufficiency reduced the recruitment of the anti-apoptotic proteins, including Bcl-2 and Bcl-XL, and repressed caspase-3 activation and poly (ADP-ribose) polymerase cleavage, which consequently accelerated the T cell apoptotic process. In contrast, C1QBP knockdown rendered T cells with relatively weaker proliferation due to the inhibition of AKT/mTOR signaling pathway. To investigate the exact role of C1QBP in anti-tumor response, C1QBP+/- and C1QBP+/+ mice were given a subcutaneous injection of murine MC38 cells. We found that C1QBP deficiency attenuated T cell tumor infiltration and aggravated tumor-infiltrating T lymphocytes (TIL) exhaustion. Moreover, we further clarified the potential function of C1QBP in chimeric antigen receptor (CAR) T cell immunotherapy. Our data showed that C1QBP+/- CAR T cells exhibited relatively weaker anti-tumor response than the corresponding C1QBP+/+ CAR T cells. Given that C1QBP knockdown impairs T cells' anti-apoptotic capacity, proliferation as well as anti-tumor immune function, development of the strategy for potentiation of T cells' mitochondrial fitness through C1QBP could potentially optimize the efficacy of the related immunotherapy.


Asunto(s)
Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Linfocitos T/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Humanos , Inmunoterapia Adoptiva , Linfocitos Infiltrantes de Tumor/citología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Proteínas Mitocondriales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/terapia , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores Quiméricos de Antígenos , Transducción de Señal , Linfocitos T/citología , Linfocitos T/inmunología
11.
Dermatology ; 238(2): 218-225, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34237729

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has resurged in localized areas in China. Individuals wear masks to prevent the spread of droplets. However, skin barrier damage occurs because of the prolonged use of masks. OBJECTIVE: To investigate the prevalence and associated risk factors of skin injuries among healthcare workers (HCWs) and the general population during the COVID-19 outbreak. METHODS: A multicenter cross-sectional study of skin barrier damage caused by wearing masks was conducted using an online questionnaire between December 10 and December 31, 2020. Data regarding demographics, characteristics of facial skin damage, and information on masks were registered. Multivariate logistic regression was used to analyze factors associated with skin barrier damage, and odds ratios (OR) with 95% confidence intervals (CI) were used to establish correlation strength. RESULTS: A total of 1,538 responses were retrieved from 1,700 questionnaires (response rate, 90.47%), and 1,409 questionnaires were valid (effective response rate, 91.61%). The respondents comprised 567 HCWs (40.24%) and 842 individuals from the general population (59.76%). The prevalence of skin injuries was 46.03% among HCWs and 46.20% among the general population. History of chronic skin disease (OR, 6.01; 95% CI, 4.75-7.75), type of mask used (OR, 2.77; 95% CI, 1.95-3.93), daily wearing time (OR, 1.57; 95% CI, 1.36-1.82), and mask replacement cycle (OR, 0.76; 95% CI, 0.68-0.86) were associated with skin barrier damage. CONCLUSION: There was a high incidence of skin barrier damage due to prolonged mask use among HCWs and the general population, and treatment and prevention were inadequate. Attention needs to be given to strengthening comprehensive health education and popularization of science.


Asunto(s)
COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , China/epidemiología , Estudios Transversales , Personal de Salud , Humanos , Máscaras/efectos adversos , Pandemias/prevención & control , Estudios Prospectivos , SARS-CoV-2
12.
Photodermatol Photoimmunol Photomed ; 38(4): 373-381, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34964167

RESUMEN

BACKGROUND: The two-step irradiance schedule in photodynamic therapy (PDT) is an emerging treatment method with a remarkable analgesic effect. We evaluated the influencing factors of pain in condyloma acuminate (CA) treatment with a two-step irradiance schedule. METHODS: All patients were randomly divided into a two-step irradiance group and control group. The two-step irradiance group used 40 mW/cm2 for the first 8min, followed by 80 mW/cm2 for 16 min, while the control group used 80 mW/cm2 for 20 min. The Numerical Rating Scale (NRS) scores and pain-influencing factors were recorded accordingly. RESULTS: In the two-step irradiance and control groups, 64 and 63 patients completed the treatment, respectively. The NRS scores of the two-step irradiance group were significantly lower than that of the control group (p < .001), with a low fluence rate inducing less pain compared with a high fluence rate (p < .001). Moreover, when the total fluence accumulated to 57.6 J/cm2 , the pain experienced by patients reached its peak. The NRS score of the urethral orifice group was the highest, and the male external genitalia group was the lowest. The NRS score was at its lowest in the first session and highest in the second session. There was a linear relationship between pain and wart size. Among these influencing factors, the fluence rate had the greatest impact on pain. CONCLUSION: The two-step irradiance schedule provides better analgesic effects than standard treatment irradiation while showing similar treatment efficacy. Factors that influence pain include high fluence rate, CA at the urethral orifice, second therapy session, wart size, and the interval between CO2  laser and ALA-PDT.


