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Hypoglycemic foods have attracted increasing research interest. This study prepared a hypoglycemic product from Bacillus subtilis fermented with Pyropia (PBP), which has promising industrial potential, and elucidated its hypoglycemic mechanism. The aqueous PBP solution was orange, with protein as the main functional component. In vivo experiments demonstrated that PBP could increase insulin secretion and inhibit α-glucosidase activity, resulting in a hypoglycemic effect superior to that of acarbose at the same dose. Molecular docking revealed that the peptides APPVDID, GPPDSPY, PPSSPRP, and SPPPPPA from PBP could inhibit both α-glucosidase and dipeptidyl peptidase-IV (DPP-IV) activities. Pro residues promoted PBP peptide binding to the hydrophobic pocket S1 of DPP-IV. Additionally, PBP reduced inflammation and promoted the growth of beneficial gut bacteria (Prevotellaceae_UCG_003, Lachnospiraceae_UCG_001). This study presents a novel approach for the high-value utilization of Pyropia and a new option for the production of hypoglycemic functional foods and medicines.
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OBJECTIVE: Oligosaccharides have been shown to enhance the production of short chain fatty acids (SCFAs) by gut probiotics and regulate gut microbiota, to improve intestinal health. Recent research indicates that oligosaccharides may also positively impact skin microbiota by selectively promoting the growth of skin commensal bacteria and inhibiting pathogenic bacteria. However, the specific metabolic and regulatory mechanisms of skin commensal bacteria in response to oligosaccharides remain unclear. This study aims to explore the influence of four oligosaccharides on the growth and metabolism of Staphylococcus epidermidis and further identify skin prebiotics that can enhance its probiotic effects on the skin. METHODS: Fructooligosaccharides (FOS), isomaltooligosaccharide (IMO), galactooligosaccharides (GOS) and inulin were compared in terms of their impact on cell proliferation, SCFAs production of S. epidermidis CCSM0287 and the biofilm inhibition effect of their fermentation supernatants on Staphylococcus aureus CCSM0424. Furthermore, the effect of FOS on S. epidermidis CCSM0287 was analysed by the transcriptome analysis. RESULTS: All four oligosaccharides effectively promoted the growth of S. epidermidis CCSM0287 cells, increased the production of SCFAs, with FOS demonstrating the most significant effect. Analysis of the SCFAs indicated that S. epidermidis CCSM0287 predominantly employs oligosaccharides to produce acetic acid and isovaleric acid, differing from the SCFAs produced by gut microbiota. Among the four oligosaccharides, the addition of 2% FOS fermentation supernatant significantly inhibited S. aureus CCSM0424 biofilm formation. Furthermore, RNA sequencing revealed 162 differentially expressed genes (84 upregulated and 78 downregulated) of S. epidermidis CCSM0287 upon FOS treatment compared with glucose treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis highlighted differences in the amino acid synthesis pathway, particularly in terms of arginine biosynthesis. CONCLUSION: FOS promotes cell proliferation, increases the SCFA production of S. epidermidis CCSM0287 and enhance the inhibition of S. aureus biofilm formation, suggesting that FOS serves as a potential prebiotic for strain S. epidermidis CCSM0287.
