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1.
Artigo em Inglês | MEDLINE | ID: mdl-39102131

RESUMO

Under the background of cap-and-trade mechanisms, this article constructs a game model of the electricity supply chain, which is dominated by electricity generators and followed by electricity sellers, taking into account the situation of electricity generators investing in renewable energy and energy storage under the grandfathering mechanism (GM) and benchmarking mechanism (BM). By comparing the equilibrium solutions in different cases, the research finds that (1) compared with the grandfathering mechanism, the benchmarking mechanism has more investment in renewable energy and higher energy storage quality; (2) in the consumer market, compared with GM, the electricity price and the electricity demand are higher under BM; (3) an increase in the renewable energy preference coefficient or carbon price will lead to an increase in the electricity wholesale price, renewable energy investment, energy storage quality, electricity price, and electricity demand. Further, an increase in the energy storage cost coefficient or renewable energy investment cost coefficient will result in lower electricity wholesale price, renewable energy investment, energy storage quality, electricity price, and electricity demand; and (4) the profit of the generator under GM is higher than that under BM when the total carbon quota is larger, while the profit of the generator under BM is higher than that under GM when the unit carbon quota is larger.

2.
Sci Rep ; 14(1): 18278, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39107424

RESUMO

To decipher the molecular bases governing seed germination, this study presents the pivotal role of the cap-binding complex (CBC), comprising CBP20 and CBP80, in modulating the inhibitory effects of abscisic acid (ABA) in barley. Using both single and double barley mutants in genes encoding the CBC, we revealed that the double mutant hvcbp20.ab/hvcbp80.b displays ABA insensitivity, in stark contrast to the hypersensitivity observed in single mutants during germination. Our comprehensive transcriptome and metabolome analysis not only identified significant alterations in gene expression and splicing patterns but also underscored the regulatory nexus among CBC, ABA, and brassinosteroid (BR) signaling pathways.


Assuntos
Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Germinação , Hordeum , Proteínas de Plantas , Hordeum/genética , Hordeum/metabolismo , Hordeum/crescimento & desenvolvimento , Germinação/genética , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Splicing de RNA , Mutação , Transdução de Sinais , Transcriptoma , Perfilação da Expressão Gênica , Proteínas de Ligação ao Cap de RNA/metabolismo , Proteínas de Ligação ao Cap de RNA/genética , Sementes/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo
3.
Cureus ; 16(7): e63976, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39109109

RESUMO

This systematic review aimed to consolidate findings on the etiology of community-acquired pneumonia (CAP) among Indian adults. We adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines 2020 and conducted a comprehensive search across databases including PubMed, Scopus-Elsevier, and hand-searched reference lists using key terms such as "Community-Acquired Pneumonia," "CAP," "Indian," and "adults." Articles published between January 2010 and January 2024 were included, with exclusions for studies involving pediatric populations, non-Indian patients, or those published before 2010. From an initial pool of 344 articles, duplicates were removed and titles and abstracts were screened, resulting in nine studies meeting the inclusion criteria. The analysis of pooled data comprising 1,643 Indian adult participants revealed the following pathogen distribution: Streptococcus pneumoniae was the most common organism, accounting for 33% of the cases. This was followed by Klebsiella pneumoniae at 23%, Staphylococcus aureus at 10%, Mycoplasma pneumoniae and Legionella pneumophila each at 7%, and Chlamydia pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa each at 4%. Notably, the review highlights a rising incidence of K. pneumoniae in CAP cases, which is a significant concern and should be considered when treating CAP patients in India. The findings emphasize the importance of comprehensive diagnostic testing, including advanced methods such as bronchoalveolar lavage, urinary antigen tests, serology for atypical pathogens, and enzyme-linked immunosorbent assays, to improve diagnostic yield and guide targeted antibiotic therapy. This review underscores the need for updated empirical treatment guidelines that account for dominant pathogens. Future research should focus on employing advanced diagnostic methods to enhance understanding of CAP etiology.

