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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124821, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39167898

RESUMEN

Detection of specific ions using fluorescent probes has relevance in several areas of therapeutics development and environmental science. Here, we provide new perspectives to the sensing of a styryl benzothiazolium-based fluorescent compound 1 and report that sensing properties are for sulfite ions in general with highest preference for metabisulfite ions (S2O52-) adding to its previously determined role as a bisulfite ion sensor. This probe exhibits its sensing action via an addition reaction in which the styryl double bond gets reduced. The interference studies highlighted that the sequence of addition of nitrite and metabisulfite has a bearing on the overall interference outcome. Spectroscopic studies revealed that the order of preferential sensing of sulfites and sulfide ion is S2O52- > HSO3- > SO32- > S2-. Although this probe displays robust sensing on its own through fluorescence quenching, its fluorescence emission can be enhanced at much lower concentrations in the presence of a G-quadruplex DNA without compromising the outcome of the sensing.

2.
Contemp Clin Trials ; 146: 107684, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236782

RESUMEN

BACKGROUND: Clinical drug trials are intricate, involving numerous stakeholders, substantial data, and stringent regulations. Traditional systems for recording, storing, and sharing trial data often face data integrity, transparency, security, and interoperability challenges. The utilization of blockchain technology has emerged as a transformative influence in various industries, and its potential within healthcare, particularly in clinical drug trials, is increasingly gaining recognition. METHODS: Blockchain technology presents a decentralized and immutable ledger system that holds promise in effectively addressing these challenges. As the healthcare industry continues its journey of digital transformation, the incorporation of blockchain technology for monitoring clinical drug trials represents a paradigm shift that can result in more reliable, efficient, and transparent trials. RESULTS AND CONCLUSION: This review explores the innovative application of blockchain technology in transforming the monitoring and management of clinical drug trials and provides a comprehensive overview of the possibilities, challenges, and future directions of blockchain-based monitoring in the context of clinical drug trials, contributing to the progress of both blockchain technology and healthcare research practices.

3.
ACS Appl Bio Mater ; 7(9): 5861-5884, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39192748

RESUMEN

The evolution of targeted cancer theranostics has revolutionized personalized medicine by integrating diagnostic and therapeutic capabilities. Prostate-specific membrane antigen (PSMA) has emerged as a key theranostic target in the context of prostate cancer, paving the way for the clinical approval of multiple drugs. However, the persistent challenge of off-target toxicity, which plagues both conventional and advanced treatment modalities such as targeted chemotherapy and radiotherapy, thus demands further innovation. Considering this critical issue, this review discusses the recent advances in the binary treatment techniques, i.e., phototherapies, that have the potential to circumvent the key concern of off-target toxicity associated with personalized chemotherapy and radiotherapy. Precisely, an up-to-date overview of the latest developments in the near-infrared (NIR)-based phototheranostic strategies for prostate cancer by targeting PSMA has been presented. Furthermore, we have discussed the associated particulars that require specific attention in enhancing the translational potential of phototheranostic techniques.


Asunto(s)
Rayos Infrarrojos , Neoplasias de la Próstata , Nanomedicina Teranóstica , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Masculino , Glutamato Carboxipeptidasa II/metabolismo , Antígenos de Superficie/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Fototerapia , Animales , Ensayo de Materiales , Antineoplásicos/química , Antineoplásicos/farmacología , Tamaño de la Partícula
4.
Sci Rep ; 14(1): 19652, 2024 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179785

RESUMEN

A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25-100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25-100 µl), and Pseudomonas spp. inoculums (50-150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC-MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8th day. From LC-MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 106 and 210 × 106 CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties.


