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Genetic variants play an important role in conferring risk for cardiovascular diseases (CVDs). With the rapid development of next-generation sequencing (NGS), thousands of genetic variants associated with CVDs have been identified by genome-wide association studies (GWAS), but the function of more than 40% of genetic variants is still unknown. This gap of knowledge is a barrier to the clinical application of the genetic information. However, determining the pathogenicity of a variant of uncertain significance (VUS) is challenging due to the lack of suitable model systems and accessible technologies. By combining clustered regularly interspaced short palindromic repeats (CRISPR) and human induced pluripotent stem cells (iPSCs), unprecedented advances are now possible in determining the pathogenicity of VUS in CVDs. Here, we summarize recent progress and new strategies in deciphering pathogenic variants for CVDs using CRISPR-edited human iPSCs.
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Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Células Madre Pluripotentes Inducidas , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Edición Génica , Estudio de Asociación del Genoma Completo , Humanos , VirulenciaRESUMEN
Specified intestinal epithelial cells reprogram and contribute to the regeneration and renewal of the epithelium upon injury. Mutations that deregulate such renewal processes may contribute to tumorigenesis. Using intestinal organoids, we show that concomitant activation of Notch signaling and ablation of p53 induce a highly proliferative and regenerative cell state, which is associated with increased levels of Yap and the histone methyltransferase Mll1. The induced signaling system orchestrates high proliferation, self-renewal, and niche-factor-independent growth, and elevates the trimethylation of histone 3 at lysine 4 (H3K4me3). We demonstrate that Yap and Mll1 are also elevated in patient-derived colorectal cancer (CRC) organoids and control growth and viability. Our data suggest that Notch activation and p53 ablation induce a signaling circuitry involving Yap and the epigenetic regulator Mll1, which locks cells in a proliferative and regenerative state that renders them susceptible for tumorigenesis.
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Proteínas de Ciclo Celular/fisiología , N-Metiltransferasa de Histona-Lisina/fisiología , Proteína de la Leucemia Mieloide-Linfoide/fisiología , Receptores Notch/metabolismo , Transducción de Señal , Factores de Transcripción/fisiología , Proteína p53 Supresora de Tumor/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Mutación , Organoides/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Recent studies have shown that the gut microbiota regulates intestinal function and maintains intestinal homeostasis, as well as interacting with the central nervous system to affect brain function and human behavior. Microglia are the most common immune cell type in the central nervous system during homeostasis. These cells play an important role in immune surveillance by responding to infections and other pathological conditions. Microglia also play a major role in maintaining brain homeostasis in both developing and adult mice by phagocytosing cell debris and regulating the formation of neural networks. The specific signaling pathways and cytokines that control the maturation and activation of microglia are currently not fully established. However, research on germ-free (GF) mice and specific pathogen-free (SPF) mice indicate that gut microbiota have important interactions with microglia. Here, we review the latest research findings on how gut microbiota can affect the morphology, maturation, phenotype and function of microglia. We also discuss recent advances in the gut microbiota-microglia-disease axis.
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Microbioma Gastrointestinal , Humanos , Animales , Ratones , Microglía/fisiología , Sistema Nervioso Central , EncéfaloRESUMEN
Nitrogen-based nutrients are the main factors affecting rice growth and development. As the nitrogen (N) application rate increased, the nitrogen use efficiency (NUE) of rice decreased. Therefore, it is important to understand the molecular mechanism of rice plant morphological, physiological, and yield formation under low N conditions to improve NUE. In this study, changes in the rice morphological, physiological, and yield-related traits under low N (13.33 ppm) and control N (40.00 ppm) conditions were performed. These results show that, compared with control N conditions, photosynthesis and growth were inhibited and the carbon (C)/N and photosynthetic nitrogen use efficiency (PNUE) were enhanced under low N conditions. To understand the post-translational modification mechanism underlying the rice response to low N conditions, comparative phosphoproteomic analysis was performed, and differentially modified proteins (DMPs) were further characterized. Compared with control N conditions, a total of 258 DMPs were identified under low N conditions. The modification of proteins involved in chloroplast development, chlorophyll synthesis, photosynthesis, carbon metabolism, phytohormones, and morphology-related proteins were differentially altered, which was an important reason for changes in rice morphological, physiological, and yield-related traits. Additionally, inconsistent changes in level of transcription and protein modification, indicates that the study of phosphoproteomics under low N conditions is also important for us to better understand the adaptation mechanism of rice to low N stress. These results provide insights into global changes in the response of rice to low N stress and may facilitate the development of rice cultivars with high NUE by regulating the phosphorylation level of carbon metabolism and rice morphology-related proteins.
