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1.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 1-7, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39097902

RESUMEN

Improving crop plants using biotechnological implications is a promising and modern approach compared to traditional methods. High-temperature exposure to the reproductive stage induces flower abortion and declines grain filling performance, leading to smaller grain production and low yield in lentil and other legumes. Thus, cloning effective candidate genes and their implication in temperature stress tolerance in lentil (Lens culinaris Medik.) using biotechnological tools is highly demandable. The 12-oxophytodienoic acid reductases (OPRs) are flavin mononucleotide-dependent oxidoreductases with vital roles in plants. They are members of the old yellow enzyme (OYE) family. These enzymes are involved in the octadecanoid pathway, which contributes to jasmonic acid biosynthesis and is essential in plant stress responses. Lentil is one of the vital legume crops affected by the temperature fluctuations caused by global warming. Therefore, in this study, the LcOPR1 gene was successfully cloned and isolated from lentils using RT-PCR to evaluate its functional responses in lentil under heat stress. The bioinformatics analysis revealed that the full-length cDNA of LcOPR1 was 1303 bp, containing an 1134 bp open reading frames (ORFs), encoding 377 amino acids with a predicted molecular weight of 41.63 and a theoretical isoelectric point of 5.61. Bioinformatics analyses revealed that the deduced LcOPR1 possesses considerable homology with other plant 12-oxophytodienoic acid reductases (OPRs). Phylogenetic tree analysis showed that LcOPR1 has an evolutionary relationship with other OPRs in different plant species of subgroup I, containing enzymes that are not required for jasmonic acid biosynthesis. The expression analysis of LcOPR1 indicated that this gene is upregulated in response to the heat-stress condition and during recovery in lentil. This study finding might be helpful to plant breeders and biotechnologists in LcOPR1 engineering and/or plant breeding programs in revealing the biological functions of LcOPR1 in lentils and the possibility of enhancing heat stress tolerance by overexpressing LcOPR1 in lentil and other legume plants under high temperature.


Asunto(s)
Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Lens (Planta) , Filogenia , Lens (Planta)/genética , Lens (Planta)/enzimología , Clonación Molecular/métodos , Regulación de la Expresión Génica de las Plantas/genética , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Secuencia de Aminoácidos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Calor , Genes de Plantas , Respuesta al Choque Térmico/genética , Oxilipinas/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH
2.
Pathol Res Pract ; 261: 155501, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39116569

RESUMEN

BACKGROUND: The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA). METHODS: The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.-9-154 C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed. RESULTS: The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models. CONCLUSIONS: This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.


Asunto(s)
Neoplasias de la Mama , Citocromo P-450 CYP1A2 , Predisposición Genética a la Enfermedad , Humanos , Femenino , Estudios de Casos y Controles , Neoplasias de la Mama/genética , Citocromo P-450 CYP1A2/genética , Persona de Mediana Edad , Adulto , Polimorfismo de Nucleótido Simple
3.
Sci Rep ; 14(1): 16351, 2024 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013994

RESUMEN

To sustainably increase wheat yield to meet the growing world population's food demand in the face of climate change, Conservation Agriculture (CA) is a promising approach. Still, there is a lack of genomic studies investigating the genetic basis of crop adaptation to CA. To dissect the genetic architecture of 19 morpho-physiological traits that could be involved in the enhanced adaptation and performance of genotypes under CA, we performed GWAS to identify MTAs under four contrasting production regimes viz., conventional tillage timely sown (CTTS), conservation agriculture timely sown (CATS), conventional tillage late sown (CTLS) and conservation agriculture late sown (CALS) using an association panel of 183 advanced wheat breeding lines along with 5 checks. Traits like Phi2 (Quantum yield of photosystem II; CATS:0.37, CALS: 0.31), RC (Relative chlorophyll content; CATS:55.51, CALS: 54.47) and PS1 (Active photosystem I centers; CATS:2.45, CALS: 2.23) have higher mean values in CA compared to CT under both sowing times. GWAS identified 80 MTAs for the studied traits across four production environments. The phenotypic variation explained (PVE) by these QTNs ranged from 2.15 to 40.22%. Gene annotation provided highly informative SNPs associated with Phi2, NPQ (Quantum yield of non-photochemical quenching), PS1, and RC which were linked with genes that play crucial roles in the physiological adaptation under both CA and CT. A highly significant SNP AX94651261 (9.43% PVE) was identified to be associated with Phi2, while two SNP markers AX94730536 (30.90% PVE) and AX94683305 (16.99% PVE) were associated with NPQ. Identified QTNs upon validation can be used in marker-assisted breeding programs to develop CA adaptive genotypes.


