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1.
Nature ; 625(7995): 468-475, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38096900

RESUMEN

Large language models (LLMs) have demonstrated tremendous capabilities in solving complex tasks, from quantitative reasoning to understanding natural language. However, LLMs sometimes suffer from confabulations (or hallucinations), which can result in them making plausible but incorrect statements1,2. This hinders the use of current large models in scientific discovery. Here we introduce FunSearch (short for searching in the function space), an evolutionary procedure based on pairing a pretrained LLM with a systematic evaluator. We demonstrate the effectiveness of this approach to surpass the best-known results in important problems, pushing the boundary of existing LLM-based approaches3. Applying FunSearch to a central problem in extremal combinatorics-the cap set problem-we discover new constructions of large cap sets going beyond the best-known ones, both in finite dimensional and asymptotic cases. This shows that it is possible to make discoveries for established open problems using LLMs. We showcase the generality of FunSearch by applying it to an algorithmic problem, online bin packing, finding new heuristics that improve on widely used baselines. In contrast to most computer search approaches, FunSearch searches for programs that describe how to solve a problem, rather than what the solution is. Beyond being an effective and scalable strategy, discovered programs tend to be more interpretable than raw solutions, enabling feedback loops between domain experts and FunSearch, and the deployment of such programs in real-world applications.

2.
Nature ; 607(7918): 345-350, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35768512

RESUMEN

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.


Asunto(s)
Saliva , Glándulas Salivales , Virosis , Virus , Astroviridae , Lactancia Materna , Células Cultivadas , Heces/virología , Femenino , Humanos , Inmunoglobulina A/inmunología , Lactante , Norovirus , Rotavirus , Saliva/virología , Glándulas Salivales/virología , Esferoides Celulares/virología , Virosis/transmisión , Virosis/virología , Virus/crecimiento & desarrollo
3.
Pharmacol Rev ; 76(2): 228-250, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38351070

RESUMEN

The role of advanced drug delivery strategies in drug repositioning and minimizing drug attrition rates, when applied early in drug discovery, is poised to increase the translational impact of various therapeutic strategies in disease prevention and treatment. In this context, drug delivery to the lymphatic system is gaining prominence not only to improve the systemic bioavailability of various pharmaceutical drugs but also to target certain specific diseases associated with the lymphatic system. Although the role of the lymphatic system in lupus is known, very little is done to target drugs to yield improved clinical benefits. In this review, we discuss recent advances in drug delivery strategies to treat lupus, the various routes of drug administration leading to improved lymph node bioavailability, and the available technologies applied in other areas that can be adapted to lupus treatment. Moreover, this review also presents some recent findings that demonstrate the promise of lymphatic targeting in a preclinical setting, offering renewed hope for certain pharmaceutical drugs that are limited by efficacy in their conventional dosage forms. These findings underscore the potential and feasibility of such lymphatic drug-targeting approaches to enhance therapeutic efficacy in lupus and minimize off-target effects of the pharmaceutical drugs. SIGNIFICANCE STATEMENT: The World Health Organization estimates that there are currently 5 million humans living with some form of lupus. With limited success in lupus drug discovery, turning to effective delivery strategies with existing drug molecules, as well as those in the early stage of discovery, could lead to better clinical outcomes. After all, effective delivery strategies have been proven to improve treatment outcomes.


Asunto(s)
Sistemas de Liberación de Medicamentos , Lupus Eritematoso Sistémico , Humanos , Preparaciones Farmacéuticas , Sistema Linfático , Lupus Eritematoso Sistémico/tratamiento farmacológico
4.
Nature ; 588(7836): 66-70, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33230333

RESUMEN

Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields-a longstanding technological goal in spintronics and multiferroics1,2-can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator3-6, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered7-14. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands15-17. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects18 with transverse resistance approximately equal to h/2e2 (where h is Planck's constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis19 indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.

