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Bone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.
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Adipocitos , Envejecimiento , Senescencia Celular , Animales , Adipocitos/metabolismo , Senescencia Celular/fisiología , Ratones , Envejecimiento/fisiología , Ratones Endogámicos C57BL , Células de la Médula Ósea/metabolismo , Huesos/metabolismo , Huesos/fisiología , Masculino , Osteogénesis/fisiología , Transducción de Señal , Macrófagos/metabolismoRESUMEN
The transmission of flaviviruses, such as dengue virus (DENV) and Zika virus (ZIKV), poses a significant threat to global public health. Zhang et al. recently showed that Rosenbergiella sp. YN46 (Rosenbergiella_YN46), a bacterium from the mosquito gut, inhibits flavivirus transmission and thus offers a potential biocontrol strategy with broad public health implications.
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Flavivirus , Animales , Flavivirus/fisiología , Humanos , Infecciones por Flavivirus/transmisión , Infecciones por Flavivirus/virología , Infecciones por Flavivirus/prevención & control , Virus Zika/fisiología , Culicidae/microbiología , Culicidae/virología , Virus del Dengue/fisiología , Microbioma Gastrointestinal/fisiología , Mosquitos Vectores/virología , Mosquitos Vectores/microbiologíaRESUMEN
Peas (Pisum sativum L.) are widely cultivated in temperate regions and are susceptible hosts for various viruses across different families. The discovery and identification of new viruses in peas has significant implications for field disease management. Here, we identified a mixed infection of two viruses from field-collected peas exhibiting virus-like symptoms using metatranscriptome and small RNA sequencing techniques. Upon identification, one of the viruses was determined to be a newly isolated and discovered bymovirus from peas, named "pea bymovirus 1 (PBV1)". The other was identified as a novel variant of bean yellow mosaic virus (BYMV-HZ1). Subsequently, mechanical inoculation and RT-PCR assays confirmed that both viruses could be inoculated back onto peas and tobaccos, showing mixed infection by PBV1 and BYMV-HZ1. To our knowledge, this is the first isolation of a bymovirus from pea and the first documented case of mixed infection of peas by PBV1 and BYMV-HZ1 in China.
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Pisum sativum , Enfermedades de las Plantas , ARN Viral , Enfermedades de las Plantas/virología , Pisum sativum/virología , ARN Viral/genética , Filogenia , Coinfección/virología , China , Genoma Viral , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
Exposure of articular cartilage to excessive mechanical loading is closely related to the pathogenesis of osteoarthritis (OA). However, the exact molecular mechanism by which excessive mechanical loading drives OA remains unclear. In vitro, primary chondrocytes were exposed to cyclic tensile strain at 0.5 Hz and 10 % elongation for 30 min to simulate excessive mechanical loading in OA. In vivo experiments involved mice undergoing anterior cruciate ligament transection (ACLT) to model OA, followed by interventions on Rcn2 expression through adeno-associated virus (AAV) injection and tamoxifen-induced gene deletion. 10 µL AAV2/5 containing AAV-Rcn2 or AAV-shRcn2 was administered to the mice by articular injection at 1 week post ACLT surgery, and Col2a1-creERT: Rcn2flox/flox mice were injected with tamoxifen intraperitoneally to obtain Rcn2-conditional knockout mice. Finally, we explored the mechanism of Rcn2 affecting OA. Here, we identified reticulocalbin-2 (Rcn2) as a mechanosensitive factor in chondrocytes, which was significantly elevated in chondrocytes under mechanical overloading. PIEZO type mechanosensitive ion channel component 1 (Piezo1) is a critical mechanosensitive ion channel, which mediates the effect of mechanical loading on chondrocytes, and we found that increased Rcn2 could be suppressed through knocking down Piezo1 under excessive mechanical loading. Furthermore, chondrocyte-specific deletion of Rcn2 in adult mice alleviated OA progression in the mice receiving the surgery of ACLT. On the contrary, articular injection of Rcn2-expressing adeno-associated virus (AAV) accelerated the progression of ACLT-induced OA in mice. Mechanistically, Rcn2 accelerated the progression of OA through promoting the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (Stat3).
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Condrocitos , Ratones Noqueados , Osteoartritis , Animales , Masculino , Ratones , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrocitos/metabolismo , Condrocitos/patología , Modelos Animales de Enfermedad , Canales Iónicos/metabolismo , Canales Iónicos/genética , Ratones Endogámicos C57BL , Osteoartritis/patología , Osteoartritis/metabolismo , Osteoartritis/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Estrés Mecánico , Regulación hacia Arriba , Soporte de PesoRESUMEN
Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.
