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1.
Int J Burns Trauma ; 14(4): 90-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310245

RESUMO

Neurofibromas, in association with NF-1, can undergo a malignant transformation, giving rise to Malignant peripheral nerve sheath tumours (MPNSTs), a relatively rare entity. Clinically, it presents with non-specific symptoms like pain and numbness, distinguishing it from other nerve lesions difficult. There is a lack of data on the occurrence of MPNST in NF-1 in children and adults, and distant metastasis to the brain and bones is reported only in a few cases. In this case report, we present the unusual presentation of MPNST with metastasis to the proximal femur and liver in a patient with NF-1 and its management. Patients and clinicians should be made aware of the relatively high risk of MPNST in NF-1, which is characterized by pain and rapid growth, and regular follow-up is needed for NF-1 patients for early diagnosis of malignant transformation. So, this case report is presented to enhance the understanding and awareness regarding this rare presentation.

2.
Int J Burns Trauma ; 14(4): 65-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310248

RESUMO

BACKGROUND: The incidence of adhesive capsulitis varies from 2-5% in the general population to 20% in people with diabetes. One of the most effective treatment methods is hydrodilatation, which can be done under US-guidance or Fluoroscopic guidance. However, the clinical effectiveness of US-guided injections in comparison to fluoroscopy-guided injections is still debatable. The possibility of severe side effects, the expense, and the time required to carry out this minimally invasive procedure highlight how crucial it is for patients to have a precise intra-articular injection. This study aims to compare the effectiveness of Ultrasound-guided vs. Fluoroscopic guided hydrodilatation for patients with adhesive capsulitis. METHODS: Sixty-four patients were randomly selected for hydrodilatation using any one of the techniques. The patients were evaluated for clinical improvements using the visual analog scale (VAS), oxford shoulder score (OSS), and range of motion (ROM). RESULTS: The US-guided group experienced more pain reduction than the fluoroscopy group within the first four weeks (P < 0.001). The increase in ROM was much more significant in the US-guided group for the first 8 weeks. Improvement in Abduction and External rotation was much more significant (P < 0.001) in the first 4 weeks after hydrodilatation in the US-guided group. The improvement in ROM was maintained on long-term follow-up (mean 24 months), with 45 out of 64 (70.3%) reporting a normal or near normal ROM. On assessing the Oxford shoulder score improvements, the US-guided group's score significantly increased after the first week (P = 0.003), but the fluoroscopy-guided group's score increased after the second week. On comparison between the two groups, the amount of score improvement was more significant in the US-guided group than in the fluoroscopy-guided group in the first 4 weeks (P < 0.001). CONCLUSION: US-guided technique for intra-articular injection for patients with adhesive capsulitis provided a quicker pain reduction and a larger improvement in range of motion and overall shoulder functions.

3.
Cell Biochem Biophys ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167281

RESUMO

Single Nucleotide Polymorphisms (SNPs) are key in understanding complex diseases. Nonsynonymous single-nucleotide polymorphisms (nsSNPs) occur in protein-coding regions, potentially altering amino acid sequences, protein structure and function. Computational methods are vital for distinguishing deleterious nsSNPs from neutral ones. We investigated the role of NLRP3 gene in neuroinflammation associated with Alzheimer's disease (AD) pathogenesis. A total of 893 missense (nsSNPs) were obtained from the dbSNP database and subjected to rigorous filtering using bioinformatics tools like SIFT, Align GVGD, PolyPhen-2, and PANTHER to identify potentially damaging variants. Of these, 18 nsSNPs were consistently predicted to have deleterious effects across all tools. Notably, 16 of these variants exhibited reduced protein stability, while only 4 were predicted to be buried within the protein structure. Among the identified nsSNPs, rs180177442 (R262L and R262P), rs201875324 (T659I), and rs139814109 (T897M) were classified as high-risk variants due to their significant deleterious impact, probable damaging effects, and association with decreased protein stability. Molecular docking and simulation analyses were conducted utilizing Memantine, a standard drug utilized in AD treatment, to investigate potential interactions with the altered protein structures. Additional clinical and genetic investigations are necessary to elucidate the underlying mechanisms that link NLRP3 polymorphisms with the initiation of AD.

