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1.
Mol Brain ; 15(1): 57, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35725567

ABSTRACT

Cerebral malaria is the most serious complication of malaria infection, with 26% of surviving children having neurological sequelae, which may be caused by neuron damage, but the mechanism is not clear. Ferroptosis has been reported to play an important role in neuron damage in several nervous system diseases. However, the occurrence of ferroptosis in experimental cerebral malaria (ECM) pathogenesis is still unknown. In this study, we firstly detected increased levels of malondialdehyde (MDA) and iron, which are indicators of ferroptosis, in the cerebrum of ECM mice. Some important regulators of ferroptosis, including upregulated expression of transferrin receptor 1 (TfR1) and acyl-CoA synthetase long-chain family member 4 (ACSL4), and downregulation of glutathione peroxidase 4 (GPX4) levels, were also confirmed in ECM mice. Consistently, neuron damage, which was detected in the cerebrum of ECM mice, was positively correlated with reduced GPX4 expression and furtherly rescued by administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). In addition, primary neurons were damaged by activated CD8+ T cells, an effect that was also partially rescued by Fer-1 on amyloid precursor protein expression and mitochondrial membrane potential levels in vitro. Activated CD8+ T cells were also shown to infiltrate the cerebrum of ECM mice and upregulate TfR1 expression in primary neurons, which may be an important event for inducing ferroptosis in ECM. Altogether, we show that ferroptosis contributes to neuron damage in ECM pathogenesis, and activated CD8+ T cells may be important inducers of neuronal ferroptosis. Hence, targeting ferroptosis may be a promising adjuvant therapeutic strategy for neurological sequelae in patients with cerebral malaria.


Subject(s)
Ferroptosis , Malaria, Cerebral , Animals , CD8-Positive T-Lymphocytes , Malaria, Cerebral/metabolism , Malaria, Cerebral/pathology , Mice , Neurons/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase
2.
Cancer Gene Ther ; 29(7): 973-983, 2022 07.
Article in English | MEDLINE | ID: mdl-34754077

ABSTRACT

Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.


Subject(s)
Andrographis , Hedyotis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Plant Preparations , Andrographis/chemistry , Animals , Cell Line, Tumor , Cell Proliferation , DNA Damage , Hedyotis/chemistry , Humans , Mice , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Plant Preparations/therapeutic use , Tumor Suppressor Protein p53/genetics
3.
Food Funct ; 12(24): 12659-12670, 2021 Dec 13.
Article in English | MEDLINE | ID: mdl-34821900

ABSTRACT

In this study, sterols were isolated from Lotus plumule by Soxhlet extraction and saponification and were further characterized by GC-MS analysis. The results showed that the sterols extracted from Lotus plumule mainly contained ß-sitosterol, fucosterol, and campesterol. Models were established in vitro to investigate the protective effects of Lotus plumule sterols (LPSs) on ethanol-induced injury in human gastric epithelium (GES-1) cells. The results showed that appropriate concentrations of LPSs and ß-sitosterol could protect GES-1 cells from ethanol-induced injury by reducing ROS levels, reducing calcium ion release, increasing antioxidant enzyme activity and maintaining mitochondrial membrane potential. Western blot experiment results also showed that appropriate concentrations of LPSs and ß-sitosterol could up-regulate the expression of the anti-apoptotic protein Bcl-2 and down-regulate the pro-apoptotic proteins Bax and caspase-3 in GES-1 cells. Meanwhile, sterol pretreatment groups down-regulated the protein expression levels of p-P38 and p-JNK in ethanol-damaged GES-1 cells and up-regulated the expression level of p-ERK, suggesting that sterols protect GES-1 cells from ethanol-induced damage by regulating the MAPK signaling pathway. Taken together, Lotus plumule sterols could effectively prevent gastric cell damage in vitro and suggest the potential application of LPSs as bioactive ingredients for healthy foods.


Subject(s)
Ethanol/administration & dosage , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Lotus/metabolism , Plant Extracts/pharmacology , Sterols/pharmacology , Cells, Cultured , In Vitro Techniques
4.
Medicine (Baltimore) ; 99(41): e22597, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33031313

