Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 96
Filtrar
1.
BMC Res Notes ; 17(1): 6, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167220

RESUMEN

Mosquitoes are notorious insects that transmit a wide range of infectious diseases, including zika, malaria, chikungunya, filariasis, and dengue. The overuse and incorrect application of synthetic pesticides to control mosquitoes has resulted in resistance development and environmental contamination, both of which have had a negative impact on human health. To address this issue, the larvicidal and pupicidal potential of acetone extract from Casearia tomentosa fruits was investigated. The extract was evaluated in a lab setting against all larval instars and pupa of Culex quinquefasciatus and Aedes albopictus, as well as against third instar larvae in a semi-field condition. Purified compounds through TLC were also tested against 3rd instar larvae of both mosquito and non-target organisms. The FT-IR and GC-MS analyses were used to characterise the extract. Morphological aberration caused by the acetone extract was observed using FESEM. The anal gills and respiratory siphon of both mosquitoes showed significant deformation from their normal state. 100 ppm was found to cause 100% larval mortality at 24 h of exposure in case of Cx. quinquefasciatus and at 72 h of exposure in Ae. albopictus larvae. After 72 h of exposure under in vitro conditions, the extract demonstrated considerable larvicidal activity with LC50 values of 38.33 and 47.56 against 3rd instar larvae of Culex quinquefasciatus and Aedes albopictus, respectively. The acetone extract can be considered as a highly effective mosquito larvicidal agent that is safe for the environment.


Asunto(s)
Anopheles , Casearia , Culex , Insecticidas , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Frutas , Acetona , Espectroscopía Infrarroja por Transformada de Fourier , Insecticidas/farmacología , Larva , Extractos Vegetales/farmacología , Hojas de la Planta
2.
Sci Rep ; 13(1): 17202, 2023 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821538

RESUMEN

Recent research has focused on nanoparticles. Aedes albopictus is a potential vector that transmits fatal diseases. Recently, Phyto-reduced silver nanoparticles (AgNPs) were shown to be mosquito larvicides. This study aimed to synthesize silver nanoparticles using Diospyros montana leaf extract, characterize them, and test their efficacy as larvicide and pupicide against Ae. albopictus mosquitoes, determine their duration of effectiveness as a larvicide, identify plant compounds that help to synthesize nanoparticles, and assess their effects on non-target organisms. Quercetin, luteolin, kaempferol, gallocatechin gallate, epigallocatechin gallate, and capsaicin are among the novel reducing and capping agents found in D. montana leaf through LCMS analysis. The color shift and distinctive peak in UV-Vis spectroscopy made it simple to see how biogenic AgNPs were produced by converting Ag+ ions into Ag0. Substantial negative value (- 19.10 mv) of zeta potential demonstrated the long-term stability of AgNPs. A moderate range (8.72 - 50.75 nm) of particle size distribution pattern was obtained using the DLS technique. SEM and TEM images depicted the quasi-spherical (or polyhedral) and spherical shape of the nanoparticles, having approximately 16.75 nm average size. Synthesized AgNPs had a low LC90 value (< 10 ppm) for all larval instars and pupae of Ae. albopictus and had negligible mal effect on non-target organisms. Regression equations showed dose-dependent mortality by the positive correlation between mortality rate and AgNPs concentration, and each time the regression coefficient (R2) value was larger than zero. This study shows that D. montana leaf extract is an environment-friendly and sustainable source of an effective reducing and capping agent to synthesize highly stable, ecologically acceptable silver nanoparticles and their application as mosquitocide.


