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1.
Methods Mol Biol ; 2846: 181-189, 2024.
Article de Anglais | MEDLINE | ID: mdl-39141237

RÉSUMÉ

Cleavage Under Targets and Tagmentation (CUT&Tag) provides high-resolution sequencing libraries for profiling diverse chromatin components. This protocol details the steps to generate CUT&Tag libraries from fresh or frozen tissues. This CUT&Tag workflow has nine main steps: isolation of nuclei from tissues, binding of nuclei to Concanavalin A-coated beads, binding of the primary antibody, binding of the secondary antibody, binding pA-Tn5 adapter complex, tagmentation, DNA extraction, PCR, and post-PCR cleanup and size selection. This protocol enabled us to generate and sequence CUT&Tag libraries across a broad range of fresh and frozen tissue types.


Sujet(s)
Épigénomique , Épigénomique/méthodes , Humains , Banque de gènes , Chromatine/génétique , Chromatine/métabolisme , Animaux , Séquençage nucléotidique à haut débit/méthodes , Noyau de la cellule/génétique , Noyau de la cellule/métabolisme , Congélation , Réaction de polymérisation en chaîne/méthodes
2.
Biomed Environ Sci ; 37(7): 716-725, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39198236

RÉSUMÉ

Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5. Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.


Sujet(s)
Virus de l'encéphalite japonaise (espèce) , Encéphalite japonaise , Génotype , Humains , Encéphalite japonaise/épidémiologie , Encéphalite japonaise/virologie , Chine/épidémiologie , Virus de l'encéphalite japonaise (espèce)/génétique , Virus de l'encéphalite japonaise (espèce)/isolement et purification , Virus de l'encéphalite japonaise (espèce)/immunologie , Femelle , Mâle , Adulte , Adulte d'âge moyen , Jeune adulte , Adolescent , Enfant , Enfant d'âge préscolaire , Sujet âgé , Anticorps antiviraux/sang
3.
Cell Rep ; 43(8): 114535, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39088322

RÉSUMÉ

Cartilage maintains the structure and function of joints, with disturbances leading to potential osteoarthritis. N6-methyladenosine (m6A), the most widespread post-transcriptional modification in eukaryotes, plays a crucial role in regulating biological processes. While current research has indicated that m6A affects the progression of osteoarthritis, its function in the development and homeostasis of articular cartilage remains unclear. Here we report that Mettl3 deficiency in chondrocytes leads to mandibular condylar cartilage morphological alterations, early temporomandibular joint osteoarthritis, and diminished adaptive response to abnormal mechanical stimuli. Mechanistically, METTL3 modulates Lats1 mRNA methylation and facilitates its degradation in an m6A-YTHDF2-dependent manner, which subsequently influences the degradation and nuclear translocation of YAP1. Intervention with the Hippo pathway inhibitor XMU-MP-1 alleviates condylar abnormality caused by Mettl3 knockout. Our findings demonstrate the role of METTL3 in cartilage development and homeostasis, offering insights into potential treatment strategies for osteoarthritis.


Sujet(s)
Adénosine , Chondrocytes , Homéostasie , Methyltransferases , Protein-Serine-Threonine Kinases , Stabilité de l'ARN , Protéines de liaison à l'ARN , Methyltransferases/métabolisme , Methyltransferases/génétique , Animaux , Protein-Serine-Threonine Kinases/métabolisme , Protein-Serine-Threonine Kinases/génétique , Souris , Chondrocytes/métabolisme , Adénosine/analogues et dérivés , Adénosine/métabolisme , Protéines de liaison à l'ARN/métabolisme , Protéines de liaison à l'ARN/génétique , Protéines de signalisation YAP/métabolisme , Souris knockout , Arthrose/métabolisme , Arthrose/génétique , Arthrose/anatomopathologie , ARN messager/métabolisme , ARN messager/génétique , Cartilage articulaire/métabolisme , Cartilage articulaire/anatomopathologie , Cartilage/métabolisme , Souris de lignée C57BL , Chondrogenèse/génétique , Méthylation , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Humains , Mâle , Condyle mandibulaire/métabolisme
4.
Pharmaceutics ; 16(8)2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39204373

