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1.
Indian J Orthop ; 58(8): 1126-1133, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39087039

RESUMEN

Purpose: Perception that extra-medullary fixation of these fractures are fraught with difficulties and deficiencies is becoming inappropriate. This device provides angular stable fixation retaining fracture biology with minimum interference to osseous and soft-tissue vascularity and it does not require reaming which destroys 80% of endosteal vasculature for 6-12 weeks. PFLCP averts iatrogenic fracture in lateral trochanteric wall (LTW) which is frequent with DHS, protects LTW from secondary fracture in post-operative period. Aim is to assess outcome of unstable proximal femur fracture fixation by PFLCP. Methods: Study included 64 from 2016 to 2020, divided in two groups. (A) Unstable intertrochanteric fracture and (B) subtrochanteric fracture (Seinsheimer types II-V). All fractures fixed by MIPO with PFLCP. Loss of reduction, infection, cut-out, cut-through, backing of screws, bending or breaking of plate and screw, malunion, non-union and revision were evaluated. Fracture healing and functional recovery assessed by Reborne Score and Parker Mobility Score (PMS) respectively. Results: Out of 64, 24 achieved pre-injury PMS, 32 declined by 1 point, 6 declined by 2 points and 1 by 3 points, one required revision. Using various parameters 37.5% patients had excellent results and 50% had good results, 9.38% had average and 3.12% had poor result. None reported non-union or breakage of plate. Conclusions: PFLCP provides angular stable fixation, torsional stability with high biomechanical strength to resist deforming stresses. MIPO avoids soft-tissue stripping reducing blood-loss, retains periosteal blood supply to inter-fragmentary bone fragments, enhancing fracture healing, reducing complications, such as delayed healing, nonunion, infection and implant failure.

2.
Toxicology ; 508: 153904, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39106909

RESUMEN

Ecosystems and human health are being negatively impacted by the growing problem of electrical waste, especially in developing countries. E-waste poses a significant risk to ecological systems because it can release a variety of hazardous substances into the environment, containing polybrominated diphenyl ethers and heavy metals, brominated flame retardants, polychlorinated dibenzofurans and polycyclic aromatic hydrocarbons, and dioxins. This review article provides a critical assessment of the toxicological consequences of e-waste on ecosystems and human health and data analyses from scientific journals and grey literature on metals, BFRs, PBDEs, PCDFs, and PAHs in several environmental compartments of commercial significance in informal electronic trash recycling. The currently available techniques and tools employed for treating e-waste are sustainable techniques such as bioremediation, chemical leaching, biological leaching, and pyrometallurgy have been also discussed along with the necessity of implementing strong legislation to address the issue of unregulated exports of electronic trash in recycling practices. Despite the ongoing hurdles, implementing environmentally sustainable recycling methods have the potential to address the detrimental impacts of e-waste and foster positive economic development.

3.
Cureus ; 16(7): e64363, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130830

RESUMEN

OBJECTIVE: The objective of this study is to investigate the occurrence and factors that influence the development of contrast-induced nephropathy (CIN) in high-risk patients undergoing angioplasty and to evaluate the effectiveness of the Mehran risk score in predicting CIN among this patient population. MATERIALS AND METHOD: This prospective, observational study enrolled patients undergoing elective coronary angiography or a percutaneous coronary intervention (PCI) procedure. The patients were stratified into four risk groups based on the Mehran risk score, a validated tool for predicting the risk of CIN. Univariate and multivariate analyses were conducted to evaluate the risk factors associated with the development of CIN. A p-value of <0.05 was considered to indicate statistical significance. RESULTS: During the study period, a total of 55 high-risk patients underwent PCI. The incidence of CIN was 25.5% (n=14). Univariate and multivariate analyses revealed that age >75 years and estimated glomerular filtration rate (eGFR) <60 (p<0.05) were independently associated with a significantly increased risk of developing CIN. A considerable proportion of patients (23; 41.8%) in the study were categorized as having an intermediate risk for CIN based on the Mehran risk score. CONCLUSION: This study observed a high incidence of CIN and encourages the use of predictive tools like the Mehran risk score to assess the risk of CIN occurrence, with age over 70 years and eGFR less than 60 emerging as significant.