5.
Arch Microbiol ; 206(3): 96, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38349547

RESUMEN

Aphids shelter several bacteria that benefit them in various ways. The associates having an obligatory relationship are non-culturable, while a few of facultative associates are culturable in insect cell lines, axenic media or standard microbiology media. In the present investigation, isolation, and characterization of the culturable bacterial associates of various aphid species, viz., Rhopalosiphum maidis, Rhopalosiphum padi, Sitobion avenae, Schizaphis graminum, and Lipaphis erysimi pseudobrassicae were carried out. A total of 42 isolates were isolated using different growth media, followed by their morphological, biochemical, and molecular characterization. The isolated culturable bacterial associates were found to belong to the genera Acinetobacter, Bacillus, Brevundimonas, Cytobacillus, Fictibacillus, Planococcus, Priestia, Pseudomonas, Staphylococcus, Sutcliffiella, and Tumebacillus which were grouped under seven families of four different orders of phyla Bacillota (Firmicutes) and Pseudomonata (Proteobacteria). Symbiont-entomopathogen interaction study was also conducted, in which the quantification of colony forming units of culturable bacterial associates of entomopathogenic fungal-treated aphids led us to the assumption that the bacterial load in aphid body can be altered by the application of entomopathogens. Whereas, the mycelial growth of entomopathogens Akanthomyces lecanii and Metarhizium anisopliae was found uninhibited by the bacterial associates obtained from Sitobion avenae and Rhopalosiphum padi. Analyzing persistent aphid microflora and their interactions with entomopathogens enhances our understanding of aphid resistance. It also fosters the development of innovative solutions for agricultural pest management, highlighting the intricate dynamics of symbiotic relationships in pest management strategies.


Asunto(s)
Áfidos , Bacillaceae , Bacillus , Animales , Bacterias/genética , Firmicutes
6.
Arch Virol ; 169(7): 150, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38898334

RESUMEN

Secoviruses are single-stranded RNA viruses that infect plants. In the present study, we identified 61 putative novel secoviral genomes in various plant species by mining publicly available plant transcriptome data. These viral sequences represent the genomes of 13 monopartite and 48 bipartite secovirids. The genome sequences of 52 secovirids were coding-complete, and nine were partial. Except for small open reading frames (ORFs) determined in waikaviral genomes and RNA2 of torradoviruses, all of the recovered genomes/genome segments contained a large ORF encoding a polyprotein. Based on genome organization and phylogeny, all but three of the novel secoviruses were assigned to different genera. The genome organization of two identified waika-like viruses resembled that of the recently identified waika-like virus Triticum aestivum secovirus. Phylogenetic analysis revealed a pattern of host-virus co-evolution in a few waika- and waika-like viruses and increased phylogenetic diversity of nepoviruses. The study provides a basis for further investigation of the biological properties of these novel secoviruses.


Asunto(s)
Variación Genética , Genoma Viral , Sistemas de Lectura Abierta , Filogenia , Secoviridae , Transcriptoma , Genoma Viral/genética , Sistemas de Lectura Abierta/genética , Secoviridae/genética , Secoviridae/clasificación , Enfermedades de las Plantas/virología , Plantas/virología , ARN Viral/genética
7.
J Gastroenterol Hepatol ; 39(3): 422-430, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38058246

RESUMEN

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.


Asunto(s)
Enfermedad de Crohn , Tuberculosis Gastrointestinal , Humanos , Inteligencia Artificial , Enfermedad de Crohn/diagnóstico por imagen , Redes Neurales de la Computación , Estudios Retrospectivos , Tuberculosis Gastrointestinal/diagnóstico , Diagnóstico por Computador
8.
Phys Chem Chem Phys ; 26(31): 21186-21196, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39072697

