ABSTRACT
With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.
Subject(s)
Tomography, X-Ray Computed , Whipple Disease , Aged , Humans , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , China , High-Throughput Nucleotide Sequencing , Lung/diagnostic imaging , Lung/pathology , Pneumonia, Bacterial/diagnostic imaging , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/diagnosis , Tropheryma/genetics , Tropheryma/isolation & purification , Whipple Disease/diagnosis , Whipple Disease/drug therapy , Whipple Disease/diagnostic imagingABSTRACT
AIM: To analyse the risk factors and incidence of falls in geriatric outpatients in a university hospital ward in Hangzhou, China. METHODS: From May 2020 to August 2022, 1712 geriatric outpatients in a university hospital ward in Hangzhou, China, were screened using a socio-demographic questionnaire (e.g. gender, age, living arrangement, etc.) and assessment scales. The correlation between each factor and falls was preliminarily analysed by chi-squared tests. Finally, binary logistic regression analysis was conducted to further analyse the risk factors of falls. The STROBE checklist was used in reporting this study. RESULTS: Of the 1712 geriatric outpatients recruited, 1626 participants (60-79 and ≥ 80 years old) with complete questionnaire and assessment data were included. The occurrence of falls for those in the 60-79 age group was 8.4%, and for those in the ≥80 age group it was 13.4%. Age (p = .007), use of a walking assistance device (p < .001), the Stay Independent Brochure Questionnaire (SIB) (OR = 7.751, 95% CI = 5.089-11.806, p < .001), living arrangement (p = .004), timed up and go test (TUGT) (p = .007) and three diseases or above (OR = 2.496, 95% CI = 1.358-11.4.586, p = .003) reached statistical significance. CONCLUSIONS: Older people have a high incidence of falls. In this study, age, disease history, SIB scores (≥4 points), living arrangement, TUGT and walking assistance device increased the probability of falls in older Chinese adults. Personalised interventions should be carried out according to the specific situation of older people to effectively reduce their incidence of falls and improve their quality of life. RELEVANCE TO CLINICAL PRACTICE: The basic characteristics and fall risk factors of the older can help nurses identify fall risk, and early intervention by caregivers can reduce fall-related injuries, which has practical significance for promoting healthy aging. PATIENT OR PUBLIC CONTRIBUTION: The subjects of this study were older patients ≥60 years old, and the demographic characteristics and fall-related information of patients were obtained by questionnaire. The team worked closely with a team of experts in the field of health care. Some researchers collect data and rewrite them, while other researchers analyse the information and write a paper. All authors read and approved the final manuscript.
Subject(s)
Accidental Falls , Humans , Accidental Falls/statistics & numerical data , Accidental Falls/prevention & control , Aged , Cross-Sectional Studies , Male , China/epidemiology , Female , Risk Factors , Aged, 80 and over , Surveys and Questionnaires , Middle Aged , Incidence , Geriatric Assessment/methods , East Asian PeopleABSTRACT
BACKGROUND: Glehnia littoralis is an economic herb with both medicinal and edible uses. It also has important ecological value and special phylogenetic status as it is a monotypic genus species distributing around beach. Little information on its reproductive biology has been reported so far, which has hindered conservation and application of this species. In this study, we observed morphological changes from buds emergence to seeds formation and internal changes during sporogenesis, gametophyte development and embryo and endosperm development of G. littoralis using paraffin-embedded-sectioning and stereo microscope. RESULTS: The results showed that the stages of internal development events of G. littoralis corresponded to obvious external morphological changes, most of developmental features were consistent with other Apiaceae species. The development of male and female gametophytes was not synchronized in the same flower, however, exhibited temporal overlap. From mid-late April to mid-May, the anther primordial and ovule primordial developed into the trinucleate pollen grain and eight-nuclear embryo sac, respectively. From late-May to mid-July, the zygote developed into mature embryo. In addition, some defects in gynoecium or ovule development and abnormal embryo and endosperm development were found. We induced that the possible causes of abortion in G. littoralis were as follows: nutrient limitation, poor pollination and fertilization, and bad weather. CONCLUSIONS: This study revealed the whole process and morphological characteristics of the development of reproductive organ in G. littoralis, which not only provided important data for the study of systematic and conservation biology, but also provided a theoretical basis for cross breeding.