Asunto(s)
Fotoquimioterapia , Verrugas , Ácido Aminolevulínico , Analgésicos/uso terapéutico , Humanos , Masculino , Dolor/etiología , Dimensión del Dolor , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Verrugas/tratamiento farmacológico
13.
Cutan Ocul Toxicol ; 41(2): 187-193, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35658705

RESUMEN

Nuclear factor-kappa B (NF-κB) has important but complex functions in the photoaging of the human skin. This protein complex is activated upon UV irradiation and plays a key role in the signalling pathway of the inflammatory cascade. NF-κB induces the expression of various proinflammatory cytokines, such as tumour necrosis factor (TNF) and interleukin-1 (IL-1). These proinflammatory cytokines can in turn stimulate the activation of NF-κB, forming a vicious cycle. These processes cause chronic inflammation and contribute to skin ageing. In addition, the activation of NF-κB upregulates the expression of matrix metalloproteinases (MMPs) and leads to the degradation of structural proteins in the dermis. NF-κB disrupts the barrier function of the skin under prolonged and repeated UV stimulations in these ways. Such activity causes chronic skin damage, followed by the formation of wrinkles, dryness, roughness, laxity, and other photoaging manifestations. This study on the NF-κB signalling pathway and effector molecules provides a new perspective to understand and prevent photoaging.


Asunto(s)
FN-kappa B , Envejecimiento de la Piel , Citocinas , Humanos , FN-kappa B/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Rayos Ultravioleta/efectos adversos
14.
Dermatol Ther ; 34(4): e14954, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33835635

RESUMEN

Dermatofibrosarcoma protuberans (DFSP) is a tumor with low-grade malignancy and high recurrence rates. Wide local excision (WLE) is essential for DFSP, but its surgical excision margin is controversial. This study aimed to examine whether resection margin is associated with the prognosis of patients with DFSP by systematically reviewing related literature. Studies that evaluated the relationship between excision margins and outcomes after WLE were retrieved from the Cochrane Library, PubMed, Embase, and Web of Science databases. Relative risk (RR) estimates and 95% confidence intervals (CIs) were measured via a random-effect model to evaluate the subsequent outcomes: recurrence rate, mortality, and positive surgical margin rate. Sensitivity and subgroup analyses were simultaneously carried out. The meta-analysis of eight observational literatures demonstrated a significant positive correlation of ≥3 cm margin with the recurrence rate (RR = 0.17, 95% CI 0.09-0.31) and the positive surgical margin rate (RR = 0.09, 95% CI 0.02-0.46). The same result was observed in the recurrence rate in all subgroups. The stability of the above outcomes was authenticated via sensitivity analyses. Our meta-analysis illustrated that excision with <3 cm surgical margin exhibited an increased risk of poor DFSP prognosis (high recurrence rate and increasing positive margin rate).


Asunto(s)
Dermatofibrosarcoma , Neoplasias Cutáneas , Dermatofibrosarcoma/cirugía , Estudios de Seguimiento , Humanos , Márgenes de Escisión , Cirugía de Mohs , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Neoplasias Cutáneas/cirugía
15.
Med Sci Monit ; 27: e928393, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33417590

