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1.
Environ Res ; 252(Pt 2): 118927, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38631467

RESUMEN

Effective drug delivery for is the foremost requirement for the complete recovery of the disease. Nanomedicine and nanoengineering has provided so many spaces and ideas for the drug delivery design, whether controlled, targeted, or sustained. Different types of nanocarriers or nanoparticles are aggressively designed for the drug delivery applications. Clay minerals are identified as a one of the potential nanocarrier for the drug delivery. Owing to their biocompatibility and very low cytotoxicity, clay minerals showing effective therapeutic applications. In the present investigation, clay mineral, i.e., Halloysite nano tubes are utilized as a nanocarrier for the delivery of antibiotic cefixime (CFX), a third-generation cephalosporin. The HNT was first functionalized with the sulfuric acid and then further treated with the 3-(aminopropyl)triethoxysilane (APTES). The drug is loaded on three different classifications of HNTs, i.e., Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT and their comparative analysis is established. Different characterization techniques such as X-ray diffractometry (XRD), Fourier transform infra-red (FT-IR), Transmission electron microscopy TEM), Brunauer-Emmett-Teller (BET), adsorption studies, and Thermogravimetric analysis (TGA) were performed to evaluate their chemical, structural, morphological, and thermal properties. TGA confirmed the encapsulation efficiency of Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT as 42.65, 52.19, and 53.43%, respectively. Disk diffusion and MTT assay confirmed that the drug loaded HNTs have potential antibacterial activities and less cytotoxicity. The adsorption capacity of CFX with different HNTs are evaluated and Different adsorption and kinetic models have been discussed. Drug release studies shows that APTES-CFX-HNT showing sustained release of cefixime as compared to Bare-CFX-HNT and Acid-CFX-HNT.


Asunto(s)
Antibacterianos , Cefixima , Arcilla , Cefixima/química , Antibacterianos/química , Arcilla/química , Portadores de Fármacos/química , Silicatos de Aluminio/química , Nanopartículas/química , Silanos/química , Espectroscopía Infrarroja por Transformada de Fourier , Propilaminas
2.
Food Technol Biotechnol ; 62(2): 188-204, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39045303

RESUMEN

Research background: Coccinia grandis L. is traditionally used for the treatment of diabetes mellitus. Since the scientific evidence and mechanism of action have not yet been extensively investigated, this study aims to evaluate the antidiabetic and cytotoxic effects together with the optimisation and development of a scale-up process design for higher yields of bioactive phytocompounds from C. grandis. Experimental approach: The in silico study was conducted to predict the binding affinity of phytocompounds of C. grandis for α-amylase and α-glucosidase enzymes involved in the pathophysiology of diabetes with pharmacokinetic assessment. Response surface methodology was used to determine the optimum total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC) and antioxidant activities (DPPH and FRAP) in 17 different experimental runs in which the parameters of microwave-assisted extraction such as temperature (50-70 °C), power (400-1000 W) and time (15-45 min) were varied. The phytocompounds were purified and identified using column chromatography, thin-layer chromatography (TLC), UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and liquid chromatography-mass spectrometry (LC-MS). The in vitro antidiabetic activity was determined by α-amylase and α-glucosidase enzymatic inhibitory assays, while cytotoxic investigations were done by measuring haemolytic activity, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and chorioallantoic membrane (CAM) assays. Results and conclusions: The reported major bioactive compounds have shown an excellent binding affinity for α-amylase and α-glucosidase enzymes in the range of -14.28 to -36.12 kJ/mol with good pharmacokinetic properties and toxicities ranging from low to medium. The bioactive constituents such as total phenols, total flavonoids, total tannins and antioxidant activities such as DPPH and FRAP were found to be high and dependent on the optimised microwave-assisted extraction parameters such as temperature, time and power: 55 °C, 45 min and 763 W, respectively. Sixteen compounds were identified by FTIR and LC-MS spectra in the plant sample after preliminary identification, purification and TLC. The percentage of enzyme inhibition depended on the concentration of the extract (7.8-125.0 µg/mL) and was higher than that of acarbose. The haemolytic activity was in accordance with ISO standards and low toxicity was observed in the MTT and CAM assays in the range of 7.8-125.0 µg/mL, suggesting its potential use as an antidiabetic drug and for functional food development. Novelty and scientific contribution: The results of the study open up new opportunities for researchers, scientists and entrepreneurs in the food and pharmaceutical sectors to develop antidiabetic foods and medicines that help diabetics to better control their condition and maintain overall health.