Subject(s)
Apiaceae , Germ Cells, Plant , Phylogeny , Plant Breeding , Embryonic DevelopmentABSTRACT
BACKGROUND: Anemone shikokiana (Makino) Makino, disjunctly distributed in Shandong Peninsula of China and Shikoku Island of Japan, is a rare and endangered species. To provide genetic information and understand its phylogeny, we conducted research on the chloroplast (cp) genome of A. shikokiana. METHODS AND RESULTS: The complete cp genome sequence of A. shikokiana was constructed in this study. The results showed that the cp genome of A. shikokiana has a typical quadripartite cyclic with a total length of 159,286 bp. In total, 111 unique genes were identified, including 78 protein-coding genes, 29 tRNA-coding genes and 4 rRNA-coding genes. A total of 37 long repeat sequences and 67 microsatellites were found in this cp genome. The cp genome of A. shikokiana was compared with eleven other Anemone cp genomes available from the Genbank database. We found some variations among the different genomes, especially in the LSC and SSC regions, and identified some regions as potential molecular markers such as ycf1, ndhE, ndhD, ndhF-trnL, ndhA and ndhF. The results of phylogenetic analysis suggested that A. narcissiflora was the closest relative of A. shikokiana. CONCLUSIONS: The results filled the gap of cp genome sequence information of A. shikokiana, laying the foundation to explore the evolutionary relationships of A. shikokiana in future studies. It provided a valuable genetic resource for the molecular identification and phylogenetic study of Anemone.
Subject(s)
Anemone , Chloroplasts , Genome, Chloroplast , Phylogeny , Chloroplasts/genetics , Anemone/classification , Anemone/cytology , Anemone/genetics , Genome, Chloroplast/genetics , Japan , China , Endangered Species , Conservation of Natural Resources , Codon/genetics , Mutagenesis , Repetitive Sequences, Nucleic AcidABSTRACT
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.
Subject(s)
Phosphatidylinositol 3-Kinases , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor A/metabolism , Molecular Docking Simulation , Cell Line, Tumor , Cell Movement , Hypoxia-Inducible Factor 1, alpha SubunitABSTRACT
Microplastics (MPs) are widespread in the environment and can be ingested through food, water, and air, posing a threat to human health. In addition, MPs can have a potential combined effect with other toxic compounds. Polystyrene (PS) has been shown to enhance the cytotoxicity of okadaic acid (OA). However, it remains unclear whether this enhancement effect is related to the size of PS particles. In this study, we investigated the mechanism of the combined effect of PS microplastics (PS-MPs) or PS nanoplastics (PS-NPs) and OA on Caco-2 cells. The results indicated that PS-NPs enhanced the cytotoxicity of OA and induced endoplasmic reticulum (ER) stress-mediated apoptosis in Caco-2 cells, compared to PS-MPs. Specifically, PS-NPs and OA cause more severe oxidative stress, lactate dehydrogenase (LDH) release, and mitochondrial membrane depolarization. Furthermore, it induced intracellular calcium overload through store-operated channels (SOCs) and activated the PERK/ATF-4/CHOP pathway to cause ER stress. ER stress promoted mitochondrial damage and finally activated the caspase family to induce apoptosis. This study provided an indirect basis for the assessment of the combined toxicity of MPs or NPs with OA.
Subject(s)
Apoptosis , Microplastics , Okadaic Acid , Polystyrenes , Water Pollutants, Chemical , Humans , Apoptosis/drug effects , Caco-2 Cells , Microplastics/toxicity , Okadaic Acid/toxicity , Plastics , Polystyrenes/toxicity , Water Pollutants, Chemical/toxicityABSTRACT
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.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , tau Proteins/metabolism , Benzaldehydes , Amyloid beta-Peptides/metabolism , CaspasesABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Genes, Bacterial , Humans , Anti-Bacterial Agents/pharmacology , Plastics , Environmental Monitoring , Drug Resistance, Microbial/geneticsABSTRACT
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.
Subject(s)
Dermatitis , Extracellular Vesicles , Pinctada , Animals , Humans , Extracellular Vesicles/metabolism , Inflammasomes/metabolism , Inflammation , Mucus/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pinctada/metabolism , Mitogen-Activated Protein KinasesABSTRACT
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.