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Inflamación , Placa Aterosclerótica , Tomografía de Emisión de Positrones , Animales , Conejos , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/metabolismo , Inflamación/metabolismo , Inflamación/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Masculino , Macrófagos/metabolismo , Receptores de GABA/metabolismo , Radiofármacos/farmacocinética , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Radioisótopos de Flúor , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , AcetanilidasRESUMEN
PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).
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Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.
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BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.
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Quemaduras , Microbioma Gastrointestinal , Microbiota , Humanos , Animales , Ratones , Bacterias/genética , Firmicutes/genética , ARN Ribosómico 16S/genéticaRESUMEN
The new sensible thermal energy storage materials were prepared by the sintering method with low-grade pyrophyllite mineral powders as main raw materials, Suzhou clay as the sintering aid and sulfite liquors as the binder. Further, the performance of sensible thermal energy storage under different size distributions and sintering temperatures was investigated and analyzed. The results show that the optimum particle size distribution is 50:15:35, the bulk density, thermal conductivity, and specific heat capacity are the largest values, which are 1.97 g cm-3, 0.87 W m-1 K-1 and 0.63 kJ kg-1 K-1, respectively. Other properties including porosity, water absorption, flexural and compressive strength and so on are optimal under this size distribution. When the sintering temperature is 1200 °C, the material has a good thermal conductivity of 0.89 W m-1 K-1 and a high bulk density of 2.05 g cm-3. Meanwhile, the sample with the used temperature from 50 to 900 °C has the best thermal energy storage capacity of 306.29 kWh·m-3.
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Four common Patrinia species, including P. heterophylla, P. monandra, P. scabiosifolia and P. villosa, have been documented as herbal medicines with various clinical applications, such as anti-cancer, anti-diarrhea and sedative. However, the authentication of medicinal Patrinia species poses a problem, particularly with the processed herbal materials. This study aimed to systematically authenticate the four medicinal Patrinia species in the market using morphological and chemical characterization, as well as DNA markers. We found the species identity authenticated by traditional morphologies were in good agreement with both chemical and molecular results. The four species showed species-specific patterns in chromatographic profiles with distinct chemical markers. We also revealed the power of complete chloroplast genomes in species authentication. The sequences of targeted loci, namely atpB, petA, rpl2-rpl23 and psaI-ycf4, contained informative nucleotides for the species differentiation. Our results also facilitate authentication of medicinal Patrinia species using new DNA barcoding markers. To the best of our knowledge, this is the first report on the application of morphology, chemical fingerprinting, complete chloroplast genomes and species-specific Insertion-Deletions (InDels) in differentiating Patrinia species. This study reported on the power of a systematic, multidisciplinary approach in authenticating medicinal Patrinia species.
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Patrinia , Plantas Medicinales , Patrinia/química , Plantas Medicinales/genética , Plantas Medicinales/químicaRESUMEN
The power capacity of reflectarray antennas (RAs) is investigated through full-wave simulations and high-power microwave (HPM) experiments in this paper. In order to illustrate the results in detail, two RA elements are designed. The simulated power handling capacity of two RA elements are 7.17 MW/m2 and 2.3 GW/m2, respectively. To further study the HPM RA, two RA prototypes operating at 2.8 GHz are constructed with the aperture size of 1 m × 1 m. Simulations and experimental measurements are conducted for the two prototypes. The experimental results demonstrate that, even when subjected to 1 GW of power, the radiation beam of the RA with the second elements can still propagate in the intended direction. This research will establish a basis for advancing the practicality of RAs in HPM applications.
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Light detection and ranging (LiDAR) systems have made significant contributions in different applications. The laser ranging (LR) system is one of the core components of LiDARs. However, existing coaxial LR systems suffer from low energy efficiency due to obstruction of the reflection mirror. In this study, we carefully design a laser transmitter and receiver subsystem and consequently propose a highly energy-efficient coaxial design for a time of light-based LR system, where a perforated mirror and splicing lens account for the promotion of energy efficiency. The small hole in the perforated mirror is located on the object focus of the focusing lens to ensure the laser beam will pass through the perforated mirror without obstructions. The ring-shape splicing lens, consisting of two parts, is used for laser collimation and laser reception simultaneously. Laboratory experiments proved that the proposed design eliminates the complex calibration process for noncoaxial LR systems while reaching a comparable energy efficiency, which is higher than 98%. We believe it is an economical yet efficient way to promote the energy efficiency of coaxial LR systems.