Asunto(s)
Aedes , Dengue , Diospyros , Insecticidas , Nanopartículas del Metal , Animales , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Montana , Extractos Vegetales/farmacología , Extractos Vegetales/química , Insecticidas/farmacología , Insecticidas/química , Mosquitos Vectores , Larva , Hojas de la Planta
3.
BMC Res Notes ; 16(1): 212, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700379

RESUMEN

The present study was designed aiming at finding novel botanicals for controlling the vector population. Objective was to evaluate the larvicidal and pupicidal efficacies of crude and solvent extracts of Michelia champaca seed against the notorious dengue vector Aedes albopictus. 0.5% concentration of the crude extractive and 40 ppm concentration of ethyl acetate extractive were enough to execute 100% of larval mortality of all the instars after 72 h of exposure and the LC50 and LC90values (95% confidence level) of ethyl acetate extractive were 0.9880 ppm and 36.0491 ppm. In case of pupicidal bioassay, 100% mortality was observed at 200 ppm of ethyl acetate extract. Through TLC techniques, the bioactive compounds were isolated, which caused remarkable larval toxicity at 15 ppm concentration. Three-way factorial ANOVA analysis showed different concentrations, time intervals, and instars revealed a significant difference in larval death. FT-IR analysis revealed the presence several important functional groups. Presence of methyl 5,12-octadecadienoate and ethyl 9cis,11trans-octadecadienoate were ascertained by GC-MS analysis. The said bioactive compounds showed very low toxicity in non-target organisms such as damselfly (Ischnura sp.) and water bug (Diplonychus sp.) Thus, proclaiming the potentialities of Michelia champaca seed extracts as larvicidal and pupicidal agents against Ae. albopictus.


Asunto(s)
Aedes , Dengue , Magnoliaceae , Animales , Espectroscopía Infrarroja por Transformada de Fourier , Mosquitos Vectores , Larva , Semillas , Extractos Vegetales/farmacología , Dengue/prevención & control
4.
Sci Rep ; 13(1): 7403, 2023 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149703

RESUMEN

Larvae of the elephant mosquitoes, Toxorhynchites spp. (Diptera: Culicidae) are predacious on larvae of other mosquito species and some small aquatic organisms; this predatory behavior can be applied in (mosquito) vector control. The present study examined the feeding behavior of Toxorhynchites splendens on Aedes albopictus in relation to search area [volume of water (X1)] and prey density (X2), prey instars, predatory preference and larvae's functional response on variable prey densities. Experiments were conducted to determine changes in the feeding activity of T. splendens with different search areas and showed that rate of prey consumption was inversely proportional to the search area as evidenced by a negative value of X1 in the regression equation and positively related to prey density. The non-linear polynomial logistic regression estimated a significant linear parameter (P1 < 0) for the functional response analysis suggesting a Type II functional response. Differences in feeding response related to the different combinations of prey instars were statistically not significant (p > 0.05), expressing that all the instars of prey were equally susceptible to the predator. Toxorhynchites splendens preferred to consume Ae. albopictus larvae rather than Tubifex when supplied together as a food source.


Asunto(s)
Aedes , Culicidae , Animales , Aedes/fisiología , Larva/fisiología , Conducta Predatoria/fisiología , Mosquitos Vectores , Culicidae/fisiología , Control Biológico de Vectores
5.
Sci Rep ; 13(1): 8651, 2023 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-37244906

RESUMEN

Selection of plant extracts as bioactive phytochemical source to synthesize nanoparticles is highly demanding due to the biocompatibility, nontoxicity, and cost-effectiveness over other available physical and chemical methods. Here, for the first time, Coffee arabica leaf extracts (CAE) were used to produce highly stable silver nanoparticles (AgNPs) and the corresponding bio reduction, capping and stabilization mechanism mediated by dominant isomer 5-caffeoylquinic acid (5-CQA) is discussed. UV-Vis, FTIR, µRaman spectroscopy, TEM, DLS and Zeta potential analyzer measurements were employed to characterize these green synthesized NPs. The affinity of 5-CQA capped CAE-AgNPs to thiol moiety of amino acid is utilized for the selective as well as sensitive detection of L-cysteine (L-Cys) to a low detection limit of 0.1 nM, as obtained from its µRaman spectra. Hence, the proposed novel, simple, eco-friendly, and economically sustainable method can provide a promising nanoplatform in the field of biosensors compliant with large-scale industrial production of AgNPs without aid of further instrumentation.