4.
Front Public Health ; 12: 1412671, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091520

RESUMO

Introduction: Community-acquired pneumonia (CAP) is a major health concern in the United States (US), with its incidence, severity, and outcomes influenced by social determinants of health, including socioeconomic status. The impact of neighborhood socioeconomic status, as measured by the Distressed Communities Index (DCI), on CAP-related admissions remains understudied in the literature. Objective: To determine the independent association between DCI and CAP-related admissions in Maryland. Methods: We conducted a retrospective study using the Maryland State Inpatient Database (SID) to collate data on CAP-related admissions from January 2018 to December 2020. The study included adults aged 18-85 years. We explored the independent association between community-level economic deprivation based on DCI quintiles and CAP-related admissions, adjusting for significant covariates. Results: In the study period, 61,467 cases of CAP-related admissions were identified. The patients were predominantly White (49.7%) and female (52.4%), with 48.6% being over 65 years old. A substantive association was found between the DCI and CAP-related admissions. Compared to prosperous neighborhoods, patients living in economically deprived communities had 43% increased odds of CAP-related admissions. Conclusion: Residents of the poorest neighborhoods in Maryland have the highest risk of CAP-related admissions, emphasizing the need to develop effective public health strategies beneficial to the at-risk patient population.


Assuntos
Infecções Comunitárias Adquiridas , Hospitalização , Pneumonia , Humanos , Maryland/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/economia , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Adulto , Pneumonia/epidemiologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adolescente , Hospitalização/estatística & dados numéricos , Hospitalização/economia , Adulto Jovem , Características da Vizinhança/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos
5.
Dev Biol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094818

RESUMO

CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. It catalyzes 2'-O-ribose methylation of the second transcribed nucleotide of mRNAs, potentially serving to mark RNAs as "self" to evade the cellular innate immune response. Here we analyze the consequences of Cmtr2 deficiency in mice. We discover that constitutive deletion of Cmtr2 results in mouse embryos that die during mid-gestation, exhibiting defects in embryo size, placental malformation and yolk sac vascularization. Endothelial cell deletion of Cmtr2 in mice results in vascular and hematopoietic defects, and perinatal lethality. Detailed characterization of the constitutive Cmtr2 KO phenotype shows an activation of the p53 pathway and decreased proliferation, but no evidence of interferon pathway activation. In summary, our study reveals the essential roles of Cmtr2 in mammalian cells beyond its immunoregulatory function.

6.
Environ Sci Technol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105719

RESUMO

Under climatic warming, glaciers are becoming a secondary source of atmospheric contaminants originally released into the environment decades ago. This phenomenon has been well-documented for glaciers near emission sources. However, less is known about polar ice sheets and ice caps. Radionuclides are one of the contaminants that can be remobilised through ice melting and accumulate in cryoconite material on the surface of glaciers. To understand the cycling of radionuclides in polar glacial contexts, we evaluate the radioactivity of cryoconite samples from Flade Isblink, a High Arctic ice cap in northeast Greenland. The measured radioactivity is among the highest reported across the High Arctic and the highest from Greenland. The high variability observed among the samples is explained by considering the different macroscopic features of single cryoconite deposits. The radioactivity source is compatible with the stratospheric reservoir established during atmospheric nuclear tests and with weapons-grade fissile fuel, likely originating from Novaya Zemlya proving grounds. This study shows that the ability of cryoconite to accumulate radioactivity in remote areas is undisputed, highlighting the need for a deeper understanding of the remobilisation of radioactive species in polar glacial contexts.

7.
Stem Cell Rev Rep ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951308

RESUMO

Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc. Previous biochemical investigations and loss-of-function studies in mice have provided insights into the mechanism of STAMBP, however, it remains controversial how STAMBP deficiency leads to malformation of those affected tissues in patients. In this study, we investigated the function and underlying mechanism of STAMBP during neural differentiation of human embryonic stem cells (hESCs). We found that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STAMBP-deficiency. Our study not only provides novel insight into the mechanism of neural defects in STAMBP mutant patients, it also indicates that the death receptor mediated apoptosis is an obstacle for long-term maintenance/expansion of NPCs in vitro thus counteracting this cell death pathway could be beneficial to the generation of NPCs in vitro.

