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Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.
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Biomarcadores de Tumor , Ensamble y Desensamble de Cromatina , Regulación Neoplásica de la Expresión Génica , Neoplasias , Humanos , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Pronóstico , Mutación , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Terapia Molecular Dirigida , Perfilación de la Expresión GénicaRESUMEN
Although enhanced performances of photovoltaic devices by embedding metal nanoparticals in charge transport layer, doping into active layer bulk, decorating the active layer surface, and inserting at the interface between semiconductor and the electrode were reported, the effect of incorporating metal NPs at the interface of single crystal semiconductor and perovskite is rarely tackled. Herein the effects of incorporating Ag nanoparticals (AgNPs) at p-Si/MAPbI3 perovskite interface on the photodiode performances were investigated. The results showed that compared with reference device (without AgNPs) the photoresponsivity of the device incorporating AgNPs is greatly improved with the exception for light with wavelengths fall in the spectral range where AgNPs have strong optical absorption. This effect is extremely significant for relatively shorter wavelengths in visible region, and a maximal improvement of around 10.6 times in photoresponsivity was achieved. The physical origin of the exception for spectral range that AgNPs have strong optical absorption is the cancelation of scatter resulted enhancement through AgNPs by band-to-band absorption resulted reduction of photocurrent, in which the generated electron has energy near the fermi level and the hole has large effective mass, which relax by nonradiative recombination, thus making not contribution to the photocurrent. More importantly, the AgNP decorated device showed much faster photo response speed than reference device, and a maximal improvement of around 7.9 times in rise and fall time was achieved. These findings provide a novel approach for high responsive and high speed detection for weak light.
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The term "schizophrenia" can indeed carry stigmatizing connotations. Proposals to rename schizophrenia have emerged as a potential strategy to alleviate this stigma, but the impact of such a change is not yet fully understood. In several Asian countries that have adopted a new name for schizophrenia, there is evidence that renaming is associated with improved attitudes towards individuals with schizophrenia and an increased willingness to disclose diagnoses. However, the portrayal of schizophrenia in the media seems unaffected by these name changes. In other countries where "schizophrenia" is still the standard term, alternative names have been suggested, but research on their effectiveness in reducing stigma shows mixed results. Mental health professionals frequently support a name change, recognizing the term's negative implications. However, it is crucial to recognize that a mere semantic revision, devoid of substantial conceptual alterations, may only offer a temporary decrease in stigma. Thus, renaming schizophrenia, coupled with a re-conceptualization of the disorder, may be a constructive step toward reducing its stigmatization.
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Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases.
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L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.
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Tuning cell adhesion geometry can affect cytoskeleton organization and the distribution of cytoskeleton forces, which play critical roles in controlling cell functions. To elucidate the geometrical relationship with cytoskeleton force distribution, it is necessary to control cell morphology. In this study, a series of dextral vortex micropatterns were prepared to precisely control cell morphology for investigating the influence of the curvature degree of adhesion curves on intracellular force distribution and stem cell differentiation at a sub-cellular level. Peripherial actin filaments of micropatterned cells were assembled along the adhesion curves and showed different orientations, filament thicknesses and densities. Focal adhesion and cytoskeleton force distribution were dependent on the curvature degree. Intracellular force distribution was also regulated by adhesion curves. The cytoskeleton and force distribution affected the osteogenic differentiation of mesenchymal stem cells through a YAP/TAZ-mediated mechanotransduction process. Thus, regulation of cell adhesion curvature, especially at cytoskeletal filament level, is critical for cell function manipulation. STATEMENT OF SIGNIFICANCE: In this study, a series of dextral micro-vortexes were prepared and used for the culture of human mesenchymal stem cells (hMSCs) to precisely control adhesive curvatures (0°, 30°, 60°, and 90°). The single MSCs on the micropatterns had the same size and shape but showed distinct focal adhesion (FA) and cytoskeleton orientations. Cellular nanomechanics were observed to be correlated with the curvature degrees, subsequently influencing nuclear morphological features. As a consequence, the localization of the mechanotransduction sensor and activator-YAP/TAZ was affected, influencing osteogenic differentiation. The results revealed the pivotal role of adhesive curvatures in the manipulation of stem cell differentiation via the machanotransduction process, which has rarely been investigated.