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Targeting the trap-assisted non-radiative recombination losses and photochemical degradation occurring at the interface and bulk of perovskite, especially the overlooked buried bottom interface, a strategy of tailored-phase two-dimensional (TP-2D) crystal seed layer has been developed to improve the charge transport dynamics at the buried interface and bulk of perovskite films. Using this approach, TP-2D layer constructed by TP-2D crystal seeds at the buried interface can induce the formation of homogeneous interface electric field, which effectively suppress the accumulation of charge carriers at the buried interface. Additionally, the presence of TP-2D crystal seed has a positive effect on the crystallization process of the upper perovskite film, leading to optimized crystal quality and thus promoted charge transport inside bulk perovskites. Ultimately, the best performing PSCs based on TP-2D layer deliver a power conversion efficiency of 24.58 %. The devices exhibit an improved photostability with 88.4 % of their initial PCEs being retained after aging under continuous 0.8-sun illumination for 2000â h in air. Our findings reveal how to regulate the charge transport dynamics of perovskite bulk and interface by introducing homogeneous components.
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Skylight polarization, inspired by the foraging behavior of insects, has been widely used for navigation for various platforms, such as robots, unmanned aerial vehicles, and others, owing to its stability and non-error-accumulation. Among the characteristics of skylight-polarized patterns, the angle of polarization (AOP) and the degree of polarization (DOP) are two of the most significant characteristics that provide abundant information regarding the position of the sun. In this study, we propose an accurate method for detecting the solar meridian for real-time bioinspired navigation through image registration. This method uses the AOP pattern to detect the solar meridian and eliminates the ambiguity between anti-solar meridian and solar meridian using the DOP pattern, resulting in an accurate heading of the observer. Simulation experiments demonstrated the superior performance of the proposed method compared to the alternative approaches. Field experiments demonstrate that the proposed method achieves real-time, robust, and accurate performance under different weather conditions with a root mean square error of 0.1° under a clear sky, 0.18° under an overcast sky with a thin layer of clouds, and 0.32° under an isolated thick cloud cover. Our findings suggest that the proposed method can be potentially used in skylight polarization for real-time and accurate navigation in GPS-denied environments.
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The expression level of PD-L1 in tumor tissue is considered one of the effective biomarkers to guide PD-1/PD-L1 therapy. Quantifying whole-body PD-L1 expression by SPECT imaging may help in selecting patients that potentially respond to PD-1/PD-L1 therapy. Nanobody is the smallest antibody fragment with antigen-binding ability that is well suited for radionuclide imaging. Nevertheless, high retention of radioactivity in the kidney may limit its clinical translation. The present study aimed to screen, design, and prepare a nanobody-based SPECT probe with rapid renal clearance to evaluate the PD-L1 expression level in vivo noninvasively. A phage library was constructed by immunizing alpaca with recombinant human PD-L1 protein, and 17 anti-PD-L1 nanobodies were screened by the phage display technique. After sequence alignment and flow cytometry analysis, APN09 was selected as the candidate nanobody, and a GGGC chelator was attached to its C-terminus for 99mTc labeling to prepare a SPECT imaging probe. The affinity and specificity of 99mTc-APN09 were evaluated by protein and cell-binding experiments, and SPECT imaging and biodistribution were performed in a mouse model with bilateral transplantation of A549 and A549PD-L1 tumors. The ability of 99mTc-APN09 to quantify the PD-L1 expression level in vivo was validated in tumor models with different PD-L1 expression levels. 99mTc-APN09 had a radiochemical purity higher than 99% and a binding equilibrium dissociation constant of 21.44 ± 1.65 nM with hPD-L1, showing high affinity. SPECT imaging results showed that 99mTc-APN09 could efficiently detect PD-L1-positive tumors within 0.5 h, and the quantitative results of SPECT were well correlated with the expression level of PD-L1 in cell lines. SPECT imaging and biodistribution results also showed that 99mTc-APN09 was rapidly cleared from the kidney in 2 h postinjection. 99mTc-APN09 was a simple and stable tool for visualizing PD-L1 expression in the whole body. In addition, due to its significant reduction in renal retention, it has better prospects for clinical translation.
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Antígeno B7-H1 , Neoplasias , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Neoplasias/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único/métodos , Camélidos del Nuevo MundoRESUMEN
Bionics, the interdisciplinary field that draws inspiration from nature to design and develop innovative technologies, has paved the way for the creation of "bio-inspired robots" [...].