OBJECTIF: Il a été démontré que les oligosaccharides améliorent la production d'acides gras à chaîne courte (AGCC) par les probiotiques intestinaux et régulent le microbiote intestinal, pour améliorer la santé intestinale. Des recherches récentes indiquent que les oligosaccharides peuvent également avoir un impact positif sur le microbiote cutané en favorisant sélectivement la croissance des bactéries commensales de la peau et en inhibant les bactéries pathogènes. Cependant, les mécanismes métaboliques et régulateurs spécifiques des bactéries commensales de la peau en réponse aux oligosaccharides restent incertains. Cette étude vise à étudier l'influence de quatre oligosaccharides sur la croissance et le métabolisme de Staphylococcus epidermidis, et à identifier de manière plus approfondie les prébiotiques cutanés qui peuvent améliorer ses effets probiotiques sur la peau. MÉTHODES: Les fructooligosaccharides (FOS), les isomaltooligosaccharides (IMO), les galactooligosaccharides (GOS) et l'inuline ont été comparés en termes d'impact sur la prolifération cellulaire, de production d'AGCC du S. epidermidis CCSM0287 et d'effet d'inhibition du biofilm de leurs surnageants de fermentation sur le staphylococoque CCSM0424. En outre, l'effet des FOS sur S. epidermidis CCSM0287 a été analysé par analyse du transcriptome. RÉSULTATS: Les quatre oligosaccharides ont efficacement favorisé la croissance des cellules du S. epidermidis CCSM0287, augmenté la production d'AGCC, le FOS démontrant l'effet le plus significatif. L'analyse des AGCC a indiqué que S. epidermidis CCSM0287 emploie principalement des oligosaccharides pour produire de l'acide acétique et de l'acide isovalérique, ce qui diffère des AAGC produites par le microbiote intestinal. Parmi les quatre oligosaccharides, l'ajout d'un surnageant de fermentation de FOS à 2% a inhibé significativement la formation du biofilm de S. aureus CCSM0424. En outre, le séquençage de l'ARN a révélé 162 gènes exprimés de manière différentielle (84 régulés à la hausse et 78 régulés à la baisse) de S. epidermidis CCSM0287 lors du traitement par FOS par rapport au traitement par glucose. L'analyse d'enrichissement de Kyoto Encyclopedia of Genes and Genomes (KEGG) a mis en évidence des différences dans la voie de synthèse des acides aminés, en particulier en termes de biosynthèse de l'arginine. CONCLUSION: Le FOS favorise la prolifération cellulaire, augmente la production des AGCC du S. epidermidis CCSM0287 et améliore l'inhibition de la formation du biofilm de S. aureus, ce qui indique que le FOS sert de prébiotique potentiel pour la souche S. epidermidis CCSM0287.
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OBJECTIVE: To evaluate the clinical outcomes of arthroscopic inside-out ganglionectomy of dominant dorsal wrist ganglion. METHODS: Patients with dominant wrist ganglion cyst treated in our hospital from January 1, 2014 to June 31, 2023 was enrolled in this retrospective analysis. All patients underwent dye-assist arthroscopic inside-out ganglionectomy. After discharge, the patients were followed for a minimum of 6 months. The primary outcomes were to assess patient wrist function using the Patient-Rated Wrist Evaluation (PRWE) and Mayo Modified Wrist Score (MMWS). The secondary outcomes were visual analog score (VAS), wrist active range of motion (ROM), grip strength, recurrence rate and complication. RESULTS: All ganglion were successfully resected after dye staining. Patients were followed for an average of 12.17 months. There were no significant changes between preoperative and postoperative wrist active ROM or grip strength, except for wrist flexion (which showed a slightly greater improvement after surgery, P = 0.049), there were notable improvements in VAS, MMWS, and PRWE postoperatively. Recurrence occurred in 3 patients. No major complications observed during the follow-up period. CONCLUSION: Dye-assist arthroscopic inside-out ganglionectomy is safe and uncomplicated, worth of clinical promotion.
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Artroscopía , Ganglión , Ganglionectomía , Humanos , Estudios Retrospectivos , Masculino , Artroscopía/métodos , Artroscopía/efectos adversos , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Ganglión/cirugía , Ganglionectomía/métodos , Rango del Movimiento Articular , Colorantes , Articulación de la Muñeca/cirugía , Articulación de la Muñeca/fisiopatología , Adulto Joven , Estudios de Seguimiento , Fuerza de la Mano , RecurrenciaRESUMEN
Polyglutamine (PolyQ) disease is a group of hereditary neurodegenerative diseases. It has become clear that brain damage may occur decades before the onset of symptoms. As a sensitive marker for neuro-axonal damages, neurofilament light chain (NfL) has appeared as a promising biomarker for neurological diseases. it may be used as a preclinical and clinical marker for the neurodegeneration in polyQ diseases, and is closely correlated with disease severity and progression, in particular different disease stages. This article has provided a review for the value of NfL as a biomarker in polyQ disease and its future research directions.