RESUMEN

The safety of health care workers in China has received an increasing amount of attention owing to numerous incidents of hospital-based violence against medical professionals. When pictures and videos of violent injuries are posted on the internet with real-time data, such as gender or location, researchers can access the information to learn about the incident, its causes, and/or threats to survival. We examined the causes and risk factors for workplace violence by analyzing relevant data retrieved from reports by Chinese internet media for all incidents from 2000 to 2020. We present frequency data on hospital-based violence against medical professionals. A total of 345 incidents occurred in health care settings. The person who committed the violent act was a patient or sick person in the workplace or a co-worker in 95.4% of the incidents; 54 of the incidents resulted in the victim's murder. We provide the characteristics and risk factors of violent criminals. We describe China's past and current clinical practices and health care policies, and we discuss the challenges faced by medical professionals who are victims of hospital-based violence from the perspectives of patients, physicians, hospital leaders, and the government. We conclude by making recommendations for preventing violence in hospital settings. It is urgent for the public to understand that the occupational safety of health care workers must be protected, and treatment should be provided to patients in a harmonious and safe environment. This review aims to describe the trends in workplace violence involving health care professionals in China from 2000 to 2020 and to discuss possible strategies for improving working conditions in hospitals and other health care settings.


Asunto(s)
Personal de Salud/estadística & datos numéricos , Violencia Laboral/tendencias , China , Personal de Salud/psicología , Hospitales/estadística & datos numéricos , Humanos , Violencia Laboral/prevención & control , Violencia Laboral/psicología
16.
Postepy Dermatol Alergol ; 38(5): 709-715, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34849113

RESUMEN

Reflectance confocal microscopy (RCM) is abbreviated as skin three-dimensional computed tomography, which can help clearly observe the structure of the epidermis and superficial dermis. It is a non-invasive skin disease examination method and provides fast access to real-time, dynamic skin micro-anatomical images. Therefore, RCM is widely used in the clinical diagnosis of skin diseases. For example, the RCM features of vitiligo are as follows: pigment loss or partial pigment loss in the lesion area, loss of the basal layer pigment ring. The RCM findings of Riehl melanosis are as follows: basal cell liquefaction and degeneration. The RCM results for verruca plana show: the Rose-like structure. The characteristics of psoriasis under RCM include: hyperkeratosis, parakeratosis, thickening of the spinous layer, capillary dilatation and hyperaemia, peripheral inflammatory cell infiltration. Epidermal brain-like structure was observed under RCM of seborrheic keratosis. With RCM, image acquisition and preservation of the skin is convenient, and the technique is convenient for comparing the development of lesions during long-term follow-up observation. Therefore, it helps to understand disease development in real time and dynamically and can be used to evaluate the curative effect. In this article, we briefly review the technical principles, diagnostic criteria for RCM application and RCM-related research progress in the diagnosis of pigmentary diseases, inflammatory diseases, skin tumours, and other common skin diseases.

17.
Postepy Dermatol Alergol ; 38(6): 931-936, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35125996

RESUMEN

Skin photoaging, which is a kind of exogenous aging, refers to skin elasticity degradation, skin roughening, and wrinkle formation processes because of cascading reactions of a series of kinases after growth factor receptors and cytokine receptors are activated on a cell surface under the UV effect. An extensively recognized skin photoaging mechanism is free radical-oxidative stress concept, proposed by Sohal who represents the authority of the US aging studies. Over the past decade, many new developments in the oxidative stress mechanism have been achieved in terms of the occurrence, development, prevention, and treatment of photodamage.

18.
Cancer Sci ; 111(1): 84-97, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31774615

RESUMEN

Although accumulating evidence has indicated the intimate association between epithelial-mesenchymal transition (EMT) and acquired resistance to chemotherapy for colorectal cancer (CRC), the underlying mechanisms remain elusive. Herein, we reported that Snail, a crucial EMT controller, was upregulated in CRC tissues. Colorectal cancer cells overexpressing Snail were found to be more resistant to 5-fluorouracil (5-Fu). Mechanistic studies reveal that Snail could increase the expression of ATP-binding cassette subfamily B member 1 (ABCB1) rather than the other 23 chemoresistance-related genes. Additionally, knockdown of ABCB1 significantly attenuated Snail-induced 5-Fu resistance in CRC cells. Oxaliplatin increased Snail and ABCB1 expression in CRC cells. Snail and ABCB1 were upregulated in 5-Fu-resistant HCT-8 (HCT-8/5-Fu) cells and inhibition of Snail decreased ABCB1 in HCT-8/5-Fu cells. These results confirm the vital role played by ABCB1 in Snail-induced chemoresistance. Further investigation into the relevant molecular mechanism revealed Snail-mediated ABCB1 upregulation was independent of ß-catenin, STAT3, PXR, CAR and Foxo3a, which are commonly involved in modulating ABCB1 transcription. Instead, Snail upregulated ABCB1 transcription by directly binding to its promoter. Clinical analysis confirms that increased Snail expression correlated significantly with tumor size (P = .018), lymph node metastasis (P = .033), distant metastasis (P = .025), clinical stage grade (P = .024), and poor prognosis (P = .045) of CRC patients. Moreover, coexpression of Snail and ABCB1 was observed in CRC patients. Our study revealed that direct regulation of ABCB1 by Snail was critical for conferring chemoresistance in CRC cells. These findings unraveled the mechanisms underlying the association between EMT and chemoresistance, and provided potential targets for CRC clinical treatment.