8.
Cureus ; 16(6): e63243, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070455

RESUMO

Displacement of dental implants into the maxillary sinus is one of the common dental complications. However, it is rare that dental implants cause the displacement of multiple components due to separation. Here, we describe an unusual case of a 43-year-old man who had a missing implant in the maxillary sinus after an implant procedure. There was a two-week waiting period before we performed the removal during which the cap had unexpectedly separated from the body and freely moved into the ostium by sinus activity. The body was independently extracted intraorally. The remaining cap was secondly removed by utilizing nasal endoscopy. There were no complications in the postoperative period and the patient reported no symptoms of sinusitis after two months of follow-up. We experience unexpected events in the course of treating a displaced implant into the maxillary sinus. Our case report may provide several learning points for the removal of a missing implant.

9.
Pharmaceutics ; 16(7)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39065630

RESUMO

The microbial contamination of eye drop tips and caps varies between 7.7% and 100%. In seeking patient protection and continuous improvement, the Pharmacy Department in the Sterile Ophthalmological and Oncological Preparations Unit at Cochin Hospital AP-HP, Paris, France, conducted a two-phase study to compare the antimicrobial efficiency and practical use of standard packaging and a marketed eye drop container incorporating a self-decontaminating antimicrobial green technology by Pylote SAS at the tip and cap sites. The first phase was conducted in situ to identify the microbial contaminants of eye drops used in the hospital and community settings. A total of 110 eye drops were included for testing. Staphylococcus species were the most prevalent bacteria. Candida parapsilosis was detected in only one residual content sample and, at the same time, on the cap and tip. The second phase was performed in vitro, according to JIS Z2801. Reductions above one log in Staphylococcus aureus and Pseudomonas aeruginosa counts were noted in Pylote SAS eye drop packaging after 24 h of contact. The practical tests showed satisfactory results. Pylote SAS antimicrobial mineral oxide technology exhibited promising effects that combined effectiveness, safety, and sustainability to protect the patient by preventing infections due to the contamination of eye drop containers.

10.
Biomedicines ; 12(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39062173

RESUMO

BACKGROUND: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. METHODS: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. RESULTS: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): -45-15 min (n = 136; 17.5%, 175.9 ± 271.0); -15-0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). CONCLUSION: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.

11.
Antiviral Res ; : 105961, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002800

RESUMO

Baloxavir acid (BXA) is a pan-influenza antiviral that targets the cap-dependent endonuclease of the polymerase acidic (PA) protein required for viral mRNA synthesis. To gain a comprehensive understanding on the molecular changes associated with reduced susceptibility to BXA and their fitness profile, we performed a deep mutational scanning at the PA endonuclease domain of an A(H1N1)pdm09 virus. The recombinant virus libraries were serially passaged in vitro under increasing concentrations of BXA followed by next-generation sequencing to monitor PA amino acid substitutions with increased detection frequencies. Enriched PA amino acid changes were each introduced into a recombinant A(H1N1)pdm09 virus to validate their effect on BXA susceptibility and viral replication fitness in vitro. The I38T/M substitutions known to confer reduced susceptibility to BXA were invariably detected from recombinant virus libraries within 5 serial passages. In addition, we identified a novel L106R substitution that emerged in the third passage and conferred greater than 10-fold reduced susceptibility to BXA. PA-L106 is highly conserved among seasonal influenza A and B viruses. Compared to the wild-type virus, the L106R substitution resulted in reduced polymerase activity and a minor reduction of the peak viral load, suggesting the amino acid change may result in moderate fitness loss. Our results support the use of deep mutational scanning as a practical tool to elucidate genotype-phenotype relationships, including mapping amino acid substitutions with reduced susceptibility to antivirals.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39042016