Asunto(s)
Biotransformación , Pseudomonas aeruginosa , Vinblastina , Vincristina , Vincristina/farmacología , Vincristina/metabolismo , Vinblastina/metabolismo , Vinblastina/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/metabolismo , Pseudomonas/metabolismo , Pseudomonas/efectos de los fármacos , Espectrometría de Masas en Tándem , Pseudomonas fluorescens/metabolismo , Pseudomonas fluorescens/efectos de los fármacos , Concentración de Iones de Hidrógeno , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/metabolismo
5.
Cell Biochem Biophys ; 82(2): 1335-1351, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38904723

RESUMEN

Depression is a neuropsychological disorder with a complex pathophysiology and its pharmacotherapy is compromised by adverse side effects. Addressing the need for effective treatment for depression, the current study aims to characterize the antidepressant activity of oil extract derived from Aethoscytus foveolus, bugs that are widely available in India, in a mice model of stress-induced depression. Chemical moieties characterized by GC-MS of A. foveolus oil extract have shown good affinity for monoamine oxidase A (MAO-A) in-silico. In-vitro MAO-inhibitory assay using mouse brain homogenates also showed similar results at IC50 1.363 nM (R2 = 0.981, SD ± 0.05, n = 3) of it. These results encouraged us to investigate the antidepressant potential of this oil extract in vivo. Stress-exposed mice (Swiss Albino, either sex, 25-30 gm) were administered 5 and 10 mg/kg doses of oil extract and classified as separate groups (N = 6 per group). Behavioral tests like the forced-swim test, tail-suspension test, and open-field test demonstrated significant attenuation of stress-induced depressive-like behavior of mice by both doses (p < 0.0001 with positive control group i.e., stress group), while biochemical tests on mice brain tissues showed amelioration of stress-induced hyperactivation of MAO (p < 0.0001) and oxidative stress (by increasing Superoxide dismutase and catalase, while reducing lipid peroxidase and nitric oxide) (p < 0.0001). The altered mRNA expression of proinflammatory cytokines (NF-κB, IL-6, IL-12, and TNF-α) (p < 0.015) was also improved by this oil extract. In addition, histopathology of hippocampus tissues of mice supports that this oil recovers stress-mediated structural changes of the brain. In conclusion our findings suggest that oil derived from A. foveolus could be beneficial in the alleviation of stress-mediated depressive-like behavior of mice, and in our knowledge, this is the first report identifying anti-neurodegenerative potential of A. foveolus.


Asunto(s)
Antidepresivos , Depresión , Monoaminooxidasa , Estrés Oxidativo , Animales , Monoaminooxidasa/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/química , Antidepresivos/uso terapéutico , Masculino , Depresión/tratamiento farmacológico , Depresión/metabolismo , Femenino , Estrés Psicológico/tratamiento farmacológico , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Conducta Animal/efectos de los fármacos
6.
Int J Biol Macromol ; 266(Pt 1): 131048, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522697

RESUMEN

Past scientific testimonials in the field of glioma research, the deadliest tumor among all brain cancer types with the life span of 10-15 months after diagnosis is considered as glioblastoma multiforme (GBM). Even though the availability of treatment options such as chemotherapy, radiotherapy, and surgery, are unable to completely cure GBM due to tumor microenvironment complexity, intrinsic cellular signalling, and genetic mutations which are involved in chemoresistance. The blood-brain barrier is accountable for restricting drugs entry at the tumor location and related biological challenges like endocytic degradation, short systemic circulation, and insufficient cellular penetration lead to tumor aggression and progression. The above stated challenges can be better mitigated by small interfering RNAs (siRNA) by knockdown genes responsible for tumor progression and resistance. However, siRNA encounters with challenges like inefficient cellular transfection, short circulation time, endogenous degradation, and off-target effects. The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment.


Asunto(s)
Neoplasias Encefálicas , Glioma , ARN Interferente Pequeño , Humanos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Glioma/genética , Glioma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Nanopartículas/química , Animales , Portadores de Fármacos/química , Terapia Genética/métodos
7.
Chem Biol Drug Des ; 103(3): e14514, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38531606

RESUMEN

Series of 7-(Trifluoromethyl) substituted indolizine 4a-g was synthesized using the one-pot method. Spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a-g compounds were tested for their anti-inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a-g selectively targeting COX-2 enzyme, tumor necrosis factor-α (TNF-α) and, interleukin-6 (IL-6). The in silico docking studies of 4a-g showed that these compounds have a higher affinity for COX-2 enzyme, TNF- α, and IL-6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood-brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX-2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF-α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL-6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti-inflammatory activities of these novel 7-(Trifluoromethyl) substituted indolizine derivatives.


