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1.
J Infect Dev Ctries ; 18(8): 1233-1240, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39288385

RESUMEN

INTRODUCTION: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region. METHODOLOGY: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software. RESULTS: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections. CONCLUSIONS: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies.


Asunto(s)
Antibacterianos , Meningitis Bacterianas , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Humanos , China/epidemiología , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/epidemiología , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/líquido cefalorraquídeo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Prevalencia , Masculino , Femenino , Adulto , Niño , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple , Persona de Mediana Edad , Farmacorresistencia Bacteriana , Preescolar , Lactante , Adolescente , Adulto Joven , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación
2.
J Colloid Interface Sci ; 678(Pt A): 827-841, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39217698

RESUMEN

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide-alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 µg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

3.
Front Med (Lausanne) ; 11: 1322870, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39175814

RESUMEN

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

4.
Sci China Life Sci ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096338

RESUMEN

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity. METTL3 enhances RNA translation independently of its catalytic activity. However, the underlying mechanism is still elusive. Here, we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3. Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177. Importantly, acetylation of METTL3 blocks its interaction with EIF3H, a subunit of the translation initiation factor, thereby reducing mRNA translation efficiency. Interestingly, acetylation of METTL3 responds to oxidative stress. Mechanistically, oxidative stress enhances the interaction of PCAF with METTL3, increases METTL3 acetylation, and suppresses the interaction of METTL3 with EIF3H, thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation. Altogether, we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

5.
Nat Commun ; 15(1): 6737, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112475

RESUMEN

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.


Asunto(s)
Lesión Pulmonar Aguda , Movimiento Celular , Interleucina-17 , Pulmón , Ratones Endogámicos C57BL , Sepsis , Animales , Sepsis/inmunología , Sepsis/complicaciones , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Ratones , Interleucina-17/metabolismo , Interleucina-17/inmunología , Pulmón/inmunología , Pulmón/patología , Masculino , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Vía de Señalización Wnt/inmunología , Macrófagos Alveolares/inmunología , Intestino Delgado/inmunología , Intestino Delgado/patología , Linfocitos Intraepiteliales/inmunología , Modelos Animales de Enfermedad , Antígenos Ly/metabolismo , Memoria Inmunológica
6.
Oncol Lett ; 28(4): 497, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39211303

RESUMEN

Colon adenocarcinoma (COAD) is a malignant tumor type. Fever is the most common postoperative complication of COAD. The present study described the treatment of a patient with early-stage COAD with precancerous colon polyps and the possible cause of postoperative fever. The patient was a 48-year-old woman with intermittent hematochezia, defecation urgency and liquid feces. The patient received surgical treatment, a whole segment from the intestine was removed, which contained a 4-cm-long mass and a 2-cm-long firm mass. Within 3 days after the operation, the patient's incision healed well, but the body temperature increased to a range of 37.8-38.6°C. The suture was removed on the 10th postoperative day. After another three days, it was discovered that the upper end of the patient's surgical incision split to the anterior rectus abdominis sheath. The patient was provided with recombinant human acidic fibroblast growth factor to promote wound healing. The patient was finally diagnosed with rectosigmoid junction adenocarcinoma and precancerous colon polyps according to pathological examination results. The patient was given intravenous bevacizumab combined with irinotecan hydrochloride and oral capecitabine, and all drugs were repeatedly applied every 3 weeks, and a total of four treatment cycles were used. The cause of this postoperative fever was concluded to be anemia coming from chronic hematochezia and combined with deep wound dehiscence with secondary infection. The present study showcased that low-dose and short-course prophylactic adjuvant therapy is feasible for early-stage COAD with precancerous colon polyps.