3.
Am J Trop Med Hyg ; 111(1): 59-63, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38834057

RESUMEN

Post-kala-azar dermal leishmaniasis (PKDL) is widely prevalent in the endemic regions of India, but its treatment remains unsatisfactory. The WHO recommends a 12-week treatment with oral miltefosine, but its ocular toxicities are a serious concern. The late 1980s and early 1990s saw the use of sodium stibogluconate and amphotericin B (AmB) for a brief period. Both drugs had frequent adverse events and were expensive, and the duration of treatments was unacceptably long. This retrospective study evaluated, analyzed, and reported the outcomes of PKDL patients treated with a shorter course of AmB, the most effective antileishmanial drug. The hospital records of PKDL patients treated with AmB by 30 alternate-day infusions over 60 days (instead of conventional 60-80 infusions over 100-120 days) between September 2010 and August 2016 were reviewed. Only patients with confirmed parasitological diagnosis were included. Their records were studied for treatment-related adverse events, end-of-treatment parasitological status, and 12-month follow-up results. One hundred two patients were eligible for this study between September 2010 and August 2016. After therapy, 92/102 (90.2%) patients improved; 3 (2.9%) had to cease treatment owing to severe adverse effects, and one died of severe diarrhea unrelated to AmB. Six (5.9%) patients withdrew consent before the treatment was complete. At the 12-month evaluation, 89/102 (87.3%) patients attained a final cure. A 30-infusion regimen of AmB remains highly effective in PKDL. Without a shorter, safer, and more economical regimen for the treatment of PKDL, it should be used until a better regimen is available.


Asunto(s)
Anfotericina B , Antiprotozoarios , Ácido Desoxicólico , Combinación de Medicamentos , Leishmaniasis Cutánea , Leishmaniasis Visceral , Humanos , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Masculino , India/epidemiología , Leishmaniasis Visceral/tratamiento farmacológico , Femenino , Antiprotozoarios/uso terapéutico , Antiprotozoarios/efectos adversos , Antiprotozoarios/administración & dosificación , Adulto , Ácido Desoxicólico/uso terapéutico , Ácido Desoxicólico/administración & dosificación , Ácido Desoxicólico/efectos adversos , Estudios Retrospectivos , Leishmaniasis Cutánea/tratamiento farmacológico , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Resultado del Tratamiento , Anciano
4.
Cancers (Basel) ; 16(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38672545

RESUMEN

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed drugs, comprising FDA-approved (in other disease indications), generic, off-patent, and failed medications, offer distinct advantages including established safety profiles, cost-effectiveness, and expedited development timelines compared to novel drug discovery processes. Various methodologies, such as knowledge-based analyses, drug-centric strategies, and computational approaches, play pivotal roles in identifying potential candidates for repurposing. However, despite the promise of repurposed drugs, drug repositioning confronts formidable obstacles. Patenting issues, financial constraints associated with conducting extensive clinical trials, and the necessity for combination therapies to overcome the limitations of monotherapy pose significant challenges. This review provides an in-depth exploration of drug repurposing, covering a diverse array of approaches including experimental, re-engineering protein, nanotechnology, and computational methods. Each of these avenues presents distinct opportunities and obstacles in the pursuit of identifying novel clinical uses for established drugs. By examining the multifaceted landscape of drug repurposing, this review aims to offer comprehensive insights into its potential to transform cancer therapeutics.

5.
Indian Heart J ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39069072

RESUMEN

BACKGROUND: We aimed to assess the utility of B-type natriuretic peptide (BNP) and 6-min walk test (6 MWT) together as predictors of re-hospitalization and mortality in acute decompensated heart failure (ADHF) patients. METHODS: This prospective, observational, comparative study was conducted at a tertiary care center in India between October 2016 and March 2018. Patients (aged≥18 years) with ADHF and left ventricular systolic dysfunction were included in this study. The study group (N = 100 patients) consisted of patients undergoing a second BNP test along with the 6 MWT at the time of discharge and at 3-months of discharge. The control group (N = 100 patients) consisted of patients who did not undergo these tests at discharge and/or at 3-months of discharge. Study endpoints were re-hospitalization within 6-months, and in-patient and 6-month mortality. RESULTS: Total 200 patients diagnosed with ADHF were enrolled. Mean age was 53.46 ± 10.12 years in the study group and 52.98 ± 9.88 years in the control group. ROC analysis of BNP level to predict re-hospitalization revealed AUC of 0.935 (p < 0.001) at admission, 0.915 (p < 0.001) at discharge, and 0.783 (p < 0.001) at 3-months. Similarly, at discharge, ROC analysis of 6 MWT to predict death gave AUC of 0.670 (p = 0.011), and at 3-months, it was 0.838 (p < 0.001). ROC analysis of BNP level to predict mortality showed AUC of 0.960 (p < 0.001) at admission, 0.947 (p < 0.001) after discharge, and 0.960 (p = 0.002) at 3-months. CONCLUSION: BNP levels and 6 MWT have good prognostic utility in ADHF patients, and thus may be beneficial in making therapeutic adjustments and taking precautionary measures in these patients.