Subject(s)
Atherosclerosis , Haptophyta , Microalgae , Apoptosis , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Atherosclerosis/prevention & control , Haptophyta/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Inflammation/drug therapy , Lipoproteins, LDL , Microalgae/metabolism , Molecular Docking Simulation , Scavenger Receptors, Class E/metabolismABSTRACT
BACKGROUND: Hedgehog (Hh) signaling pathway, which is essential for cell proliferation and differentiation, is noted to be aberrantly activated in tumor from increasing studies in recent years. MicroRNAs (miRNAs) as an important non-coding RNA in cells have been proven to possess a regulatory role specific to the Hh signaling pathway. Here, in vitro and in vivo cellular/molecular experiments were adopted to clarify the regulatory mechanism linking miR-636 to the Hh signaling pathway in ovarian cancer (OVC). METHODS: Protein-protein interaction analysis was performed to identify the hub gene in the Hh pathway. TargetScan database was used to predict the potential upstream regulators for Gli2. qRT-PCR was performed to test the expression of miR-636, while Western blot was conducted to detect the expression of proteins related to the Hh pathway and epithelial-mesenchymal transition (EMT). For cell functional experiments, HO-8910PM OVC cell line was used. MTT assay and wound healing assay were used to measure the effect of miR-636 on cell proliferation and migration. Flow cytometry was carried out to examine the effect of miR-636 on cell cycle, and Western blot was used to identify the change in expression of Hh and EMT-related proteins. Dual-luciferase reporter gene assay was implemented to detect the targeting relationship between miR-636 and Gli2. Xenotransplantation models were established for in vivo examination. RESULTS: Gli2 was identified as the hub gene of the Hh pathway and it was validated to be regulated by miR-636 based on the data from TargetScan and GEO databases. In vitro experiments discovered that miR-636 was significantly lowly expressed in OVC cell lines, and overexpressing miR-636 significantly inhibited HO-8910PM cell proliferation, migration and induced cell cycle arrest in G0/G1 phase, while the inhibition of miR-636 caused opposite results. Dual-luciferase reporter gene assay revealed that Gli2 was the target gene of miR-636 in OVC. Besides, overexpressed miR-636 decreased protein expression of Gli2, and affected the expression of proteins related to the Hh signaling pathway and EMT. Rescue experiments verified that overexpression of Gli2 reversed the inhibitory effect of miR-636 on HO-8910PM cell proliferation and migration, and attenuated the blocking effect of miR-636 on cell cycle. The xenotransplantation experiment suggested that miR-636 inhibited cell growth of OVC by decreasing Gli2 expression. Besides, overexpressing Gli2 potentiated the EMT process of OVC cells via decreasing E-cadherin protein expression and increasing Vimentin protein expression, and it reversed the inhibitory effect of miR-636 on OVC cell proliferation in vivo. CONCLUSION: miR-636 mediates the activation of the Hh pathway via binding to Gli2, thus inhibiting EMT, suppressing cell proliferation and migration of OVC. TRIAL REGISTRATION: The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of The Second Affiliated hospital of Zhejiang University School of Medicine (IR2019001235). Written informed consent was obtained from individual or guardian participants.
ABSTRACT
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.
Subject(s)
Antioxidants/pharmacology , Cytochrome P-450 CYP2E1/metabolism , Dioxins/pharmacology , Hepatocytes/drug effects , Oxidative Stress/drug effects , Phaeophyceae/metabolism , Seaweed/metabolism , Antioxidants/isolation & purification , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Dioxins/isolation & purification , Ethanol/toxicity , Hep G2 Cells , Hepatocytes/enzymology , Humans , Inflammation Mediators/metabolism , Molecular Structure , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
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.
Subject(s)
Antioxidants/pharmacology , Haptophyta , Peptides/pharmacology , Antioxidants/chemistry , Apoptosis/drug effects , Aquatic Organisms , HaCaT Cells/drug effects , Humans , MAP Kinase Signaling System/drug effects , Matrix Metalloproteinases/metabolism , Peptides/chemistry , Skin Aging/drug effects , Transcription Factor AP-1/metabolism , Ultraviolet RaysABSTRACT
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.
Subject(s)
Arsenic , Nanoparticles , ATP-Binding Cassette Transporters , Cytoskeleton , Humans , MicroplasticsABSTRACT
BACKGROUND: Hemorrhage is one of the most serious complications of endoscopic sphincterotomy (EST). The risk factors for delayed hemorrhage are not clear. This study aimed to explore the risk factors for post-EST delayed hemorrhage and suggest some precautionary measures. METHODS: This study analyzed 8477 patients who successfully underwent endoscopic retrograde cholangiopancreatography (ERCP) and EST between January 2007 and June 2015 in the First Affiliated Hospital of Nanchang University. Univariate and multivariate analyses were performed to find the risk factors for delayed hemorrhage after EST. RESULTS: Of the 8477 patients screened, 137 (1.62%) experienced delayed hemorrhage. Univariate analysis showed that male, the severity of jaundice, duodenal papillary adenoma and carcinoma, diabetes, intraoperative bleeding, moderate and large incisions, and directional deviation of incision were risk factors for post-EST delayed hemorrhage (P < 0.05). Multivariate analysis showed that intraoperative bleeding [odds ratio (OR) = 3.326; 95% CI: 1.785-6.196; P < 0.001] and directional deviation of incision (OR = 2.184; 95% CI: 1.266-3.767; P = 0.005) were independent risk factors for post-EST delayed hemorrhage. CONCLUSIONS: Delayed hemorrhage is the most common and dangerous complication of EST. Intraoperative bleeding and directional deviation of incision are independent risk factors for post-EST delayed hemorrhage.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Postoperative Hemorrhage/etiology , Sphincterotomy, Endoscopic/adverse effects , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase ) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.
