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1.
Cureus ; 16(8): e66885, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280472

RESUMO

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by the production of autoantibodies against post-synaptic proteins at the neuromuscular junction (NMJ). An 18-year-old male who had symptoms of drooping eyelids and double vision was diagnosed with ocular myasthenia gravis on investigations and examinations. Treatment was initiated with a tablet of pyridostigmine 60 mg twice daily per oral for two weeks, followed by three times daily for four weeks. The patient demonstrated significant improvement in ptosis and diplopia. There are still a considerable number of challenges in the diagnosis and treatment of ocular myasthenia gravis, with the typical treatment involving acetylcholinesterase inhibitors and immunosuppressants.

2.
Sensors (Basel) ; 24(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39275529

RESUMO

The rapid evolution of drone technology has introduced unprecedented challenges in security, particularly concerning the threat of unconventional drone and swarm attacks. In order to deal with threats, drones need to be classified by intercepting their Radio Frequency (RF) signals. With the arrival of Sixth Generation (6G) networks, it is required to develop sophisticated methods to properly categorize drone signals in order to achieve optimal resource sharing, high-security levels, and mobility management. However, deep ensemble learning has not been investigated properly in the case of 6G. It is anticipated that it will incorporate drone-based BTS and cellular networks that, in one way or another, may be subjected to jamming, intentional interferences, or other dangers from unauthorized UAVs. Thus, this study is conducted based on Radio Frequency Fingerprinting (RFF) of drones identified to detect unauthorized ones so that proper actions can be taken to protect the network's security and integrity. This paper proposes a novel method-a Composite Ensemble Learning (CEL)-based neural network-for drone signal classification. The proposed method integrates wavelet-based denoising and combines automatic and manual feature extraction techniques to foster feature diversity, robustness, and performance enhancement. Through extensive experiments conducted on open-source benchmark datasets of drones, our approach demonstrates superior classification accuracies compared to recent benchmark deep learning techniques across various Signal-to-Noise Ratios (SNRs). This novel approach holds promise for enhancing communication efficiency, security, and safety in 6G networks amidst the proliferation of drone-based applications.

3.
Cureus ; 16(8): e65915, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39221311

RESUMO

Aim The objective of this study is to evaluate the feasibility of using iliac branch endoprosthesis (IBE) devices and to examine their short-term outcomes. Materials and methods This was a descriptive, retrospective observational study involving 15 patients diagnosed with either aortoiliac or isolated iliac artery aneurysms and treated with an IBE device. Data were collected for patients who received IBE devices at Glan Clwyd Hospital in Rhyl, United Kingdom, from February 2020 to May 2023. Results Most patients presented with asymptomatic aneurysms; 86.7% (n = 13) had bilateral common iliac artery (CIA) aneurysms. The mean diameter of the CIA was 38.7 ± 8.8 mm, and the mean diameter of the abdominal aortic aneurysm (AAA) was 39.8 ± 23 mm. For the indications of IBE use, 60% (n = 9) of the patients had iliac aneurysms reaching the intervention threshold, 20% (n = 3) had AAA reaching the threshold, and 20% (n = 3) had aortoiliac aneurysms reaching the threshold. The majority of patients underwent bilateral femoral access (86.7%; n = 13), while 13.3% (n = 2) required both femoral and brachial access. Technical success was achieved in all cases. Aside from 20% (n = 3) of cases where the sac size remained static, the majority of patients (80%; n = 12) experienced sac regression. All patients were free from buttock claudication. A type II endoleak was observed in 33.3% (n = 5) of patients. No reinterventions were reported. The mean primary patency was 30.9 ± 0.7 months, and the follow-up period ranged from 12 to 36 months. Conclusions IBEs are an effective medical device, demonstrating a high rate of technical success, minimal need for additional procedures, and a low incidence of complications while maintaining a satisfactory rate of primary patency.