RÉSUMÉ

Immunotherapy combats tumors by enhancing the body's immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA tumor vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, and oligonucleotides that can be used as immune adjuvants. Nucleic acid drugs, which are prone to nuclease degradation in the circulation and find it difficult to enter the target cells, typically necessitate developing appropriate vectors for effective in vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, and cells, can protect the cargos from degradation and clearance, and deliver them to the target cells to ensure safety. Moreover, they can activate the immune system through their endogenous activities and active components, thereby improving the efficacy of antitumor immunotherapeutic nucleic acid drugs. In this review, biomimetic nucleic acid delivery systems for relieving a tumor immunosuppressive microenvironment are introduced. Their immune activation mechanisms, including upregulating the proinflammatory cytokines, serving as tumor vaccines, inhibiting immune checkpoints, and modulating intratumoral immune cells, are elaborated. The advantages and disadvantages, as well as possible directions for their clinical translation, are summarized at last.

5.
World J Gastrointest Oncol ; 16(8): 3410-3427, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39171180

RÉSUMÉ

Pyroptosis is a type of programmed cell death mediated by gasdermines (GSDMs). The N-terminal domain of GSDMs forms pores in the plasma membrane, causing cell membrane rupture and the release of cell contents, leading to an inflammatory response and mediating pyrodeath. Pyroptosis plays an important role in inflammatory diseases and malignant tumors. With the further study of pyroptosis, an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence, development, treatment and prognosis of colorectal cancer. This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence, development, treatment and prognosis of colorectal cancer (CRC) and to provide ideas for the clinical diagnosis and treatment of CRC.

6.
Article de Anglais | MEDLINE | ID: mdl-39193631

RÉSUMÉ

The development of multifunctional wound adhesives is critical in clinical settings due to the scarcity of dressings with effective adhesive properties while protecting against infection by drug-resistant bacteria. Polysaccharide and gelatin-based hydrogels, known for their biocompatibility and bioactivity, assist in wound healing. This study introduces a multifunctional bioadhesive hydrogel developed through dynamic covalent bonding and light-triggered covalent bonding, comprising oxidized hyaluronic acid, methacrylated gelatin, and the bacteriocin recently discovered by our lab, named jileicin (JC). The adhesion strength of the hydrogel, measured at 180 kPa, was 4.35 times higher than that of the fibrin glue. Furthermore, the hydrogel demonstrated robust platelet adhesion, procoagulant activity, and outstanding hemostatic properties in a mouse liver injury model. Incorporating JC significantly enhanced the phagocytosis and bactericidal capabilities of the macrophages. This immunomodulatory function on host cells, coupled with its potent bacterial membrane-disrupting ability, makes JC an effective killer against methicillin-resistant Staphylococcus aureus. In wound repair experiments on diabetic mice with infected full-thickness skin defects, the hydrogel treatment group showed a notable reduction in bacterial load, accelerated M2-type macrophage polarization, diminished inflammation, and hastened wound healing. Owing to its outstanding biocompatibility, antibacterial activity, and controlled adhesion, this hydrogel presents a promising therapeutic option for treating infected skin wounds.

8.
Sci Rep ; 14(1): 16745, 2024 07 20.
Article de Anglais | MEDLINE | ID: mdl-39033185

RÉSUMÉ

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.