Asunto(s)
Adaptación Fisiológica , Agricultura , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Triticum/crecimiento & desarrollo , Adaptación Fisiológica/genética , Agricultura/métodos , Polimorfismo de Nucleótido Simple , Fitomejoramiento/métodos , Fenotipo , Genoma de Planta , Genotipo , Pan
4.
Cancer Cell Int ; 24(1): 244, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003454

RESUMEN

Paclitaxel is commonly used to treat breast, ovarian, lung, esophageal, gastric, pancreatic cancer, and neck cancer cells. Cancer recurrence is observed in patients treated with paclitaxel due to paclitaxel resistance emergence. Resistant mechanisms are observed in cancer cells treated with paclitaxel, docetaxel, and cabazitaxel including changes in the target molecule ß-tubulin of mitosis, molecular mechanisms that activate efflux drug out of the cells, and alterations in regulatory proteins of apoptosis. This review discusses new molecular mechanisms of taxane resistance, such as overexpression of genes like the multidrug resistance genes and EDIL3, ABCB1, MRP1, and TRAG-3/CSAG2 genes. Moreover, significant lncRNAs are detected in paclitaxel resistance, such as lncRNA H19 and cross-resistance between taxanes. This review contributed to discovering new treatment strategies for taxane resistance and increasing the responsiveness of cancer cells toward chemotherapeutic drugs.

5.
Int J Biol Macromol ; 270(Pt 2): 132254, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729501

RESUMEN

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.


Asunto(s)
Péptidos , Humanos , Péptidos/química , Péptidos/uso terapéutico , Animales , Virosis/tratamiento farmacológico , Virosis/prevención & control , Proteínas Recombinantes/uso terapéutico , Ingeniería de Proteínas/métodos , Antivirales/uso terapéutico , Virus
7.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 10-17, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38430047

RESUMEN

The present study aimed to identify and characterize new sources of salt tolerance among 94 rice varieties from varied geographic origins. The genotypes were divided into five groups based on their morphological characteristics at both vegetative and reproductive stages using salinity scores from the Standard Evaluation System (SES). The experiment was designed as per CRD (Completely Randomized Design) with 2 sets of salinity treatments for 8 dS/meter and 12 dS/meter, respectively compared with one non-salinized control set. Using a Soil Plant Analysis Development (SPAD) meter, assessments of the apparent chlorophyll content (greenness) of the genotypes were done to comprehend the mechanism underlying their salt tolerance.  To evaluate molecular genetic diversity, a panel of 1 K RiCA SNP markers was employed. Utilizing TASSEL 5.0 software, 598 filtered SNPs were used for molecular analysis. Whole-genome association studies (GWAS) were also used to investigate panicle number per plant (pn, tiller number per plant (till), SPAD value (spad), sterility (percent) (str), plant height (ph) and panicle length (pl. It is noteworthy that these characteristics oversee conveying the visible signs of salt damage in rice. Based on genotype data, diversity analysis divided the germplasm groups into four distinct clusters (I, II, III and IV). For the traits studied, thirteen significant marker-trait associations were discovered. According to the phenotypic screening, seven germplasm genotypes namely Koijuri, Asha, Kajal, Kaliboro, Hanumanjata, Akundi and Dular, are highly tolerant to salinity stress. The greenness of these genotypes was found to be more stable over time, indicating that these genotypes are more resistant to stress. Regarding their tolerance levels, the GWAS analysis produced comparable results, supporting that salinity-tolerant genotypes having minor alleles in significant SNP positions showed more greenness during the stress period. The Manhattan plot demonstrated that at the designated significant SNP position, the highly tolerant genotypes shared common alleles. These genotypes could therefore be seen as important genomic resources for accelerating the development and release of rice varieties that are tolerant to salinity.


Asunto(s)
Oryza , Tolerancia a la Sal , Tolerancia a la Sal/genética , Oryza/genética , Estudio de Asociación del Genoma Completo , Genotipo , Amantadina , Salinidad
8.
Biochem Genet ; 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38522064