Asunto(s)
Nanopartículas del Metal , Nanopartículas del Metal/química , Cisteína , Plata/química , Café , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de Fourier , Hojas de la Planta/metabolismo , Antibacterianos
6.
J Clin Invest ; 132(1)2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34981776

RESUMEN

Efficient sarcolemmal repair is required for muscle cell survival, with deficits in this process leading to muscle degeneration. Lack of the sarcolemmal protein dysferlin impairs sarcolemmal repair by reducing secretion of the enzyme acid sphingomyelinase (ASM), and causes limb girdle muscular dystrophy 2B (LGMD2B). The large size of the dysferlin gene poses a challenge for LGMD2B gene therapy efforts aimed at restoring dysferlin expression in skeletal muscle fibers. Here, we present an alternative gene therapy approach targeting reduced ASM secretion, the consequence of dysferlin deficit. We showed that the bulk endocytic ability is compromised in LGMD2B patient cells, which was addressed by extracellularly treating cells with ASM. Expression of secreted human ASM (hASM) using a liver-specific adeno-associated virus (AAV) vector restored membrane repair capacity of patient cells to healthy levels. A single in vivo dose of hASM-AAV in the LGMD2B mouse model restored myofiber repair capacity, enabling efficient recovery of myofibers from focal or lengthening contraction-induced injury. hASM-AAV treatment was safe, attenuated fibro-fatty muscle degeneration, increased myofiber size, and restored muscle strength, similar to dysferlin gene therapy. These findings elucidate the role of ASM in dysferlin-mediated plasma membrane repair and to our knowledge offer the first non-muscle-targeted gene therapy for LGMD2B.


Asunto(s)
Dependovirus , Terapia Genética , Vectores Genéticos , Hígado/enzimología , Distrofia Muscular de Cinturas , Esfingomielina Fosfodiesterasa , Animales , Línea Celular Transformada , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Mutantes , Distrofia Muscular de Cinturas/enzimología , Distrofia Muscular de Cinturas/genética , Distrofia Muscular de Cinturas/terapia , Esfingomielina Fosfodiesterasa/biosíntesis , Esfingomielina Fosfodiesterasa/genética
7.
NeuroImmune Pharm Ther ; 1(1): 7-22, 2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-36720111

RESUMEN

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and this study underlines the significance of a small molecule glyceryl tribenzoate (GTB), a FDA approved food additive, in preventing parkinsonian pathologies in MPTP-induced animal models. The study conducted in MPTP-induced mice demonstrated dose-dependent protection of nigral tyrosine hydroxylase (TH) and striatal dopamine level by GTB oral treatment and the optimum dose was found to be 50 mg/kg/d. In the next phase, the study was carried out in MPTP-injected hemiparkinsonian monkeys, which recapitulate better clinical parkinsonian syndromes. GTB inhibited MPTP-driven induction of glial inflammation, which was evidenced by reduced level of GTP-p21Ras and phospho-p65 in SN of monkeys. It led to decreased expression of inflammatory markers such as IL-1ß and iNOS. Simultaneously, GTB oral treatment protected nigral TH cells, striatal dopamine, and improved motor behaviour of hemiparkinsonian monkeys. Presence of sodium benzoate, a GTB metabolite and a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain suggests that the neuroprotective effect imparted by GTB might be mediated by sodium benzoate. Although the mechanism of action of GTB is poorly understood, the study sheds light on the therapeutic possibility of a food additive GTB in PD.