4.
Ageing Res Rev ; : 102450, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39134179

RESUMEN

Diabetic encephalopathy (DE), a significant micro-complication of diabetes, manifests as neurochemical, structural, behavioral, and cognitive alterations. This condition is especially dangerous for the elderly because aging raises the risk of neurodegenerative disorders and cognitive impairment, both of which can be made worse by diabetes. Despite its severity, diagnosis of this disease is challenging, and there is a paucity of information on its pathogenesis. The pivotal roles of various cellular pathways, activated or influenced by hyperglycemia, insulin sensitivity, amyloid accumulation, tau hyperphosphorylation, brain vasculopathy, neuroinflammation, and oxidative stress, are widely recognized for contributing to the potential causes of diabetic encephalopathy. We also reviewed current pharmacological strategies for DE encompassing a comprehensive approach targeting metabolic dysregulations and neurological manifestations. Antioxidant-based therapies hold promise in mitigating oxidative stress-induced neuronal damage, while anti-diabetic drugs offer neuroprotective effects through diverse mechanisms, including modulation of insulin signaling pathways and neuroinflammation. Additionally, tissue engineering and nanomedicine-based approaches present innovative strategies for targeted drug delivery and regenerative therapies for DE. Despite significant progress, challenges remain in translating these therapeutic interventions into clinical practice, including long-term safety, scalability, and regulatory approval. Further research is warranted to optimize these approaches and address remaining gaps in the management of DE and associated neurodegenerative disorders.

5.
Egypt Heart J ; 76(1): 100, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120759

RESUMEN

BACKGROUND: Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology characterized by a large vessel vasculitis involving the aorta and its branches. Myocardial involvement is extremely unusual in TA and is mostly in the form of myocarditis, ventricular hypertrophy, and ventricular dysfunction secondary to coronary ischemia. Submitral aneurysms have been reported in TA and has been attributed to the chronic inflammatory process in TA. CASE PRESENTATION: We report a novel instance of left ventricular apical aneurysm in a 37-year-old lady with TA and normal epicardial coronaries. She was diagnosed with a left ventricular apical aneurysm, moderate aortic regurgitation, and moderate pericardial effusion. The coronary arteries were normal. The patient had concomitant chronic active Epstein-Barr virus infection complicating patient outcome. CONCLUSIONS: Left ventricular apical aneurysm with normal epicardial coronaries is a rare cause of heart failure in Takayasu arteritis. Concomitant chronic active Epstein-Barr virus infection can potentially accentuate the inflammatory process in Takayasu arteritis and complicate management and patient outcomes.

6.
Materials (Basel) ; 17(15)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39124512

RESUMEN

Pharmaceutical drugs, including antibiotics and hormonal agents, pose a significant threat to environmental and public health due to their persistent presence in aquatic environments. Colistin (KOL), fluoxetine (FLUO), amoxicillin (AMO), and 17-alpha-ethinylestradiol (EST) are pharmaceuticals (PhCs) that frequently exceed regulatory limits in water and wastewater. Current removal methods are mainly ineffective, necessitating the development of more efficient techniques. This study investigates the use of synthetic zeolite (NaP1_FA) and zeolite-carbon composites (NaP1_C), both derived from fly ash (FA), for the removal of KOL, FLUO, AMO, and EST from aquatic environments. Batch adsorption experiments assessed the effects of contact time, adsorbent dosage, initial concentration, and pH on the removal efficiency of the pharmaceuticals. The results demonstrated that NaP1_FA and NaP1_C exhibited high removal efficiencies for all tested pharmaceuticals, achieving over 90% removal within 2 min of contact time. The Behnajady-Modirshahla-Ghanbary (BMG) kinetic model best described the adsorption processes. The most effective sorption was observed with a sorbent dose of 1-2 g L-1. Regarding removal efficiency, the substances ranked in this order: EST was the highest, followed by AMO, KOL, and FLUO. Sorption efficiency was influenced by the initial pH of the solutions, with optimal performance observed at pH 2-2.5 for KOL and FLUO. The zeolite-carbon composite NaP1_C, due to its hydrophobic nature, showed superior sorption efficiency for hydrophobic pharmaceuticals like FLUO and EST. The spectral analysis reveals that the primary mechanism for immobilizing the tested PhCs on zeolite sorbents is mainly due to physical sorption. This study underscores the potential of utilizing inexpensive, fly ash-derived zeolites and zeolite-carbon composites to remove pharmaceuticals from water effectively. These findings contribute to developing advanced materials for decentralized wastewater treatment systems, directly addressing pollution sources in various facilities.