ABSTRACT

INTRODUCTION: Recurrent tonsillitis (RT) is often treated with antibiotic therapy and surgery. Although these treatments have advantages, they are also controversial. The purpose of this study is to analyze the safety and effectiveness of traditional Chinese medicine (TCM) cauterization in the treatment of RT, so as to provide an alternative for the clinicians and to cover the shortage of therapeutic methods. METHODS AND ANALYSIS: This protocol is guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and by the Cochrane Collaboration Handbook. We will formulate strict inclusion and exclusion criteria in English databases (PubMed, EMBASE, and Web of Science), Chinese databases (CNKI, Wanfang databases, CBM, and VIP), and search literatures in different clinical registration platforms (Cochrane Library, Chinese Cochrane Centre's Clinical Trial Registry Platform). The included articles will be evaluated using Cochrane RCT evaluation criteria. Stata 15.0 will be used for data analysis. Subgroup analysis, sensitivity analysis, and meta-regression will detect sources of heterogeneity. Egger's Test or Begg's Test will detect publication bias quantitatively. CONCLUSION: Cauterization can effectively control the recurrence of tonsillitis through clinical trials, but evidence-based medicine needs to be adopted to provide strong evidence for its effectiveness. The purpose of our research is to provide the evidence. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/PZ69Q.


Subject(s)
Cautery/methods , Medicine, Chinese Traditional , Research Design , Tonsillitis/surgery , Humans , Meta-Analysis as Topic , Recurrence , Systematic Reviews as Topic
5.
Appl Microbiol Biotechnol ; 104(17): 7467-7481, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32696296

ABSTRACT

Potato late blight caused by Phytophthora infestans is one of the most serious plant diseases worldwide. Cyclic lipopeptides (CLPs) extracted from Bacillus strains exhibit a promising effect in the biocontrol of a variety of phytopathogens. However, the specific inhibitory effects and underlying mechanisms of CLPs against P. infestans are poorly understood. In this study, we showed that Bacillus pumilus W-7 can inhibit the growth of P. infestans mycelium. Two metabolites from W-7, surfactin and fengycin B, were identified using MS/MS. Fengycin B inhibited mycelium growth by inducing mycelium deformations, oxidative damage, and mitochondrial dysfunction. Surfactin induced potato plant defense responses by increasing the expression of the biocontrol genes (pod, pal, and cat) and their enzyme activities (POD, PAL, and CAT). Also, surfactin and fengycin B could exhibit a synergistic inhibitory effect on P. infestans. Taken together, our findings indicate that B. pumilus W-7 and its CLPs are potential environmentally friendly and effective biocontrol agents for the preservation of potato crops. KEY POINTS: • Lipopeptides of surfactin and fengycin B are extracted from Bacillus pumilus W-7. • Fengycin B inhibits Phytophthora infestans mycelium growth in a direct manner. • Surfactin induces potato plant defense responses to control late blight.


Subject(s)
Bacillus pumilus , Phytophthora infestans , Solanum tuberosum , Lipopeptides/pharmacology , Peptides, Cyclic , Plant Diseases/prevention & control , Sulfonamides , Tandem Mass Spectrometry
6.
Tree Physiol ; 38(3): 397-408, 2018 03 01.
Article in English | MEDLINE | ID: mdl-28927239

ABSTRACT

Plant cell walls exhibit architectural and compositional changes throughout their development and in response to external cues. While tubulins are involved in cell wall biogenesis, much remains unknown about the scope of their involvement during the orchestration of this resource-demanding process. A transgenic approach coupled with cell wall compositional analysis, RNA-seq and mining of publicly available diurnal gene expression data was used to assess the involvement of tubulins in poplar leaf cell wall biogenesis. Leaf cell walls of transgenic poplar lines with constitutive overexpression of α-tubulin (TUA) exhibited an increased abundance of homogalacturonan, along with a reduction in xylose. These changes were traced to altered expression of UDP-glucuronic acid decarboxylase (GADC) in the transgenic leaves. A model is postulated by which altered diurnal control of TUA through its constitutive overexpression led to a metabolic tradeoff affecting cellular utilization of GADC substrate UDP-glucuronic acid. While there were no effects on cellulose, hemicellulose or lignin abundance, subtle effects on hemicellulose composition and associated gene expression were noted. In addition, expression and enzymatic activity of pectin methylesterase (PME) decreased in the transgenic leaves. The change is discussed in a context of increased levels of PME substrate homogalacturonan, slow stomatal kinetics and the fate of PME product methanol. Since stomatal opening and closing depend on fundamentally contrasting microtubule dynamics, the slowing of both processes in the transgenic lines as previously reported appears to be directly related to underlying cell wall compositional changes that were caused by tubulin manipulation.


