Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.

BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.

Microalgae Octapeptide IIAVEAGC Alleviates Oxidative Stress and Neurotoxicity in 6-OHDA-Induced SH-SY5Y Cells by Regulating the Nrf2/HO-1and Jak2/Stat3 Pathways.

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.

Neuroprotection of Truncated Peptide IIAVE from Isochrysis zhanjiangensis: Quantum Chemical, Molecular Docking, and Bioactivity Studies.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile-Ile-Ala-Val-Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.

The impact of the chalcogen-substitution element and initial spectroscopic state on excited-state relaxation pathways in nucleobase photosensitizers: a combination of static and dynamic studies.

The substitution of oxygen with chalcogen in carbonyl group(s) of canonical nucleobases gives an impressive triplet generation, enabling their promising applications in medicine and other emerging techniques. The excited-state relaxation S2(ππ*) → S1(nπ*) → T1(ππ*) has been considered the preferred path for triplet generation in these nucleobase derivatives. Here, we demonstrate enhanced quantum efficiency of direct intersystem crossing from S2 to triplet manifold upon substitution with heavier chalcogen elements. The excited-state relaxation dynamics of sulfur/selenium substituted guanines in a vacuum is investigated using a combination of static quantum chemical calculations and on-the-fly excited-state molecular dynamics simulations. We find that in sulfur-substitution the S2 state predominantly decays to the S1 state, while upon selenium-substitution the S2 state deactivation leads to simultaneous population of the S1 and T2,3 states in the same time scale and multi-state quasi-degeneracy region S2/S1/T2,3. Interestingly, the ultrafast deactivation of the spectroscopic S3 state of both studied molecules to the S1 state occurs through a successive S3 → S2 → S1 path involving a multi-state quasi-degeneracy S3/S2/S1. The populated S1 and T2 states will cross the lowest triplet state, and the S1 → T intersystem crossing happens in a multi-state quasi-degeneracy region S1/T2,3/T1 and is accelerated by selenium-substitution. The present study reveals the influence of both the chalcogen substitution element and initial spectroscopic state on the excited-state relaxation mechanism of nucleobase photosensitizers and also highlights the important role of multi-state quasi-degeneracy in mediating the complex relaxation process. These theoretical results provide additional insights into the intrinsic photophysics of nucleobase-based photosensitizers and are helpful for designing novel photo-sensitizers for real applications.

Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells.

Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.

The Mechanism of Two Benzaldehydes from Aspergillus terreus C23-3 Improve Neuroinflammatory and Neuronal Damage to Delay the Progression of Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disease, is the most common cause of dementia in humans worldwide. Although more in-depth research has been carried out on AD, the therapeutic effect of AD is not as expected, and natural active substances are increasingly sought after by scientists. In the present study, we evaluated two benzaldehydes from a coral-derived Aspergillus terreus strain C23-3, their anti-neuroinflammatory activity in microglia (BV-2), and their neuroprotective activity and mechanisms in hippocampal neuronal cells (HT-22). These include the protein expression of iNOS, COX-2, MAPKs pathways, Tau protein-related pathways, caspases family-related signaling pathways. They also include the levels of TNF-α, IL-6, IL-18 and ROS, as well as the level of mitochondrial oxidative stress and neuronal cell apoptosis. The results showed that both benzaldehydes were effective in reducing the secretion of various inflammatory mediators, as well as pro-inflammatory factors. Among these, benzaldehyde 2 inhibited mitochondrial oxidative stress and blocked neuronal cell apoptosis through Tau protein-related pathways and caspases family-related signaling pathways, thereby inhibiting ß-amyloid (Aß)-induced neurological damage. This study reveals that benzaldehyde 2 has potential as a therapeutic agent for Alzheimer's disease, and offers a new approach to the high-value use of marine natural products.

Plastic wastes and surface antibiotic resistance genes pollution in mangrove environments.