Asunto(s)
Antiinflamatorios no Esteroideos , Indolizinas , Antiinflamatorios no Esteroideos/química , Ciclooxigenasa 2/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa , Interleucina-6 , Antiinflamatorios/farmacología , Indometacina , Indolizinas/química , Simulación del Acoplamiento Molecular
8.
J Drug Target ; 32(4): 347-364, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38253594

RESUMEN

PRIMARY OBJECTIVE: The primary objective of the review is to assess the potential of lymphatic-targeted drug delivery systems, with a particular emphasis on their role in tumour therapy and vaccination efficacy. REASON FOR LYMPHATIC TARGETING: The lymphatic system's crucial functions in maintaining bodily equilibrium, regulating metabolism, and orchestrating immune responses make it an ideal target for drug delivery. Lymph nodes, being primary sites for tumour metastasis, underscore the importance of targeting the lymphatic system for effective treatment. OUTCOME: Nanotechnologies and innovative biomaterials have facilitated the development of lymphatic-targeted drug carriers, leveraging endogenous macromolecules to enhance drug delivery efficiency. Various systems such as liposomes, micelles, inorganic nanomaterials, hydrogels, and nano-capsules demonstrate significant potential for delivering drugs to the lymphatic system. CONCLUSION: Understanding the physiological functions of the lymphatic system and its involvement in diseases underscores the promise of targeted drug delivery in improving treatment outcomes. The strategic targeting of the lymphatic system presents opportunities to enhance patient prognosis and advance therapeutic interventions across various medical contexts, indicating the importance of ongoing research and development in this area.


Asunto(s)
Vasos Linfáticos , Nanopartículas , Neoplasias , Humanos , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Sistema Linfático/metabolismo , Neoplasias/metabolismo
9.
Environ Toxicol Pharmacol ; 106: 104355, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38154758

RESUMEN

BACKGROUND: Ferroptosis is a newly recognized cell death pathway having distinct characteristics compared to traditional cell death pathways such as apoptosis, necroptosis, or autophagy. However, the potential involvement of ferroptosis in bisphenol A (BPA)-induced neurotoxicity has not been well explored so far. In present study, we analyzed the relationship between ferroptosis and BPA-induced neurotoxicity. METHODS: In this study, a human neuroblastoma cell line, SH-SY5Y, was treated with BPA, ferrostatin-1 (FS-1, ferroptosis inhibitor) and RSL-3 (ferroptosis inducer). The cell viability was measured using MTT assay. Additionally, the levels of lipid peroxidation, total iron content, reactive oxygen species (ROS) generation, and nitrite content were measured to evaluate the key markers of ferroptosis. To further confirm the involvement of ferroptosis in BPA-induced neurotoxicity, other ferroptosis markers such as glutathione peroxidase (GPx) activity, total glutathione contents and antioxidant parameters were also evaluated. RESULTS: The cell viability of SH-SY5Y cells was down-regulated by BPA treatment in a concentration-dependent manner, the cell viability at 0.1 µM concentration was 97.63% whereas at highest BPA concentration i.e. 10 µM, the cell viability was 86.05% (p < 0.0001). Also the antioxidant parameters including catalase and superoxide dismutase activity of neuronal cells were down-regulated upon BPA exposure. However, the levels of lipid peroxidation, total iron, reactive oxygen species, and nitrite contents were increased in a concentration-dependent manner which could be rescued by FS-1 and exacerbated by RSL-3. The total iron in SH-SY5Y cells at 0.1 µM concentration was found to be 1.2 fold (p < 0.05) of control and at highest BPA concentration total iron was about 1.41 fold (p < 0.001) of control. CONCLUSIONS: The present study indicated that, ferroptosis plays an important role in the progression of BPA-induced neurotoxicity, and ferroptosis may become a novel target in the treatment of various neurological disorders.