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Enfermedades Neurodegenerativas , Proteínas de Neurofilamentos , Péptidos , Humanos , Péptidos/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Proteínas de Neurofilamentos/genética , Biomarcadores , AnimalesRESUMEN
Natural products play a significant role in new drug discovery and anticancer therapy, making the evaluation of their anticancer efficiency crucial for clinical application. However, delivering natural products to single cells and in situ monitoring of induced signaling molecule fluctuation to evaluate anticancer efficiency remain significant challenges. Hence, we proposed a universal and straightforward strategy to construct a bifunctional nanoelectrode that integrates drug loading and monitoring of signal molecule fluctuations at the single-cell level. Platinum (Pt) nanoparticles/reduced graphene oxide (rGO) composites were first electrochemically deposited on the carbon fiber nanoelectrode (CFNE@Pt/rGO) to serve as electrocatalytic materials for the monitoring of natural-product-induced reactive oxygen species (ROS) generation. The GO/natural product complex, formed by π-π stacking and hydrophobic interactions, was further electrochemically reduced on the surface of CFNE@Pt/rGO to enable the CFNE drug-loading function. Using this bifunctional functional nanoelectrode, a series of natural products (such as capsaicin, curcumin, and chrysin) were delivered into single cancer cells, and their anticancer efficiency was evaluated by measuring ROS generation. The results showed that intracellular ROS production induced by chrysin was 1.5-fold greater than that of curcumin and 2.1-fold greater than that of capsaicin. This work proposes an effective tool to evaluate the anticancer efficiency of various natural products. Additionally, this nanotool can be expanded to monitor the fluctuation of other biomolecules (such as RNS, GSH, NADH, etc.) by replacing Pt nanoparticles with other electrocatalytic materials, which is significant for comprehensively exploring the anticancer efficiency of new drugs and for the clinical treatment of various diseases.
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BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.
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Carcinoma de Células Escamosas , Metástasis Linfática , Neoplasias de la Boca , Estadificación de Neoplasias , Tromboelastografía , Humanos , Tromboelastografía/métodos , Masculino , Femenino , Neoplasias de la Boca/patología , Neoplasias de la Boca/sangre , Neoplasias de la Boca/cirugía , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Pronóstico , Periodo PreoperatorioRESUMEN
Parkinson's disease (PD) is a prevalent and advancing age-related neurodegenerative disorder, distinguished by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron regional deposit in SNpc is a significant pathological characteristic of PD. Brain iron homeostasis is precisely regulated by iron metabolism related proteins, whereas disorder of these proteins can damage neurons and glial cells in the brain. Additionally, growing studies have reported iron metabolism related proteins are involved in the ferroptosis progression in PD. However, the effect of these proteins in the ferroptosis of PD has not been systematically summarized. This review focuses on the roles of iron metabolism related proteins in the ferroptosis of PD. Finally, we put forward the iron early diagnosis according to the observation of iron deposits in the brain and showed the recent advances in iron chelation therapy in PD.
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The effect of Fe3O4 nanoparticles (Fe3O4 NPs) on the electron transfer process in aerobic composting systems remains unexplored. In this study, we compared the electron transfer characteristics of DOM in sludge composting without additives (group CK) and with the addition of 50 mg/kg Fe3O4 NPs additive (group Fe). It was demonstrated that the electron transfer capacity (ETC) and electron donating capacity (EDC) of compost-derived DOM increased by 13%-29% and 40%-47%, respectively, with the addition of Fe3O4 NPs during sludge composting. Analyzing the composition and structure of DOM revealed that Fe3O4 NPs promoted the formation of humic acid-like substances and enhanced the aromatic condensation degree of DOM. Correlation analysis indicated that the increase in EDC of DOM was closely associated with the phenolic group in DOM and influenced by quinone groups and the degree of aromatization of DOM. The higher EDC and the structural evolution of DOM in group Fe reduced the bioaccessibility of Cu, Cr, Ni, Zn. This study contributes to a deeper understanding of the redox evolutionary mechanism of DOM in sludge composting and broadens the application of iron oxides additives.
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Compostaje , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Sustancias Húmicas/análisis , Electrones , Compuestos Férricos/químicaRESUMEN
In this paper, a feedback controller based on the extended state observer is proposed for fully actuated systems. First, a generalized proportional-integral observer is designed to estimate states and disturbances simultaneously. Using the linear parameter varying approach and the convexity principle, a linear matrix inequality condition is given to obtain the observer gains. Second, on the basis of the full-actuation property and the estimated states, a feedback controller, utilizing estimated disturbances to compensate for system disturbances, is designed to make all the states of the closed-loop system uniformly ultimately bounded. In addition, if disturbances are constant or slow time-varying, the observation errors and the states of closed-loop system are all exponentially convergent. Two illustrations are provided to show the validity and practicality of the proposed approach. Simulation results show that the estimated disturbances can follow the true values with relatively small errors, so compensating the system disturbances with estimated values can effectively reduce the ultimate bounds of states of the closed-loop system.