7.
Life Sci ; 356: 123021, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39209249

RESUMEN

Chronic caloric restriction triggers unfavorable alterations in cardiac function albeit responsible scenarios remain unclear. This work evaluated the possible involvement of Akt2 in caloric restriction-evoked cardiac geometric and functional changes and responsible processes focusing on autophagy and mitophagy. Akt2 knockout and WT mice were subjected to caloric restriction for 30 weeks prior to assessment of myocardial homeostasis. Caloric restriction compromised echocardiographic parameters (decreased LV wall thickness, LVEDD, stroke volume, cardiac output, ejection fraction, fractional shortening, and LV mass), cardiomyocyte contractile and intracellular Ca2+ capacity, myocardial atrophy, interstitial fibrosis and mitochondrial injury associated with elevated blood glucocorticoids, autophagy (LC3B, p62, Atg7, Beclin-1), and mitophagy (Pink1, Parkin, TOM20), dampened cardiac ATP levels, mitochondrial protein PGC1α and UCP2, anti-apoptotic protein Bcl2, intracellular Ca2+ governing components Na+-Ca2+ exchanger, phosphorylation of SERCA2a, mTOR (Ser2481) and ULK1 (Ser757), and upregulated Bax, phospholamban, phosphorylation of Akt2, AMPK, and ULK1 (Ser555), the responses except autophagy markers (Beclin-1, Atg7), phosphorylation of AMPK, mTOR and ULK1 were negated by Akt2 ablation. Levels of CDK1 and DRP1 phosphorylation were overtly upregulated with caloric restriction, the response was reversed by Akt2 knockout. Caloric restriction-evoked changes in cardiac remodeling and cardiomyocyte function were alleviated by glucocorticoid receptor antagonism, Parkin ablation and Mdivi-1. In vitro experiment indicated that serum deprivation or glucocorticoids evoked GFP-LC3B accumulation and cardiomyocyte dysfunction, which was negated by inhibition of Akt2, CDK1 or DRP1, whereas mitophagy induction reversed Akt2 ablation-evoked cardioprotection. These observations favor a protective role of Akt2 ablation in sustained caloric restriction-evoked cardiac pathological changes via correction of glucocorticoid-induced mitophagy defect in a CDK1-DRP1-dependent manner.


Asunto(s)
Proteína Quinasa CDC2 , Restricción Calórica , Mitofagia , Miocitos Cardíacos , Proteínas Proto-Oncogénicas c-akt , Animales , Masculino , Ratones , Autofagia/fisiología , Proteína Quinasa CDC2/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Remodelación Ventricular/fisiología
8.
EMBO Mol Med ; 16(8): 1817-1839, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39009885

RESUMEN

Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.


Asunto(s)
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Canales Catiónicos TRPC , Infección por el Virus Zika , Virus Zika , Infección por el Virus Zika/virología , Infección por el Virus Zika/metabolismo , Animales , Humanos , Virus Zika/fisiología , Virus Zika/efectos de los fármacos , Ratones , Canales Catiónicos TRPC/metabolismo , Canales Catiónicos TRPC/antagonistas & inhibidores , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Células HEK293 , Proteínas Virales/metabolismo , Convulsiones/virología , Convulsiones/metabolismo , Convulsiones/tratamiento farmacológico , Proteasas Virales , Serina Endopeptidasas , Nucleósido-Trifosfatasa , ARN Helicasas DEAD-box
9.
Artículo en Inglés | MEDLINE | ID: mdl-39002660