RESUMEN

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

9.
Saudi Pharm J ; 32(3): 101962, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38318318

RESUMEN

Background: Tetrazole-based derivatives and their electronic structures have displayed interesting antimicrobial activity. Methods: The tetrazole-based hybrids linked with thiazole, thiophene and thiadiazole ring systems have been synthesized through various chemical reactions. The computational method DFT/B3LYP has been utilized to calculate their electronic properties. The antimicrobial effectiveness was investigated against representative bacterial and fungal strains. Additionally, the synthesized derivatives binding interaction was stimulated by docking program against PDB ID: 4URO as a model of the ATP binding domain of S. aureus DNA Gyrase subunit B. Results: The structures of the synthesized tetrazole-based derivatives were confirmed by IR, NMR, and Mass spectroscopic data. The DFT/B3LYP method showed that the thiadiazole derivatives 9a-c had lower ΔEH-L than the thiophenes 7a-c and thiazoles 5a-c. The hybrids 5b, 5c, and 7b exhibited proper antibacterial activity against Gram's +ve bacterial strains (S. aureus and S. pneumonia), while 9a displayed potent activity towards Gram's -ve bacterial strains (S. typhimurium and E. coli). Meanwhile, derivatives 5a-b, 7a, 7c, and 9c showed good effectiveness towards fungal strain (C. albicans). Conclusion: The study provides valuable tetrazole core-linked heterocyclic rings and opens the door to further research on their electrical characteristics and applications. Tetrazoles and thiazoles have antibacterial properties in pharmacological frameworks, making these hybrids potential lead molecules for drug development. The conclusion summarizes the data and suggests that the synthesized chemicals' interaction with a particular protein domain suggests focused biological activity.

10.
Int J Biol Macromol ; 264(Pt 1): 130454, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417758

RESUMEN

The demand for the functionalization of additive materials based on bacterial cellulose (BC) is currently high due to their potential applications across various sectors. The preparation of BC-based additive materials typically involves two approaches: in situ and ex situ. In situ modifications entail the incorporation of additive materials, such as soluble and dispersed substances, which are non-toxic and not essential for bacterial cell growth during the production process. However, these materials can impact the yield and self-assembly of BC. In contrast, ex situ modification occurs subsequent to the formation of BC, where the additive materials are not only adsorbed on the surface but also impregnated into the BC pellicle, while the BC slurry was homogenized with other additive materials and gelling agents to create composite films using the casting method. This review will primarily focus on the in situ and ex situ functionalization of BC then sheds light on the pivotal role of functionalized BC in advancing biomedical technologies, wound healing, tissue engineering, drug delivery, bone regeneration, and biosensors.


Asunto(s)
Celulosa , Ingeniería de Tejidos , Celulosa/metabolismo , Bacterias/metabolismo , Materiales Biocompatibles/metabolismo
11.
Sci Rep ; 13(1): 22782, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38129495

RESUMEN

Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity.


Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Cisplatino/farmacología , Resistencia a Antineoplásicos , Apoptosis , Hormonas/farmacología , Línea Celular Tumoral , Neoplasias Ováricas/genética
12.
Int Immunopharmacol ; 125(Pt A): 111180, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37939515

RESUMEN

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.


Asunto(s)
Carcinoma , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Pulmón/patología
13.
ACS Omega ; 8(39): 35746-35754, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37810661

RESUMEN

Drought is a prime stress, drastically affecting plant growth, development, and yield. Plants have evolved various physiological, molecular, and biochemical mechanisms to cope with drought. Investigating specific biochemical pathways related to drought tolerance mechanisms of plants through biotechnology approaches is one of the quickest and most effective strategies for enhancing crop production. Among them, microRNAs (miRNAs) are the principal post-transcriptional regulators of gene expression in plants during plant growth under biotic and abiotic stresses. In this study, five different chickpea genotypes (Inci, Hasan bey, Arda, Seçkin, and Diyar 95) were grown under normal and drought stress. We recorded the expression levels of microRNAs in these genotypes and found differential expression (miRNA396, miR408, miRNA414, miRNA528, and miRNA1533) under contrasting conditions. Results revealed that miRNA414 and miRNA528 considerably increased in all genotypes under drought stress, and expression levels of miRNA418, miRNA1533, and miRNA396 (except for the Seçkin genotype) were found to be higher under the watered conditions. These genotypes were also investigated for heavy metal, phenolic acid, protein, and nitrogen concentrations under normal and drought stress conditions. The Arda genotype showed a significant increase in nitrogen (5.46%) and protein contents (28.3%), while protein contents were decreased in the Hasan bey and Seçkin genotypes subjected to drought stress. In the case of metals, iron was the most abundant element in all genotypes (Inci = 15.4 ppm, Hasan bey = 29.6 ppm, Seçkin = 37.8 ppm, Arda = 26.3 ppm, and Diyar 95 = 40.8 ppm) under normal conditions. Interestingly, these results were related to miRNA expression in the chickpea genotypes and hint at the regulation of multiple pathways under drought conditions. Overall, the present study will help us to understand the miRNA-mediated regulation of various pathways in chickpea genotypes.