RESUMO

The pulmonary epithelial glycocalyx is rich in glycosaminoglycans such as hyaluronan and heparan sulfate. Despite their presence, the importance of these glycosaminoglycans in bacterial lung infections remains elusive. To address this, we intranasally inoculated mice with Streptococcus pneumoniae in the presence or absence of enzymes targeting pulmonary hyaluronan and heparan sulfate, followed by characterization of subsequent disease pathology, pulmonary inflammation, and lung barrier dysfunction. Enzymatic degradation of hyaluronan and heparan sulfate exacerbated pneumonia in mice, as evidenced by increased disease scores and alveolar neutrophil recruitment. However, targeting epithelial hyaluronan in combination with Streptococcus pneumoniae infection further exacerbated systemic disease, indicated by elevated splenic bacterial load and plasma levels of pro-inflammatory cytokines. In contrast, enzymatic cleavage of heparan sulfate resulted in increased bronchoalveolar bacterial burden, lung damage and pulmonary inflammation in mice infected with Streptococcus pneumoniae. Accordingly, heparinase-treated mice also exhibited disrupted lung barrier integrity as evidenced by higher alveolar edema scores and vascular protein leakage into the airways. This finding was corroborated in a human alveolus-on-a-chip platform, confirming that heparinase treatment also disrupts the human lung barrier during Streptococcus pneumoniae infection. Notably, enzymatic pre-treatment with either hyaluronidase or heparinase also rendered human epithelial cells more sensitive to pneumococcal-induced barrier disruption, as determined by transepithelial electrical resistance measurements, consistent with our findings in murine pneumonia. Taken together, these findings demonstrate the importance of intact hyaluronan and heparan sulfate in limiting pneumococci-induced damage, pulmonary inflammation, and epithelial barrier function and integrity.

13.
BMC Gastroenterol ; 24(1): 226, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026172

RESUMO

OBJECTIVES: To determine how fetuin-A contributes to diagnosing and assessing MASLD severity. METHODS: Fifty MASLD patients and fifty healthy control participants were involved in this retrospective case-control research. Abdominal ultrasonography, fibroscan with controlled attenuated parameter scan (CAP scan), laboratory investigation (including fetuin-A assessment), clinical examination, and history-taking were performed on every case. RESULTS: Fetuin-A level was considerably higher in the Cases group (1154.85 ± 629.89) than in the Control group (505.29 ± 150.4) (p < 0.001). Fetuin-A had significant validity in the prediction of MASLD at a cut-off > 702.5 with 82% sensitivity, 90% specificity, and 86% overall accuracy. CONCLUSION: One possible marker for MASLD diagnosis could be fetuin-A. Furthermore, a substantial association between such marker and the severity of the disease as it revealed a significant correlation with ultrasound grading and fibroscan with controlled attenuated parameters. Trial registration 1- Pan African Clinical Trial Registry. Unique Identifying number/registration ID: PACTR202309644280965. URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=26860 . Registration Approval date: 21/09/2023. 2- ClinicalTrials.gov. Unique Identifying number /registration ID: NCT06097039. URL: https://clinicaltrials.gov/study/NCT06097039?cond=NCT06097039&rank=1 . Registration Approval date: 25/10/2023.


Assuntos
Biomarcadores , alfa-2-Glicoproteína-HS , Humanos , Estudos Retrospectivos , Feminino , Masculino , Biomarcadores/sangue , Estudos de Casos e Controles , alfa-2-Glicoproteína-HS/análise , alfa-2-Glicoproteína-HS/metabolismo , Pessoa de Meia-Idade , Adulto , Índice de Gravidade de Doença , Sensibilidade e Especificidade , Técnicas de Imagem por Elasticidade , Ultrassonografia , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/diagnóstico , Idoso
14.
Biochem Biophys Res Commun ; 727: 150326, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38968768