Mangroves are located at the intersection of land and sea and are also heavily affected by plastic wastes. Biofilms of plastic wastes in mangroves are reservoirs for antibiotic resistance genes (ARGs). In this study, plastic wastes and ARG pollution were investigated from three typical mangrove areas in Zhanjiang, South China. Transparent was the dominant colors of plastic wastes in three mangroves. Fragment and film shape accounted for 57.73-88.23% of plastic waste samples in mangroves. In addition, 39.50% of plastic wastes in protected area mangroves are PS. The metagenomic results shows that the 175 ARGs were found on plastic wastes of the three mangroves, the abundance accounting for 91.11% of the total ARGs. The abundance of Vibrio accounted for 2.31% of the total bacteria genera in aquaculture pond area mangrove. Correlation analysis shows that a microbe can carry multiple ARGs that may improve resistance to antibiotics. Microbes are the potential hosts of most ARGs, suggesting that ARGs can be transmitted by microbes. Because the mangroves are closely related to human activities and the high abundance of ARGs on plastic increases the ecological risks, people should improve plastic waste management and prevent the spread of ARGs by reducing plastic pollution.

Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows.

In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins, and lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNA profile of heat-stressed and normal Holstein cows. We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was upregulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.

Extracellular vesicles derived from Pinctada martensii mucus regulate skin inflammation via the NF-κB/NLRP3/MAPK pathway.

Extracellular vesicles (EVs) and their exosome subsets are vesicle-like nanoparticles (EVs) that are secreted by cells and contain various factors that treat various diseases. However, studies on extracting EVs from marine shellfish are still relatively lacking. In this study, EVs were isolated from Pinctada martensii mucus and the efficacy of EVs in modulating the inflammatory environment was demonstrated. A human skin inflammatory cell model was established to investigate the effect of Pinctada martensii mucus-derived EVs on inflammation. The results showed that EVs could restore the viability of inflammatory HaCaT cells and decrease the level of reactive oxygen species (ROS), as well as the mRNA expression of IL-6, IL-8 and TNF-α. The inflammation of HaCaT cells was treated by inhibiting the activation of the MAPK, NF-κB and NLRP3 inflammasome signaling pathways, which prevented the phosphorylation of related inflammatory proteins and the entry of P65 protein into the nucleus. This study provides novel EVs from marine shellfish-derived bioactive materials.

Depletion of serum-derived exosomes aggravates heat stress-induced damage of bovine mammary epithelial cells.

BACKGROUND: Exosomes are involved in intercellular communication, affecting many physiological and pathological process. The present study evaluated the effects of serum exosomes on the function of bovine mammary epithelial cells (BMECs) and milk synthesis under heat stress. METHODS AND RESULTS: We cultured the BMECs in fetal bovine serum (FBS) or exosome-free FBS medium and examined, their viability using CCK-8 kit. The results showed that culturing the cells in an exosome-free medium decreased viability and increased the levels of reactive oxygen species. The BMECs cultured in the exosome-free medium had reduced mitochondrial membrane potential, decreased manganese superoxide dismutase activity, and disrupted mitochondrial dynamics. They exhibited apoptosis due to upregulated Drp1, Fis1, Bax and HSP70. Lastly, we observed downregulation of milk fat and lactoprotein-related genes: mTOR, PPARγ, p-mTOR and ADD1 and SREBP1, ELF5, and CSN2, respectively, after culturing the cells in an exosome-free medium. These negative effects of the exosome-free medium on the BMECs could be further reinforced under heat stress. CONCLUSION: Our results demonstrated that exosomes from serum are critical for maintaining the normal function of BMECs.

First Report of Rhizopus arrhizus (syn. R. oryzae) Causing Garlic Bulb Soft Rot in Hebei Province, China.