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Oryza , Oryza/metabolismo , Nitrógeno/metabolismo , Fotosíntesis , Aclimatación , Carbono/metabolismoRESUMEN
RNA-binding proteins (RBPs) play pivotal roles in directing RNA fate and function. Yet the current annotation of RBPs is largely limited to proteins carrying known RNA-binding domains. To systematically reveal dynamic RNA-protein interactions, we surveyed the human proteome by a protein array-based approach and identified 671 proteins with RNA-binding activity. Among these proteins, 525 lack annotated RNA-binding domains and are enriched in transcriptional and epigenetic regulators, metabolic enzymes, and small GTPases. Using an improved CLIP (crosslinking and immunoprecipitation) method, we performed genome-wide target profiling of isocitrate dehydrogenase 1 (IDH1), a novel RBP. IDH1 binds to thousands of RNA transcripts with enriched functions in transcription and chromatin regulation, cell cycle and RNA processing. Purified IDH1, but not an oncogenic mutant, binds directly to GA- or AU-rich RNA that are also enriched in IDH1 CLIP targets. Our study provides useful resources of unconventional RBPs and IDH1-bound transcriptome, and convincingly illustrates, for the first time, the in vivo and in vitro RNA targets and binding preferences of IDH1, revealing an unanticipated complexity of RNA regulation in diverse cellular processes.
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Isocitrato Deshidrogenasa/metabolismo , Proteoma/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Transcriptoma , Elementos Ricos en Adenilato y Uridilato , Cromatina/genética , Cromatina/metabolismo , Reactivos de Enlaces Cruzados/química , Células Madre Embrionarias , GTP Fosfohidrolasas/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Inmunoprecipitación , Isocitrato Deshidrogenasa/genética , Redes y Vías Metabólicas/genética , Motivos de Nucleótidos , Análisis por Matrices de Proteínas , Unión Proteica , ARN Mensajero/genética , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. METHODS: We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. RESULTS: BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. CONCLUSIONS: Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Biomarcadores de Tumor , Metilación de ADN , Sistema de Señalización de MAP Quinasas , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas Supresoras de Tumor/genética , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Modelos Biológicos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fosforilación , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Chemically stable ester derivatives of taxifolin have become a focus of interest for their role in the satisfactory effects on human health. Accordingly, the aim of this study was to evaluate the physical and chemical stability of different formulations containing 0.02% taxifolin tetra-octanoate, which was proved to possess higher inhibitory effect on tyrosinase activity compared with taxifolin in a cell-free system. In the studies of physical stability, a Brookfield viscometer was used to determine rheological behavior of formulations containing taxifolin tetra-octanoate, and a portable pH meter was used to determine pH change. Moreover, chemical stability was determined by HPLC with UV detection. Formulations were evaluated for 12 weeks stored at 25 and 40°C. Results showed that storage time had no significant influence on viscosity of the formulations containing taxifolin tetra-octanoate, and pH value was relatively stable, which was within the limits of normal skin pH range. In the chemical stability studies, taxifolin tetra-octanoate in the essence formulation was most unstable at 40°C with about 81% degradation in 12 weeks of storage, however, the percentage of remaining taxifolin tetra-octanoate in cream formulation stored for 12 weeks at 25°C was the highest, about 93%. The results in this study may contribute to the development of more stable formulations containing taxifolin tetra-octanoate.
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Caprilatos/farmacología , Inhibidores Enzimáticos/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Quercetina/análogos & derivados , Caprilatos/síntesis química , Caprilatos/química , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Concentración de Iones de Hidrógeno , Estructura Molecular , Monofenol Monooxigenasa/metabolismo , Quercetina/síntesis química , Quercetina/química , Quercetina/farmacología , Relación Estructura-Actividad , ViscosidadRESUMEN
Nanofibers or nanofibrous membranes prepared by electrospinning possess many attractive properties, including excellent mechanical properties, high specific surface area and high porosity, making them attractive for sensor application, especially for the electrochemical sensors. Many nanomaterials are used as additives to improve the conductivity, sensitivity and selectivity of sensors. Based on the different modifiers of electrode materials, electrochemical sensors can be divided into enzyme sensors and non-enzyme sensors. In this review, we summarize the recent progress of the electrochemical sensors fabricated by electrospinning, including hydrogen peroxide (H2O2) sensors, glucose sensors and other sensors. In addition, the sensing mechanisms of various electrochemical sensors are introduced in detail. Finally, future research directions of electrochemical sensors based on electrospinning and the challenges faced by large-scale applications of electrospun electrochemical sensors are presented.