Sujet(s)
Rectocolite hémorragique , Sulfate dextran , Modèles animaux de maladie humaine , Microbiome gastro-intestinal , Sesquiterpènes , Animaux , Rectocolite hémorragique/induit chimiquement , Rectocolite hémorragique/traitement médicamenteux , Rectocolite hémorragique/microbiologie , Rectocolite hémorragique/métabolisme , Souris , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Sesquiterpènes/pharmacologie , Heme oxygenase-1/métabolisme , Nitric oxide synthase type II/métabolisme , Mâle , Anti-inflammatoires/pharmacologie , Dysbiose/induit chimiquement , Dysbiose/microbiologie , Souris de lignée C57BL , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/usage thérapeutique
9.
Gynecol Endocrinol ; 40(1): 2375568, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38976752

RÉSUMÉ

BACKGROUND: Iron metabolism plays a significant role in the development of metabolic disorders in women with polycystic ovary syndrome (PCOS). Despite the importance of hepcidin, a key iron regulator, current research on serum hepcidin levels in PCOS patients shows conflicting results. METHODS: PubMed, Embase, Web of Science, Cochrane Library and the China National Knowledge Infrastructure (CNKI) database were systematically searched from their inception to 9 September 2023. The search aimed to identify studies in English and Chinese that examined hepcidin levels in women with PCOS compared to healthy control subjects. Standardized mean differences (SMDs) with corresponding 95% confidence intervals (95% CIs) were calculated to evaluate the difference in serum hepcidin levels between women with and without PCOS. RESULTS: The meta-analysis included a total of 10 eligible studies, which encompassed 499 PCOS patients and 391 control subjects. The pooled analysis revealed a significant reduction in serum hepcidin levels among the PCOS patients compared to the healthy controls (SMD = -3.49, 95% CI: -4.68 to -2.30, p < .05). There was no statistically significant difference in serum hepcidin levels between PCOS patients with a body mass index (BMI) < 25 and those with a BMI ≥ 25 (p > .05). CONCLUSION: The serum hepcidin levels of women with PCOS were significantly lower than those of healthy controls, which suggests that serum hepcidin could be a potential biomarker for PCOS.


Sujet(s)
Hepcidines , Syndrome des ovaires polykystiques , Syndrome des ovaires polykystiques/sang , Humains , Hepcidines/sang , Femelle , Indice de masse corporelle
10.
Arch Dermatol Res ; 316(7): 368, 2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38850361

RÉSUMÉ

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.


Sujet(s)
Chéloïde , Triamcinolone acétonide , Chéloïde/traitement médicamenteux , Chéloïde/anatomopathologie , Humains , Triamcinolone acétonide/pharmacocinétique , Triamcinolone acétonide/administration et posologie , Adulte , Femelle , Distribution tissulaire , Mâle , Adulte d'âge moyen , Injections intralésionnelles , Peau/métabolisme , Peau/anatomopathologie , Peau/imagerie diagnostique , Cryo-ultramicrotomie/méthodes , Jeune adulte , Imagerie tridimensionnelle , Systèmes de délivrance de médicaments/méthodes
11.
Dermatol Surg ; 2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38874219

RÉSUMÉ

BACKGROUND: The efficacy of keloid treatment in randomized studies is highly variable. However, no systematic review has been performed to evaluate the effect of different keloid properties on treatment efficacy. OBJECTIVE: To identify clinically relevant keloid properties that may influence treatment efficacy. MATERIALS AND METHODS: An electronic database search was conducted. Two reviewers independently selected randomized controlled trials (RCTs) and performed a methodologic quality assessment using the Cochrane risk-of-bias 2.0 tool. RESULTS: One thousand five hundred twenty studies were screened, and 16 RCTs, involving 1,113 patients, were included. The authors found lower efficacy in older keloids ( n = 3), keloids located on the chest, extremities, pinna, and shoulder ( n = 3), larger keloids ( n = 2), lower baseline Vancouver Scar Scale score ( n = 1), and keloids with history of recurrence ( n = 1). Overall, most studies had a high risk of bias. CONCLUSION: Only a minority of studies specifically addressed keloid properties, which makes comparisons between studies challenging. The authors' results suggest that keloid location, duration prior to treatment, size, history of recurrence, and severity are clinically relevant keloid properties that affect treatment efficacy. Further studies are crucial to corroborate the authors' findings, establish a clinically relevant keloid classification, and ultimately develop an evidence-based treatment algorithm that takes these properties into account.