RESUMEN

OBJECTIVE: We aimed to assess the performance of common pneumonia severity scores, such as pneumonia severity index (PSI), CURB-65, CRB-65, A-DROP, and SMART-COP, in predicting adverse outcomes in elderly community-acquired pneumonia cohort and to determine the optimal scoring system for specific outcomes of interest. METHODS: A total of 822 elderly inpatients were included in the retrospective cohort study. Clinical and laboratory results on admission were used to calculate the above scores. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, need for mechanical ventilation (MV) and ICU admission. Model discrimination was evaluated by the area under receiver operating characteristic curves (AUCs). RESULTS: The 30-day and in-hospital mortality rates were 6.8% (56/822) and 8.6% (71/822), respectively. One hundred and ninety-eight (24.0%) received MV and 111 (13.5%) were admitted to the ICU. All five scoring systems showed the same trend of increasing rates of each adverse outcome with increasing risk groups (all p < 0.001). PSI had the highest AUC, sensitivity, and negative predictive value (NPV) in predicting 30-day mortality and in-hospital mortality. SMART-COP had the highest AUC for predicting the need for MV and ICU admission, but PSI had the highest sensitivity and NPV for these two outcomes. DISCUSSION: PSI performed well in identifying elderly patients at risk for 30-day mortality and its high NPV is helpful in excluding patients who are not at risk. Considering their effectiveness and simplicity, SMART-COP and CURB-65 are easier to perform in clinical practice than PSI.

10.
PLoS One ; 19(7): e0305479, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39024286

RESUMEN

Based on a quantitative analysis of a novel dataset comprising 10,093 publicly available judgments of adjudicated child custody disputes from the China Judgments Online website, this article identifies potential gender bias in Chinese family courts under certain conditions. Key findings include: 1. Mothers are generally more proactive in seeking custody and are awarded custody in the majority of cases compared to fathers. 2. Specifically, mothers have a significant advantage in cases involving daughters, while their advantage in cases involving sons is less pronounced. 3. In rural courts, the results are notably different: mothers are disadvantaged overall, fathers are particularly assertive in seeking custody of sons compared to daughters, and mothers are less likely than fathers to be awarded custody of sons. Building on existing literature, this study highlights potential judicial biases rooted in societal gender norms prevalent in rural areas. This raises questions about whether courts have achieved substantive gender equality and whether the legal principle of 'the best interests of the child' is consistently upheld in every court decision. This study enhances the understanding of gender bias within China's family court system by providing valuable insights for those interested in addressing gender inequality. It not only highlights specific challenges women face in custody cases but also calls for broader societal and policy changes to support women and combat gender discrimination in all its forms.


Asunto(s)
Custodia del Niño , Sexismo , Humanos , Femenino , Masculino , China , Custodia del Niño/legislación & jurisprudencia , Niño , Sexismo/legislación & jurisprudencia , Juicio , Población Rural , Adulto , Madres , Padre , Pueblos del Este de Asia
11.
Eur J Med Chem ; 275: 116637, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959728

RESUMEN

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 µg/mL to 0.5 µg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 µg/mL to 16.0 µg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans, compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity.


Asunto(s)
Antifúngicos , Candida , Pruebas de Sensibilidad Microbiana , Pirazoles , Triazoles , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Relación Estructura-Actividad , Candida/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Cryptococcus neoformans/efectos de los fármacos , Humanos , Farmacorresistencia Fúngica/efectos de los fármacos , Saccharomyces cerevisiae/efectos de los fármacos , Candida albicans/efectos de los fármacos
12.
Biomater Sci ; 12(17): 4452-4470, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39052032

RESUMEN

The aim of this study was to develop a semi-interpenetrating network (IPN) hydrogel system suitable for the oral environment, capable of controlled release of DNase-I and oridonin (ORI), to exert antimicrobial, anti-inflammatory, and reparative effects on chemoradiotherapy-induced oral mucositis (OM). This IPN was based on the combination of ε-polylysine (PLL) and hetastarch (HES), loaded with DNase-I and ORI (ORI/DNase-I/IPN) for OM treatment. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, and bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner, exerting inhibitory effects on bacteria and degrading NETs in wound tissues. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on OM in rats by significantly accelerating the healing process. These findings provide new insights into possible therapies for OM.