RESUMEN

The present work shows the improved humidity sensing characteristics of TiO2 nanoparticles in the form of a nanocomposite with multiwalled carbon nanotubes (MWCNTs) prepared by a hydration-dehydration method. The structural and morphological characterizations of TiO2-MWCNTs confirm the nanocomposite formation without any other impurities and with an improved surface area. The pure TiO2 and nanocomposite films are deposited on IDE coated flexible poly-ethylene terephthalate (PET) substrates by a drop casting method. The nanocomposite shows improved sensitivity (1246.2 MΩ/%RH) and an ultrafast response/recovery time (2 s/1 s) with a minimal hysteresis of 0.27%RH. Further, the flexible nanocomposite sensor is tested for human healthcare applications including respiratory monitoring, apnea like situations, and skin moisture detection. The sensor can distinguish different breath patterns like normal, fast, deep and apnea like situations significantly. Skin moisture detection can also be performed using the nanocomposite sensor in a non-invasive manner. Overall, this study represents an environmentally friendly, easy to fabricate, flexible TiO2-MWCNT nanocomposite based improved humidity sensor for application in human healthcare and wearable devices.


Asunto(s)
Humedad , Nanocompuestos , Nanotubos de Carbono , Titanio , Titanio/química , Nanotubos de Carbono/química , Nanocompuestos/química , Humanos , Dispositivos Electrónicos Vestibles
9.
J Biochem Mol Toxicol ; 38(8): e23790, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108137

RESUMEN

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.


Asunto(s)
Quimioradioterapia , Transición Epitelial-Mesenquimal , Fibrosis Pulmonar , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/etiología , Quimioradioterapia/efectos adversos , Animales , Estrés Oxidativo/efectos de los fármacos , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo
10.
Pediatr Nephrol ; 39(6): 1817-1824, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38253887

RESUMEN

BACKGROUND: Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: This cross-sectional study enrolled children (2-18 years) both with steroid sensitive nephrotic syndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. RESULTS: Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. CONCLUSIONS: A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.


Asunto(s)
Insuficiencia Suprarrenal , Síndrome Nefrótico , Masculino , Niño , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Hidrocortisona , Estudios Transversales , Corticoesteroides/uso terapéutico , Hormona Adrenocorticotrópica , Prednisolona/uso terapéutico
11.
Environ Res ; 252(Pt 4): 119030, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38677409

RESUMEN

Bifunctional electrocatalysts are the attractive research in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in the overall water-splitting reactions. The design and development of the cost-effective OER/HER bifunctional electrocatalysts with superior catalytic activity are still remaining as the big challenges. Herein, we have developed the CuO-ZnO nanocomposite as a bifunctional OER/HER electrocatalyst via simple chemical precipitation method. The nanocomposite was investigated for its crystalline structure, surface morphology and the functions of elements using XRD, FT-IR, SEM, TEM and XPS characterization techniques, respectively. The nanocomposite exhibited the excellent activity for the overall water-splitting in an alkaline medium. The CuO-ZnO nanocomposite showed the less onset potential of 1.4 and 0.15 V versus RHE in 1M KOH (Tafel slopes value of 0.180 and 0.400 V dec-1) for OER and HER, respectively. Hence, the as-prepared bifunctional electrocatalyst displayed the high stability for 10 h in the water electrolysis processes.


Asunto(s)
Cobre , Oxígeno , Óxido de Zinc , Cobre/química , Óxido de Zinc/química , Catálisis , Oxígeno/química , Hidrógeno/química , Técnicas Electroquímicas , Nanocompuestos/química , Nanoestructuras/química , Agua/química , Electrólisis
12.
Environ Res ; 251(Pt 2): 118701, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38508362