4.
Front Microbiol ; 15: 1421143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135876

RESUMO

Background: Rumex vesicarius is a wild leafy plant belonging to the family Polygonaceae, renowned for its therapeutic benefits. The genus Rumex comprises approximately 150 species distributed globally. Objective: The study aimed to investigate the biological activities of R. vesicarius using in vitro and in silico methods. Methods: Rumex vesicarius was collected from the mountains in Hail and extracted with methanol. The phytochemical composition was qualitatively determined using colorimetric detection methods. Additional analyses included elemental analysis, in silico docking, antioxidant, antibacterial, and anti-biofilm properties. Results: The extract contained various classes of phytochemicals, including flavonoids, phenolics, tannins, terpenes, and saponins. Sixteen constituents were identified through molecular docking, revealing inhibition against the filamentous temperature-sensitive protein Z (FtsZ), a crucial factor in bacterial cell division. Six compounds exhibited low binding scores ranging from -8.3 to -5.0 kcal/mol, indicating efficient interaction at the active site. Elemental analysis identified 15 elements, with potassium being the most abundant, followed by calcium, aluminum, silicon, iron, phosphorus, sulfur, magnesium, titanium, strontium, zinc, manganese, bromine, and chromium. Antioxidant analysis revealed significant properties at lower concentrations compared to ascorbic acid, butylated hydroxytoluene, and ß-carotene. Antibacterial analysis demonstrated inhibitory effects on Bacillus subtilis MTCC121 and Pseudomonas aeruginosa MTCC 741, with inhibition zones of 13.67 ± 1.0 mm and 11.50 ± 1.0 mm, respectively. The MIC and MBC values ranged from 250 to 500 µg/mL. R. vesicarius also exhibited anti-biofilm activity. Conclusion: Wild-grown R. vesicarius from the mountains of Hail is rich in bioactive phytochemicals and essential minerals, exhibiting notable antioxidant and antibacterial properties.

6.
Int J Burns Trauma ; 14(3): 48-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022442

RESUMO

The objective of this clinical appraisal was to assess the clinical-radiological results of ankle deformity correction secondary to physeal injury, utilizing the methods based on the age of the child, site & severity of the deformity, remaining growth potential, condition of the soft tissue envelop and integrity of neurovascular status. Fifteen subjects ≤ 16 years of age, with angular deformities of the ankle secondary to physeal injury, were included. Deformities secondary to infection and pathological fractures were excluded. Demographic data, type of injury, treatment method, and follow-up were recorded from the case files. Treatment categories included osteotomies for acute correction (> 10 years) and growth modulation (≤ 10 years). Male to female ratio was 7:8, with an average age of 11.8 ± 2.31 years (range 9-16 years). The right and left ratio was 7:8. Mean duration of follow-up was 1 year and 4 months. Gradual deformity correction was done in 2 cases utilizing the principle of growth modulation, while acute correction by osteotomy was done in 13 cases. The average pre-operative ankle deformity was 20.8 ± 3.11 degrees (Range -25 to 24 degrees). Radiological union was attained at a mean of 11 weeks (8-24). Nine patients achieved neutral ankle alignment. The mean residual varus was 2.3°, and the valgus was 4°. There was a statistically significant improvement of the AOFAS score by 17 points from a mean pre-operative score of 57 (44-84) to 74 (56-100) points at the final follow-up (p-value < 0.001). The average pre-operative shortening was 2.36 ± 0.21 cm, which was completely corrected in 9 individuals. Management of angular deformities around the ankle calls attention to correcting the resultant angular deformity and/or limb length disparity, utilizing acute or gradual correction. A successful outcome depends on early recognition and patient-specific treatment of paediatric ankle fracture patterns. Correlating the results of our study with the available literature, we feel that both acute or gradual correction for angular deformities around the ankle is a feasible solution as long as principles of deformity correction are adhered to. Techniques for salvaging and restoring the viability of injured physeal plate warrant additional research.

7.
Noncoding RNA Res ; 9(4): 1140-1158, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39022680

RESUMO

Irrespective of medical technology improvements, cancer ranks among the leading causes of mortality worldwide. Although numerous cures and treatments exist, creating alternative cancer therapies with fewer adverse side effects is vital. Since ancient times, plant bioactive compounds have already been used as a remedy to heal cancer. These plant bioactive compounds and their anticancer activity can also deregulate the microRNAs (miRNAs) in the cancerous cells. Therefore, the deregulation of miRNAs in cancer cells by plant bioactive compounds and the usage of the related miRNA could be a promising approach for cancer cure, mainly to prevent cancer and overcome chemotherapeutic side effect problems. Hence, this review highlights the function of plant bioactive compounds as an anticancer agent through the underlying mechanism that alters the miRNA expression in cancer cells, ultimately leading to apoptosis. Moreover, this review provides insight into using plant bioactive compounds -driven miRNAs as an anticancer agent to develop miRNA-based cancer gene therapy. They can be the potential resource for gene therapy and novel strategies targeting cancer therapeutics.

