Artemisia argyi extract exerts antioxidant properties and extends the lifespan of Drosophila melanogaster.

BACKGROUND: Chinese mugwort (Artemisia argyi) possesses extensive pharmacological activities associated with anti-tumour, antioxidative and anti-inflammatory effects. The present study aimed to investigate the antioxidant and anti-ageing effects of A. argyi extract (AAE) on the fruit fly (Drosophila melanogaster) ageing model by detecting antioxidant enzyme activities and the mRNA level of antioxidant genes. RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes. CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.

Covalent organic framework-MnO2 nanoparticle composites for shape-selective sensing of bithiols.

Covalent organic frameworks (COFs) for detecting biological macromolecules in water or biological environments are generally challenging. In this work, a composite material IEP-MnO2 is obtained by combining manganese dioxide (MnO2) nanocrystals and a fluorescent COF (IEP), which is synthesized by using 2,4,6-tris(4-aminophenyl)-s-triazine and 2,5-dimethoxyterephthalaldehyde. By the addition of biothiols, such as glutathione, cysteine or homocysteine with different sizes, the fluorescence emission spectra of IEP-MnO2 changed ("turn-on" or "turn-off") via different mechanisms. The fluorescence emission of IEP-MnO2 increased in the presence of GSH by the elimination of the FRET (Förster resonance energy transfer) effect between MnO2 and IEP. Surprisingly, due to the formation of a hydrogen bond between Cys/Hcy and IEP, the fluorescence quenching for IEP-MnO2 + Cys/Hcy may be explained via the photoelectron transfer (PET) process, which endows IEP-MnO2 with specificity in distinguishing the detection of GSH and Cys/Hcy compared to other MnO2 complex materials. Therefore, IEP-MnO2 was used to detect GSH and Cys in human whole blood and serum, respectively. The limit of detection for GSH in whole blood and Cys in human serum was calculated to be 25.58 µM and 4.43 µM, which indicates that IEP-MnO2 can be used to investigate some diseases related to GSH and Cys concentration. Moreover, the research expands the application of covalent organic frameworks in the fluorescence sensing field.

Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe.

Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.

A Novel Fluorescent Probe Strategy Activated by ß-Glucuronidase for Assisting Surgical Resection of Liver Cancer.

Liver cancer is a primary malignant tumor with a very high fatality rate, which has seriously threatened human health and life. In normal hepatocellular lesions, ß-glucuronidase (GLU) activity in liver cancer tissues is significantly increased. Therefore, GLU has become one of the important biomarkers of primary liver cancer. Here, a series of fluorescent probes (DCDH, DCDCH3, DCDOCH3, and DCDNO2) for early diagnosis of liver cancer and auxiliary surgical resection were successfully synthesized. Since the electron-withdrawing group -NO2 connected to the probe DCDNO2 accelerates the rapid cleavage of the glycosidic bond, DCDNO2 exhibits superior fluorescence properties that are more sensitive and rapid than the other three probes DCDH, DCDCH3, and DCDOCH3 when detecting GLU. DCDNO2 has been well-applied in real-time fluorescent visualization imaging for the detection of GLU activity in liver cancer cells and tumor tissues. In addition, DCDNO2 has also been successfully used in the early diagnosis of liver cancer and real-time imaging to guide the surgical resection of liver cancer tumors. Therefore, DCDNO2 has great potential for development in bioclinical medicine for the early detection and treatment of liver cancer.

Efficacy and safety of bismuth quadruple regimens containing tetracycline or furazolidone for initial eradication of Helicobacter pylori.

ABSTRACT: Helicobacter pylori (H pylori) infection can cause chronic gastritis, peptic ulcer, and even gastric cancer, so effective eradication is critical.This study compared the efficacy and safety of bismuth quadruple regimens including either tetracycline or furazolidone for initial eradication.Patients newly diagnosed with H pylori infection from January 2020 to January 2021 were randomly assigned to receive either the tetracycline-containing regimen (n = 116) or furazolidone-containing regimen (n = 168). Both regimens included 1 proton pump inhibitor (rabeprazole 20 mg, or esomeprazole 20 mg, or eprazole 5 mg), colloidal pectin bismuth 300 mg, and amoxicillin 1000 mg in addition to tetracycline 1.0 g or furazolidone 0.1 g. All drugs were administered twice daily for 12 consecutive days. The 14C urea breath test was used for diagnosis, and re-test negativity at one-month follow-up was considered successful eradication. Adverse events were recorded during follow-up by telephone interview.In total, 109 patients in the tetracycline group and 157 in the furazolidone group were re-examined at 1 month. In the tetracycline group, 101 patients tested negative at follow-up, yielding an eradication rate of 92.7% according to per-protocol analysis and 87.1% by intention-to-treat analysis. In the furazolidone group, 141 patients tested negative, yielding eradication rates of 89.8% by PP and 83.9% by ITT. Eradication rates did not differ significantly between regimens (per-protocol: χ2 = 0.637, P = .517; intention-to-treat: χ2 = 0.537, P = .501). However, total adverse events incidence was significantly lower in the tetracycline group (20.2% vs 37.6%; χ2 = 9.193, P = .003).Both bismuth quadruple regimens produce high initial eradication, but the tetracycline regimen appears safer.