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Sepsis is generally triggered by a dysfunctional host response to infection, and it can result in life-threatening organ dysfunction. Alpinia officinarum Hance (AO) exhibits regulatory functions in some diseases. However, whether AO extract (AOE) plays a promoting role in sepsis--triggered myocardial injury is unclear. This study was aimed at investigating the regulatory effects of AOE on myocardial ferroptosis and inflammation in sepsis, and the regulation effects on the lncRNA MIAT/TRAF6/NF-κB axis. Lipopolysaccharide (LPS) was used to treat mice for establishing an in vivo sepsis model. The pathological changes in heart tissues were observed through hematoxylin-eosin (HE) staining. The levels of CK-MB, cTnl, MDA, SOD, IL-1ß, IL-18, IL-6, and TNF-α in serum were detected through enzyme-linked immunosorbent assay (ELISA). The level of Fe2+ was assessed, and the protein expressions (ACSL4, GPX4, TRAF6, p-P65, and P65) were examined through western blot. The expressions of lncRNA MIAT and TRAF6 were measured through real-time quantitative polymerase chain reaction (RT-qPCR). Our results demonstrated that AOE treatment ameliorated sepsis-triggered myocardial damage by reducing the disordered cardiomyocytes, the destroyed sarcolemma, and the CK-MB and cTnl levels. In addition, AOE treatment inhibited sepsis-induced myocardial ferroptosis and inflammation by regulating Fe2+, ACSL4, GPX4, IL-1ß, IL-18, IL-6, and TNF-α levels. Moreover, the improvement effect of AOE was strengthened with the increase in the dose of AOE (25, 50, 100 mg/kg). It was also revealed that AOE treatment retarded the lncRNA MIAT/TRAF6/NF-κB axis. Rescue assays manifested that overexpression of MIAT reduced the cardioprotective effect of AOE. In conclusion, AOE relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis. These findings may provide a potential therapeutic drug for the treatment of sepsis.
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Alpinia , Ferroptosis , FN-kappa B , Extractos Vegetales , ARN Largo no Codificante , Sepsis , Factor 6 Asociado a Receptor de TNF , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/inmunología , Ratones , FN-kappa B/metabolismo , Ferroptosis/efectos de los fármacos , Factor 6 Asociado a Receptor de TNF/metabolismo , Extractos Vegetales/farmacología , Masculino , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Miocardio/patología , Miocardio/inmunología , Humanos , Lipopolisacáridos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Paclitaxel , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angioplastia Coronaria con Balón/métodos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Anciano , Sirolimus/uso terapéutico , Sirolimus/administración & dosificación , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , China/epidemiología , Intervención Coronaria Percutánea/métodosRESUMEN
The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.
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OBJECTIVE: To investigate the protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell (BMEC) injury, and elucidate the possible underlying mechanism. METHODS: BMECs were treated with different concentrations of hydrocortisone at different time points, and the viability as well as migration of BMECs were evaluated; furthermore, the release of LDH, levels of VEGF, PAI-1, t-PA, and the content of NO by BMECs have been evaluated by commercially available kits; moreover, the expressions of eNOS, p-PI3K, p-Akt and p-mTOR in BMECs were examined by WB methods. Next, hydrocortisone treated BMECs were co-treated with Gumibao recipe, and the viability, migration and autophagy of BMECs were evaluated. RESULTS: 0.2 mg/ml and 0.3 mg/ml hydrocortisone significantly decreased viability and migration ability of BMECs, and also impeded the endothelial function of BMECs by decreasing the levels of VEGF, t-PA, the content of NO, and increasing the level of PAI-1. Gumibao medicated serum markedly increased the viability and migration of BMECs, and also increased the levels of VEGF, t-PA, the content of NO, meanwhile decreased the level of PAI-1 in 0.3 mg/ml hydrocortisone treated BMECs; moreover, glucocorticoids inhibited the autophagy of BMECs, and Gumibao recipe significantly increased the autophagy of BMECs; meanwhile, autophagy inhibitor 3-MA partially blocked the protective effects of Gumibao recipe. Finally, gumibao recipe partially abrogated the inhibitory effects of hydrocortisone on the activation of PI3K/Akt/mTOR singling, and these effects were further counteracted by PI3K and mTOR inhibitor NVP-BEZ235. CONCLUSIONS: We reported for the first time the protective effects of Gumibao recipe on glucocorticoid-included BMECs injury, and the possible underlying mechanism may be regulating the autophagy of BMECs via PI3K/AKT/mTOR signaling pathway.