7.
J Environ Manage ; 367: 121979, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39088904

RESUMEN

Cadmium (Cd) is readily absorbed by tobacco and accumulates in the human body through smoke inhalation, posing threat to human health. While there have been many studies on the negative impact of cadmium in tobacco on human health, the specific adaptive mechanism of tobacco roots to cadmium stress is not well understood. In order to comprehensively investigate the effects of Cd stress on the root system of tobacco, the combination of transcriptomic, biochemical, and physiological methods was utilized. In this study, tobacco growth was significantly inhibited by 50 µM of Cd, which was mainly attributed to the destruction of root cellular structure. By comparing the transcriptome between CK and Cd treatment, there were 3232 up-regulated deferentially expressed genes (DEGs) and 3278 down-regulated DEGs. The obvious differential expression of genes related to the nitrogen metabolism, metal transporters and the transcription factors families. In order to mitigate the harmful effects of Cd, the root system enhances Cd accumulation in the cell wall, thereby reducing the Cd content in the cytoplasm. This result may be mediated by plant hormones and transcription factor (TF). Correlational statistical analysis revealed significant negative correlations between IAA and GA with cadmium accumulation, indicated by correlation coefficients of -0.91 and -0.93, respectively. Conversely, ABA exhibited a positive correlation with a coefficient of 0.96. In addition, it was anticipated that 3 WRKY TFs would lead to a reduction in Cd accumulation. Our research provides a theoretical basis for the systematic study of the specific physiological processes of plant roots under Cd stress.


Asunto(s)
Cadmio , Reguladores del Crecimiento de las Plantas , Factores de Transcripción , Transcriptoma , Cadmio/toxicidad , Cadmio/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcriptoma/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/metabolismo , Nicotiana/genética , Nicotiana/efectos de los fármacos , Estrés Fisiológico , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos
8.
RSC Adv ; 14(33): 23730-23743, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39091373

RESUMEN

The low cost and ecological compatibility of green technology makes it superior to chemical approaches in the generation of metal nanoparticles. The current study shows the use of cranberry fruit extract in the environmentally friendly green production of palladium nanoparticles. It is well known that the fruit extract from cranberries has a rich phytochemical composition that makes it a useful bio reducing agent for the formation of PdNPs. Several spectroscopic techniques, including ultraviolet-visible spectroscopy (UV-vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX), were used to characterize the palladium nanoparticles (PdNPs). The diffractogram of the XRD analysis shows significant reflections at 39.98° (111), 46.49° (200), and 67.95° (220), which indicate the face-centered cubic (FCC) structure of PdNPs and demonstrate the crystallinity of the produced nanoparticles from the green method. The SEM and TEM structural and morphological analyses reveal that the synthesized nanoparticles have a spherical shape with size ranging between 2 nm to 50 nm. In addition, the synthesized PdNPs demonstrated possible antibacterial activity on both Gram-positive and Gram-negative bacteria as well as a cytotoxic effect on the MCF-7 breast cancer cell line. The degradation of Indigo Carmine (IC) and Sunset Yellow (SY) dyes can be effectively catalyzed by biogenic PdNPs, according to the results.