Long-Wavelength Ratiometric Fluorescent Probe for the Early Diagnosis of Diabetes.

Diabetes is a metabolic disease caused by high blood sugar. Patients are often suffering from high blood pressure and arteriosclerosis, which may even evolve into liver disease, kidney disease, and other diabetic complications. Dipeptide peptidase IV (DPP-IV) plays an important role in regulating blood sugar levels and is one of the targets for the diagnosis and treatment of diabetes. Here, a long-wavelength ratiometric fluorescent probe DCDHFNH2-dpp4 for detecting DPP-IV was designed and synthesized. DCDHFNH2-dpp4 was used to detect DPP-IV in healthy, tumor-bearing, and diabetic mice, and only diabetic mice showed strong fluorescence signals. In organ imaging, it is found that DPP-IV is relatively enriched in the liver of diabetic mice. In addition, probe DCDHFNH2-dpp4 also exhibited a significant ratiometric fluorescence signal in the serum of diabetic mice. Therefore, the fluorescent probe DCDHFNH2-dpp4 has shown outstanding potential in the early diagnosis of diabetes, and DCDHFNH2-dpp4 is hopeful to be applied to actual clinical medicine.

In vivo imaging via a red-emitting fluorescent probe to diagnosing liver cancer or drug-induced liver disease.

Leucine aminopeptidase (LAP) as an important proteolytic enzyme, has been mainly found in hepatobiliary cells, and overexpressed in hepatoma cells. Herein, a new highly selective red-emitting fluorescent probe (DCDHF-Ala) for LAP has been synthesized based on 2-dicyanomethyldiene-3-cyano-2, 5-dihydrofuran (DCDHF) as fluorophore, and alanine (Ala) as the detection group. More importantly, it's the first time to use Ala as a reactive group for LAP. DCDHF-Ala has a low detection limit (0.20 U/L), excellent water solubility and cell membrane permeability. In addition, the probe has been successfully applied to fluorescent imaging in cells and zebrafish. It's especially worth mentioning that, DCDHF-Ala has a high biosafety and enables a real-time detection of LAP levels in mice model. What's the most important is that DCDHF-Ala may be an effective tool to qualitatively monitor the upregulation of LAP induced by liver injury and liver cancer.

Red emission ratio fluorescent probe for the activity of vanin-1 and imaging in vivo.

Pantetheinase, also known as Vanin-1, catalyzes pantetheine to decompose into the precursor of CoA - pantothenic acid and aminothiol cysteamine. Studies have shown that Vanin-1 plays an important role in many important physiological pathologies. In this paper, a new red emission ratio fluorescent probe DCM-PA (I640 nm/I564 nm) has been implemented to detect the activity of Vanin-1 in cells and vivo. DCM-PA has short response time (30 min), high selectivity and low sensitivity (DL =0.69 ng/mL). Also, we have applied DCM-PA for imaging in cells and mice, and the results have indicated that the probe has a non-negligible potential for monitoring the activity of Vanin-1 in situ, benefiting further to study the role of Vanin-1 in physiology and pathology. In addition, the up-regulation of this enzyme by starvation confirmed the inevitable connection between diabetes and abnormal expression of Vanin-1.

Visible to Near-Infrared Emission Ratiometric Fluorescent Probe for the Detection of Vanin-1 In Vivo.