8.
J Environ Manage ; 366: 121808, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39025012

RESUMO

Photocatalysis, as an alternative for treating persistent water pollutants, holds immense promise. However, limitations hinder sustained treatment and recycling under varying light conditions. This comprehensive review delves into the novel paradigm of metal and non-metal doping to overcome these challenges. It begins by discussing the fundamental principles of photocatalysis and its inherent limitations. Understanding these constraints is crucial for developing effective strategies. Band gap narrowing by metal and non-metal doping modifies the band gap, enabling visible-light absorption. Impurity energy levels and oxygen vacancies influenced the doping energy levels and surface defects. Interfacial electron transfer and charge carrier recombination are the most important factors that impact overall efficiency. The comparative analysis of nanomaterials are reviewed on various, including nanometal oxides, nanocarbon materials, and advanced two-dimensional structures. The synthesis process are narratively presented, emphasizing production yields, selectivity, and efficiency. The review has potential applications in the environment for efficient pollutant removal and water purification, economic cost-effective and scalable production and technological advancement catalyst design, in spite of its challenges in material stability, synthesis methods and optimizing band gaps. The novelty of the review paper is on the proposal of a new paradigm of heterojunctions of doped metal and non-metal photocatalysts to promise highly efficient water treatment. This review bridges the gap between fundamental research and practical applications, offering insights into tailored nano photocatalysts.


Assuntos
Nanoestruturas , Águas Residuárias , Purificação da Água , Nanoestruturas/química , Purificação da Água/métodos , Águas Residuárias/química , Catálise , Poluentes Químicos da Água/química
9.
J Microencapsul ; 41(6): 403-418, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39007845

RESUMO

OBJECTIVE: The main purpose of the present study was to evaluate the therapeutic efficacy of Aloe vera-coated curcumin encapsulated nanoparticles in mitigating Alzheimer's disease progression in mice, by examining behavioural changes, biochemical markers, and histopathological alterations, thus elucidating its potential as a treatment strategy. METHODS: The green synthesis method was used to synthesise this nanoformulation, which was then characterised using a variety of techniques, including percentage encapsulation efficacy, UV-visible spectroscopy, DLS, FT-IR, FESEM, and EDX. Several in-vivo assessments, including behavioural evaluations, dose optimisation studies, oxidative stress marker estimation, and histological studies, were conducted to determine the potential therapeutic impact of nanoformulation on the Alzheimer-induced mice model. RESULTS: The synthesised nanoparticles show a mean diameter of 76.12 nm ±1.23, a PDI of 0.313 ± 0.02, a zeta potential of 6.27 ± 0.65 mV, and the percentage encapsulation efficiency between 90% and 95% indicating good stability of synthesised nanoformulation. With the help of Morris water maze, Y-maze, and novel object recognition assay, the learning capacity and memory were assessed, and the results show that the synthesised nanoformulation significantly decreased the transfer latency to reach baited arm or to the hidden platform within 7 days. CONCLUSION: The formulation demonstrated significant biochemical benefits and remarkable cognitive advantages, establishing it as a prospective therapeutic intervention option that is both safe and effective.


Assuntos
Aloe , Doença de Alzheimer , Curcumina , Modelos Animais de Doenças , Nanopartículas , Animais , Curcumina/farmacologia , Curcumina/administração & dosagem , Curcumina/química , Aloe/química , Doença de Alzheimer/tratamento farmacológico , Camundongos , Nanopartículas/química , Masculino , Comportamento Animal/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos
10.
J Genet ; 1032024.
Artigo em Inglês | MEDLINE | ID: mdl-39049485

RESUMO

Knowledge of genetic variability within and among types and breeds of dromedary (Camelus dromedarius L.) can be a valuable asset in selective breeding of desirable characteristics and will shed light on their origin, dynamics of domestication, and dispersion. Variability in an 809 bp segment of the mtDNA genome was measured within and among dromedaries from eight indigenous and one exogenous breed from Ha'il in north-central Saudi Arabia. Sixteen mtDNA haplotypes were identified among 47 camels. Haplotypic diversity among breeds is high (Hd = 0.817); most of the AMOVA variance (55.05%) occurs within breeds. Phylogenetic comparison of these haplotypes with those obtained across their geographic range showed that most haplotypes were placed within the same cluster with ancient wild dromedaries and the two newly identified haplotypes in this study. The most prevalent haplotypes found in dromedaries from this area appear to be ancestral to most other dromedaries and differ from each other by only one SNP. These results support the hypothesis that the Arabian Peninsula is a hub of diversification for dromedaries.