Asunto(s)
Quimioradioterapia , Desoxirribonucleasa I , Diterpenos de Tipo Kaurano , Hidrogeles , Ratas Sprague-Dawley , Estomatitis , Cicatrización de Heridas , Animales , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/administración & dosificación , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Humanos , Desoxirribonucleasa I/farmacología , Desoxirribonucleasa I/administración & dosificación , Ratas , Estomatitis/tratamiento farmacológico , Estomatitis/inducido químicamente , Estomatitis/terapia , Masculino , Polilisina/química , Polilisina/farmacología , Proliferación Celular/efectos de los fármacos
13.
Sci Adv ; 10(27): eadk8958, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959315

RESUMEN

The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs.


Asunto(s)
Células Epiteliales , Receptores Notch , Transducción de Señal , Animales , Células Epiteliales/metabolismo , Femenino , Receptores Notch/metabolismo , Humanos , Ratones , Linaje de la Célula , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/citología , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Diferenciación Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genética
14.
Infect Drug Resist ; 17: 3081-3088, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050829

RESUMEN

Anaerobic bacterial meningitis is a serious infection of the central nervous system (CNS) that leads to severe neurological complications, resulting in high levels of disability and mortality worldwide. However, accurately diagnosing and isolating the responsible pathogens remains challenging due to the difficulty in culturing anaerobic bacteria, as they require harsh anaerobic culture conditions. Anaerobic bacteria have rarely been reported in meningitis, especially in children. This report details the first infant with anaerobic meningitis caused by Prevotella bivia. Additionally, we present a case of infant anaerobic meningitis caused by P. bivia, detected using metagenomics next-generation sequencing (mNGS). Our clinical experience highlights the importance of early identification of Prevotella spp. through mNGS and anaerobic culture, the effectiveness of antimicrobial medications, and the timely implementation of carefully planned precision therapeutic regimens. Furthermore, we have conducted a comprehensive review of 10 cases of Prevotella spp. infection, summarized their clinical and laboratory examination characteristics, and identified their commonalities.

15.
Biomater Res ; 28: 0033, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040621

RESUMEN

Bacterial keratitis is a serious ocular infection that can impair vision or even cause blindness. The clinical use of antibiotics is limited due to their low bioavailability and drug resistance. Hence, there is a need to develop a novel drug delivery system for this infectious disease. In this study, erythromycin (EM) was encapsulated into a bifunctional polyhedral oligomeric silsesquioxane (BPOSS) with the backbone of the poly-PEG/PPG urethane (BPEP) hydrogel with the aim of improving the drug efficiency in treating bacterial keratitis. A comprehensive characterization of the BPEP hydrogel was performed, and its biocompatibility was assessed. Furthermore, we carried out the evaluation of the antimicrobial effect of the BPEP-EM hydrogel in S. aureus keratitis using in vivo mouse model. The BPEP hydrogel exhibited self-assembling and thermogelling properties, which assisted the drug loading of drug EM and improved its water solubility. Furthermore, the BPEP hydrogel could effectively bind with mucin on the ocular surface, thereby markedly prolonging the ocular residence time of EM. In vivo testing confirmed that the BPEP-EM hydrogel exerted a potent therapeutic action in the mouse model of bacterial keratitis. In addition, the hydrogel also exhibited an excellent biocompatibility. Our findings demonstrate that the BPEP-EM hydrogel showed a superior therapeutic effect in bacterial keratitis and demonstrated its potential as an ophthalmic formulation.