Asunto(s)
Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos/genética , Factores de Transcripción de la Familia Snail/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Línea Celular , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Transducción de Señal/genética , Regulación hacia Arriba/genética
19.
Dermatol Ther ; 33(6): e14025, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32677163

RESUMEN

Syphilis is a very serious infection that causes acute cutaneous manifestations. Penicillin is the gold standard for treating syphilis. This meta-analysis was conducted based on self-published randomized controlled trials (RCTs) data to compare the efficacy of azithromycin with penicillin for treating syphilis. RCTs on azithromycin vs penicillin for the treatment of syphilis were retrieved from the Cochrane Library, MEDLINE, EBSCO, Embase, Ovid, and other databases, and the estimated risk ratio (RR) and 95% confidence interval (CI) were used to study the following outcome indicators: 3-month response rate, 6-month response rate, 12-month response rate, recurrence rate, serum fixation rate, and failure rate. This meta-analysis included seven RCTs involving 639 subjects (of whom 335 were treated with azithromycin and 304 were treated with penicillin). There was no significant difference in the 3-month response rate (RR = 0.97, 95% CI: 0.79-1.19), 6-month response rate (RR = 1.01, 95% CI: 0.85-1.20), 12-month response rate (RR = 1.02, 95% CI: 0.97-1.09), serum fixation rate (RR = 0.71, 95% CI: 0.24-2.12), and failure rate (RR = 0.62, 95% CI: 0.33-1.16). In summary, there is no evidence in the literature that azithromycin is less effective than penicillin for treating syphilis.


Asunto(s)
Penicilina G Benzatina , Sífilis , Antibacterianos/efectos adversos , Azitromicina/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico
20.
Curr Microbiol ; 77(8): 1381-1389, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32152756

RESUMEN

Two rare strains of Proteus mirabilis with swarming migration deficiency were isolated from urine samples of two patients with urinary tract infections and were named as G121 and G137. Migration experiments showed that P. mirabilis HI4320 had typical migration on blood agar, while G121 and G137 had significantly weakened migration ability. Results of adhesion tests showed that the adhesion ability of G121 and G137 to the bladder epithelial cell line 5637 was significantly reduced. High-throughput sequencing and alignment analysis of the transcriptomes of the three P. mirabilis strains were conducted, with P. mirabilis HI4320 as the reference strain. Reverse transcription quantitative PCR (RT-qPCR) was used to verify differentially expressed genes. Results of transcriptome analysis and RT-qPCR showed that, compared to the HI4320 strain, genes related to flagellum and fimbria formation, dicarboxylate transport, and cystathionine and anthranilate metabolism were down-regulated in G121 and G137, while genes related to iron transport, molybdenum metabolism, and metalloprotease were up-regulated, suggesting that these genes may be involved in the migration ability and epithelial cell adhesion ability of P. mirabilis. These results provide important insight to the search for virulence genes and the screening of new antibacterial targets for P. mirabilis.


Asunto(s)
Perfilación de la Expresión Génica , Infecciones por Proteus/microbiología , Infecciones por Proteus/orina , Proteus mirabilis/genética , Infecciones Urinarias/microbiología , Anciano de 80 o más Años , Adhesión Bacteriana , Proteínas Bacterianas/genética , Línea Celular , Células Epiteliales/microbiología , Femenino , Flagelos , Regulación Bacteriana de la Expresión Génica , Humanos , Persona de Mediana Edad , Movimiento , Proteus mirabilis/aislamiento & purificación , Virulencia
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