14.
Int J Biol Macromol ; 251: 126318, 2023 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-37579903

RESUMEN

Targeting the remediation of oil pollution in water, the construction of super magnetic adsorbent nanocomposites (NCs) was achieved using the nanoparticles of chitosan (Cht), lignin (Lg) and phycosynthesized iron nanoparticles (Fe MNPs) using Gelidium amansii extract. The syntheses and conjugations of nanomaterials were authenticated via infrared spectral analysis and the structural physiognomies of them were appraised via electron microscopy and zeta analysis. The Lg NPs, Cht NPs, Fe MNPs and their composites (Lg/Cht MNCs) had mean particles' sizes of 42.3, 76.4, 14.2 and 108.3 nm, and were charged with - 32.7, + 41.2, + 28.4 and +37.5 mV, respectively. The magnetometer revealed the high magnetic properties of both Fe MNPs and Lg/Cht MNCs; the maximum swelling of Lg/Cht NPs (46.3 %), and Lg/Cht MNPs (33.8 %) was detected after 175 min. The diesel oil adsorption experiments with Lg/Cht MNPs, using batch adsorption practices, revealed the powerful potentiality of magnetic NCs to remove oil pollution in water; the maximum adsorption capacity (qt) was achieved with the conditions of pH = 7.5, adsorption period = 90 min and adsorbent dose = 200 mg/L. The magnetic Lg/Cht MNCs exhibited excellent recovery/reusability attributes for five adsorption cycles; the qt differences were negligible after the entire oil-adsorption cycles, with oil removal of >90 %. The innovative fabricated Lg/Cht MNCs could provide an effectual, sustainable and eco-friendly approach for the removal of pollutant oil in water resources.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123063, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37390719

RESUMEN

The target of the current study is to create a novel hybrid nanocomposite (Cs@Pyc.SOF) by combining the anti-hepatitis C virus (HCV) drug sofosbuvir with the nano antioxidant pycnogenol (Pyc) and nano biomolecules like chitosan nanoparticles (Cs NPs). The characterization procedure works to verify the creation of nanocomposite (NCP) using several different techniques. UV-Vis spectroscopy is used to measure SOF loading efficiency. The various concentrations of the SOF drug were used to determine the binding constant rate Kb, which was found to be 7.35 ± 0.95 min-1 with an 83% loading efficiency. At pH 7.4, the release rate was 80.6% after two hours and 92% after 48 h, whereas at pH 6.8, it was 29% after two hours and 94% after 48 h. After 2 and 48 h, the release rate in water was 38% and 77%, respectively. . The SRB technique for fast screening is used for the cytotoxicity test, where the investigated composites show a safety status and high viability against the examined cell line. The cytotoxicity assay of the SOF hybrid materials has been identified with cell lines like mouse normal liver cells (BNL). So, Cs@Pyc.SOF was recommended as a substitute medication for the therapy of HCV, but the results need clinical studies.


Asunto(s)
Quitosano , Hepatitis C , Animales , Ratones , Sofosbuvir , Antivirales/uso terapéutico , Hepacivirus , Preparaciones Farmacéuticas , Quimioterapia Combinada , Hepatitis C/tratamiento farmacológico , Análisis Espectral , Ribavirina
16.
Molecules ; 27(22)2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36431959

RESUMEN

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Enfermedades del Sistema Digestivo , Hepatopatías , Persea , Humanos , Ratas , Animales , Ciclosporina/efectos adversos , Persea/metabolismo , Estrés del Retículo Endoplásmico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Antioxidantes/farmacología , Estrés Oxidativo , Semillas/metabolismo
17.
ACS Chem Neurosci ; 13(16): 2529-2539, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35930676

RESUMEN

The aggregation of Aß42 is established as a key factor in the development of Alzheimer's disease (AD). Consequently, molecules that inhibit aggregation of peptide may lead to therapies to prevent or control AD. Several studies suggest that oligomeric intermediates present during aggregation may be more cytotoxic than fibrils themselves. In this work, we examine the inhibitory activity of an antibiotic MXF on aggregation (fibrils and oligomers) and disaggregation of Aß42 using various biophysical and microscopic studies. Computational analysis was done to offer mechanistic insight. The amyloid formation of Aß42 is suppressed by MXF, as demonstrated by the decrease in both the corresponding ThT fluorescence intensity and other biophysical techniques. The lag phase of amyloid formation doubled from 4.53 to 9.66 h in the presence of MXF. The addition of MXF at the completion of the fibrillation reaction, as monitored by ThT, led to a rapid, concentration dependent, exponential decrease in fluorescence signal that was consistent with loss of fibrils. We used TEM to directly demonstrate that MXF caused fibrils to disassemble. Our docking results show that MXF binds to both monomeric and fibrillar forms of Aß42 with significant affinities. We also observed breaking of fibrils in the presence of MXF through molecular dynamics simulation. These findings suggest that antibiotic MXF could be a promising lead compound with dual role as fibril/oligomer inhibitor and disaggregase for further development as potential repurposed therapeutic against AD.