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Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother-infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD's neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families.
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Biomarcadores , Depresión Posparto , Humanos , Depresión Posparto/metabolismo , Femenino , Animales , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Estrés Psicológico/metabolismoRESUMEN
BACKGROUND: The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity. METHODS: In vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24 hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7-P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively. RESULTS: Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine. CONCLUSION: This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.
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Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.9 ± 6.3 years old), 37 of which had a clinical dementia rating greater than 0. We observed elevated neurofilament light chain in preclinical Alzheimer's disease plasma for two measures (NfL101 and NfL324) and CSF for seven measures (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 and NfL530). We found five plasma peptides (NfL92, NfL101, NfL117, NfL324 and NfL530) significantly associated with age and two (NfL148 and NfL324) with body mass index.
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Presented herein is an atom- and step-economical method enabling the precise assembly of a heptacyclic scaffold containing both azocine and indoline units through the cascade reactions of indolin-1-yl(aryl)methanimines with diazo indanediones. The formation of products involves C-H bond activation and double carbene insertion followed by intramolecular condensation, retro-[2 + 2] cycloaddition, and recyclization. This cascade reaction not only provided a concise and straightforward strategy for the synthesis of the otherwise difficult to obtain heptacyclic compounds from readily available substrates but also disclosed an unprecedented reaction mode for indoline derivatives and diazo compounds. In general, this novel synthetic protocol has advantages, such as easily obtainable substrates, structurally sophisticated products, concise synthetic procedure, good compatibility with diverse functional groups, and ready scalability. Moreover, the products thus obtained showed decent antiproliferative activity against three human cancer cell lines.
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Heavy metal pollutants are important abiotic environmental factors affecting pest habitats. In this study, Cd pre-exposure significantly increased the tolerance of Lymantria dispar larvae to ß-cypermethrin, but did not significantly alter their tolerance to λ-cyhalothrin and bifenthrin. The activation of P450 by Cd exposure is the key mechanism that induces insecticide cross-tolerance in L. dispar larvae. Both before and after ß-cypermethrin treatment, Cd exposure significantly increased the expression of CYP6AB224 and CYP6AB226 in L. dispar larvae. Silencing CYP6AB224 and CYP6AB226 reduced the tolerance of Cd-treated L. dispar larvae to ß-cypermethrin. Transgenic CYP6AB224 and CYP6AB226 genes significantly increased the tolerance of Drosophila and Sf9 cells to ß-cypermethrin, and the recombinant proteins of both genes could significantly metabolise ß-cypermethrin. Cd exposure significantly increased the expression of CnCC and Maf. CnCC was found to be a key transcription factor regulating CYP6AB224- and CYP6AB226-activated insecticide cross-tolerance in Cd-treated larvae. Decreasing reactive oxygen species (ROS) levels in the Cd-treated larvae or increasing ROS levels in the untreated larvae reduced or enhanced the expression of CnCC, CYP6AB224 and CYP6AB226 and ß-cypermethrin tolerance in L. dispar larvae, respectively. Collectively, Cd exposure confers ß-cypermethrin tolerance in L. dispar larvae through the ROS/CnCC signalling pathway-mediated P450 detoxification.
Asunto(s)
Cadmio , Insecticidas , Larva , Mariposas Nocturnas , Piretrinas , Especies Reactivas de Oxígeno , Transducción de Señal , Piretrinas/toxicidad , Piretrinas/farmacología , Animales , Especies Reactivas de Oxígeno/metabolismo , Insecticidas/toxicidad , Insecticidas/farmacología , Larva/efectos de los fármacos , Larva/metabolismo , Transducción de Señal/efectos de los fármacos , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/metabolismo , Cadmio/toxicidad , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Resistencia a los Insecticidas/genética , Inactivación Metabólica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Complejo de Polillas Esponjosas VoladorasRESUMEN
Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.