Targeted juglone blocks the invasion and metastasis of HPV-positive cervical cancer cells.

Human papillomaviruses (HPVs), for instance, HPV 16 and HPV 18, are concerned associated with cervical cancer. Thus, it is essential to suppress HPVs-in HPV-positive cervical cancer for treating cervical cancer. The purpose of this study was to explore the proposed molecular mechanisms, which that underlies the antintumor potential of juglone to treat of HPV-positive on cervical cancer cells. The results showed that juglone suppressed HPV-positive cell growth in a dose- and time-dependent way. In addition, cell invasion and metastasis were also inhibited by juglone. Nevertheless, when pin 1 was knocked down in HPV-positive cells, cell proliferation, invasion and metastasis were reduced. This study was designed to acquire an understanding of the mechanism of invasion and metastasis in HPV-positive cells suppressed by juglone. It provides evidence of the advantageous use of juglone in the future.

Juglone Inhibits Proliferation of HPV-Positive Cervical Cancer Cells Specifically.

Human papillomaviruses (HPVs), such as HPV 16 and HPV 18 are related to cervical cancer. Therefore, it is important to inhibit HPV-positive cervical cancer for treating cervical cancer. This study is aiming at investigating the proposed molecular mechanism, which underlies the antineoplastic potential of the aqueous extract of juglone of HPV-positive cervical cancer cells. According to the results, it is showed that, juglone prohibited HPV positive cervical cancer cells' growth through dose-dependent way. Nevertheless, when pin 1 was knocked down, the proliferation inhibition reduced. The detection of apoptosis and cell cycle also illustrated that juglone influenced HPV positive cells. Western blot expressed the influence mechanism that it affected the B-cell lymphoma 2 (Bcl-2) family and later activated the Caspase-depended apoptosis way. It is contributable for this study to understand the mechanism of inhibiting HPV positive cells by juglone and it also provides an effective strategy for the application of it in the future.

Astaxanthin Esters as Functional Food: A Review of Their Nutrition, Phytochemical Structure, Biological Features, and Food Industry Prospects.

Astaxanthin (AST), mainly found in algae and shrimp, is a liposoluble ketone carotenoid with a wide range of biological activities and is commonly used in healthcare interventions and cosmetics. AST has a long chain of conjugated double bonds with hydroxyl and ketone groups at both ends, enabling it to form astaxanthin esters (AST-Es) through esterification with fatty acids. The fatty acid structure of AST plays a key role in the stability, antioxidant activity, and bioavailability of AST-Es. Antarctic krill (Euphausia superba) and blood-red algae Haematococcus Pluvialis (H pluvialis)-derived AST-Es exhibit strong antioxidant activity and numerous biological activities, such as improving insulin resistance, preventing Parkinson's disease, regulating intestinal flora, and alleviating inflammatory bowel disease. This review discusses the significance of AST-Es as functional food ingredients, highlighting their nutritional value, phytochemical structure, biological activities, and potential applications in the food industry.

Effect of contrast agent on T2-weighted fat-suppressed imaging and diffusion-weighted imaging in the diagnosis of breast tumors.

Background: Although previous studies have shown that the injection of contrast agents can improve image quality, the specific impact of this on T2-weighted fat-suppressed (T2 FS) and diffusion-weighted imaging (DWI) sequences in the diagnosis of breast cancer remains incompletely understood. In particular, there is insufficient research on how contrast agents affect the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values within these sequences, and how these changes influence the diagnosis of benign and malignant breast tumors. Methods: Breast magnetic resonance images (MRI) were obtained from 178 consecutive patients on a 3T scanner. The SNR and CNR of lesions on T2 FS sequence were calculated before and after contrast agent injection and compared. Differences between pre- and post-contrast ADC in identifying different tumor types were compared using the Kruskal-Wallis H-test and the paired comparison test. The accuracy of ADC values between pre- and post-contrast in distinguishing benign and malignant breast masses was assessed using receiver operating characteristic (ROC) curves. Results: The SNR and CNR of T2 FS sequence increased after contrast injection, and especially for invasive cancer and benign tumor, the increase was significant. For DWI, there was a slight increase or decrease of ADC values after contrast injection, but the ADC values before and after contrast had a similar effect in identifying different types of tumors. In the ROC curve analysis for assessing benign and malignant breast tumors, the area under the curve (AUC) before and after contrast showed similar results. Conclusions: Contrast agent injection can improve the SNR and CNR of T2 FS sequence, thus providing higher quality images for the diagnosis of breast lesions. Furthermore, injection of contrast agent had little effect on the ability of ADC values to identify different types of lesions and both ADC values before and after the contrast agent were able to distinguish between benign and malignant tumors with almost the same accuracy.

A RabGAP negatively regulates plant autophagy and immune trafficking.