9.
BMC Geriatr ; 24(1): 679, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138405

RESUMEN

INTRODUCTION: Quality of life (QoL) is a subjective measure reflecting individuals' evaluations based on their personal goals and values. While global research shows the role of neighborhood factors like ethnic diversity and socio-cultural dynamics on QoL, these are unexplored in the Nepali context. Therefore, this study examined the relationship between neighborhood environment and QoL among Nepali older adults in eastern Nepal. METHODS: This cross-sectional study involved 847 non-institutionalized older adults (aged ≥ 60 years) from two districts in eastern Nepal. QoL was evaluated using the 13-item brief Older People's Quality of Life questionnaire, where a mean score of < 3 indicated low/poor QoL. The neighborhood environment, conceptualized across three domains (demographic, socio-cultural, and built environment), included ethnic diversity, connections with family, friends, and neighbors, cultural ties, residential stability, and rurality. Their association with QoL was examined using multivariable logistic regression. RESULTS: Around 20% of older adults reported poor QoL. Higher ethnic diversity (adjusted Odds Ratio [aOR] = 0.12, 95% confidence interval [CI]: 0.04-0.36), moderate contact with family and relatives (aOR = 0.26, CI: 0.11-0.61), and high contact with neighbors (aOR = 0.09, CI: 0.03-0.21) were associated with lower odds of poor QoL. Conversely, high contact with friends (aOR = 2.29, CI: 1.30-4.04) and unstable residence (OR = 6.25, CI: 2.03-19.23) increased the odds of poor QoL. Additionally, among the covariates, chronic disease, tobacco use, unemployment, and lack of education were also significantly associated with poor QoL. CONCLUSION: Overall, the demographic environment, socio-cultural factors, and the built environment of the neighborhood influence QoL. Therefore, diversifying the neighborhood's ethnic composition, promoting social connections such as frequent contact with family, relatives, and neighbors, and ensuring residential stability can enhance the QoL of older adults.


Asunto(s)
Calidad de Vida , Humanos , Nepal/epidemiología , Nepal/etnología , Estudios Transversales , Masculino , Anciano , Femenino , Calidad de Vida/psicología , Persona de Mediana Edad , Características del Vecindario , Características de la Residencia , Anciano de 80 o más Años , Encuestas y Cuestionarios
10.
J Basic Microbiol ; : e2400035, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004868

RESUMEN

Nanomaterial synthesis is a growing study area because of its extensive range of uses. Nanoparticles' high surface-to-volume ratio and rapid interaction with various particles make them appealing for diverse applications. Traditional physical and chemical methods for creating metal nanoparticles are becoming outdated because they involve complex manufacturing processes, high energy consumption, and the formation of harmful by-products that pose major dangers to human health and the environment. Therefore, there is an increasing need to find alternative, cost-effective, dependable, biocompatible, and environmentally acceptable ways of producing nanoparticles. The process of synthesizing nanoparticles using microbes has become highly intriguing because of their ability to create nanoparticles of varying sizes, shapes, and compositions, each with unique physicochemical properties. Microbes are commonly used in nanoparticle production because they are easy to work with, can use low-cost materials, such as agricultural waste, are cheap to scale up, and can adsorb and reduce metal ions into nanoparticles through metabolic activities. Biogenic synthesis of nanoparticles provides a clean, nontoxic, ecologically friendly, and sustainable method using renewable ingredients for reducing metals and stabilizing nanoparticles. Nanomaterials produced by bacteria can serve as an effective pollution control method due to their many functional groups that can effectively target contaminants for efficient bioremediation, aiding in environmental cleanup. At the end of the paper, we will discuss the obstacles that hinder the use of biosynthesized nanoparticles and microbial-based nanoparticles. The paper aims to explore the sustainability of microorganisms in the burgeoning field of green nanotechnology.