4.
Int Immunopharmacol ; 141: 112833, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153303

RESUMO

Mycoplasma pulmonis (M. pulmonis) is an emerging respiratory infection commonly linked to prostate cancer, and it is classified under the group of mycoplasmas. Improved management of mycoplasma infections is essential due to the frequent ineffectiveness of current antibiotic treatments in completely eliminating these pathogens from the host. The objective of this study is to design and construct effective and protective vaccines guided by structural proteomics and machine learning algorithms to provide protection against the M. pulmonis infection. Through a thorough examination of the entire proteome of M. pulmonis, four specific targets Membrane protein P80, Lipoprotein, Uncharacterized protein and GGDEF domain-containing protein have been identified as appropriate for designing a vaccine. The proteins underwent mapping of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) (IFN)-γ ±, and B-cell epitopes using artificial and recurrent neural networks. The design involved the creation of mRNA and peptide-based vaccine, which consisted of 8 CTL epitopes associated by GGS linkers, 7 HTL (IFN-positive) epitopes, and 8 B-cell epitopes joined by GPGPG linkers. The vaccine designed exhibit antigenic behavior, non-allergenic qualities, and exceptional physicochemical attributes. Structural modeling revealed that correct folding is crucial for optimal functioning. The coupling of the MEVC and Toll-like Receptors (TLR)1, TLR2, and TLR6 was examined through molecular docking experiments. This was followed by molecular simulation investigations, which included binding free energy estimations. The results indicated that the dynamics of the interaction were stable, and the binding was strong. In silico cloning and optimization analysis revealed an optimized sequence with a GC content of 49.776 % and a CAI of 0.982. The immunological simulation results showed strong immune responses, with elevated levels of active and plasma B-cells, regulatory T-cells, HTL, and CTL in both IgM+IgG and secondary immune responses. The antigen was completely cleared by the 50th day. This study lays the foundation for creating a potent and secure vaccine candidate to combat the newly identified M. pulmonis infection in people.


Assuntos
Vacinas Bacterianas , Epitopos de Linfócito B , Epitopos de Linfócito T , Aprendizado de Máquina , Infecções por Mycoplasma , Proteômica , Vacinas Bacterianas/imunologia , Infecções por Mycoplasma/prevenção & controle , Infecções por Mycoplasma/imunologia , Proteômica/métodos , Animais , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Linfócitos T Citotóxicos/imunologia , Humanos , Proteínas de Bactérias/imunologia , Camundongos , Simulação de Acoplamento Molecular , Mapeamento de Epitopos/métodos , Antígenos de Bactérias/imunologia
5.
Front Plant Sci ; 15: 1445786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170781

RESUMO

Plant diseases caused by microbial pathogens pose a severe threat to global food security. Although genetic modifications can improve plant resistance; however, environmentally sustainable strategies are needed to manage plant diseases. Nano-enabled immunomodulation involves using engineered nanomaterials (ENMs) to modulate the innate immune system of plants and enhance their resilience against pathogens. This emerging approach provides unique opportunities through the ability of ENMs to act as nanocarriers for delivering immunomodulatory agents, nanoprobes for monitoring plant immunity, and nanoparticles (NPs) that directly interact with plant cells to trigger immune responses. Recent studies revealed that the application of ENMs as nanoscale agrochemicals can strengthen plant immunity against biotic stress by enhancing systemic resistance pathways, modulating antioxidant defense systems, activating defense-related genetic pathways and reshaping the plant-associated microbiomes. However, key challenges remain in unraveling the complex mechanisms through which ENMs influence plant molecular networks, assessing their long-term environmental impacts, developing biodegradable formulations, and optimizing targeted delivery methods. This review provides a comprehensive investigation of the latest research on nano-enabled immunomodulation strategies, potential mechanisms of action, and highlights future perspectives to overcome existing challenges for sustainable plant disease management.