Plants rely on autophagy and membrane trafficking to tolerate stress, combat infections, and maintain cellular homeostasis. However, the molecular interplay between autophagy and membrane trafficking is poorly understood. Using an AI-assisted approach, we identified Rab3GAP-like (Rab3GAPL) as a key membrane trafficking node that controls plant autophagy negatively. Rab3GAPL suppresses autophagy by binding to ATG8, the core autophagy adaptor, and deactivating Rab8a, a small GTPase essential for autophagosome formation and defense-related secretion. Rab3GAPL reduces autophagic flux in three model plant species, suggesting that its negative regulatory role in autophagy is conserved in land plants. Beyond autophagy regulation, Rab3GAPL modulates focal immunity against the oomycete pathogen Phytophthora infestans by preventing defense-related secretion. Altogether, our results suggest that Rab3GAPL acts as a molecular rheostat to coordinate autophagic flux and defense-related secretion by restraining Rab8a-mediated trafficking. This unprecedented interplay between a RabGAP-Rab pair and ATG8 sheds new light on the intricate membrane transport mechanisms underlying plant autophagy and immunity.

The plant unique ESCRT component FREE1 regulates autophagosome closure.

The energy sensor AMP-activated protein kinase (AMPK) can activate autophagy when cellular energy production becomes compromised. However, the degree to which nutrient sensing impinges on the autophagosome closure remains unknown. Here, we provide the mechanism underlying a plant unique protein FREE1, upon autophagy-induced SnRK1α1-mediated phosphorylation, functions as a linkage between ATG conjugation system and ESCRT machinery to regulate the autophagosome closure upon nutrient deprivation. Using high-resolution microscopy, 3D-electron tomography, and protease protection assay, we showed that unclosed autophagosomes accumulated in free1 mutants. Proteomic, cellular and biochemical analysis revealed the mechanistic connection between FREE1 and the ATG conjugation system/ESCRT-III complex in regulating autophagosome closure. Mass spectrometry analysis showed that the evolutionary conserved plant energy sensor SnRK1α1 phosphorylates FREE1 and recruits it to the autophagosomes to promote closure. Mutagenesis of the phosphorylation site on FREE1 caused the autophagosome closure failure. Our findings unveil how cellular energy sensing pathways regulate autophagosome closure to maintain cellular homeostasis.

Plant autophagosomes mature into amphisomes prior to their delivery to the central vacuole.

Autophagosomes are double-membraned vesicles that traffic harmful or unwanted cellular macromolecules to the vacuole for recycling. Although autophagosome biogenesis has been extensively studied, autophagosome maturation, i.e., delivery and fusion with the vacuole, remains largely unknown in plants. Here, we have identified an autophagy adaptor, CFS1, that directly interacts with the autophagosome marker ATG8 and localizes on both membranes of the autophagosome. Autophagosomes form normally in Arabidopsis thaliana cfs1 mutants, but their delivery to the vacuole is disrupted. CFS1's function is evolutionarily conserved in plants, as it also localizes to the autophagosomes and plays a role in autophagic flux in the liverwort Marchantia polymorpha. CFS1 regulates autophagic flux by bridging autophagosomes with the multivesicular body-localized ESCRT-I component VPS23A, leading to the formation of amphisomes. Similar to CFS1-ATG8 interaction, disrupting the CFS1-VPS23A interaction blocks autophagic flux and renders plants sensitive to nitrogen starvation. Altogether, our results reveal a conserved vacuolar sorting hub that regulates autophagic flux in plants.

Friendly mediates membrane depolarization-induced mitophagy in Arabidopsis.

The oxidative environment within the mitochondria makes them particularly vulnerable to proteotoxic stress. To maintain a healthy mitochondrial network, eukaryotes have evolved multi-tiered quality control pathways. If the stress cannot be alleviated, defective mitochondria are selectively removed by autophagy via a process termed mitophagy. Despite significant advances in metazoans and yeast, in plants, the molecular underpinnings of mitophagy are largely unknown. Here, using time-lapse imaging, electron tomography, and biochemical assays, we show that uncoupler treatments cause loss of mitochondrial membrane potential and induce autophagy in Arabidopsis. The damaged mitochondria are selectively engulfed by autophagosomes that are labeled by ATG8 proteins in an ATG5-dependent manner. Friendly, a member of the clustered mitochondria protein family, is recruited to the damaged mitochondria to mediate mitophagy. In addition to the stress, mitophagy is also induced during de-etiolation, a major cellular transformation during photomorphogenesis that involves chloroplast biogenesis. De-etiolation-triggered mitophagy is involved in cotyledon greening, pointing toward an inter-organellar crosstalk mechanism. Altogether, our results demonstrate how plants employ mitophagy to recycle damaged mitochondria during stress and development.