Asunto(s)
Compuestos de Bencidrilo , Ferroptosis , Neuroblastoma , Fenoles , Humanos , Antioxidantes , Nitritos , Especies Reactivas de Oxígeno , Hierro
10.
J Phys Chem B ; 127(46): 9915-9925, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37956021

RESUMEN

Nile Blue (NB) is a red-emissive dye that is well-known for imaging and staining applications. In this work, we describe the interaction of NB with various types of G-quadruplexes belonging to different topologies, molecularities, and conformations. Using spectroscopic techniques, we have determined the preferential binding of NB to c-Myc G-quadruplex and the other aspects of its binding. Concentration- and temperature-dependent studies showed that NB exists in a dynamic equilibrium between monomeric and H-aggregated states, which could be modulated by the addition of external agents such as anionic surfactants. NB displayed differential self-assembly with different types of G-quadruplex and duplex DNAs modulating its dynamic equilibrium between the monomeric and H-aggregated states. Fluorescence-based displacement studies revealed a 1:1 binding stoichiometry upon interaction with c-Myc G-quadruplex and an association constant of Kapp = 6.7 × 106 M-1. Circular dichroism studies indicated that NB does not cause changes in the overall conformation of either G-quadruplexes or duplexes; however, it does indicate nucleic acid-dependent self-assembly at higher concentrations. Heat capacity measurement showed a more negative change when compared to that in DNA duplex, indicating more burial of the polar surface area by NB to the G-quadruplex host.


Asunto(s)
Colorantes Fluorescentes , G-Cuádruplex , Colorantes Fluorescentes/química , ADN/química , Dicroismo Circular
11.
J Crohns Colitis ; 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870484

RESUMEN

BACKGROUND AND AIMS: To study frailty screening in association with hospitalization and decline in quality of life (QoL) and functional status in older patients with Inflammatory Bowel Diseases (IBD). METHODS: A prospective multicentre cohort study in IBD patients ≥65 years using frailty screening (G8 Questionnaire). Outcomes were all-cause, acute and IBD-related hospitalization, any infection, any malignancy, QoL (EQ5D-3L) and functional decline (Instrumental Activities of Daily Living, (IADL)) during 18 months follow-up. Confounders: age, IBD type, biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g), comorbidity (Charlson Comorbidity Index). RESULTS: Out of 405 patients, median age 70 years, 196 (48%) screened at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients (23.7%), acute hospitalizations 103 times in 74 (18.3%). Risk of frailty did not associate with all-cause (aHR 1.5, 95% CI 0.9-2.4), but did associate with acute hospitalizations (aHR 2.2, 95% CI 1.3-3.8). Infections occurred in 86 patients (21.2%) and were not associated with frailty. Decline in QoL was experienced by 108 (30.6%) patients, decline in functional status by 46 (13.3%). Frailty screening associated with decline in QoL (aOR 2.1, 95% CI 1.3-3.6) and functional status (aOR 3.7, 95% CI 1.7-8.1). CONCLUSIONS: Frailty screening associates with worse health outcomes in older patients with IBD. Further studies are needed to assess feasibility and effectiveness of implementation in routine care.

12.
3 Biotech ; 13(2): 46, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36643397

RESUMEN

The peels of C.sativus are produced in large quantities in food processing industries and as kitchen-waste, resulting into tremendous loss of valuable bioactive components. Considering this, the flavanoids from C.sativus peels (CSP) were isolated and characterized by the column chromatography, high-performance thin-layer chromatography (HPTLC), Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) methods. The antioxidant and antibacterial activity of CSP extract against Escherichia coli, Streptococcus mutans and Pseudomonas aeruginosa was assessed. Scanning electron microscopy (SEM) was also used to investigate the killing efficacy of CSP extract against selected bacterial strains. Cytotoxic activity of extract was analyzed on L929 (connective tissue, Mouse, Mus Muscular) cell lines to check their viability. According to the results, total flavanoid content in CSP extract was found as 55.3 ± 1.154 µg/g QE and the chromatographic and spectral data of the isolated compound was elucidated as quercetin-a flavanoid. The CSP extract has also found to give significant antioxidant activity for both DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assay. The CSP extract was found to inhibit growth of E. coli, P. aeruginosa and S. mutans by forming inhibitory zones of 11.36 ± 0.47, 6.7 ± 0.36 mm and 10.16 ± 0.11 mm, respectively. The SEM results also confirm the rupturing of cells or biofilms of bacterial cells as compare to control strains. Additionally, CSP extract was found to not inhibit the proliferation of L929 cells and more than 90% viability of cells was achieved. The present finding highlights the phytochemical profile and therapeutic applications of C.sativus peels.