RESUMEN

The study focused on the production of the tyrosinase enzyme from Streptomyces sp. MR28 and its potency in removal of phenol content from water using free and immobilized tyrosinase enzyme. The tyrosinase was produced by Streptomyces sp. MR28 in liquid tyrosine broth medium, and it was further purified to near its homogeneity by employing, precipitation, dialysis, and column chromatography. After the purification, 44.49% yield with a 4 fold purification was achieved. The characterization of the purified enzyme showed a single major peak on HPLC and a solitary band on SDS-PAGE. The purified tyrosinase enzyme was active at a pH of 7.0 and a temperature of 30 °C. Further immobilization of purified tyrosinase was performed using the sodium alginate entrapment method. The capacity of the purified tyrosinase to remove phenol in water was evaluated by spectrophotometric method. The free tyrosinase enzyme-treated solutions showed a gradual decrease in the concentration of phenol with increased incubation time at 30 °C and 40 °C, at 90 min of the incubation time, it showed maximum efficacy in removing phenol from the solution. At 50 °C and 60 °C, the free tyrosinase enzyme exhibited very less capacity to remove the phenol. The immobilized enzyme showed good capacity for the removal of phenol from the solutions; the concentration of phenol in the solution decreased with an increase in the incubation time. At temperatures of 40 °C and 50 °C, the immobilized tyrosinase enzyme beads showed significant removal of phenol from the solution, and at temperatures of 30 °C and 60 °C, they also exhibited good capacity for the removal of phenol. At the end of the 90 min incubation period, it exhibited good capability. The current study suggests using immobilized microbial tyrosinase enzyme can be used for the removal of phenol from the contaminated water in a greener manner.


Asunto(s)
Enzimas Inmovilizadas , Monofenol Monooxigenasa , Fenol , Streptomyces , Monofenol Monooxigenasa/metabolismo , Streptomyces/enzimología , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Contaminantes Químicos del Agua , Temperatura , Concentración de Iones de Hidrógeno
13.
J Sep Sci ; 47(5): e2300605, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38466156

RESUMEN

An analytical quality by design-based high-performance liquid chromatography method for determining metformin (MET) and sitagliptin (SIT) in stress-degraded samples was developed and validated. The analytical target profile and risk assessment-driven critical method variables, for example, pH, % aqueous, and buffer concentration, were studied for their effect on method responses of retention time and resolution using a central composite design. The correlation regression coefficient was more than 0.8, and variables interaction was significant on method responses with curvature effect. The method operable design region afforded an aqueous range of 55%-70% and an ortho-phosphoric acid buffer of 0.1% with a pH of 3.0-4.0 as a robust region for the suitable method performance characteristics. The separation of MET and SIT from their degradants (m/z 85.0509; m/z 193.0694) on the C8 column was achieved using a mobile phase consisting of 0.1% ortho-phosphoric acid and methanol (60:40% v/v; pH 3.0). The optimized method eluted MET and SIT at 4.3 ± 0.2 and 7.1 ± 0.2 min, respectively, with acceptable specificity and resolution. The linearity ranges of 25-250 µg/mL (r2 : 0.9982) and 5-50 µg/mL (r2 : 0.9989) was established for MET and SIT, respectively. The % recovery (98.81%-102.17%), precision (0.55%-1.65%), and robustness study for method variables were acceptable.


Asunto(s)
Metformina , Ácidos Fosfóricos , Fosfato de Sitagliptina , Cromatografía Líquida de Alta Presión , Metanol
14.
Indian J Med Res ; 159(2): 180-192, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38494626