13.
Adv Sci (Weinh) ; 11(30): e2401793, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38874469

RÉSUMÉ

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.


Sujet(s)
Diabète expérimental , Modèles animaux de maladie humaine , Cicatrisation de plaie , Animaux , Souris , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Diabète expérimental/traitement médicamenteux , Staphylococcus aureus résistant à la méticilline/effets des médicaments et des substances chimiques , Peptides antimicrobiens/pharmacologie , Infection de plaie/traitement médicamenteux , Infection de plaie/microbiologie , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Escherichia coli/effets des médicaments et des substances chimiques , Tests de sensibilité microbienne
14.
Biochem Pharmacol ; 225: 116310, 2024 07.
Article de Anglais | MEDLINE | ID: mdl-38788960

RÉSUMÉ

Targeting the DNA damage response (DDR) is a promising strategy in oncotherapy, as most tumor cells are sensitive to excess damage due to their repair defects. Ataxia telangiectasia mutated and RAD3-related protein (ATR) is a damage response signal transduction sensor, and its therapeutic potential in tumor cells needs to be precisely investigated. Herein, we identified a new axis that could be targeted by ATR inhibitors to decrease the DNA-dependent protein kinase catalytic subunit (DNAPKcs), downregulate the expression of the retinoblastoma (RB), and drive G1/S-phase transition. Four-way DNA Holliday junctions (FJs) assembled in this process could trigger S-phase arrest and induce lethal chromosome damage in RB-positive triple-negative breast cancer (TNBC) cells. Furthermore, these unrepaired junctions also exerted toxic effects to RB-deficient TNBC cells when the homologous recombination repair (HRR) was inhibited. This study proposes a precise strategy for treating TNBC by targeting the DDR and extends our understanding of ATR and HJ in tumor treatment.


Sujet(s)
Protéines mutées dans l'ataxie-télangiectasie , ADN cruciforme , Tumeurs du sein triple-négatives , Protéines mutées dans l'ataxie-télangiectasie/métabolisme , Protéines mutées dans l'ataxie-télangiectasie/antagonistes et inhibiteurs , Protéines mutées dans l'ataxie-télangiectasie/génétique , Humains , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/génétique , Tumeurs du sein triple-négatives/traitement médicamenteux , Lignée cellulaire tumorale , ADN cruciforme/métabolisme , ADN cruciforme/génétique , Protéine du rétinoblastome/métabolisme , Protéine du rétinoblastome/génétique , Femelle , Phase S/effets des médicaments et des substances chimiques , Phase S/physiologie , Animaux , Antinéoplasiques/pharmacologie , Altération de l'ADN/physiologie , Altération de l'ADN/effets des médicaments et des substances chimiques
15.
Exp Cell Res ; 438(1): 114052, 2024 May 01.
Article de Anglais | MEDLINE | ID: mdl-38636651

RÉSUMÉ

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.


Sujet(s)
Artémisinines , Protéines proto-oncogènes c-akt , Transduction du signal , Sérine-thréonine kinases TOR , Immunité entraînée , Animaux , Souris , Artémisinines/pharmacologie , Candida albicans/effets des médicaments et des substances chimiques , Sous-unité alpha du facteur-1 induit par l'hypoxie/métabolisme , Sous-unité alpha du facteur-1 induit par l'hypoxie/génétique , Inflammasomes/métabolisme , Inflammasomes/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Souris knockout , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Sérine-thréonine kinases TOR/métabolisme , Immunité entraînée/effets des médicaments et des substances chimiques
16.
Vet Res ; 55(1): 52, 2024 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-38622656

RÉSUMÉ

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.