Rhizopus soft rot occurs on the succulent tissues of vegetables, fruits, and ornamental plants throughout the world (Cui et al. 2019). When the garlic is in the seedling stage in the fields (Fig. S1) in November 2021, a disease outbreak on garlic bulbs suspected as Rhizopus soft rot occurred in Daming County, Handan City, Hebei Province of China (N 36°17', E 115° 13'). This disease symptom was first found in the garlic seedling stage in China. Disease incidence was 10% to 30% in cultivated garlic bulbs. There were soft water-soaked lesions on the surface of diseased garlic bulbs and the interiors were brown and soft. In the disease severe field, white to gray mycelia were observed on the diseased garlic bulbs. Infected garlic bulbs were sampled to isolate and determine the identity of the disease-causing organism. Symptomatic bulbs were surface sterilized with 1% NaClO for 2 min, dipped in 75% ethanol for 3 min and rinsed three times with autoclaved distilled water. Small pieces of the inner decayed tissue were removed and cultured on potato dextrose agar (PDA) at 28°C for 2 to 3 days. Five white colonies grew on PDA and then they became brownish gray to blackish-gray mycelium. The fungal strains were purified by hyphal-tip isolation method. To determine the identity of the five isolated fungi, we analyzed their internal transcribed spacer (ITS) region sequences (Jung et al. 2012). BLAST analysis of the ITS sequences from DSF-0-2 (accession no. ON706022), DSF-0-3 (accession no. ON706021), DSF-0-4 (accession no. ON706020), DSF-0-5 (accession no. ON706019) and DSF-0-6 (accession no. ON706018) were all 100% identical with Rhizopus arrhizus (syn. Rhizopus oryzae). Phylogenetic trees were constructed using the neighbor-joining method of MEGA11 based on the sequences of ITS rRNA gene (Walther et al. 2013). Phylogenetic trees indicated that isolates were most likely Rhizopus arrhizus (syn. Rhizopus oryzae) (Fig. S2). We selected one isolated strain, DSF-0-2, for characterize the morphology and test its ability to cause garlic bulb soft rot. Under the microscope, nonseptate rhizoids, sporangia, and sporangiospores were observed (Fig. S1). Sporangiospores were unequal, subglobose, numerous irregular, or oval, and 9.7 (6.2 - 12.5) × 6.5 (4.1 - 8.5) µm (n = 50) in diameter. The sporangia were globose, black, 121.5 (65 - 198) µm (n = 50) in diameter. Based on the rDNA-ITS sequencing and the morphological characteristics, the DSF-0-2 isolate was identified as Rhizopus arrhizus (syn. Rhizopus oryzae) (Zheng et al. 2007; Abeywickrama et al. 2020). To complete Koch's postulates, surface-sterilized healthy garlic bulbs were inoculated with R. arrhizus isolate DSF-0-2. A 1.0-ml sterile syringe was used to inject 50 µl of a 106 conidia/ml suspension into each of five healthy bulbs. As a control, garlic bulbs were treated with sterile distilled water. The inoculated and control bulbs were incubated at 28°C for 7 days. The bulbs inoculated with R. arrhizus DSF-0-2 showed symptoms of water soaking, and the tissues were brown and soft throughout the bulb at 7 days (Fig. S1). Results of the three trials were the same. No symptoms were observed in the control group. R. arrhizus was reisolated from the symptomatic garlic bulb and confirmed as such based-on colony and sporangia morphology and ITS sequence. There were some reports that R. arrhizus infects cassava tubers and potato tubers (Amadioha and Markson 2007; Cui et al. 2019). To our knowledge, this is the first report of R. arrhizus (syn. Rhizopus oryzae) associated with soft rot on garlic bulb in the seedling stage in China. This disease has posed a potential threat during garlic seedling stage in the field. Management measures should be considered before this disease outbreaks widely. Garlic bulbs died in the seedling stage, which caused production reduction, serious economic loss and soil pollution. This finding may help to take effective control measures for this disease.

SIRT4 Expression Ameliorates the Detrimental Effect of Heat Stress via AMPK/mTOR Signaling Pathway in BMECs.

Sirtuin 4 (SIRT4), a member of the SIRT family, has been reported to be a key factor involved in antioxidant defense in mitochondria. This study aimed to explore the potential molecular mechanism via which SIRT4 regulates heat stress-induced oxidative stress and lactoprotein synthesis in bovine mammary epithelial cells (BMECs). Our results showed that SIRT4 was significantly decreased in heat stressed mammary tissue. Depletion of SIRT4 in BMECs induced the generation of ROS, which, as exhibited by the decreased activity of antioxidant enzymes, changed mitochondrial morphology through mediating protein and mRNA levels related to mitochondrial fission and fusion. Moreover, we found that depletion of SIRT4 or stress conditions inhibited the expression of milk proteins, as well as lipid and glucose synthesis-related genes, and activated the AMPK/mTOR signaling pathway. Increased SIRT4 expression was found to have the opposite effect. However, blocking the AMPK/mTOR signaling pathway could inhibit the regulatory function of SIRT4 in milk synthesis-related gene expression. In summary, our results suggest that SIRT4 may play critical roles in maintaining mammary gland function by regulating the AMPK/mTOR signaling pathway in dairy cows, indicating that SIRT4 may be a potential molecular target for curing heat stress-induced BMEC injury and low milk production in dairy cows.