6.
Brain Res ; 1845: 149171, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39168264

RESUMO

BACKGROUND: MicroRNAs (miRNAs) participate in diverse cellular changes following acute ischemic stroke (AIS). Circulating miRNAs, stabilized and delivered to target cells via extracellular vesicles (EVs), are potential biomarkers to facilitate diagnosis, prognosis, and therapeutic modulation. We aimed to identify distinctive expression patterns of circulating EV-miRNAs in AIS patients. METHODS: miRNA profiles from EVs, isolated from plasma samples collected within 24 h following AIS diagnosis, were examined between a dataset of 10 age-, gender- and existing comorbidities-matched subjects (5 AIS and 5 healthy controls, HC). We measured 2578 miRNAs and identified differentially expressed miRNAs between AIS and HC. An enrichment analysis was conducted to delineate the networks and biological pathways implicated by differentially expressed microRNAs. An enrichment analysis was conducted to delineate the networks and biological pathways implicated by differentially expressed microRNAs. RESULTS: Five miRNAs were differentially expressed between stroke (AIS) versus control (HC). hsa-let-7b-5p, hsa-miR-16-5p, and hsa-miR-320c were upregulated, whereas hsa-miR-548a-3p and hsa-miR-6808-3p, with no previously reported changes in stroke were downregulated. The target genes of these miRNAs affect various cellular pathways including, RNA transport, autophagy, cell cycle progression, cellular senescence, and signaling pathways like mTOR, PI3K-Akt, and p53. Key hub genes within these networks include TP53, BCL2, Akt, CCND1, and NF-κB. These pathways are crucial for cellular function and stress response, and their dysregulation can have significant implications for the disease processes. CONCLUSION: Our findings reveal distinct circulating EV-miRNA expression patterns in AIS patients from Qatar, highlighting potential biomarkers that could aid in stroke diagnosis and therapeutic strategies. The identified miRNAs are involved in critical cellular pathways, offering novel insights into the molecular mechanisms underlying stroke pathology. Circulating EV-miRNAs differentially expressed in AIS may have a pathophysiological role and may guide further research to elucidate their precise mechanisms.

7.
Biometals ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39127845

RESUMO

Here, we report for the first time, green-synthesized selenium nanoparticles (SeNPs) using pharmacologically potent herb of Polygonum bistorta Linn. for multiple biomedical applications. In the study, a facile and an eco-friendly approach is utilized for synthesis of SeNPs using an aqueous roots extract of P. bistorta Linn. followed by extensive characterization via Fourier transform infrared spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Energy Dispersive X-Ray (EDX) analysis. The XRD and FTIR data determine the phase composition and successful capping of plant extract onto the surface of NPs while SEM and TEM micrographic examination reveals the elliptical and spherical morphology of the particles with a mean size of 69 ± 23 nm. After comprehensive characterization, the NPs are investigated for antifungal, antibacterial, antileishmanial, antioxidant, and biocompatibility properties. The study reveals that Polygonum bistorta Linn. synthesized SeNPs exhibit significant antibacterial and antifungal activities with Staphylococcus aureus and Fusarium oxysporum inducing the highest zone of inhibition of 14 ± 1.0 mm and 20 ± 1.2 mm, respectively at the concentration of 40 mg/mL. The NPs are also found to have antiparasitic potential against promastigote and amastigote forms of Leishmania tropica. Furthermore, the NPs are discovered to have excellent potential in neutralizing harmful free radicals thus exhibiting considerable antioxidant potential. Most importantly, Polygonum bistorta Linn. synthesized SeNPs showed substantial compatibility against blood cells in vitro studies, which signifies the nontoxic nature of the NPs. The study thus concludes that medicinally important Polygonum bistorta Linn. roots can be utilized as an eco-friendly, sustainable, and green source for the synthesis of pharmacologically potent selenium nanoparticles.