Subject(s)
Galactosides/pharmacology , Laurencia/chemistry , Liver Diseases, Alcoholic/drug therapy , Oxidative Stress/drug effects , Antioxidants/chemistry , Antioxidants/pharmacology , Apoptosis/drug effects , Ethanol/toxicity , Galactosides/chemistry , Gene Expression Regulation/drug effects , Glutathione/genetics , Hep G2 Cells , Humans , Liver Diseases, Alcoholic/pathology , Molecular Docking Simulation , Polysaccharides/chemistry , Polysaccharides/pharmacology , Protective Agents/chemistry , Protective Agents/pharmacology , Reactive Oxygen Species/chemistryABSTRACT
BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50 = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemistry , Antihypertensive Agents/chemistry , Captopril/chemistry , Hypertension/drug therapy , Peptides/chemistry , Amino Acid Sequence , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/metabolism , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/metabolism , Blood Pressure/drug effects , Captopril/administration & dosage , Cichlids , Digestion , Fish Proteins/chemistry , Gastrointestinal Tract/metabolism , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Hypertension/metabolism , Hypertension/physiopathology , Kinetics , Male , Molecular Docking Simulation , Peptides/metabolism , Peptides/pharmacology , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Hydrolysates/chemistry , Protein Hydrolysates/metabolism , Rats , Rats, Inbred SHRABSTRACT
The transport of ions in nanochannels has received considerable interest owing to the unique transport properties and potential applications. In this study, ultrasmall nanochannels (0.8-1.2 nm) were fabricated in porous anodized aluminum (PAA) membrane in situ growth. 2-Methylimidazole and zinc nitrate were used as the reaction precursor solkution, and then zeolitic imidazolate framework (ZIF-8) nanoparticles were sufficiently filled in PAA nanochannels to form a ZIF-8/PAA nanochannels composite membrane. Because ZIF-8 is a microporous material and has a strong ability to adsorb heavy metals, the composite membrane was used as a biosensor to detect lead ion (Pb2+) by the coordination interaction between Pb2+ and nitrogen atoms. The detection limit reached to 0.03 nM due to the enrichment of nanochannels under electric field. The sensor has a good linear range for Pb2+ from 10 nM to 10 µM.
ABSTRACT
Bacterial magnetosomes (BMs) are used as carriers for antibodies, enzymes, and nucleic acids. This study aimed to demonstrate the clinical utility of BMs derived from Magnetospirillum gryphiswaldense for use in anti-tumor immunotherapy. Bis(sulfosuccinimidyl) suberate (BS3) was used to prepare BM-anti-4-1BB antibody complexes. We used syngeneic TC-1 mouse models of cancer to investigate whether BMs combined with an anti-4-1BB agonistic antibodies could enhance the therapeutic effects of anti-4-1BB antibodies in localized disease settings. Anti-4-1BB antibodies were combined with purified BMs at a concentration of 168 mg antibody per milligram BM (mg IgG/mg BM) using BS3. The anti-4-1BB antibody-coupled BMs (BM-Ab complexes) and control BMs displayed similar morphologies and measurements when examined by transmission electron microscope (TEM). In a mouse tumor model, intravenous injection of BM-Abs combined with magnetic treatment resulted in greater tumor protection than did other treatment methods (P < 0.05). These results demonstrate the in vivo anti-tumor properties of BM-Abs complexes. The coupling of anti-4-1BB antibodies to magnetosomes may have potential for clinical application to antitumor antibody therapy.
Subject(s)
Antibodies/pharmacology , Antineoplastic Agents/pharmacology , Magnetosomes/chemistry , Magnetospirillum/chemistry , Animals , Antibodies/chemistry , Antibodies/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Carriers/chemistry , Drug Carriers/isolation & purification , Female , Mice , Mice, Inbred C57BL , Particle Size , Surface PropertiesABSTRACT
Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.