Assuntos
Camelus , DNA Mitocondrial , Variação Genética , Haplótipos , Filogenia , Animais , Camelus/genética , Camelus/classificação , Arábia Saudita , DNA Mitocondrial/genética , Polimorfismo de Nucleotídeo Único , Cruzamento
11.
ACS Omega ; 9(24): 26724-26734, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911808

RESUMO

The cactus family plant has been used in folk medicine for a long time. In this work, Opuntia stricta chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that O. stricta is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 µg/g), apigenin-7-Glu (3.15 µg/g), and catechin (2.85 µg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. In vivo, the methanol extract from Opuntia stricta showed anti-inflammatory activity. The computational modeling reveals that O. stricta compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both in vitro and in vivo findings. These data indicate that Opuntia stricta cladode powder could be potentially useful in pharmaceutical and food applications.

12.
Int J Lab Hematol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38924350

RESUMO

OBJECTIVES: Haematological parameters have been used for a long time for clinical evaluations, however the dynamics of these parameters has not been studied at length, in healthy populations. We aim to understand the dependence of haematological parameters on human physiotypes. DESIGN AND METHODS: Using an age and gender restricted healthy human (male) population (n = 100), we attempt to analyse the dynamics of haemoglobin and red blood cells, with reference to age, height and weight of individuals. Using advanced generalised additive modelling and classical hierarchical structural analysis we aim to establish relationships between these parameters and human physiotypes. RESULTS: We demonstrate that definitive relationships can be established for number of red blood cells, haemoglobin levels, RDW-CV, RDW-SD and weight, height and age of individuals. CONCLUSION: This study provides a proof of principle, that haematological parameters are dependent on physiotypic variation, within the normal ranges in a healthy population. It may also be noted that there is a definitive influence of height, weight and age on normal ranges and stratification by these factors might therefore make reference intervals narrower, in turn, possibly allowing more precise clinical decisions based on the complete blood count (CBC).

13.
Biogerontology ; 25(4): 705-737, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38619670

RESUMO

Polyalthia longifolia is well-known for its abundance of polyphenol content and traditional medicinal uses. Previous research has demonstrated that the methanolic extract of P. longifolia leaves (PLME, 1 mg/mL) possesses anti-aging properties in Saccharomyces cerevisiae BY611 yeast cells. Building on these findings, this study delves deeper into the potential antiaging mechanism of PLME, by analyzing the transcriptional responses of BY611 cells treated with PLME using RNA-sequencing (RNA-seq) technology. The RNA-seq analysis results identified 1691 significantly (padj < 0.05) differentially expressed genes, with 947 upregulated and 744 downregulated genes. Notably, the expression of three important aging-related genes, SIR2, SOD1, and SOD2, showed a significant difference following PLME treatment. The subsequent integration of these targeted genes with GO and KEGG pathway analysis revealed the multifaceted nature of PLME's anti-aging effects in BY611 yeast cells. Enriched GO and KEGG analysis showed that PLME treatment promotes the upregulation of SIR2, SOD1, and SOD2 genes, leading to a boosted cellular antioxidant defense system, reduced oxidative stress, regulated cell metabolism, and maintain genome stability. These collectively increased longevities in PLME-treated BY611 yeast cells and indicate the potential anti-aging action of PLME through the modulation of SIR2 and SOD genes. The present study provided novel insights into the roles of SIR2, SOD1, and SOD2 genes in the anti-aging effects of PLME treatment, offering promising interventions for promoting healthy aging.


Assuntos
Extratos Vegetais , Folhas de Planta , Polyalthia , Saccharomyces cerevisiae , Sirtuína 2 , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Metanol/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Polyalthia/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Análise de Sequência de RNA/métodos , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/genética , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/metabolismo , Sirtuína 2/genética , Sirtuína 2/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
14.
Int J Biol Macromol ; 264(Pt 1): 130544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428778

RESUMO

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Distrofia Muscular de Duchenne , Masculino , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Distrofia Muscular de Duchenne/patologia , Distrofina/genética , Distrofina/metabolismo , Distrofina/uso terapêutico , Fibras Musculares Esqueléticas/metabolismo
15.
Front Public Health ; 12: 1364221, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550311