11.
Nature ; 631(8021): 686-693, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38961287

RESUMEN

The µ-opioid receptor (µOR) is a well-established target for analgesia1, yet conventional opioid receptor agonists cause serious adverse effects, notably addiction and respiratory depression. These factors have contributed to the current opioid overdose epidemic driven by fentanyl2, a highly potent synthetic opioid. µOR negative allosteric modulators (NAMs) may serve as useful tools in preventing opioid overdose deaths, but promising chemical scaffolds remain elusive. Here we screened a large DNA-encoded chemical library against inactive µOR, counter-screening with active, G-protein and agonist-bound receptor to 'steer' hits towards conformationally selective modulators. We discovered a NAM compound with high and selective enrichment to inactive µOR that enhances the affinity of the key opioid overdose reversal molecule, naloxone. The NAM works cooperatively with naloxone to potently block opioid agonist signalling. Using cryogenic electron microscopy, we demonstrate that the NAM accomplishes this effect by binding a site on the extracellular vestibule in direct contact with naloxone while stabilizing a distinct inactive conformation of the extracellular portions of the second and seventh transmembrane helices. The NAM alters orthosteric ligand kinetics in therapeutically desirable ways and works cooperatively with low doses of naloxone to effectively inhibit various morphine-induced and fentanyl-induced behavioural effects in vivo while minimizing withdrawal behaviours. Our results provide detailed structural insights into the mechanism of negative allosteric modulation of the µOR and demonstrate how this can be exploited in vivo.


Asunto(s)
Analgésicos Opioides , Evaluación Preclínica de Medicamentos , Naloxona , Receptores Opioides mu , Bibliotecas de Moléculas Pequeñas , Animales , Humanos , Masculino , Ratones , Regulación Alostérica/efectos de los fármacos , Analgésicos Opioides/antagonistas & inhibidores , Analgésicos Opioides/farmacología , Sitios de Unión/efectos de los fármacos , Microscopía por Crioelectrón , Fentanilo/antagonistas & inhibidores , Fentanilo/farmacología , Cinética , Ligandos , Modelos Moleculares , Morfina/antagonistas & inhibidores , Morfina/farmacología , Naloxona/administración & dosificación , Naloxona/química , Naloxona/metabolismo , Naloxona/farmacología , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/química , Antagonistas de Narcóticos/metabolismo , Antagonistas de Narcóticos/farmacología , Sobredosis de Opiáceos/tratamiento farmacológico , Conformación Proteica/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacos , Receptores Opioides mu/agonistas , Receptores Opioides mu/antagonistas & inhibidores , Receptores Opioides mu/química , Receptores Opioides mu/metabolismo , Células Sf9 , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Ratones Endogámicos C57BL
12.
World J Clin Pediatr ; 13(2): 91268, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38948002

RESUMEN

The choledochal cyst (CC) can be better termed as biliary tract malformation because of the close association of embryology and etiology in the causation of CC. Contrary to Babbitt's postulation of reflux, damage and dilatation, reflux was not demonstrable as the causative factor in all varieties of CC. High pressure in the biliary system, otherwise termed ductal hypertension, is put forth as an alternative to explain the evolution of CC. The forme fruste type, which does not find a place in the standard classification, typifies the ductal hypertension hypothesis. Hence a closer, in-depth review would be able to highlight this apt terminology of biliary tract malformation.

13.
Iran J Basic Med Sci ; 27(9): 1197-1208, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055869

RESUMEN

Objectives: In this study, the SP-38 (Diterpene Lactone derivative) was designed, synthesized from clerodane diterpene (lactone) isolated from Polyanthia longifolia var. pendula, and tested for anti-arthritic activity using the FCA-induced arthritic rat model. Materials and Methods: This study examined the in vivo effects of SP-38 using three different doses (20, 10, and 5 mg/kg) by oral administration for 21 days from day 8 after 0.1 ml FCA sub-planter injection until day 28. Arthritis index, paw swelling, ankle diameter, body weight as well as biochemical, hematological, histopathological, and radiological parameters were examined. Results: Administered SP-38 reduced arthritis index, paw volume, and joint swelling compared to the arthritic control group. Accordingly, rats treated with SP-38 showed a remarkable increase in body weight and improved biochemical, hematological, histopathological, and radiological parameters. Furthermore, it reduced the increased production of CRP and RF while simultaneously decreasing ESR in all SP-38-treated rats. However, SP-38 showed promising liver protection by reducing elevated serum levels of liver and kidney function markers SGOT, SGPT, and ALP. Furthermore, splenic index, TNF-α, and IL-6 levels were significantly reduced compared to arthritic control rats at certain doses. Conclusion: The result of the present study concludes that SP-38 has significant anti-arthritic potential in FCA-induced arthritis in Wistar rats. SP-38 therefore showed promising anti-arthritic activity, as evidenced by attenuation of inflammation, inflammatory markers, and pro-inflammatory cytokine levels.