A Novel Peptide Isolated from Microalgae Isochrysis zhanjiangensis Exhibits Anti-apoptosis and Anti-inflammation in Ox-LDL Induced HUVEC to Improve Atherosclerosis.

In the early stage, oxidized low density lipoprotein (ox-LDL) caused atherosclerosis, followed by human umbilical vein endothelial cells (HUVEC) damage, leading to a variety of cardiovascular related diseases. This study investigated the mechanism of nonapeptide (EMFGTSSET, ETT) isolated from in vitro gastrointestinal digestion of Isochrysis zhanjiang on endothelial cell inflammation and apoptosis induced by ox-LDL in atherosclerosis. At the cellular level, the results shown that ETT inhibited the up-regulation of oxidized low-density lipoprotein receptor-1 (LOX-1) induced by ox-LDL. Furthermore, ETT inhibited the fluorescence intensity of ROS, inflammatory factors (interleukin-6, interleukin-1ß, and tumor necrosis factor-α) and the expression of cell adhesion molecules (vascular cell adhesion protein 1 and intercellular cell adhesion molecule-1). In addition, it also upregulates nuclear red blood cell 2 related factor 2 (Nrf2), heme oxygenase-1 (HO -1), p-Akt, and bcl-2 levels. But down-regulated the expression of p-p65, p-IκB-α, p-p38, p-ERK, p-JNK, bax, and cleaved caspase-9/-3 (c-c-9/-3), thereby inhibited ox-LDL induction inflammation and apoptosis of atherosclerosis. Through molecular docking, it was judged that the stable interaction between ETT and LOX-1 and VCAM-1 was maintained through hydrogen bonding. These results can provide a theoretical basis for ETT as a potential substance for the prevention and treatment of atherosclerosis, and further improve the value of Isochrysis zhanjiangensis.

S-allyl cysteine ameliorates heat stress-induced oxidative stress by activating Nrf2/HO-1 signaling pathway in BMECs.

Heat stress-induced oxidative stress in bovine mammary epithelial cells (BMECs) threatens the normal growth and development of bovine mammary tissue, resulting in lower milk production of dairy cows. The aim of the present study is to investigate the protective effects of S-allyl cysteine (SAC), an organosulfur component extracted from aged garlic, on heat stress-induced oxidative stress and apoptosis in BMECs and to explore its underlying mechanisms. Our results showed that heat stress treatment considerably decreased cell viability, whereas SAC treatment dose-dependently restored cell viability of BMECs under heat-stress conditions. In addition, SAC protected BMECs from heat stress-induced oxidative damage by inhibiting the excessive accumulation of reactive oxygen species (ROS) and increasing the activity of antioxidant enzymes. It also inhibited heat stress-induced apoptosis by reducing the ratio of Bax/Bcl-2 and blocking proteolytic the cleavage of caspase-3 in BMECs. Interestingly, we found that the protective effect of SAC on heat stress-induced oxidative stress and apoptosis was dependent on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. SAC promoted the Nrf2 nuclear translocation in heat stress-induced BMECs. The results were also validated by Nrf2 and Keap1 knockdown experiments further demonstrating that Nrf-2 was indeed involved in the protective effect of SAC on heat stress-induced oxidative damage and apoptosis. In summary, our results showed that SAC could protect BMECs from heat stress-induced injury by mediating the Nrf2/HO-1 signaling pathway, suggesting that SAC could be considered as a therapeutic drug for attenuating heat stress-induced mammary gland diseases.

The Inhibition Effect of the Seaweed Polyphenol, 7-Phloro-Eckol from Ecklonia Cava on Alcohol-Induced Oxidative Stress in HepG2/CYP2E1 Cells.