RESUMO

Pharmacogenomics (PGx) is an important component of precision medicine that promises tailored treatment approaches based on an individual's genetic information. Exploring the initiatives in research that help to integrate PGx test into clinical setting, identifying the potential barriers and challenges as well as planning the future directions, are all important for fruitful PGx implementation in any population. Qatar serves as an exemplar case study for the Middle East, having a small native population compared to a diverse immigrant population, advanced healthcare system, national genome program, and several educational initiatives on PGx and precision medicine. This paper attempts to outline the current state of PGx research and implementation in Qatar within the global context, emphasizing ongoing initiatives and educational efforts. The inclusion of PGx in university curricula and healthcare provider training, alongside precision medicine conferences, showcase Qatar's commitment to advancing this field. However, challenges persist, including the requirement for population specific implementation strategies, complex genetic data interpretation, lack of standardization, and limited awareness. The review suggests policy development for future directions in continued research investment, conducting clinical trials for the feasibility of PGx implementation, ethical considerations, technological advancements, and global collaborations to overcome these barriers.


Assuntos
Farmacogenética , Medicina de Precisão , Humanos , Catar , Saúde Pública , Atenção à Saúde
16.
Inflammopharmacology ; 32(2): 1593-1606, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308794

RESUMO

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.


Assuntos
Antineoplásicos , Ácido Oleanólico , Plectranthus , Antioxidantes/uso terapêutico , Fator de Necrose Tumoral alfa , Interleucina-6 , Ácido Oleanólico/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/uso terapêutico , Inflamação/tratamento farmacológico , Citocinas , Antineoplásicos/uso terapêutico , Óxido Nítrico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Lipopolissacarídeos/farmacologia
17.
Front Pharmacol ; 15: 1343569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348393

RESUMO

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood-brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

19.
J Biomol Struct Dyn ; : 1-22, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174738

RESUMO

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and other small molecules across biological membranes. AQPs are involved in various physiological processes and pathological conditions, including cancer, making them as potential targets for anticancer therapy. However, the development of selective and effective inhibitors of AQPs remains a challenge. In this study, we explored the possibility of using natural sapogenins, a class of plant-derived aglycones of saponins with diverse biological activities, as potential inhibitors of AQPs. We performed molecular docking, dynamics simulation and binding energy calculation to investigate the binding and inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are overexpressed in various cancers. Our results showed that out of 19 sapogenins, 8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. These sapogenin also exhibited favourable binding affinities in the range of -7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. Furthermore, MD simulations provided insights into stability and dynamics of the sapogenin-AQP complexes. Most of the fluctuations in binding pocket were observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining protein-ligand complex showed stable root mean square deviation (RMSD) plots, strong hydrogen bonding interactions, stable solvent-accessible surface area (SASA) values and minimum distance to the receptor. These observations suggest that natural sapogenin hold promise as novel inhibitors of AQPs, offering a basis for the development of innovative therapeutic agents for cancer treatment. However, further validation of the identified compounds through experiments is essential for translating these findings into therapeutic applications.Communicated by Ramaswamy H. Sarma.

20.
Mol Neurobiol ; 61(8): 5117-5128, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38165583

RESUMO

Duchenne muscular dystrophy (DMD) is a genetic disorder that causes muscle weakness and degeneration. In this study, we identified potential biomarkers and drug targets for DMD through a comprehensive meta-analysis of mRNA profiles. We conducted an in-depth analysis of three microarray datasets from the GEO database, utilizing the Affymetrix platform. A rigorous data pre-processing pipeline encompassed background correction, normalization, log2 transformation and probe-to-gene symbol mapping. Robust multi-array average method followed by Limma package in R was employed to ensure differential expression analysis within individual datasets, yielding gene-specific p-values. We identified 63 genes exhibiting statistically significant differential expression across the three datasets (p < 0.05) and an absolute log fold change > 1.5. Functional enrichment analyses of these differentially expressed genes were done, followed by pathway analyses. Our results suggested pertinent biological processes, molecular functions and cellular components associated with DMD. Finally, eight hub genes-COL6A3, COL1A1, COL3A1, COL1A2, POSTN, TIMP1, THBS2 and SPP1-were pinpointed as central players in the network. Two differentially expressed genes with substantial absolute log-fold changes, namely, DMD, downregulated and MYH3, upregulated, were identified as potential therapeutic candidates. In light of these findings, our work contributes not only to understanding DMD at the molecular level but also presents potential targets for therapeutic strategies. Finally, our study facilitates the development of therapeutic interventions that can effectively control and mitigate the impact of DMD.


Assuntos
Biomarcadores , Distrofia Muscular de Duchenne , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Humanos , Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Terapia de Alvo Molecular , Multiômica
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