RESUMEN

BACKGROUND OBJECTIVES: Scrub typhus, caused by Orientia tsutsugamushi present in small mammals harbouring the ectoparasites. A study was undertaken to detect the pathogen present in small mammals and its ectoparasites in the scrub typhus-reported areas. METHODS: The small mammals (rodents/shrews) and its ectoparasites were screened for O. tsutsugamushi using nested PCR amplification of the groEL gene. Small mammals were collected by trapping and screened for ectoparasites (mites, ticks and fleas) by combing method. RESULTS: All the chigger mites collected were tested negative for O. tsutsugamushi . Interestingly, adult non-trombiculid mites ( Oribatida sp., Dermanyssus gallinae ), fleas ( Xenopsylla astia, X. cheopis, Ctenophalides felis and Ctenophalides sp.) and ticks ( Rhipicephalus sanguineus , R. haemaphysaloides ) screened were found to be positive for O. tsutsugamushi , which the authors believe is the first report on these species globally. Bandicota bengalensis with O. tsutsugamushi infection is reported for the first time in India. The O. tsutsugamushi groEL sequences from the positive samples were similar to the reference strains, Karp and Ikeda and phylogenetically clustered in clade IV with less evolutionary divergence. The blood samples of Rattus rattus , Suncus murinus and B. bengalensis collected from this area were tested positive for O. tsutsugamushi ; interestingly, the sequence similarity was much pronounced with their ectoparasites indicating the transmission of the pathogen to host or vice versa . INTERPRETATION CONCLUSIONS: The outcome of the present investigations widened our scope on the pathogens present in ectoparasites and rodents/shrews from this area. This will help to formulate the required vector control methods to combat zoonotic diseases.


Asunto(s)
Orientia tsutsugamushi , Tifus por Ácaros , Garrapatas , Trombiculidae , Ratas , Animales , Tifus por Ácaros/epidemiología , Orientia tsutsugamushi/genética , Musarañas , India/epidemiología , Roedores/parasitología , Trombiculidae/genética
15.
Regul Toxicol Pharmacol ; 147: 105538, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38151226

RESUMEN

Organically synthesized fully saturated form of Anacardic acid (AA) has previously shown to be effective in the treatment of inflammatory autoimmune disease. In this study, organically synthesized fully saturated form of AA was orally administered to male and female Swiss albino mice for 90 consecutive days at doses of 25, 50 and 100 mg/kg BW (n = 20 per sex/group). Administration of AA was well tolerated at all dose levels. The treated animals did not show a dose-response toxicity in their hematology, liver, or metabolic profile. Minimally significant changes in serum biochemistry and hematology parameters were noted, but these were not considered to be of biological or toxicological importance and were not outside the known accepted ranges. Sporadic differences in organ weights were observed between groups, but all were minimal (<10%) and unlikely to indicate toxicity. The incidence of histopathological lesions was comparable between treated and control groups across all tested organs. Based upon these findings, the no-observed-adverse-effect level was determined to be ≥ 100 mg/kg BW, which was the highest dose tested. There were no genotoxic (mutagenic and clastogenic) effects seen in In-vivo micronucleus test, In-vitro chromosomal aberration test and Bacterial reverse mutation test. These results support, no genotoxicity and no toxicity associated with oral consumption of AA in mice as a dietary supplement for beverages and food.


Asunto(s)
Ácidos Anacárdicos , Mutágenos , Ratones , Masculino , Femenino , Animales , Ácidos Anacárdicos/toxicidad , Nivel sin Efectos Adversos Observados , Mutación , Daño del ADN
16.
Orthod Craniofac Res ; 27 Suppl 1: 109-114, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38265116

RESUMEN

INTRODUCTION: Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. MATERIALS AND METHODS: This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. RESULTS: Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. CONCLUSION: As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.


Asunto(s)
Fisura del Paladar , Prometazina , Humanos , Prometazina/uso terapéutico , Fisura del Paladar/cirugía , Preescolar , Masculino , Femenino , Método Doble Ciego , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Ansiedad , Cuidados Preoperatorios , Resultado del Tratamiento , Frecuencia Cardíaca/efectos de los fármacos , Periodo Preoperatorio
17.
Chem Biodivers ; : e202400534, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771305