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Diferenciación Celular , Adhesiones Focales , Mecanotransducción Celular , Células Madre Mesenquimatosas , Osteogénesis , Adhesiones Focales/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Mecanotransducción Celular/fisiología , Humanos , Osteogénesis/fisiología , Actinas/metabolismo , Adhesión Celular , Forma de la Célula , Proteínas Señalizadoras YAPRESUMEN
Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.
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We report a case of a 4-year-old boy with lysinuric protein intolerance in China. The patient presented with interstitial lung disease with obvious clubbing of the fingers and toes. During the course of diagnosis and treatment, we found he was averse to a high-protein diet, intolerant to activity, and had a history of diarrhea and fractures. Physical examination revealed hepatosplenomegaly and clubbing of the fingers and toes. Next-generation sequencing revealed compound heterozygous mutations (c.1387delG, c.958T > C) in SLC7A7, which was confirmed as a disease-causing gene for lysinuric protein intolerance. After a literature review, we found that c.958T > C had not been previously reported, and summarized the clinical and genetic characteristics of patients from different continents. His symptoms improved significantly after 3 months of being on a low-protein diet, supplementation with lysine, citrulline, carnitine, and trace elements, and oral corticosteroid treatment for 2 months. The patient is still under follow-up.
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Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by applying high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). After intragastric administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine were comparatively studied for the first time. The plasma concentration of demethyleneberberine reached its peak within 5 min after intragastric administration in both rats and mice. Furthermore, its bioavailability was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of demethyleneberberine in the urine, feces and bile was 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on demethyleneberberine.
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Berberina , Humanos , Ratas , Ratones , Animales , Distribución Tisular , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Metal-organic frameworks (MOFs) have been broadly applied in biomedical and other fields. MOFs have high porosity, a large comparative area, and good biostability and have attracted significant attention, especially in cancer therapies. This paper presents the latest applications of MOFs in chemodynamic therapy (CDT), sonodynamic therapy (SDT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and combination therapy for breast cancer. A combination therapy is the combination of two different treatment modalities, such as CDT and PDT combination therapy, and is considered more effective than separate therapies. Herein, we have also discussed the advantages and disadvantages of combination therapy in the treatment of breast cancer. This paper aims to illustrate the potential of MOFs in new cancer therapeutic approaches, discuss their potential advantages, and provide some reflections on the latest research results.
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Neoplasias de la Mama , Estructuras Metalorgánicas , Neoplasias , Fotoquimioterapia , Humanos , Femenino , Terapia Combinada , Terapia Fototérmica , Porosidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias/tratamiento farmacológicoRESUMEN
This article mainly reviews the biomedicine applications of two metal-organic frameworks (MOFs), MIL-100(Fe) and MIL-101(Fe). These MOFs have advantages such as high specific surface area, adjustable pore size, and chemical stability, which make them widely used in drug delivery systems. The article first introduces the properties of these two materials and then discusses their applications in drug transport, antibacterial therapy, and cancer treatment. In cancer treatment, drug delivery systems based on MIL-100(Fe) and MIL-101(Fe) have made significant progress in chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), photodynamic therapy (PDT), immunotherapy (IT), nano-enzyme therapy, and related combined therapy. Overall, these MIL-100(Fe) and MIL-101(Fe) materials have tremendous potential and diverse applications in the field of biomedicine.
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INTRODUCTION: Porous coordination networks (PCNs) have been widely used in large number of applications such as light harvesting, catalysis, and biomedical applications. Inserting porphyrins into PCNs scaffolds can alleviate the solubility and chemical stability problems associated with porphyrin ligands and add functionality to PCNs. The discovery that some PCNs materials have photosensitizer and acoustic sensitizer properties has attracted significant attention in the field of biomedicine, particularly in cancer therapy. This article describes the latest applications of the porphyrin ligand-based family of PCNs in cancer chemodynamic therapy (CDT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and combination therapies and offers some observations and reflections on them. AREAS COVERED: This article discusses the use of the PCN family of MOFs in cancer treatment, specifically focusing on chemodynamic therapy, sonodynamic therapy, photodynamic therapy, photothermal therapy, and combination therapy. EXPERT OPINION: Although a large number of PCNs have been developed for use in novel cancer therapeutic approaches, further improvements are needed to advance the use of PCNs in the clinic. For example, the main mechanism of action of PCNs against cancer and the metabolic processes in organisms, and how to construct PCNs that maintain good stability in the complex environment of organisms.