Pantetheinase (Vanin-1) is an ectoenzyme, which involves the metabolic pathway of coenzyme A (CoA), and can decompose pantetheine into pantothenic acid (CoA precursor) and aminothiol cysteamine. Previous studies have revealed that Vanin-1 with essential biological functions is closely related to many diseases. However, the lack of simple and effective detection methods has severely hindered the further study of Vanin-1's physiological functions. In this work, we have developed a near-infrared (NIR) emission ratio fluorescent probe TMN-PA (I645 nm/I568 nm) that enables us to detect Vanin-1 rapidly (in 15 min) with a minimum detection limit of 0.37 ng/mL. What is more, this probe shows excellent potential in in situ real-time monitoring of the endogenous Vanin-1, contributing to further research on Vanin-1 and understanding its mechanisms in physiological pathology. To our knowledge, this probe is the first NIR emission ratio (I645 nm/I568 nm) fluorescent probe ever reported to monitor the activity of Vanin-1 in vivo.

Edwardsiella induces microtubule-severing in host epithelial cells.

Edwardsiella bacteria cause economic losses to a variety of commercially important fish globally. Human infections are rare and result in a gastroenteritis-like illness. Because these bacteria are evolutionarily related to other Enterobacteriaceae and the host cytoskeleton is a common target of enterics, we hypothesized that Edwardsiella may cause similar phenotypes. Here we use HeLa and Caco-2 infection models to show that microtubules are severed during the late infections. This microtubule alteration phenotype was not dependant on the type III or type VI secretion system (T3SS and T6SS) of the bacteria as ΔT3SS and ΔT6SS mutants of E. piscicida EIB202 and E. tarda ATCC15947 that lacks both also caused microtubule disassembly. Immunolocalization experiments showed the host katanin catalytic subunits A1 and A like 1 proteins at regions of microtubule severing, suggesting their involvement in the microtubule disassembly events. To identify bacterial components involved in this phenotype, we screened a 2,758 transposon library of E. piscicida EIB202 and found that 4 single mutations in the atpFHAGDC operon disrupted microtubule disassembly in HeLa cells. We then constructed three atp deletion mutants; they all could not disassemble host microtubules. This work provides the first clear evidence of host cytoskeletal alterations during Edwardsiella infections.

BODIPY-based asymmetric monosubstituted (turn-on) and symmetric disubstituted (ratiometric) fluorescent probes for selective detection of phosgene in solution and gas phase.

Here, we designed and synthesized two fluorescent probes for detecting phosgene by nucleophilic substitution reaction using BODIPY as a fluorophore and 2-aminobenzylamine as reactive functional group. For the first time, we have studied the similarities and differences between asymmetric monosubstituted (1) and symmetric disubstituted (2) probes. A monosubstituted probe 1 (having a 2-aminobenzylamine group at the 3-position of BODIPY) has fluorescence-enhancing (weak green fluorescence to strong green fluorescence) responce to phosgene in 30 s with a large Stokes shift (∼70 nm) and sensitive property (DL = 0.81 nM); while the disubstituted probe 2 (having two 2-aminobenzylamine groups at the 3, 5-position of BODIPY) has a ratiometric fluorescent responce to phosgene in 2 min. The linear range of the response is wider than that of the monosubstitution probe 1, and the detection limit is also lower (2.36 nM). In addition, probes 1 and 2 can effectively eliminate the interference of other substances with similar chemical structure as phosgene. They can not only detect phosgene in solution environment, but also in gaseous environment quickly and sensitively.

Transcriptome-wide piRNA profiling in human brains for aging genetic factors.

OBJECTIVE: Piwi-interacting RNAs (piRNAs) represent a molecular feature shared by all nonaging biological systems, including the germline and somatic cancer stem cells, which display an indefinite renewal capacity and lifespan-stable genomic integrity and are potentially immortal. Here, we tested the hypothesis that piRNA is a critical genetic determinant of aging in humans. METHODS: Expression of transcriptome-wide piRNAs (n=24k) was profiled in the human prefrontal cortex of 12 subjects (84.9±9.5, range 68-100, years of age) using microarray technology. We examined the correlation between these piRNAs' expression levels and age, adjusting for covariates including disease status. RESULTS: A total of 9,453 piRNAs were detected in brain. Including seven intergenic and three intronic piRNAs, ten piRNAs were significantly associated with age after correction for multiple testing (|r|=0.9; 1.9×10-5≤p≤9.9×10-5). CONCLUSION: We conclude that piRNAs might play a potential role in determining the years of survival of humans. The underlying mechanisms might involve the suppression of transposable elements (TEs) and expression regulation of aging-associated genes.

ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway.

BACKGROUND: Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells. OBJECTIVE: The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM. METHODS: The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis. RESULTS: ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling. CONCLUSION: ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.

Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC.

Triptolide inhibits proliferation and induces apoptosis of human melanoma A375 cells.