RESUMEN

Pyrrole, with its versatile heterocyclic ring structure, serves as a valuable template for generating a diverse range of lead compounds with various pharmacophores. Researchers and scientists globally are intrigued by pyrrole and its analogs for their broad pharmacological potential, prompting thorough investigations aimed at advancing human welfare. This comprehensive review delves into the diverse activities exhibited by pyrrole compounds, encompassing their synthesis, reactions, and pharmacological properties alongside their derivatives. In addition to detailing the characteristics of pyrrole and its derivatives within the context of green chemistry, the review also examines microwave-assisted reactions. It provides insights into their chemical structures, natural occurrences, and potential applications across various domains. Furthermore, the article investigates structural alterations of pyrrole compounds and their implications on their functionality, highlighting their versatility as foundational elements for both functional materials and bioactive compounds. The review emphasizes the need for ongoing research and development in the field of pyrrole compounds to discover new activities and benefits.

18.
Arch Pharm (Weinheim) ; : e2400194, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877616

RESUMEN

Tanacetum nitens ( Boiss. & Noë)  Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, ß-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.

19.
Arch Pharm (Weinheim) ; 357(5): e2300728, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38314893

RESUMEN

In the present study, we aimed to investigate the chemical profiles and biological activities of different extracts (ethyl acetate, dichloromethane, ethanol, and water) of Pelargonium endlicherianum parts (aerial parts and roots). Free radical scavenging, reducing power, phosphomolybdenum, and metal chelating were assayed for antioxidant properties. To detect enzyme inhibitory properties, cholinesterase, amylase, glucosidase, and tyrosinase were chosen as target enzymes. The ethanol extract of the aerial parts contained higher amounts of total bioactive compounds (120.53 mg GAE/g-24.46 mg RE/g). The ethanol and water extracts of these parts were tentatively characterized by UHPLC-ESI-QTOF-MS and 95 compounds were annotated. In addition, the highest acetylcholiesterase (3.74 mg GALAE/g) and butyrylcholinesterase (3.92 mg GALAE/g) abilities were observed by the ethanol extract of roots. The water extract from aerial parts exhibited the most pronounced inhibitory effects on multiple cancer cell lines, especially A549 (IC50: 23.2 µg/mL) and HT-29 (IC50: 27.43 µg/mL) cells. Using network pharmacology, P. endlicherianum compounds were studied against cancer, revealing well-connected targets such as epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), AKT, receptor tyrosine-protein kinase erbB-2, and growth factor receptor bound protein 2 (GRB2) with significant impact on cancer-related pathways. The results could open a new path from natural treasure to functional applications with P. endlicherianum and highlight a new study on other uninvestigated Pelargonium species.


Asunto(s)
Pelargonium , Extractos Vegetales , Espectrometría de Masa por Ionización de Electrospray , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Pelargonium/química , Farmacología en Red , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Componentes Aéreos de las Plantas/química , Raíces de Plantas/química
20.
J Food Sci Technol ; 61(3): 503-515, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38327858

RESUMEN

Goat milk has achieved significant place in human diet owing to its enormous therapeutic properties. There exists a scope of value-addition of goat milk to potentiate its health benefits by incorporating herbs and plants. Giloy (Tinospora cordifolia), a traditional medicinal plant with rich bioactive composition, can enhance the bioactive properties and shelf-life of goat milk. To this end, a study was conducted to develop shelf-stable giloy-goat milk beverage (GGB) by adding debittered giloy juice to goat milk (GM) and analyse the detailed product profile including proximate composition, bioactive properties, sensory, rheological, and structural characterisation. GGB resulted in two-fold increase (P < 0.05) in antioxidant activity and total phenolic content, thus enhancing the bioactive properties of the beverage as compared to GM. Further, increase in the particle size of GGB was observed along with components interaction, which was confirmed by FTIR, scanning electron and fluorescent microscopy. Storage stability studies indicated that bioactive properties of GGB remained unaffected (P > 0.05) by the sterilization process up to 90 days and sensory characteristics were not compromised till 105 days of storage. Therefore, the developed GGB is considered to be a shelf-stable beverage that retains its bioactive and sensory properties even after sterilization, making it a promising functional dairy product.

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