14.
Perit Dial Int ; : 8968608241263396, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042940

RESUMEN

Peritoneal dialysis (PD) is a well-established modality for kidney replacement therapy (KRT) globally, offering benefits such as better preservation of residual kidney function, improved quality of life, and reduced resource requirements. Despite these advantages, the global utilization of PD remains suboptimal, particularly in South Asia (SA), where a significant gap in PD delivery exists. This study aims to uncover the perceived barriers hindering PD utilization among nephrologists in SA. This is a cross-sectional survey involving 732 nephrologists from SA region. . The majority of respondents (44.7%) reported initiating less than six PD cases annually, reflecting low PD utilization. Cost and financial reimbursement policies emerged as major barriers, with 44.3% considering PD more expensive than haemodialysis (HD). Accessibility, negative attitudes toward PD, and fear of complications were identified as critical factors influencing PD adoption. The study also highlighted variations in PD costs among SA countries, emphasizing the need for tailored health economic strategies. This analysis provides insights into the multifaceted challenges faced by SA nephrologists in promoting PD and underscores the importance of targeted interventions.

15.
Plant Physiol Biochem ; 215: 108977, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39084167

RESUMEN

Silicon (Si) can significantly improve the salt tolerance of plants, but its mechanism remains unclear. In this study, role of abscisic acid (ABA) in Si derived salt resistance in tobacco seedling was investigated. Under salt stress, the photosynthetic rate, stomatal conductance, and transpiration rate of tobacco seedlings were reduced by 86.17%, 80.63%, and 67.54% respectively, resulting in a decrease in biomass. The application of Si found to mitigate these stress-induced markers. However, positive role of Si was mainly attributed to the enhanced expression of aquaporin genes, which helped in enhancing root hydraulic conductance (Lpr) and ultimately maintaining the leaf relative water content (RWC). Moreover, sodium tungstate, an ABA biosynthesis inhibitor, was used to test the role of ABA on Si-regulating Lpr. The results indicated that the improvement of Lpr by Si was diminished in the presence of ABA inhibitor. In addition, it was observed that the ABA content was increased due to the Si-upregulated of ABA biosynthesis genes, namely NtNCED1 and NtNCED5. Conversely, the expression of ABA metabolism gene NtCYP7O7A was found to be reduced by Si. Together, this study suggested that Si increased ABA content, leading to enhanced efficiency of water uptake by the roots, ultimately facilitating an adequate water supply to maintain leaf water balance. As a result, there was an improvement in salt resistance in tobacco seedling.

16.
Ageing Res Rev ; 100: 102411, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986845

RESUMEN

Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aß) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aß drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aß plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease.

17.
J Hazard Mater ; 477: 135230, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39038376

RESUMEN

In some locations around the globe, the U concentrations may exceed WHO standards by 2-folds therefore, effective yet environmentally wise solutions to purify radioactive waters are of significant importance. Here, the optimized and fully controlled coal-fly-ash based Na-P1 zeolite functionalization by employing novel, biodegradable biosurfactant molecule - cocamidopropyl betaine (CAPB) is showcased. The zeolite's surface decoration renders three composites with varying amounts of introduced CAPB molecule (Na-P1 @ CAPB), with 0.44, 0.88, and 1.59-times External Cation Exchange Capacity (ECEC). Wet-chemistry experiments revealed extremely high U adsorption capacity (qmax = 137.1 mg U/g) unveiling preferential interactions of uranyl dimers with CAPB molecules coupled with ion-exchange between Na+ ions. Multimodal spectroscopic analyses, including Fourier-Transformed Infra-Red (FT-IR), X-ray Photoelectron (XPS), and X-ray Absorption Fine Structure (XAFS), showed the hexavalent oxidation state of U, and no secondary release of the CAPB molecule from the composite. The EXAFS signals fingerprint changes in the interatomic distances of adsorbed U, showing the impact of the O and N, heteroatoms present in the CAPB molecule on U binding mechanism. The presented research outcomes showcase the easy, scalable, optimized, and environmentally friendly synthesis of biofunctional zeolite effectively purifying the real-life U-bearing wastewaters from the vicinity of the Pribram deposit (Czech Republic).