Asunto(s)
Enfermedad de Alzheimer , Moxifloxacino , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Reposicionamiento de Medicamentos , Humanos , Moxifloxacino/farmacología , Moxifloxacino/uso terapéutico , Fragmentos de Péptidos/metabolismo
18.
Biomed Res Int ; 2022: 7380147, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35535039

RESUMEN

Staphylococcus aureus is a major human pathogen that is sometimes resistant to vancomycin. In this study, the prevalence of vancomycin-resistant Staphylococcus aureus (VRSA) was studied. 100 isolates of S. aureus were identified based on biochemical and molecular evidence. The antibiotic susceptibility of the studied isolates was tested against 13 antibiotics by the disc diffusion method that showed 24 vancomycin-resistant isolates. The minimum inhibitory concentrations (MICs) were estimated by the agar dilution method to determine vancomycin intermediate-resistant S. aureus (VISA) and VRSA. The resistance gene cluster (vanA, vanR, vanH, and vanY) was amplified by PCR and then sequenced. Amplification of vanA and vanR genes showed that they are present in 21.4% and 14.3% of VRSA isolates, respectively, whereas none of the studied genes has been detected in VISA strains. A significant antimicrobial effect toward VRSA isolates using silver nanoparticles (AgNPs) synthesized from S. aureus and rosemary leaves was recorded. This study confirmed the existence of VRSA strains in Egypt. Furthermore, the use of silver nanoparticles inhibits these vancomycin-resistant S. aureus strains in vitro.


Asunto(s)
Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Egipto , Humanos , Pruebas de Sensibilidad Microbiana , Plata/farmacología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus , Vancomicina/farmacología , Resistencia a la Vancomicina/genética
19.
Andrologia ; 54(8): e14456, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35560246

RESUMEN

Varieties of studies have been used to investigate the health benefits of Spirulina (Arthrospira platensis); however, more research is needed to examine if its nano form may be utilized to treat or prevent several chronic diseases. So, we designed this study to explore the effect and the cellular intracellular mechanisms by which Arthrospira platensis Nanoparticles (NSP) alleviates the testicular injury induced by diabetes in male Wistar rats. Eighty Wistar male rats (n = 80) were randomly allocated into eight groups. Group 1 is untreated rats (control), Group 2 including STZ-induced diabetic rats with 65 mg/kg body weight STZ (STZ-diabetic), Group 3-5: including diabetic rats treated with NSP1, NSP2, and NSP3 at 0.25, 0.5, and 1 mg/kg body weight, respectively, once daily orally by the aid of gastric gavage for 12 consecutive weeks and groups 6-8 include normal rats received NSP (0.25, 0.5, and 1 mg/kg body weight once daily orally. The identical volume of normal saline was injected into both control and diabetic rats. After 12 weeks of diabetes induction, the rats were killed. According to our findings, NSP administration to diabetic rats enhances the total body weight and the weight of testes and accessory glands; in addition, NSP significantly reduced nitric oxide and malondialdehyde in testicular tissue improved sperm parameters. Intriguingly, it raises testicular GSH and SOD activity by a significant amount (p < 0.05). As well, Oral administration of NSP to diabetic rats resulted in a decrease in the blood glucose levels, HA1C, induced in the diabetic group, which overcame the diabetic complications NSP caused down-regulation of apoptotic genes with upregulation of BCL-2 mRNA expression (p < 0.05) and prominent up-regulation of steroidogenesis genes expression level in testes in comparison to the diabetic rats which resulted in improving the decreased levels of testosterone hormone, FSH, and LH induced by diabetes. In the same way, our histopathological findings support our biochemical and molecular findings; in conclusion, NSP exerted a protective effect against reproductive dysfunction induced by diabetes not only through its high antioxidant and hypoglycemic action but also through its down-regulation of Apoptotic genes and up-regulation of steroidogenesis regulatory genes expression level in diabetic testes.


Asunto(s)
Diabetes Mellitus Experimental , Nanopartículas , Spirulina , Enfermedades Testiculares , Animales , Antioxidantes/farmacología , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Semen/metabolismo , Spirulina/química , Spirulina/metabolismo , Enfermedades Testiculares/etiología , Enfermedades Testiculares/prevención & control , Testículo
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