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Berberine has abundant beneficial properties including anti-cancer effects. In the present study, we examined the inhibitory effect of berberine on α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in B16F1 melanoma cells. The results showed that berberine decreased the expression of tyrosinase and microphthalmia-associated transcription factor (MITF) in a dose-dependent manner. In order to observe the potential target for the inhibitory effect of berberine, we examined the effect of berberine on TRP-1 and TRP-2. The results showed that berberine led to a reduction of TRP-1, while the change of TRP-2 was inconspicuous. In the end, we observed the specific effect of berberine on zebrafish skin pigmentation. Overall, the results suggested that berberine inhibits tyrosinase activity and melanin synthesis by attenuating the expression of tyrosinase and MITF. Therefore, these findings may contribute to the potential application of berberine in medicinal or cosmetic products.
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Berberina/farmacología , Melaninas/biosíntesis , Melanoma Experimental/tratamiento farmacológico , Animales , Berberina/aislamiento & purificación , Línea Celular Tumoral , Coptis chinensis , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacología , Oxidorreductasas Intramoleculares/metabolismo , Melanoma Experimental/metabolismo , Ratones , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/metabolismo , Oxidorreductasas/metabolismo , Pez Cebra , alfa-MSH/antagonistas & inhibidoresAsunto(s)
MicroARNs , Neoplasias , Sirtuinas , Cardiotoxicidad , Doxorrubicina/efectos adversos , Terapia Genética , Humanos , ARN Circular , SurvivinRESUMEN
Polychlorinated biphenyl (PCB) quinones are known to cause toxic effects, but their mechanisms are quite unclear. In this study, we examined whether 2,3,5-trichloro-6-phenyl-[1,4]benzoquinone, PCB29-pQ, induces cell death via apoptosis pathway. Our result showed PCB29-pQ exposure decreased HepG2 cell viability in a time-dependent manner. Lactate dehydrogenase leakage assay also implied the cytotoxicity of PCB29-pQ. 4',6-Diamidino-2-phenylindole dihydrochloride staining and flow cytometry assays both confirmed PCB29-pQ caused dose-dependent apoptotic cell death in HepG2 cells. Furthermore, we found that PCB29-pQ exposure increased cellular reactive oxygen species (ROS) level, decreased mitochondrial membrane potential and induced the translocation of cytochrome c from mitochondria into cytosol in HepG2 cells. Moreover, PCB29-pQ exposure induced B-cell lymphoma 2 (Bcl-2) downregulation and Bcl-2-associated X (Bax) upregulation, poly(ADP-ribose) polymerase cleavage, accompanied with the increased caspase-3/9 and p53 expressions. Taking together, these results suggested PCB29-pQ induced HepG2 cells apoptosis through a ROS-driven, mitochondrial-mediated and caspase-dependent pathway.
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Apoptosis/efectos de los fármacos , Benzoquinonas/toxicidad , Caspasa 3/metabolismo , Mitocondrias/metabolismo , Bifenilos Policlorados/toxicidad , Benzoquinonas/química , Caspasa 9/metabolismo , Citocromos c/metabolismo , Células Hep G2 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Bifenilos Policlorados/química , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
A novel surface-modification strategy has been developed for the construction of a photocontrolled silicon wafer surface with switchable wettability based on host-guest inclusion complexation. The silicon wafer was first modified by guest molecule azobenzene (Azo) via a silanization reaction. Subsequently, a series of polymers with different polarities were attached to host molecule ß-cyclodextrin (ß-CD) to prepare ß-CD-containing hemitelechelic polymers via click chemistry. Finally, a photocontrolled silicon wafer surface modified with polymers was fabricated by inclusion complexation between ß-CD and Azo, and the surface properties of the substrate are dependent on the polymers we used. The elemental composition, surface morphology, and hydrophilic/hydrophobic property of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscope, and contact angle measurements, respectively. The antifouling property of the PEG-functionalized surface was evaluated by a protein adsorption assay using bovine serum albumin, which was also characterized by XPS. The results demonstrate that the surface modified with PEG possesses good protein-resistant properties.
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Albúmina Sérica Bovina/química , Animales , Compuestos Azo/química , Bovinos , Química Clic , Tamaño de la Partícula , Procesos Fotoquímicos , Silicio/química , Propiedades de Superficie , Humectabilidad , beta-Ciclodextrinas/químicaRESUMEN
The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.