18.
Artículo en Inglés | MEDLINE | ID: mdl-38949882

RESUMEN

Oral Squamous cell carcinoma (OSCC) is the 14th most frequent cancer with 300,000 new cases and 100,000 deaths reported annually. Even with advanced therapy, the treatment outcomes are poor at advanced stages of the disease. The diagnosis of early OSCC is of paramount clinical value given the high mortality rate associated with the late stages of the disease. Recently, the role of microbiome in the disease manifestation, including oral cancer, has garnered considerable attention. But, to establish the role of bacteria in oral cancer, it is important to determine the differences in the colonization pattern in non-tumour and tumour tissues. In this study, 16S rRNA based metagenomic analyses of 13 tumorous and contralateral anatomically matched normal tissue biopsies, obtained from patients with advanced stage of OSCC were evaluated to understand the correlation between OSCC and oral microbiome. In this study we identified Fusobacterium, Prevotella, Capnocytophaga, Leptotrichia, Peptostreptococcus, Parvimonas and Bacteroidetes as the most significantly enriched taxa in OSCC lesions compared to the non-cancerous tissues. Further, PICRUSt2 analysis unveiled enhanced expression of metabolic pathways associated with L-lysine fermentation, pyruvate fermentation, and isoleucine biosynthesis in those microbes associated with OSCC tissues. These findings provide valuable insights into the distinctive microbial signatures associated with OSCC, offering potential biomarkers and metabolic pathways underlying OSCC pathogenesis. While our focus has primarily centred on microbial signatures, it is essential to recognize the pivotal role of host factors such as immune responses, genetic predisposition, and the oral microenvironment in shaping OSCC development and microbiome composition.

19.
Sci Rep ; 14(1): 16882, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043820

RESUMEN

Several farmed fish species, including carps, tilapia, salmon, and catfish, have experienced significant economic losses in aquaculture due to motile Aeromonas septicemia caused by Aeromonas hydrophila. In the present study, a novel lytic bacteriophage infecting hypervirulent Aeromonas hydrophila (vAh) was isolated and characterized. This is the first report of a phage against vAh. Phage AhFM11 demonstrated lytic activity against both vAh strains and the A. hydrophila reference strain ATCC 35654. The AhFM11 genome was sequenced and assembled, comprising 168,243 bp with an average G + C content of 41.5%. The genome did not harbor any antibiotic resistance genes. Genomic information along with transmission electron microscopy revealed that phage AhFM11 belongs to the Straboviridae family. Therapeutic application of monophage AhFM11 in fish showed 100% survival in injection, 95% in immersion and 93% in oral feeding of phage top-coated feed. Fish and chicken meat spiked with A. hydrophila and phage showed significant reduction of A. hydrophila. These findings support that phage AhFM11 can be used as a biocontrol agent against vAh as an alternative to antibiotics.


Asunto(s)
Aeromonas hydrophila , Bacteriófagos , Infecciones por Bacterias Gramnegativas , Aeromonas hydrophila/virología , Aeromonas hydrophila/patogenicidad , Bacteriófagos/genética , Bacteriófagos/fisiología , Bacteriófagos/patogenicidad , Bacteriófagos/aislamiento & purificación , Animales , Infecciones por Bacterias Gramnegativas/terapia , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Terapia de Fagos/métodos , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/terapia , Genoma Viral , Peces/microbiología , Virulencia
20.
Ecotoxicol Environ Saf ; 281: 116596, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38896899

RESUMEN

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.


Asunto(s)
Nicotiana , Nicotiana/química , Nicotiana/genética , Nicotiana/crecimiento & desarrollo , Nicotiana/metabolismo , Cadmio/toxicidad , Resistencia a Medicamentos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Antioxidantes/metabolismo , Proteínas de Transporte de Catión/metabolismo
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