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Estructuras Metalorgánicas , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Porfirinas/uso terapéutico , Porfirinas/química , Porfirinas/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
One-dimensional nanowire structures composed of perovskite are widely recognized for their exceptional optoelectronic performance and mechanical properties, making them a popular area of investigation in photodetection research. In this work, a perovskite nanowire/copper phthalocyanine heterojunction-based photodetector was fabricated, which exhibits high photoresponse in the visible-near-infrared region. The incorporation of a heterojunction significantly enhanced the photoelectric performance. Specifically, the photoresponsivity and external quantum efficiency of the nanowire-based device were elevated from 58.5 A W-1and 1.35 × 104% to 84.5 A W-1and 1.97 × 104% at 532 nm, respectively. The enhanced photoresponse of the heterojunction device can be attributed to the unique microstructure of nanowire arrays. The wrapping of the nanowires by copper phthalocyanine forms heterojunctions with a larger dissociation area, which facilitated exciton dissociation and enhanced device performance. This work provides a promising example for optimizing the performance of nanowire devices.
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Metal-organic frameworks (MOFs) combined with sonodynamic therapy (SDT) have been introduced as a new and efficient treatment method. The critical advantage of SDT is its ability to penetrate deep tissues and concentrate energy on the tumor site to achieve a non-invasive or minimally invasive effect. Using a sonosensitizer to generate reactive oxygen species (ROS) under ultrasound is the primary SDT-related method of killing tumor cells. In the presence of a sonosensitizer, SDT exhibits a more lethal effect on tumors. The fast development of micro/nanotechnology has effectively improved the efficiency of SDT, and MOFs have been broadly evaluated in SDT due to their easy synthesis, easy surface functionalization, high porosity, and high biocompatibility. This article reviews the main mechanism of action of sonodynamic therapy in cancer treatment, and also reviews the applications of MOFs in recent years. The application of MOFs in sonodynamic therapy can effectively improve the targeting ability of SDT and the conversion ability of reactive oxygen species, thus improving their killing ability on cancer cells. This provides new ideas for the application of micro/nano particles in SDT and cancer therapy.
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The mechanical properties of an extracellular microenvironment can affect cell functions. The effects of elasticity and viscoelasticity on cell functions have been extensively studied with hydrogels of tunable mechanical properties. However, investigation of the viscosity effect on cell functions is still very limited and it can be tricky to explore how viscosity affects cells in three-dimensional (3D) culture due to the lack of appropriate tools. In this study, agarose hydrogel containers were prepared and used to encapsulate viscous media for 3D cell culture to investigate the viscosity effect on the functions of bovine articular chondrocytes (BACs). Polyethylene glycol of different molecular weights was used to adjust culture medium viscosity in a large range (72.8-679.2 mPa s). The viscosity affected gene expression and secretion of cartilagenious matrices, while it did not affect BAC proliferation. The BACs cultured in the lower viscosity medium (72.8 mPa s) showed a higher level of cartilaginous gene expression and matrix secretion.
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Condrocitos , Hidrogeles , Animales , Bovinos , Hidrogeles/farmacología , Sefarosa , Viscosidad , CartílagoRESUMEN
Correction for 'Current and promising applications of Hf(IV)-based MOFs in cancer therapy' by Xuelin Chen et al., J. Mater. Chem. B, 2023, 11, 5693-5714, https://doi.org/10.1039/D3TB00267E.