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Antineoplásicos/efectos adversos , Antioxidantes/uso terapéutico , Ciclofosfamida/efectos adversos , Cistitis/prevención & control , Hematuria/prevención & control , Mesna/uso terapéutico , Sustancias Protectoras/uso terapéutico , Ácido Tióctico/uso terapéutico , Animales , Ácido Ascórbico/uso terapéutico , Cistitis/inducido químicamente , Cistitis/metabolismo , Sinergismo Farmacológico , Hematuria/inducido químicamente , Hematuria/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Tamaño de los Órganos/efectos de los fármacos , Fosforilación , Distribución Aleatoria , Especies Reactivas de Oxígeno/metabolismo , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria/fisiopatologíaRESUMEN
A 36-year-old unmarried male chef was incidentally diagnosed with hypokalemia during an evaluation for an acute perianal abscess. Despite potassium supplementation, he developed progressive weakness in his lower limbs, culminating in an inability to stand. Investigations confirmed severe hypokalemia, metabolic alkalosis, hypomagnesemia, secondary hyperaldosteronism, and low urinary calcium excretion, with normotension. The patient's long-standing stunted growth and lean physique since childhood were noted. Biochemical assays further identified type 2 diabetes mellitus and metabolic syndrome. Genetic analysis revealed three heterozygous SLC12A3 mutations (M1: c.421G>A: p.G141R, M2: c.509T>A:p.L170Q, and M3: c.704C>A: p.T235K), compound heterozygo us and derived from both parents, with M1 and M3 reported here for the first time. Treatment with spironolactone and oral potassium chloride stabilized his potassium levels. Following the administration of SGLT2 inhibitors in patients receiving hypoglycemic therapy, we observed a mild decrease in serum sodium levels. This case highlights the criticality of vigilant metabolic surveillance in Gitelman syndrome and advises prudence with SGLT2 inhibitors in those with concurrent type 2 diabetes, given the risk of potentially aggravate sodium loss.
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A 3D manipulation technique based on two optothermally generated and actuated surface-bubble robots is proposed. A single laser beam can be divided into two parallel beams and used for the generation and motion control of twin bubbles. The movement and spacing control of the lasers and bubbles can be varied directly and rapidly. Both 2D and 3D operations of micromodules were carried out successfully using twin bubble robots. The cooperative manipulation of twin bubble robots is superior to that of a single robot in terms of stability, speed, and efficiency. The operational technique proposed in this study is expected to play an important role in tissue engineering, drug screening, and other fields.
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BACKGROUND: Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. METHODS: We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. RESULT: Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. CONCLUSIONS: Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.
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Antígenos de Diferenciación de Linfocitos B , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Antígenos de Histocompatibilidad Clase II , Neoplasias Pulmonares , Factores Inhibidores de la Migración de Macrófagos , Microglía , Animales , Femenino , Humanos , Ratones , Antígenos de Diferenciación de Linfocitos B/metabolismo , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Antígenos de Histocompatibilidad Clase II/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Microglía/metabolismo , Microglía/patologíaRESUMEN
Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above. Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review. Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient. Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.
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DNA damage is a critical factor contributing to genetic alterations, directly affecting human health, including developing diseases such as cancer and age-related disorders. DNA repair mechanisms play a pivotal role in safeguarding genetic integrity and preventing the onset of these ailments. Over the past decade, substantial progress and pivotal discoveries have been achieved in DNA damage and repair. This comprehensive review paper consolidates research efforts, focusing on DNA repair mechanisms, computational research methods, and associated databases. Our work is a valuable resource for scientists and researchers engaged in computational DNA research, offering the latest insights into DNA-related proteins, diseases, and cutting-edge methodologies. The review addresses key questions, including the major types of DNA damage, common DNA repair mechanisms, the availability of reliable databases for DNA damage and associated diseases, and the predominant computational research methods for enzymes involved in DNA damage and repair.
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PURPOSE: Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. METHODS: Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. CONCLUSIONS: Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.
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Inhibidores de la Angiogénesis , Neoplasias Colorrectales , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Femenino , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Estudios Retrospectivos , Anciano , Adulto , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Anciano de 80 o más Años , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Supervivencia sin ProgresiónRESUMEN
Our understanding of plant responses to enhanced ultraviolet-B (UV-B) radiation has improved over recent decades. However, research on cryptogams is scarce and it remains controversial whether UV-B radiation causes changes in physiology related to photosynthesis. To investigate the effects of supplementary UV-B radiation on photosynthesis and chloroplast ultrastructure in Bryum argenteum Hedw., specimens were cultured for 10 days under four UV-B treatments (2.75, 3.08, 3.25 and 3.41 W m(-2) ), simulating depletion of 0% (control), 6%, 9% and 12% of stratospheric ozone at the latitude of Shapotou, a temperate desert area of northwest China. Analyses showed malondialdehyde content significantly increased, whereas chlorophyll (Chl) fluorescence parameters and Chl contents decreased with increased UV-B intensity. These results corresponded with changes in thylakoid protein complexes and chloroplast ultrastructure. Overall, enhanced UV-B radiation leads to significant decreases in photosynthetic function and serious destruction of the chloroplast ultrastructure of B. argenteum. The degree of negative influences increased with the intensity of UV-B radiation. These results may not only provide a potential mechanism for supplemental UV-B effects on photosynthesis of moss crust, but also establish a theoretical basis for further studies of adaptation and response mechanisms of desert ecosystems under future ozone depletion.