8.
Curr Neuropharmacol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39092643

RESUMO

BACKGROUND: Cadmium chloride (Cd) is a pervasive environmental heavy metal pollutant linked to mitochondrial dysfunction, memory loss, and genetic disorders, particularly in the context of neurodegenerative diseases like Alzheimer's disease (AD). METHODS: This study investigated the neurotherapeutic potential of vitamin B6 (Vit. B6) in mitigating Cd-induced oxidative stress and neuroinflammation-mediated synaptic and memory dysfunction. Adult albino mice were divided into four groups: Control (saline-treated), Cd-treated, Cd+Vit. B6- treated, and Vit. B6 alone-treated. Cd and Vit. B6 were administered intraperitoneally, and behavioral tests (Morris Water Maze, Y-Maze) were conducted. Subsequently, western blotting, antioxidant assays, blood glucose, and hyperlipidemia assessments were performed. RESULTS: Cd-treated mice exhibited impaired cognitive function, while Cd+Vit. B6-treated mice showed significant improvement. Cd-induced neurotoxic effects, including oxidative stress and neuroinflammation, were observed, along with disruptions in synaptic proteins (SYP and PSD95) and activation of p-JNK. Vit. B6 administration mitigated these effects, restoring synaptic and memory deficits. Molecular docking and MD simulation studies confirmed Vit. B6's inhibitory effect on IL-1ß, NRF2, and p-JNK proteins. CONCLUSION: These results highlight Vit. B6 as a safe therapeutic supplement to mitigate neurodegenerative disorders, emphasizing the importance of assessing nutritional interventions for combating environmental neurotoxicity in the interest of public health.

9.
Microb Pathog ; 194: 106777, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39002657

RESUMO

Francisella tularensis can cause severe disease in humans via the respiratory or cutaneous routes and a case fatality ratio of up to 10 % is reported due to lack of proper antibiotic treatment, while F. novicida causes disease in severely immunocompromised individuals. Efforts are needed to develop effective vaccine candidates against Francisella species. Thus, in this study, a systematic computational work frame was used to deeply investigate the whole proteome of Francisella novicida containing 1728 proteins to develop vaccine against F. tularensis and related species. Whole-proteome analysis revealed that four proteins including (A0Q492) (A0Q7Y4), (A0Q4N4), and (A0Q5D9) are the suitable vaccine targets after the removal of homologous, paralogous and prediction of subcellular localization. These proteins were used to predict the T cell, B cell, and HTL epitopes which were joined together through suitable linkers to construct a multi-epitopes vaccine (MEVC). The MEVC was found to be highly immunogenic and non-allergenic while the physiochemical properties revealed the feasible expression and purification. Moreover, the molecular interaction of MEVC with TLR2, molecular simulation, and binding free energy analyses further validated the immune potential of the construct. According to Jcat analysis, the refined sequence demonstrates GC contents of 41.48 % and a CAI value of 1. The in-silico cloning and optimization process ensured compatibility with host codon usage, thereby facilitating efficient expression. Computational immune simulation studies underscored the capacity of MEVC to induce both primary and secondary immune responses. The conservation analysis further revealed that the selected epitopes exhibit 100 % conservation across different species and thus provides wider protection against Francisella.


Assuntos
Imunidade Adaptativa , Vacinas Bacterianas , Francisella tularensis , Proteômica , Tularemia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Francisella tularensis/imunologia , Francisella tularensis/genética , Tularemia/prevenção & controle , Tularemia/imunologia , Tularemia/microbiologia , Humanos , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteoma , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Epitopos/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Desenvolvimento de Vacinas , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética
10.
Heliyon ; 10(13): e33271, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39055793

RESUMO

Sol-gel method was used to prepare Sr1-xCdxZn2Fe4O11 (x = 0.00, 0.02, 0.06, 0.1) R-type hexaferrite. The synthesized materials were sintered at 850oC and desired phase was obtained. X-ray diffraction analysis confirms that R-type hexaferrite exists only as a single phase. Using the Scherer formula, crystallite size for all of the prepared samples was found to be in the range of 10.39-12.62 nm. Crystallite size (D), the lattice parameters (a, c), and the cell volume (Vcell), d-spacing, bulk density, X-ray density, porosity, dislocation density and micro strain were determined in structural analysis. Fourier transform infrared spectroscopy method was used to identify the metal-oxygen vibrations at different locations. FT-IR verifies the presence of the Fe-O stretching vibration band at 743 and 867 cm-1. The typical grain size in surface morphology investigation ranges from 0.56 to 0.82 µm. Dielectric response of ferrite ceramic samples replaced with Cd2+ was investigated in the frequency range of 1 MHz-3 GHz. The AC conductivity rises with an increase in frequency because they are proportional to one another. This increasing tendency is effectively described by the theory of Maxwell-Wagner and Koop. Q-values remain constant as frequency rises and behaves independently of frequency as long as frequency reaches 1.7 GHz. These types of materials are utilized in high-frequency applications including frequency filters and resonant circuits. All of the magnetic properties determined by analyzing the M - H loops, including saturation magnetization (Ms), retentivity (Mr), and coercivity (Hc), exhibit an increasing trend as the substitution of Cd2+ rises. Ms (49.76-56.38 emu/g), Mr (15.82-18.30 emu/g) and Hc range from 203.20 Oe to 215.80 Oe. Grain size decreases cause arise in coercivity, which is caused by an enhancement in magneto-crystalline anisotropy. Overall results suggest that Cd2+ replaced R-type hexagonal ferrites are a great resource for longitudinal recording media; they have the potential to be used in a wide variety of electronic applications, including resonant circuits and high-frequency filters, security, detecting and switching.