16.
Brain Res ; 1842: 149101, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38945470

RESUMEN

Prolonged confinement in cramped spaces can lead to derangements in brain function/structure, yet the underlying mechanisms remain unclear. To investigate, we subjected mice to restraint stress to simulate long-term narrow and enclosed space confinement, assessing their mental state through behavioral tests. Stressed mice showed reduced center travel and dwell time in the Open Field Test and increased immobility in the Tail Suspension Test. We measured lower hippocampal brain-derived neurotrophic factor levels and cortical monoamine neurotransmitters (5-HT and NE) in the stressed group. Further examination of the body's immune levels and serum metabolism revealed immune dysregulation and metabolic imbalance in the stressed group. The results of the metabolic network regulation analysis indicate that the targets affected by these differential metabolites are involved in several metabolic pathways that the metabolites themselves participate in, such as the "long-term depression" and "purine metabolism" pathways. Additionally, these targets are also associated with numerous immune-related pathways, such as the TNF, NF-κB, and IL-17 signaling pathways, and these findings were validated using GEO dataset analysis. Molecular docking results suggest that differential metabolites may regulate specific immune factors such as TNF-α, IL-1ß, and IL-6, and these results were confirmed in experiments. Our research findings suggest that long-term exposure to confined and narrow spaces can lead to the development of psychopathologies, possibly mediated by immune system dysregulation and metabolic disruption.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Estrés Psicológico , Animales , Ratones , Masculino , Estrés Psicológico/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Enfermedades del Sistema Inmune/metabolismo , Ratones Endogámicos C57BL , Serotonina/metabolismo , Simulación del Acoplamiento Molecular , Trastornos Mentales/metabolismo , Norepinefrina/metabolismo
17.
J Hazard Mater ; 476: 134970, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38905977

RESUMEN

As a crucial sink of metal-containing nanoparticles (MNPs), road dust can record their spatiotemporal variations in urban environments. In this study, taking Shanghai as a representative megacity in China, a total of 272 dust samples were collected in the winter and summer of 2013 and 2021/2022 to understand the spatiotemporal variations and driving factors of MNPs. The number concentrations of Fe-, Ti-, and Zn-containing NPs were 3.8 × 106 - 8.4 × 108, 2.3 × 106-1.4 × 108, and 6.0 × 105-2.3 × 108 particles/mg, respectively, according to single particle (sp)ICP-MS analysis. These MNPs showed significantly higher number concentrations in summer than in winter. Hotspots of Fe-containing NPs were more concentrated in industrial and traffic areas, Zn-containing NPs were mainly distributed in the central urban areas, while Ti-containing NPs were abundant in areas receiving high rainfall. The structural equation model results indicates that substantial rainfall in summer can help remove MNPs from atmospheric PM2.5 into dust, while in winter industrial and traffic activities were the primary contributors for MNPs. Moreover, the contribution of traffic emissions to MNPs has surpassed industrial one over the last decade, highlighting the urgency to control traffic-sourced MNPs, especially those from non-exhaust emissions by electric vehicles.

18.
Int J Antimicrob Agents ; 64(2): 107237, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38851461

RESUMEN

The co-production of KPC and NDM carbapenemases in carbapenem-resistant Klebsiella pneumoniae (CRKP) complicates clinical treatment and increases mortality rates. The emergence of KPC-NDM CRKP is believed to result from the acquisition of an NDM plasmid by KPC CRKP, especially under the selective pressure of ceftazidime-avibactam (CZA). In this study, a CRKP-producing KPC-2 (JNP990) was isolated from a patient at a tertiary hospital in Shandong Province, China. Following sulfamethoxazole-trimethoprim (SXT) treatment, the isolate evolved into a strain that co-produces KPC and NDM (JNP989), accompanied by resistance to SXT (minimum inhibitory concentration >2/38 µg/mL) and CZA (dd ≤14 mm). Whole-genome sequencing and S1 nuclease pulsed-field gel electrophoresis revealed that JNP989 acquired an IncC plasmid (NDM plasmid) spanning 197 kb carrying sul1 and blaNDM-1 genes. The NDM plasmid could be transferred successfully into Escherichia coli J53 at a conjugation frequency of (8.70±2.47) × 10-4. The IncFⅡ/IncR plasmid carrying the blaKPC-2 gene in JNP990 could only be transferred in the presence of the NDM plasmid at a conjugation frequency of (1.93±0.41) × 10-5. Five CRKP strains with the same resistance pattern as JNP989, belonging to the same clone as JNP989, with sequence type 11 were isolated from other patients in the same hospital. Two strains lost resistance to CZA due to the loss of the blaNDM-1-carrying fragment mediated by insertion sequence 26. Plasmid stability testing indicated that the IncC plasmid was more stable than the blaNDM-1 genes in the hosts. This study describes the evolution of KPC-NDM CRKP and its spread in hospitalized patients following antibiotic treatment, highlighting the severity of the spread of resistance.