Subject(s)
Circadian Rhythm/physiology , Gene Expression Regulation, Plant , Plant Proteins/genetics , Populus/physiology , Tubulin/genetics , Cell Wall/metabolism , Circadian Rhythm/genetics , Pectins/metabolism , Plant Leaves/genetics , Plant Leaves/physiology , Plant Proteins/metabolism , Polysaccharides/metabolism , Populus/genetics , Tubulin/metabolism
7.
Trials ; 15: 397, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25319802

ABSTRACT

BACKGROUND: Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. METHODS AND DESIGN: This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. DISCUSSION: The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).


Subject(s)
Acupuncture Therapy/methods , Research Design , Tinnitus/therapy , Adolescent , Adult , Auditory Pathways/physiopathology , Auditory Perception , China , Clinical Protocols , Double-Blind Method , Female , Hearing , Hospitals, Teaching , Humans , Intention to Treat Analysis , Male , Middle Aged , Pain Measurement , Pain Perception , Pain Threshold , Prospective Studies , Quality of Life , Surveys and Questionnaires , Time Factors , Tinnitus/diagnosis , Tinnitus/physiopathology , Tinnitus/psychology , Treatment Outcome , Young Adult
8.
Mol Plant ; 2(5): 1107-22, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19825684

ABSTRACT

In order to study Brassica napus fatty acid (FA) metabolism and relevant regulatory networks, a systematic identification of fatty acid (FA) biosynthesis-related genes was conducted. Following gene identification, gene expression profiles during B. napus seed development and FA metabolism were performed by cDNA chip hybridization (>8000 EST clones from seed). The results showed that FA biosynthesis and regulation, and carbon flux, were conserved between B. napus and Arabidopsis. However, a more critical role of starch metabolism was detected for B. napus seed FA metabolism and storage-component accumulation when compared with Arabidopsis. In addition, a crucial stage for the transition of seed-to-sink tissue was 17-21 d after flowering (DAF), whereas FA biosynthesis-related genes were highly expressed primarily at 21 DAF. Hormone (auxin and jasmonate) signaling is found to be important for FA metabolism. This study helps to reveal the global regulatory network of FA metabolism in developing B. napus seeds.


Subject(s)
Arabidopsis/genetics , Brassica napus/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Plant/physiology , Lipid Metabolism/physiology , Seeds/genetics , DNA, Complementary , Expressed Sequence Tags , Fatty Acids/genetics , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation, Plant/genetics , Lipid Metabolism/genetics , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction
9.
J Biol Chem ; 278(43): 41734-41, 2003 Oct 24.
Article in English | MEDLINE | ID: mdl-12888560

ABSTRACT

Yersinia are causative agents in human diseases ranging from gastrointestinal syndromes to Bubonic Plague. There is increasing risk of misuse of infectious agents, such as Yersinia pestis, as weapons of terror as well as instruments of warfare for mass destruction. YopH is an essential virulence factor whose protein-tyrosine phosphatase (PTP) activity is required for Yersinia pathogenicity. Consequently, there is considerable interest in developing potent and selective YopH inhibitors as novel anti-plague agents. We have screened a library of 720 structurally diverse commercially available carboxylic acids and identified 26 YopH inhibitors with IC50 values below 100 mum. The most potent and specific YopH inhibitor is aurintricarboxylic acid (ATA), which exhibits a Ki value of 5 nm for YopH and displays 6-120-fold selectivity in favor of YopH against a panel of mammalian PTPs. To determine whether ATA can block the activity of YopH in a cellular context, we have examined the effect of ATA on T-cell signaling in human Jurkat cells transfected with YopH. We show that YopH severely decreases the T-cell receptor-induced cellular tyrosine phosphorylation, ERK1/2 activity, and interleukin-2 transcriptional activity. We demonstrate that ATA can effectively block the inhibitory activity of YopH and restore normal T-cell function. These results provide a proof-of-concept for the hypothesis that small molecule inhibitors that selectively target YopH may be therapeutically useful. In addition, it is expected that potent and selective YopH inhibitors, such as ATA, should be useful reagents to delineate YopH's cellular targets in plague and other pathogenic conditions caused by Yersinia infection.


Subject(s)
Aurintricarboxylic Acid/pharmacology , Bacterial Outer Membrane Proteins/antagonists & inhibitors , Plague/microbiology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Virulence Factors/antagonists & inhibitors , Yersinia pestis/drug effects , Bacterial Outer Membrane Proteins/genetics , Drug Evaluation, Preclinical , Humans , Inhibitory Concentration 50 , Interleukin-2/biosynthesis , Jurkat Cells , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Protein Tyrosine Phosphatases/genetics , Signal Transduction/drug effects , Structure-Activity Relationship , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Transfection , Virulence Factors/genetics , Yersinia pestis/pathogenicity
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