11.
Clin Case Rep ; 12(7): e8920, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952464

RESUMO

Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.

12.
Front Chem ; 12: 1413253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021388

RESUMO

MAX phases, characterized as nanolaminates of ternary carbides/nitrides structure, possess a unique combination of ceramic and metallic properties, rendering them pivotal in materials research. In this study, chromium aluminum carbide ternary compounds, Cr2AlC (211), Cr3AlC2 (312), and Cr4AlC3 (413) were successfully synthesized with high purity using a facile and cost-effective sol-gel method. Structural, morphological, and chemical characterization of the synthesized phases was conducted to understand the effects of composition changes and explore potential applications. Comprehensive characterization techniques including XRD for crystalline structure elucidations, SEM for morphological analysis, EDX for chemical composition, Raman spectroscopy for elucidation of vibrational modes, XPS to analyze elemental composition and surface chemistry, and FTIR spectroscopy to ensure the functional groups analysis, were performed. X-ray diffraction analysis indicated the high purity of the synthesized Cr2AlC phase as well as other ternary compounds Cr3AlC2 and Cr4AlC3, suggesting its suitability as a precursor for MXenes production. Additionally, the antimicrobial activity against Candida albicans and biocompatibility assessments against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and HepG2 cell line were investigated. The results demonstrated significant antifungal activity of the synthesized phases against Candida albicans and negligible impact on the viability of E. coli and S. aureus. Interestingly, lower concentrations of Cr2AlC MAX phase induced cytotoxicity in HepG2 cells by triggering intercellular oxidative stress, while Cr3AlC2 and Cr4AlC3 exhibited lower cytotoxicity compared to Cr2AlC, highlighting their potential in biomedical applications.

13.
Cureus ; 16(6): e62616, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39027799

RESUMO

Background Since bilateral nasal packing entails nasal and airway obstruction, this practice consequently leads to oral breathing. The resulting hypoxemia may then negatively impact vital signs, including blood pressure (BP), blood oxygen saturation (SpO2), and heart rate (HR). These systemic effects have a detrimental effect on patients. Objective The objective of this study is to observe the effects of bilateral nasal packing on patients' post-operative vital signs. Materials and methods This prospective study was conducted in the department of otolaryngology - head and neck surgery over a six-month period. The study included 83 post-operative patients with nasal surgery, in which bilateral merocele nasal packing was performed. The patients' pulse oximetry, systolic and diastolic BP, and HR were recorded four times the night before and after surgery. A statistical analysis was performed, and the mean values, standard deviation, and range were calculated. A paired sample t-test was also applied. The results are presented in figures and tables. Results The mean age of the participants was 27.65 ± 10.72 years, and 56 (67.5%) were male. Septoplasty was the most common surgery performed, with 63 participants having undergone this procedure (75.9%). When the pre-operative mean values of systolic and diastolic BP, SpO2, and HR were compared with the post-operative mean values, when a bilateral nasal pack was in place, a significant increase was found in all, with a p-value of <0.001 in each. Conclusion Bilateral nasal packing affects patients' vital signs by significantly increasing diastolic and systolic BP and decreasing SpO2. The HR is also significantly increased when packing is in place.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38969945