6.
Chemosphere ; 353: 141541, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38423149

RESUMEN

Plastics are a vital component of our daily lives in the contemporary globalization period; they are present in all facets of modern life. Because the bulk of synthetic plastics utilized in the market are non-biodegradable by nature, the issues associated with their contamination are unavoidable in an era dominated by polymers. Polyethylene terephthalate (PET), which is extensively used in industries such as automotive, packaging, textile, food, and beverages production represents a major share of these non-biodegradable polymer productions. Given its extensive application across various sectors, PET usage results in a considerable amount of post-consumer waste, majority of which require disposal after a certain period. However, the recycling of polymeric waste materials has emerged as a prominent topic in research, driven by growing environmental consciousness. Numerous studies indicate that products derived from polymeric waste can be converted into a new polymeric resource in diverse sectors, including organic coatings and regenerative medicine. This review aims to consolidate significant scientific literatures on the recycling PET waste for electrochemical device applications. It also highlights the current challenges in scaling up these processes for industrial application.


Asunto(s)
Plásticos , Tereftalatos Polietilenos , Reciclaje , Polímeros , Embalaje de Productos
7.
Food Chem ; 460(Pt 2): 140571, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39079358

RESUMEN

Soy protein is a promising nutritional source with improved functionality and bioactivities due to conjugation with polyphenols (PP)-the conjugates between soy protein and PP held by covalent and noncovalent bonds. Different approaches, including thermodynamics, spectroscopy, and molecular docking simulations, can demonstrate the outcomes and mechanism of these conjugates. The soy protein, PP structure, matrix properties (temperature, pH), and interaction mechanism alter the ζ-potential, secondary structure, thermal stability, and surface hydrophobicity of proteins and also improve the techno-functional properties such as gelling ability, solubility, emulsifying, and foaming properties. Soy protein-PP conjugates also reveal enhanced in vitro digestibility, anti-allergic, antioxidant, anticancer, anti-inflammatory, and antimicrobial activities. Thus, these conjugates may be employed as edible film additives, antioxidant emulsifiers, hydrogels, and nanoparticles in the food industry. Future research is needed to specify the structure-function associations of soy protein-PP conjugates that may affect their functionality and application in the food industry.

8.
PNAS Nexus ; 3(2): pgae011, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38328782

RESUMEN

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

9.
Asian Pac J Cancer Prev ; 25(7): 2283-2289, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39068559

RESUMEN

INTRODUCTION: Acute myeloid leukemia with normal cytogenetics (CN-AML) represents a heterogeneous group having diverse genetic mutations. Understanding the significance of each of these mutations is necessary. In this study, we evaluated the prognostic role of MN1 expression in adult CN-AML patients. METHOD: One hundred and sixty-three de-novo adult AML patients were evaluated for MN1 expression by real-time PCR. MN1 expression was correlated with the clinical characteristics of the patients and their outcomes. RESULTS: Higher MN1 expression was associated with NPM1 wild-type (p<0.0001), CD34 positivity (p=0.006), and lower clinical remission rate (p=0.027). FLT3-ITD and CEBPA mutations had no association with MN1 expression. On survival analysis, a high MN1 expression was associated with poor event-free survival (Hazard Ratio 2.47, 95% Confidence Interval: 1.42-4.3; p<0.0001) and overall survival (Hazard Ratio 4.18, 95% Confidence Interval: 2.17-8.08; p<0.0001). On multivariate analysis, the MN1 copy number emerged as an independent predictor of EFS (p<0.0001) and OS (p<0.0001). CONCLUSION: MN1 expression is an independent predictor of outcome in CN-AML.


Asunto(s)
Biomarcadores de Tumor , Leucemia Mieloide Aguda , Nucleofosmina , Transactivadores , Proteínas Supresoras de Tumor , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Femenino , Adulto , Persona de Mediana Edad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Pronóstico , Adulto Joven , Transactivadores/genética , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Tasa de Supervivencia , Estudios de Seguimiento , Adolescente , Mutación , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismo , Medición de Riesgo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Anciano de 80 o más Años
10.
PLoS Negl Trop Dis ; 18(6): e0012242, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38900786

RESUMEN

BACKGROUND: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF. METHODOLOGY/PRINCIPAL FINDINGS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred. CONCLUSIONS/SIGNIFICANCE: Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia. TRIAL REGISTRATION: CTRI/2017/04/008421.


Asunto(s)
Anfotericina B , Antiprotozoarios , Leishmaniasis Cutánea , Leishmaniasis Visceral , Fosforilcolina , Humanos , Anfotericina B/uso terapéutico , Anfotericina B/efectos adversos , Anfotericina B/administración & dosificación , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapéutico , Fosforilcolina/administración & dosificación , Fosforilcolina/efectos adversos , Bangladesh , Masculino , Antiprotozoarios/uso terapéutico , Antiprotozoarios/efectos adversos , Antiprotozoarios/administración & dosificación , Adulto , Adolescente , Femenino , Persona de Mediana Edad , Adulto Joven , Niño , India , Leishmaniasis Visceral/tratamiento farmacológico , Resultado del Tratamiento , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Quimioterapia Combinada
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