8.
J Neuromuscul Dis ; 8(s2): S243-S255, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34633328

RESUMEN

Mutations in the Anoctamin 5 (Ano5) gene that result in the lack of expression or function of ANO5 protein, cause Limb Girdle Muscular Dystrophy (LGMD) 2L/R12, and Miyoshi Muscular Dystrophy (MMD3). However, the dystrophic phenotype observed in patient muscles is not uniformly recapitulated by ANO5 knockout in animal models of LGMD2L. Here we describe the generation of a mouse model of LGMD2L generated by targeted out-of-frame deletion of the Ano5 gene. This model shows progressive muscle loss, increased muscle weakness, and persistent bouts of myofiber regeneration without chronic muscle inflammation, which recapitulates the mild to moderate skeletal muscle dystrophy reported in the LGMD2L patients. We show that these features of ANO5 deficient muscle are not associated with a change in the calcium-activated sarcolemmal chloride channel activity or compromised in vivo regenerative myogenesis. Use of this mouse model allows conducting in vivo investigations into the functional role of ANO5 in muscle health and for preclinical therapeutic development for LGMD2L.


Asunto(s)
Anoctaminas/genética , Músculo Esquelético/patología , Distrofia Muscular de Cinturas/genética , Animales , Canales de Cloruro/genética , Modelos Animales de Enfermedad , Ratones , Ratones Noqueados , Debilidad Muscular/genética , Distrofia Muscular de Cinturas/patología , Mutación , Fenotipo
9.
Cell Stress ; 5(5): 73-75, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33987529

RESUMEN

Cells maintain their cytosolic calcium (Ca2+) in nanomolar range and use controlled increase in Ca2+ for intracellular signaling. With the extracellular Ca2+ in the millimolar range, there is a steep Ca2+ gradient across the plasma membrane (PM). Thus, injury that damages PM, leads to a cytosolic Ca2+ overload, which helps activate PM repair (PMR) response. However, in order to survive, the cells must cope with the Ca2+ overload. In a recent study (Chandra et al. J Cell Biol, doi: 10.1083/jcb.202006035) we have examined how cells cope with injury-induced cytosolic Ca2+ overload. By monitoring Ca2+ dynamics in the cytosol and endoplasmic reticulum (ER), we found that PM injury-triggered increase in cytosolic Ca2+ is taken up by the ER. Pharmacological inhibition of ER Ca2+ uptake interferes with this process and compromises the repair ability of the injured cells. Muscle cells from patients and mouse model for the muscular dystrophy showed that lack of Anoctamin 5 (ANO5)/Transmembrane protein 16E (TMEM16E), an ER-resident putative Ca2+-activated chloride channel (CaCC), are poor at coping with cytosolic Ca2+ overload. Pharmacological inhibition of CaCC and lack of ANO5, both prevent Ca2+ uptake into ER. These studies identify a requirement of Cl- uptake by the ER in sequestering injury-triggered cytosolic Ca2+ increase in the ER. Further, these studies show that ER helps injured cells cope with Ca2+ overload during PMR, lack of which contributes to muscular dystrophy due to mutations in the ANO5 protein.

10.
J Cell Biol ; 220(5)2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33688936

RESUMEN

Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5). SERCA imports calcium into the ER, and ANO5 supports this by maintaining electroneutrality of the ER lumen through anion import. Preventing either of these transporter activities causes cytosolic calcium overload and disrupts PM repair (PMR). ANO5 deficit in limb girdle muscular dystrophy 2L (LGMD2L) patient cells compromises their cytosolic and ER calcium homeostasis. By generating a mouse model of LGMD2L, we find that PM injury causes cytosolic calcium overload and compromises the ability of ANO5-deficient myofibers to repair. Addressing calcium overload in ANO5-deficient myofibers enables them to repair, supporting the requirement of the ER in calcium homeostasis in injured cells and facilitating PMR.


Asunto(s)
Membrana Celular/fisiología , Retículo Endoplásmico/fisiología , Homeostasis/fisiología , Animales , Anoctaminas/metabolismo , Calcio/metabolismo , Línea Celular , Membrana Celular/metabolismo , Citosol/metabolismo , Citosol/fisiología , Retículo Endoplásmico/metabolismo , Femenino , Humanos , Iones/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Distrofia Muscular de Cinturas/metabolismo
11.
Curr Drug Discov Technol ; 18(4): 503-510, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32718293