RESUMO

The Cyclic GMP-AMP synthase (cGAS) and cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes belong to the key components of the innate immune sensor system that generates cyclic dinucleotide molecules in response to danger signals. Recently, it was discovered that CD-NTase in bacteria can undergo conjugation to protein substrates via an E1/E2 enzyme-mediated process, resembling ubiquitin modification system. Subsequently, these CD-NTase conjugated molecules will be hydrolyzed by the Cap3 enzyme in the same gene cluster. However, the experimental structure of bacterial CD-NTase recognized by Cap3 is unknown. Here, we first determined the crystal structure of the Cap3 enzyme in complex with the C-terminal tail of CD-NTase. Our structural and enzymatic analysis revealed that the C-terminal tail of CD-NTase is both necessary and sufficient for the Cap3-mediated hydrolysis of CD-NTase from its substrates. Interestingly, we further observed that after the hydrolysis reaction, the terminal glycine residue of the CD-NTase C-terminal tail was sequentially removed by Cap3, indicating that Cap3 might play a role in quenching the CD-NTase conjugation reaction. Our work provides experimental evidence elucidating the interaction between Cap3 and CD-NTase, and suggests a potential role for Cap3 in the bacterial Cyclic-oligonucleotide-based anti-phage signaling system (CBASS).


Assuntos
Nucleotidiltransferases , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/química , Nucleotidiltransferases/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Cristalografia por Raios X , Modelos Moleculares , Conformação Proteica , Hidrólise
15.
Intern Emerg Med ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967887

RESUMO

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

16.
Rev Cardiovasc Med ; 25(5): 168, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39076483

RESUMO

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124741, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38972097

RESUMO

Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl4)-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-ß; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC-MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski's rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-ß and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biobased materials for the pharmaceutical and food industries.

18.
Adv Sci (Weinh) ; : e2404131, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958560

RESUMO

Increasing evidence suggests the role of reactive oxygen and nitrogen species (RONS) in regulating antitumor immune effects and immunosuppression. RONS modify biomolecules and induce oxidative post-translational modifications (oxPTM) on proteins that can alarm phagocytes. However, it is unclear if and how protein oxidation by technical means could be a strategy to foster antitumor immunity and therapy. To this end, cold gas plasma technology producing various RONS simultaneously to oxidize the two melanoma-associated antigens MART and PMEL is utilized. Cold plasma-oxidized MART (oxMART) and PMEL (oxPMEL) are heavily decorated with oxPTMs as determined by mass spectrometry. Immunization with oxidized MART or PMEL vaccines prior to challenge with viable melanoma cells correlated with significant changes in cytokine secretion and altered T-cell differentiation of tumor-infiltrated leukocytes (TILs). oxMART promoted the activity of cytotoxic central memory T-cells, while oxPMEL led to increased proliferation of cytotoxic effector T-cells. Similar T-cell results are observed after incubating splenocytes of tumor-bearing mice with B16F10 melanoma cells. This study, for the first time, provides evidence of the importance of oxidative modifications of two melanoma-associated antigens in eliciting anticancer immunity.

19.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000064

RESUMO

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.


Assuntos
Apoptose , Neoplasias Ósseas , Proliferação de Células , Sobrevivência Celular , Condrossarcoma , Doxorrubicina , Gases em Plasma , Condrossarcoma/tratamento farmacológico , Condrossarcoma/patologia , Humanos , Gases em Plasma/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Vincristina/farmacologia , Terapia Combinada
20.
Cureus ; 16(6): e62516, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39022511

RESUMO

BACKGROUND: Cochlear implantation (CI) is an appropriate management strategy for prelingual hearing loss. Rehabilitation programs are essential in enabling children to cope with devices and acquire language skills.  Objectives: This study aimed to assess the hearing outcomes of CIs performed by a single surgeon in Erbil, Kurdistan region of Iraq, and compare them with the results of other CI centers worldwide. METHODS: This is a prospective study implemented in Erbil from November 1, 2013, to October 30, 2023, on a convenience sample of 161 patients with prelingual hearing loss (HL) who underwent CI by a single surgeon. The following were collected: age at implantation, use of hearing aids before implantation, parent's educational level, and duration of rehabilitation. The effect of the previous variables on Categories of Auditory Performance (CAP) score and speech intelligibility rating (SIR) on the auditory levels of children was assessed by the researcher six months and one year following surgery. RESULTS: Implantation age showed significant associations with the CAP score examined at six months and 12 months post implantation (p-value 0.001). Speech intelligibility rating was also significantly linked to implantation age (p-value 0.001).

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