13.
World J Microbiol Biotechnol ; 39(3): 71, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36622499

RESUMEN

Since ancient time, plants and there parts have been used widely against dreadful pathogens due to ability of killing microbes. Waste from fruits and vegetables are pulling in more interest in exploration due to their therapeutic properties such as anti-pathogenic activity. In the present study antimicrobial and cytotoxicity properties of herbal combination prepared from peels of Allium cepa, Cucumis sativus, Citrus reticulata, and Mangifera indica were investigated. The herbal combination was tested for broad spectrum antimicrobial activity against Streptococcus mutans, Bacillus licheniformis, Lactobacillus plantarum, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii. The presence of phytochemical markers such as phenolics and flavanoids were also investigated. The results revealed that the herbal combination exhibited antimicrobial activity against S. mutans, B. licheniformis, L. plantarum, E. coli and moderate against P. aeruginosa and C. freundii. The presence of phenolics (798 ± 1.52 µg/g) and flavanoids (355.3 ± 2.081 µg/g) was also detected. Also, the herbal combination contains flavanoids such as quercetin and rutin was confirmed with the help of column chromatography, high-performance liquid chromatography (HPLC), fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis. The herbal combination helps in the proliferation of L929 cells without affecting their viability was confirmed by MTT assay. The results of the present research suggests the possibility to use herbal combination as source for plausible antibacterial agent which could be isolated and used as a lead candidate for the development of antibacterial drug that help to limit or stop infectious illnesses caused by different pathogenic microbes.


Asunto(s)
Antiinfecciosos , Verduras , Frutas , Escherichia coli , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/química , Extractos Vegetales/química , Pruebas de Sensibilidad Microbiana
14.
Int J Biol Macromol ; 230: 123138, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36610577

RESUMEN

The moth bean is a high-protein food legume. Enzymatic hydrolysates of food proteins demostrate health benefits. Search for diet related food protein hydrolysates is therefore within the scope of functional foods. Present study asertains to produce, screen and identify natural ACE-I inhibitory peptides derived from moth bean seed protein hydrolysates. The extracted protein was hydrolysed using alcalase, chymotrypsin, flavourzyme, papain, pepsin and trypsin respectively. Alcalase achieved the greatest degree of hydrolysis and ACE inhibition. The highest ACE-I inhibitory activity was exhibited by the peptide with the lowest molecular weight i.e. <3 kDa (IC50 11.19 ± 0.15 µg/mL). This was further separated by FPLC, followed by mass spectrometry. Molecular docking analysis showed the peptides IAWDFR and ADLPGLK bind to active sites whereas DKPWWPK and AVIPNAPNLR to non-active sites of the ACE molecule. In vivo administration of MBP hydrolysate to dexamethasone-induced hypertensive rats reduced their systolic blood pressure (125 ± 0.76 mmHg) compared with positive control (155 ± 3.13 mmHg). Moth bean protein peptides exhibit functional nutraceutical properties with adequate antihypertensive activity.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Vigna , Animales , Ratas , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Angiotensinas , Antihipertensivos/química , Hidrólisis , Simulación del Acoplamiento Molecular , Péptidos/química , Peptidil-Dipeptidasa A/metabolismo , Hidrolisados de Proteína/química , Subtilisinas/metabolismo , Tripsina/metabolismo , Vigna/metabolismo , Semillas/química
15.
Clin Gastroenterol Hepatol ; 21(1): 182-191.e2, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35644343

RESUMEN

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 µg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.


Asunto(s)
Colitis Ulcerosa , Fármacos Gastrointestinales , Inhibidores de las Cinasas Janus , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Estudios Prospectivos , Sistema de Registros , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Inhibidores de las Cinasas Janus/uso terapéutico
16.
Aliment Pharmacol Ther ; 57(1): 117-126, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36282200

RESUMEN

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 µg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment.