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people's health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.

Heptapeptide Isolated from Isochrysis zhanjiangensis Exhibited Anti-Photoaging Potential via MAPK/AP-1/MMP Pathway and Anti-Apoptosis in UVB-Irradiated HaCaT Cells.

Marine microalgae can be used as sustainable protein sources in many fields with positive effects on human and animal health. DAPTMGY is a heptapeptide isolated from Isochrysis zhanjiangensis which is a microalga. In this study, we evaluated its anti-photoaging properties and mechanism of action in human immortalized keratinocytes cells (HaCaT). The results showed that DAPTMGY scavenged reactive oxygen species (ROS) and increase the level of endogenous antioxidants. In addition, through the exploration of its mechanism, it was determined that DAPIMGY exerted anti-photoaging effects. Specifically, the heptapeptide inhibits UVB-induced apoptosis through down-regulation of p53, caspase-8, caspase-3 and Bax and up-regulation of Bcl-2. Thus, DAPTMGY, isolated from I. zhanjiangensis, exhibits protective effects against UVB-induced damage.

Anti-Allergic Effect of Low Molecular Weight Digest from Abalone Viscera on Atopic Dermatitis-Induced NC/Nga.

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (<5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.

Dihydromyricetin attenuates heat stress-induced apoptosis in dairy cow mammary epithelial cells through suppressing mitochondrial dysfunction.

It is well known that the dairy cow production is very sensitive to environmental factors, including high temperature, high humidity and radiant heat sources. High temperature-induced heat stress is the main environmental factor that causes oxidative stress and apoptosis, which affects the development of mammary glands in dairy cows. Dihydromyricetin (DMY) is a nature flavonoid compound extracted from Ampelopsis grossedentata; it has been shown to have various pharmacological functions, such as anti-inflammation, antitumor and liver protection. The present study aims to evaluate the protective effect of DMY on heat stress-induced dairy cow mammary epithelial cells (DCMECs) apoptosis and explore the potential mechanisms. The results show that heat stress triggers heat shock response and reduces cell viability in DCMECs; pretreatment of DCMECs with DMY (25 µM) for 12 h significantly alleviates the negative effects of heat stress on cells. DMY can provide cytoprotective effects by suppressing heat stress-caused mitochondrial membrane depolarization and mitochondrial dysfunction, Bax and Caspase 3 activity, and modulation of oxidative enzymes, thereby preventing ROS production and apoptosis in DCMECs. Importantly, DMY treatment could attenuate heat stress-induced mitochondrial fragmentation through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (Mfn1, 2). Above all, our findings demonstrate that DMY could protect DCMECs against heat stress-induced injury through preventing oxidative stress, the imbalance of mitochondrial fission and fusion, which provides useful evidence that DMY can be a promising therapeutic drug for protecting heat stress-induced mammary glands injury and mastitis.

Nanoplastics aggravate the toxicity of arsenic to AGS cells by disrupting ABC transporter and cytoskeleton.

The coexistence of nanoplastics (NPs) and pollutants such as arsenic (As) has become an unignorable environmental problem. However, there is still a considerable knowledge gap about the impact of NPs and pollutants on human health risks. In this study, the human gastric adenocarcinoma (AGS) cells were used as a model to investigate the toxicity of NPs with different particle sizes and As by MTT assay, western blotting, immunofluorescence and so on. The results showed that 20 nm (8 µg/mL), 50 nm (128 µg/mL), 200 nm (128 µg/mL), 500 nm (128 µg/mL), 1000 nm (128 µg/mL) polystyrene (PS) did not affect cell viability, ROS, intracellular calcium and activate apoptosis pathway in AGS cells. However, noncytotoxic concentration of NPs enhanced the cytotoxicity and intracellular accumulation of As. NPs destroys the fluidity of cell membrane and cytoskeleton, inhibits the activity of ABC transporter, and leads to the accumulation of As in cells. This work highlights that the damage caused by NPs, especially at the level of noncytotoxicity, joint with As cannot be ignored and provides a specific toxicological mechanism of NPs accompanied by exposure to As.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.