Asunto(s)
Antibacterianos , Brotes de Enfermedades , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Plásmidos , Combinación Trimetoprim y Sulfametoxazol , beta-Lactamasas , Humanos , beta-Lactamasas/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Plásmidos/genética , China/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Secuenciación Completa del Genoma , Combinación de Medicamentos , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Proteínas Bacterianas/genética , Centros de Atención Terciaria
19.
Ecotoxicol Environ Saf ; 281: 116600, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38896901

RESUMEN

Arsenic pollution control technology in water was important to ensure environmental health and quality safety of agricultural products. Therefore, the adsorption performance of three adsorbents for chitosan, sepiolite, and Zeolitic Imidazolate Framework-8 (ZIF-8) were investigated in arsenate contaminated water. The results revealed that the adsorption capacity of ZIF-8 was higher than that of chitosan and sepiolite. The analysis of adsorption isotherm models showed that the behavior of ZIF-8 was more consistent with the Langmuir model. Furthermore, the adsorption mechanisms of three adsorbents for arsenate were investigated by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The analysis of FTIR showed that ZIF-8 maintained the stability of the interaction with arsenate by forming As-O chemical bonds. However, the effect of chitosan and sepiolite with arsenate was mainly physical adsorption. The analysis of XPS showed that the absorption of ZIF-8 with arsenate involved metal sites and nitrogen through the characteristic peak and the change of the binding energy. Furthermore, the impact of microplastics as a widespread coexistence pollutant in the water on adsorbent performance was investigated. The results indicated that the adsorption capacity of ZIF-8 was almost not affected by microplastics. The maximum adsorption amount of arsenate was changed from 73.45 mg/g to 81.89 mg/g. However, the maximum adsorption amount of chitosan and sepiolite decreased by 31.4 % and 11.6 %, respectively. The analysis of FTIR and XPS revealed that ZIF-8 enhances arsenate adsorption by forming N-O-As bonds in the presence of microplastics. This study provides scientific evidence for the management of arsenate pollution in water bodies, especially in complex water bodies containing microplastics.


Asunto(s)
Arseniatos , Quitosano , Microplásticos , Contaminantes Químicos del Agua , Adsorción , Arseniatos/química , Contaminantes Químicos del Agua/química , Quitosano/química , Espectroscopía Infrarroja por Transformada de Fourier , Microplásticos/química , Silicatos de Magnesio/química , Espectroscopía de Fotoelectrones , Zeolitas/química , Purificación del Agua/métodos
20.
Epilepsy Behav Rep ; 27: 100676, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38826153

RESUMEN

Although several previous studies have used resting-state functional magnetic resonance imaging and diffusion tensor imaging to report topological changes in the brain in epilepsy, it remains unclear whether the individual structural covariance network (SCN) changes in epilepsy, especially in pediatric epilepsy with visual cortex resection but with normal functions. Herein, individual SCNs were mapped and analyzed for seven pediatric patients with epilepsy after surgery and 15 age-matched healthy controls. A whole-brain individual SCN was constructed based on an automated anatomical labeling template, and global and nodal network metrics were calculated for statistical analyses. Small-world properties were exhibited by pediatric patients after brain surgery and by healthy controls. After brain surgery, pediatric patients with epilepsy exhibited a higher shortest path length, lower global efficiency, and higher nodal efficiency in the cuneus than those in healthy controls. These results revealed that pediatric epilepsy after brain surgery, even with normal functions, showed altered topological organization of the individual SCNs, which revealed residual network topological abnormalities and may provide initial evidence for the underlying functional impairments in the brain of pediatric patients with epilepsy after surgery that can occur in the future.

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