RESUMO

PURPOSE: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. METHODS: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. RESULTS: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). CONCLUSION: APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

15.
Cureus ; 16(6): e61993, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38983996

RESUMO

Objective The objective of this study was to compare K1, K2, Kmax, and pachymetry values from Pentacam and Galilei scans of corneal topography in order to assess their correlation and interchangeability in clinical practice. Methodology A total of 34 patients (68 eyes) were enrolled in the study. Corneal topography was performed using Pentacam and Galilei devices on the same day. K1, K2, Kmax, and pachymetry readings were obtained from the scans and analyzed using paired t-tests and Bland-Altman plots. Results There were minimal differences in clinical settings between Pentacam and Galilei for K1, K2, Kmax (>0.75 D), and pachymetry values (>15 um). However, there was a statistically significant difference found between Kmax and pachymetry, making their interchangeability questionable. Conclusion Pentacam and Galilei demonstrate a good correlation between corneal keratometric values (K1, K2, and Kmax) and pachymetry values in clinical settings, and they should be used interchangeably with caution.

16.
Glia ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989661

RESUMO

Rapid nerve conduction in the peripheral nervous system (PNS) is facilitated by the multilamellar myelin sheath encasing many axons of peripheral nerves. Charcot-Marie-Tooth type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsy (HNPP) are common demyelinating inherited peripheral neuropathies and are caused by mutations in the peripheral myelin protein 22 (PMP22) gene. Duplication of PMP22 leads to its overexpression and causes CMT1A, while its deletion results in PMP22 under expression and causes HNPP. Here, we investigated novel targets for modulating the protein level of PMP22 in HNPP. We found that genetic attenuation of the transcriptional coactivator Yap in Schwann cells reduces p-TAZ levels, increased TAZ activity, and increases PMP22 in peripheral nerves. Based on these findings, we ablated Yap alleles in Schwann cells of the Pmp22-haploinsufficient mouse model of HNPP and identified fewer tomacula on morphological assessment and improved nerve conduction in peripheral nerves. These findings suggest YAP modulation may be a new avenue for treatment of HNPP.

17.
Environ Sci Pollut Res Int ; 31(35): 48073-48084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39017868

RESUMO

Recent advancements in membrane technologies and disinfection methods have enhanced drinking water quality significantly. However, microorganisms, including free-living amoebae (FLA), persist and pose potential threats to humans. FLA are linked to severe neuro-ophthalmic infections and serve as hosts of pathogenic bacteria. This study examined FLA presence in chlorinated and ultrafiltration drinking water and evaluated chlorine's disinfectant. Of 115 water samples, 21 tested positive for Acanthamoeba sp., Allovahlkampfia sp., and Vermamoeba vermiformis, originating from chlorinated sources. FLA trophozoites withstand temperatures up to 37 °C, while the cysts tolerate heat shocks of 60-70 °C. Trophozoites are susceptible to 5 mg L-1 chlorine, but cysts remain viable at concentrations up to 10 mg L-1. FLAs' survival in chlorinated waters is attributed to high cyst tolerance and lower residual chlorine concentrations. These findings highlight the need for ultrafiltration or enhanced chlorination protocols to ensure safer drinking water.


Assuntos
Amoeba , Água Potável , Halogenação , Amoeba/efeitos dos fármacos , Água Potável/química , Cloro/farmacologia , Desinfecção/métodos , Desinfetantes , Purificação da Água/métodos
18.
Environ Geochem Health ; 46(8): 267, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954229