Sujet(s)
Infections à Clostridium , Animaux , Souris , Infections à Clostridium/médecine vétérinaire , Clostridium perfringens , Interleukine-6 , Lipopolysaccharides , Sérine-thréonine kinases TOR , Immunité entraînée , Facteur de nécrose tumorale alpha/métabolisme
17.
ACS Chem Neurosci ; 15(11): 2223-2232, 2024 06 05.
Article de Anglais | MEDLINE | ID: mdl-38634698

RÉSUMÉ

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis. In terms of energy metabolism, RIPostC enhanced ATP levels, suppressed lactate content, and increased the production of ketone bodies (KBs). In the ferroptosis assay, RIPostC protected against lipoperoxidation, reversed the reduction of glutathione peroxidase 4 (GPX4), and mitigated the excessive expression of long-chain acyl-CoA synthetase family member 4 (ACSL4). In oxygen-glucose deprivation/reoxygenation-treated HT22 cells, KBs maintained GPX4 levels, suppressed ACSL4 expression, and preserved the mitochondrial cristae number. However, the effect of KBs on the expression of GPX4, ACSL4, and the number of mitochondrial cristae was blocked by erastin. Moreover, both RIPostC and KBs reduced total iron and ferrous ion content by repressing iron transporters both in vitro and in vivo. In conclusion, KBs-induced mitigation of ferroptosis could represent a new therapeutic mechanism for RIPostC in treating stroke.


Sujet(s)
Coenzyme A ligases , Ferroptose , Infarctus du territoire de l'artère cérébrale moyenne , Postconditionnement ischémique , Corps cétoniques , Neuroprotection , Ferroptose/physiologie , Animaux , Rats , Postconditionnement ischémique/méthodes , Corps cétoniques/métabolisme , Mâle , Coenzyme A ligases/métabolisme , Neuroprotection/physiologie , Rat Sprague-Dawley , Phospholipid hydroperoxide glutathione peroxidase/métabolisme , Souris , Neuroprotecteurs/pharmacologie , Accident vasculaire cérébral ischémique/métabolisme , Accident vasculaire cérébral/métabolisme , Neurones/métabolisme
18.
RSC Adv ; 14(17): 12142-12146, 2024 Apr 10.
Article de Anglais | MEDLINE | ID: mdl-38628470

RÉSUMÉ

MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.

19.
Biomed Environ Sci ; 37(3): 294-302, 2024 Mar 20.
Article de Anglais | MEDLINE | ID: mdl-38582993

RÉSUMÉ

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.


Sujet(s)
Encéphalite virale , Virus , Humains , Encéphalite virale/diagnostic , Virus/génétique , Séquençage nucléotidique à haut débit/méthodes , Réaction de polymérisation en chaîne , ADN viral
20.
J Imaging Inform Med ; 2024 Apr 23.
Article de Anglais | MEDLINE | ID: mdl-38653910

RÉSUMÉ

Labelling medical images is an arduous and costly task that necessitates clinical expertise and large numbers of qualified images. Insufficient samples can lead to underfitting during training and poor performance of supervised learning models. In this study, we aim to develop a SimCLR-based semi-supervised learning framework to classify colorectal neoplasia based on the NICE classification. First, the proposed framework was trained under self-supervised learning using a large unlabelled dataset; subsequently, it was fine-tuned on a limited labelled dataset based on the NICE classification. The model was evaluated on an independent dataset and compared with models based on supervised transfer learning and endoscopists using accuracy, Matthew's correlation coefficient (MCC), and Cohen's kappa. Finally, Grad-CAM and t-SNE were applied to visualize the models' interpretations. A ResNet-backboned SimCLR model (accuracy of 0.908, MCC of 0.862, and Cohen's kappa of 0.896) outperformed supervised transfer learning-based models (means: 0.803, 0.698, and 0.742) and junior endoscopists (0.816, 0.724, and 0.863), while performing only slightly worse than senior endoscopists (0.916, 0.875, and 0.944). Moreover, t-SNE showed a better clustering of ternary samples through self-supervised learning in SimCLR than through supervised transfer learning. Compared with traditional supervised learning, semi-supervised learning enables deep learning models to achieve improved performance with limited labelled endoscopic images.

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