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Cancer is one of the greatest challenges in medical science today as it poses a serious threat to human life. In view of this, myriad of therapeutic strategies are being developed for the treatment of cancer. Despite the use of various therapeutic approaches, they are still insufficient for the treatment of cancer. The rapid advancement of nanotechnology currently offers exciting possibilities for the creation of novel cancer therapy approaches. Metal organic frameworks (MOFs) are emerging multifunctional nanomaterials that find prospective applications in the biomedical field owing to their porosity, large specific surface area, and diversified structures. Amongst varied categories of MOFs, Hf(IV)-based MOFs that have been developed since 2012 and currently have been finding new applications and hence this class of MOFs are gaining immense attention amongst the material and biomaterial chemists. Most importantly, Hf(IV)-MOFs comprising high Z-Hf metal content may be capable of offering new therapeutic options for cancer therapy, nonlinear optics, as fluorescent sensors, and photoresponsive devices. In this review, the progress in Hf(IV)-based MOFs for the treatment of cancer using radiotherapy, chemotherapy, immunotherapy, phototherapeutic techniques, or a combination of two or more of these techniques have been explored. This review also provides insight regarding the current limitations and future prospects of Hf(IV)-MOFs for cancer therapy.
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Estructuras Metalorgánicas , Nanoestructuras , Neoplasias , Humanos , Estructuras Metalorgánicas/uso terapéutico , Inmunoterapia , Materiales Biocompatibles , Colorantes , Neoplasias/tratamiento farmacológicoRESUMEN
Narrow-band photodetectors based on halide perovskite have recently attracted significant attention due to their exceptional narrow-band detection performance and tunable absorption peaks covering a wide optical range. In this work, we report mixed-halide CH3NH3PbClxBr3-xsingle crystal-based photodetectors have been fabricated, where the Cl/Br ratios were varied (3:0, 10:1, 5:1, 1:1, 1:7, 1:14 and 0:3). Vertical and parallel structures devices were fabricated which exhibited ultranarrow spectral responses under bottom illumination, with a full-width at half-maximum less than 16 nm. The observed performance can be ascribed to the unique carrier generation and extraction mechanisms within the single crystal under short and long wavelength of illumination. These findings offer valuable insights into the development of narrow-band photodetectors that do not necessitate the use of filters and hold tremendous potential for a diverse array of applications.
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Metal-phenolic networks (MPNs) are a new type of nanomaterial self-assembled by metal ions and polyphenols that have been developed rapidly in recent decades. They have been widely investigated, in the biomedical field, for their environmental friendliness, high quality, good bio-adhesiveness, and bio-compatibility, playing a crucial role in tumor treatment. As the most common subclass of the MPNs family, Fe-based MPNs are most frequently used in chemodynamic therapy (CDT) and phototherapy (PTT), where they are often used as nanocoatings to encapsulate drugs, as well as good Fenton reagents and photosensitizers to improve tumor therapeutic efficiency substantially. In this review, strategies for preparing various types of Fe-based MPNs are first summarized. We highlight the advantages of Fe-based MPNs under the different species of polyphenol ligands for their application in tumor treatments. Finally, some current problems and challenges of Fe-based MPNs, along with a future perspective on biomedical applications, are discussed.
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The present study aimed to investigate the clinical characteristics of diffuse pulmonary lymphangioma (DPL) in children to improve the diagnosis and treatment of this disease. A case of pediatric DPL was observed for its clinical symptoms, imaging features, lung biopsy pathological characteristics and immunohistochemical phenotypes, and relevant literature was also reviewed. The main clinical manifestations of this pediatric patient were a cough, shortness of breath, hemoptysis, bloody chylothorax and pericardial effusion. Chest computed tomography showed a grid-like shadow and markedly thickened interlobular septa. Pathological examination revealed lymphatic vessel hyperplasia and expansion. Immunohistochemistry showed positive staining of lymphatic endothelial cells CD31 and D2-40. The patient's condition improved after combined treatment with methylprednisone, propranolol, sirolimus and somatostatin, whose bloody chylothorax also achieved good therapeutic effect after conservative treatment. Overall, the clinical and imaging appearances of DPL are lack of characterization, and its clinical manifestations include cough, shortness of breath and chylothorax. Computed tomography may show mesh-like shadows of both lungs and thickened interlobular septa. The definite diagnosis of DPL depends on biopsy pathology. In addition to this case, B-ultrasound-guided puncture biopsy is effective and safe, and propranolol-sirolimus treatment has a certain effect, but the clinical effect may be different. Conservative treatment of pleural effusion can result in better curative effect.