Triptolide, a diterpenoid obtained from Tripteryglum wilfordii Hook.f, has attracted interest for its anti- tumor activities against human tumor cell lines in recent years. This report focuses on anti-proliferative and pro-apoptotic activities in human melanoma A375 cells assessed by CCK8 assay, Hoechst 33258 staining and flow cytometry. In addition, triptolide-induced arrest in the S phase was also observed. Caspase assays showed the apoptosis induced by triptolide was caspase-dependent and probably through intrinsic apoptotic pathways. Furthermore, expression of NF-κB (p65) and its downstream factors such as Bcl-2, Bcl-XL was down-regulated. Taken together, the data indicate that triptolide inhibits A375 cells proliferation and induces apoptosis by a caspase-dependent pathway and through a NF-κB-mediated mechanism.

Evaluation of the skin sensitization potential of chemicals in THP-1/keratinocyte co-cultures.

Many attempts have been made to develop in vitro sensitization tests that employ dendritic cells (DCs), DC-like cell lines or keratinocytes. The aim of the present investigation was to establish a co-culture of THP-1 cells and keratinocytes for evaluation of skin sensitization potential of chemicals. Co-cultures were constructed by THP-1 cells cultured in lower compartments and keratinocytes cultured in upper compartments of cell culture inserts. After 24 h exposure to sensitizers (2, 4-dinitrochlorobenzene, p-phenylenediamine, formaldehyde, nickel sulfate, isoeugenol and eugenol) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride and lactic acid), the expression of CD86 and CD54 on THP-1 cells were evaluated by flow cytometry, and cell viabilities were determined. The sensitizers induced the augmentation of CD86 and CD54 expression, but the non-sensitizers had no significant effect. Compared with mono-cultures of THP-1 cells, the augmentation of CD86 and CD54 could be detected even at a non-toxic concentration of sensitizers in THP-1 cell/keratinocyte co-cultures. Moreover, isoeugenol was distinguished as a sensitizer in co-cultures, but failed to be identified in mono-cultures. These results revealed that the co-cultures of THP-1 cells and keratinocytes were successfully established and suitable for identifying sensitizers using CD86 and CD54 expression as identification markers.

Recovery of phytosterols from waste residue of soybean oil deodorizer distillate.

This study describes a catalytic decomposition and crystallization process to recover phytosterols from the waste residue of soybean oil deodorizer distillate (WRSODD). Various solvents were used for the crystallization of phytosterols. The effect of different solvents on the purity and yield of recovered phytosterols was investigated. The composition of WRSODD was analyzed by silica gel column chromatography and FT-IR spectrum. Gas chromatography (GC), GC-MS, and FT-IR were adopted to determine the purity and structure of phytosterols. Results showed the total amount of phytosterols, in the form of fatty acid steryl esters, was up to 20 wt.% of WRSODD. Through orthogonal experiments, the optimized crystallization conditions were obtained. It's found the mixed solvent of acetone and ethanol (4/1, v/v) could generate good crystallization. The yield of recovered phytosterols was 22.95 wt.% after the 1st crystallization. The purity of phytosterols reached 91.82, 92.73, and 97.17 wt.% after the 1st, 2nd, and 3rd crystallization, respectively.

Psychosocial and immunological factors in neurasthenia.

BACKGROUND: Neurasthenia is a disorder whose pathogenesis is still unknown. OBJECTIVE: The authors sought to examine the relationships between neurasthenia and possible psychosocial and immunological correlates. METHOD: A sample of 30 Chinese neurasthenic patients was compared with a matched sample of 30 control subjects for 1) the level of serum Epstein-Barr virus (EBV) gamma G immunoglobulin (IgG) and gamma M immunoglobulin (IgM); 2) scores on the Eysenck Personality Questionnaire (EPQ); 3) the Symptom Checklist-90; and 4) the Life Event Scale (LES); 27 of the 30 neurasthenia patients were treated with medication and psychotherapy for a 4-month period, with measures taken pre- and posttreatment. RESULTS: As compared with the control group, neurasthenic patients exhibited higher EPQ scores for neuroticism, higher levels of introversion, and a higher number of negative life events. Within the neurasthenia sample, scores for neuroticism and the SCL-90 Global Severity Index were significantly lower at follow-up than at baseline. CONCLUSION: As compared with control subjects, neurasthenia patients were characterized by greater neuroticism and introversion, and they reported a higher rate of negative life events. Moreover, the positive rate of EBV in neurasthenic patients was higher, which may be associated with higher EBV activation under states of stress.