Asunto(s)
Inhibidores del Factor de Necrosis Tumoral , Humanos , Países Bajos
17.
Rev Med Virol ; 33(1): e2383, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35983697

RESUMEN

Japanese encephalitis (JE) is a vector-borne neurotropic disease caused by Japanese encephalitis virus (JEV) associated with high mortality rate distributed from Eastern and Southern Asia to Northern Queensland (Australia). The challenges in early detection and lack of point-of-care biomarkers make it the most important Flavivirus causing encephalitis. There is no specific treatment for the disease, although vaccines are licenced. In this review, we focussed on point-of-care biomarkers as early detection tools and developing the effective therapeutic agents that could halt JE. We have also provided molecular details of JEV, disease progression, and its pathogenesis with recent findings which might bring insights to overcome the disease burden.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Humanos , Encefalitis Japonesa/diagnóstico , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/prevención & control , Virus de la Encefalitis Japonesa (Especie)/genética , Zoonosis/diagnóstico , Zoonosis/epidemiología , Sur de Asia
18.
Heliyon ; 8(7): e09908, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35847613

RESUMEN

Agriculture crops encounter several biotic and abiotic stresses, including pests, diseases, nutritional deficits, and climate change, which necessitate the development of new agricultural technologies. By developing nano-based fertilizers, insecticides and herbicides, and early disease diagnostics, nanotechnology may help to increase agricultural crop quality and production. The application of silica nanoparticles (SiNPs) may be the solution for increasing the yield to combat the agriculture crisis in the near future. SiNPs have unique physiological properties, such as large surface area, aggregation, reactivity, penetrating ability, size, and structure, which enable them to penetrate plants and regulate their metabolic processes. Pesticide delivery, enhanced nutrition supply, disease management, and higher photosynthetic efficiency and germination rate are all attributed to SiNPs deposition on plant tissue surfaces. SiNPs have been demonstrated to be non-toxic in nature, making them suitable for usage in agriculture. In this regard, the current work provides the most important and contemporary applications of SiNPs in agriculture as well as biogenic and non-biogenic synthetic techniques. As a result, this review summarizes the literature on SiNPs and explores the use of SiNPs in a variety of agricultural disciplines.

19.
Fish Shellfish Immunol ; 127: 357-365, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35772676

RESUMEN

Aeromonas hydrophila is an important aquatic zoonotic pathogen that causes septicemia, necrotizing fasciitis and gastroenteritis in various aquatic and non-aquatic animals. However, the pathogenesis of A. hydrophila is not fully understood. Here, we examined the pathogenicity and histopathology of A. hydrophila in the zebrafish (Danio rerio) model system. We found that the intensity of symptoms and mortality is dose-dependent. Bacterial colonization studies demonstrated that A. hydrophila never cleared out from the fish body but stayed in a state of inactivity till it enters a fresh host. Reinfection studies showed that exposure to A. hydrophila provides immunity against future infection and hence improves fish survival. Gene expression studies revealed the crosstalk between T-helper cell and macrophage responses in fish immune system in response to A. hydrophila and infection memory. Histopathological studies showed that symptoms of tissue damage and inflammation lasted for less duration with less intensity in immunized fish when compared to non-immunized fish. Together, our results suggest that the zebrafish model is a useful system in studying the interplay between A. hydrophila pathogenesis, persistence and immunity.


Asunto(s)
Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Aeromonas hydrophila/fisiología , Animales , Virulencia , Pez Cebra
20.
Clin Chim Acta ; 527: 79-88, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35120900

RESUMEN

Cancer is the second leading cause of death worldwide after cardiovascular disease. The major cause of high mortality is delayed detection. Therefore, detection at an early stage followed by early treatment can mitigate morbidity as well as mortality. The utilization of biomarker-based detection tools helps in early-stage recognition. Fortunately, biomarkers indicating disease status are released in to the circulation. These include traditional marker proteins as well as exosomes, micro-RNA (miRNA) and circulating tumor DNA (ct-DNA). Biosensors are biological and chemical reaction devices that generate signals based on analyte concentration. Due to analyte binding, these devices demonstrate high sensitivity and specificity. This review examines the use of surface plasmon resonance (SPR)-based sensors in the diagnosis of various cancer including those of the breast, prostate, lung, ovary, cervix and pancreas. SPR is a label-free, real-time and non-invasive optical biosensing technology representing a novel diagnostic tool in cancer detection.


Asunto(s)
Técnicas Biosensibles , MicroARNs , Neoplasias , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Resonancia por Plasmón de Superficie
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