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BACKGROUND: Growth hormone-secreted pituitary adenoma (GHPA) is a prominent subtype of pituitary adenoma (PA) associated with progressive somatic disfigurement, various complications, and elevated mortality rates. Existing treatment options have limited efficacy, highlighting the urgent need for novel pharmacological interventions. Previous studies have revealed that sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) signalling have critical roles in the tumour microenvironment, but their role in GHPA remains unclear. METHODS: We performed integrative analyses including bioinformatics analyses, functional studies, and clinical validation to investigate the pathological roles of SPHK1/S1P and evaluated the effectiveness of the S1P receptor 2 (S1PR2) inhibitor JTE-013 in GHPA treatment. RESULTS: SPHK1/S1P signalling is abnormally expressed in patients with GHPA. Knockdown of SPHK1 suppresses S1P-mediated cell proliferation in GH3 Cells. Mechanistically, S1P inhibits apoptosis and autophagy while promoting the secretion of Growth Hormone (GH) by binding to the S1P receptor subtype 2 (S1PR2) in GH3 cells. Moreover, the function of S1PR2 in GH3 cells is mediated by the downstream Akt-Creb pathway. We then identify the S1PR2 as a novel target for therapeutic intervention in GHPA. Systemic administration of the potent and selective S1PR2 antagonist, JTE-013, significantly reduces both tumour size and GH secretion. Importantly, we identify preoperative serum S1P levels as a biomarker predicting poor prognosis in GHPA patients at follow-up. CONCLUSION: Our study shows that blocking SPHK1/S1P/S1PR2 axis can ameliorate the progression of GHPA, providing evidence of a promising therapeutic target for GHPA.
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Fosfotransferasas (Aceptor de Grupo Alcohol) , Neoplasias Hipofisarias , Receptores de Lisoesfingolípidos , Humanos , Receptores de Esfingosina-1-Fosfato , Receptores de Lisoesfingolípidos/metabolismo , Hormona del Crecimiento , Neoplasias Hipofisarias/tratamiento farmacológico , Esfingosina/metabolismo , Lisofosfolípidos/metabolismo , Microambiente TumoralRESUMEN
PURPOSE: Estrogen Receptor α (ERα) is a well-established therapeutic target for Estrogen Receptor (ER)-positive breast cancers. Both Selective Estrogen Receptor Degraders (SERD) and PROTAC ER degraders are synthetic compounds suppressing the ER activity through the degradation of ER. However, the differences between SERD and PROTAC ER degraders are far from clear. METHODS: The effect of PROTAC ER degrader ERD-148 and SERD fulvestrant on protein degradation was evaluated by western blot analysis. The cell proliferation was tested by WST-8 assays and the gene expressions were assessed by gene microarray and real-time RT-PCR analysis after the compound treatment. RESULTS: ERD-148 is a potent and selective PROTAC ERα degrader. It degrades not only unphosphorylated ERα but also the phosphorylated ERα in the cells. In contrast, the SERD fulvestrant showed much-reduced degradation potency on the phosphorylated ERα. The more complete degradation of ERα by ERD-148 translates into a greater maximum cell growth inhibition. However, ERD-148 and fulvestrant share a similar gene regulation profile except for the variation of regulation potency. Further studies indicate that ERD-148 degrades the ERα in fulvestrant-resistant cells. CONCLUSION: PROTAC ER degrader has a different mechanism of action compared to SERD which may be used in treating fulvestrant-resistant cancers.
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Neoplasias de la Mama , Receptor alfa de Estrógeno , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Antagonistas de Estrógenos/farmacología , Receptor alfa de Estrógeno/metabolismo , Fulvestrant/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/farmacologíaRESUMEN
Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis. Emerging evidence indicates that mitophagy plays crucial roles in tumorigenesis, particularly in cancer therapy. Mitophagy can exhibit dual effects in cancer, with both cancer-inhibiting or cancer-promoting function in a context-dependent manner. A variety of natural compounds have been found to affect cancer cell death and display anticancer properties by modulating mitophagy. In this review, we provide a systematic overview of mitophagy signaling pathways, and examine recent advances in the utilization of natural compounds for cancer therapy through the modulation of mitophagy. Furthermore, we address the inquiries and challenges associated with ongoing investigations concerning the application of natural compounds in cancer therapy based on mitophagy. Overcoming these limitations will provide opportunities to develop novel interventional strategies for cancer treatment.
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Mitofagia , Neoplasias , Humanos , Autofagia , Muerte Celular , Mitocondrias/metabolismo , Mitofagia/fisiología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
During the survey on freshwater hyphomycetes in Guangxi, Guizhou and Hainan Provinces, China, five fresh collections were encountered. Based on their morphology, these five isolates were identified as belonging to Hermatomyces, Kirschsteiniothelia, Paramonodictys, Pleopunctum and Sparticola. Multi-gene phylogenetic analyses were performed for each genus, which resulted in the identification of five new species, namely Hermatomyces hainanensis, Kirschsteiniothelia ramus, Paramonodictys globosa, Pleopunctum guizhouense, and Sparticola irregularis. Detailed descriptions and illustrations of the morphological characteristics of these new taxa were provided. This research enriches the biodiversity of freshwater dematiaceous hyphomycetes.