RESUMO

This study examines the levels of heavy metals in polyculture fish (Labeo rohita, Cyprinus carpio, and Catla catla), water, and sediment in Tanda Dam, Kohat, Pakistan, aiming to understand environmental and health risks. Samples of fish, water, and sediment were collected from 3 fish farms, and heavy metal concentrations were measured using a Flame Atomic Absorption Spectrophotometer (AAS). Results reveal that C. catla exhibited significantly higher (p < 0.05) levels of Zn than other fish species. Conversely, C. carpio showed significantly higher (p < 0.05) concentrations of Pb, Cd, Cr, Mn, Cu, As, and Ni than other species. The heavy metal hierarchy in C. carpio was found to be Zn > Cu > Pb > Cr > Cd > Mn > As > Ni. While heavy metal levels in L. rohita and C. catla generally fell within reference ranges, exceptions were noted for Zn, Pb, and Cd. Conversely, in C. carpio, all metals exceeded reference ranges except for Cu and Ni. Principal Component Analysis (PCA) indicated a close relationship between water and sediment. Additionally, cluster analysis suggested that C. catla formed a distinct cluster from L. rohita and C. carpio, implying different responses to the environment. Despite concerns raised by the Geoaccumulation Index (Igeo) and Contamination Factor (CF), particularly for Cd, which exhibited a high CF. Furthermore, Hazard Index (HI) values for all three fish species were below 1, suggesting low health risks. However, elevated Igeo and CF values for Cd suggest significant pollution originating from anthropogenic sources. This study underscores the importance of monitoring heavy metals in water for both environmental preservation and human health protection. Future research efforts should prioritize pollution control measures to ensure ecosystem and public health safety.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Metais Pesados , Poluentes Químicos da Água , Metais Pesados/análise , Animais , Poluentes Químicos da Água/análise , Humanos , Medição de Risco , Sedimentos Geológicos/química , Monitoramento Ambiental/métodos , Paquistão , Ecossistema , Carpas/metabolismo , Peixes/metabolismo , Análise de Componente Principal , Aquicultura
19.
Future Cardiol ; 20(4): 221-228, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-39049769

RESUMO

Aim: We aim to analyze past literature to evaluate the efficacy of coenzyme Q10 (CoQ-10) in the population with heart failure (HF). Methods: A systematic literature search was conducted through MEDLINE (via PubMed) and Cochrane Library. The outcomes analyzed were a reduction in HF-related mortality, an improvement in exercise capacity, and the left ventricular ejection fraction (LVEF). Results: Among 16 studies, CoQ-10 significantly reduced HF-related mortality by 40% and improved exercise capacity in patients with HF, but demonstrated no significant difference in LVEF however, the potential of its efficacy on LVEF could not be ruled out. Conclusion: CoQ-10 significantly enhances exercise capacity and reduces HF-related mortality; however, its impact on patients with reduced LVEF requires further investigation.


[Box: see text].


Assuntos
Insuficiência Cardíaca , Ubiquinona , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Ubiquinona/análogos & derivados , Ubiquinona/uso terapêutico , Ubiquinona/farmacologia , Volume Sistólico/fisiologia , Tolerância ao Exercício/fisiologia , Tolerância ao Exercício/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Resultado do Tratamento
20.
Hortic Res ; 11(7): uhae130, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974188

RESUMO

Potato is the third most important food crop, but cultivation is challenged by numerous diseases and adverse abiotic conditions. To combat diseases, frequent fungicide application is common. Knocking out susceptibility genes by genome editing could be a durable option to increase resistance. DMR6 has been described as a susceptibility gene in several crops, based on data that indicates increased resistance upon interruption of the gene function. In potato, Stdmr6-1 mutants have been described to have increased resistance against the late blight pathogen Phytophthora infestans in controlled conditions. Here, we present field evaluations of CRISPR/Cas9 mutants, in a location with a complex population of P. infestans, during four consecutive years that indicate increased resistance to late blight without any trade-off in terms of yield penalty or tuber quality. Furthermore, studies of potato tubers from the field trials indicated increased resistance to common scab, and the mutant lines exhibit increased resistance to early blight pathogen Alternaria solani in controlled conditions. Early blight and common scab are problematic targets in potato resistance breeding, as resistance genes are very scarce. The described broad-spectrum resistance of Stdmr6-1 mutants may further extend to some abiotic stress conditions. In controlled experiments of either drought simulation or salinity, Stdmr6-1 mutant plants are less affected than the background cultivar. Together, these results demonstrate the prospect of the Stdmr6-1 mutants as a useful tool in future sustainable potato cultivation without any apparent trade-offs.

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