RESUMEN

BACKGROUND: The only remedy for up surging problem of antibiotic resistance is the discovery of antibacterial agents of natural origin. OBJECTIVE: The present study was aimed at finding antibacterial potential of crude and solvent extracts of mature leaves of Plumeria pudica. METHODS: Antibacterial activity of three different solvent extracts were evaluated in four human and four fish pathogenic bacteria by measuring the zone of inhibition and determining Minimum Inhibitory Concentration and Minimum Bactericidal Concentration values. Standard antibiotics were used as positive control. Preliminary phytochemical screening of most effective extract i.e., ethyl acetate extract, Fourier Transform Infra Red analysis and GC-MS analysis of the Thin Layer Chromatographic (TLC) fraction of ethyl acetate extract were done meticulously. All experiments were done thrice and analyzed statistically. RESULTS: Crude leaf extracts and solvent extracts caused good inhibition of bacterial growth in all selected bacteria. Ethyl acetate extract showed highest inhibition zones in all tested strains with maximum inhibition (19.50±0.29 mm) in Escherichia coli (MTCC 739). MBC/MIC of the extracts indicated that all three solvent extracts were bactericidal. Preliminary phytochemical tests revealed the presence of tannins, steroids and alkaloids and FT-IR analysis revealed presence of many functional groups namely alcoholic, amide, amine salt and aldehyde groups. From the GC-MS analysis of TLC fraction of ethyl acetate extract, five different bioactive compounds e.g., 2,4-ditert -butylphenyl 5-hydroxypentanoate, Oxalic acid; allyl nonyl ester, 7,9-Ditert-butyl-1-oxaspiro(4,5)deca-6,9-diene- 2,8-dione, Dibutyl phthalate and 2,3,5,8-tetramethyl-decane were identified. CONCLUSION: Leaf extracts of P. pudica contain bioactive compounds that can be used as broad spectrum bactericidal agent.


Asunto(s)
Antibacterianos/farmacología , Apocynaceae/química , Infecciones Bacterianas/tratamiento farmacológico , Enfermedades de los Peces/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Enfermedades de los Peces/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier
12.
Cells ; 9(9)2020 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-32824910

RESUMEN

Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells. We find that injury-triggered increase in cytosolic calcium causes AnxA2 to bind dysferlin and accumulate on dysferlin-containing vesicles as well as with dysferlin at the site of membrane injury. AnxA2 accumulates on the injured plasma membrane in cholesterol-rich lipid microdomains and requires Src kinase activity and the presence of cholesterol. Lack of AnxA2 and its failure to translocate to the plasma membrane, both prevent calcium-triggered dysferlin translocation to the plasma membrane and compromise repair of the injured plasma membrane. Our studies identify that Anx2 senses calcium increase and injury-triggered change in plasma membrane cholesterol to facilitate dysferlin delivery and repair of the injured plasma membrane.


Asunto(s)
Anexina A2/metabolismo , Membrana Celular/metabolismo , Disferlina/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular de Cinturas/metabolismo , Cicatrización de Heridas/fisiología , Humanos , Distrofia Muscular de Cinturas/genética
13.
Ann Neurol ; 88(2): 332-347, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32403198

RESUMEN

OBJECTIVE: A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings and in subsequent patients with a similar constellation of findings. The goal of this study was to understand the genetic and molecular etiology of this condition. METHODS: We applied whole exome sequencing (WES) superimposed on shared haplotype regions to identify the initial biallelic variants in GGPS1 followed by GGPS1 Sanger sequencing or WES in 5 additional families with the same phenotype. Molecular modeling, biochemical analysis, laser membrane injury assay, and the generation of a Y259C knock-in mouse were done. RESULTS: A total of 11 patients in 6 families carrying 5 different biallelic pathogenic variants in specific domains of GGPS1 were identified. GGPS1 encodes geranylgeranyl diphosphate synthase in the mevalonate/isoprenoid pathway, which catalyzes the synthesis of geranylgeranyl pyrophosphate, the lipid precursor of geranylgeranylated proteins including small guanosine triphosphatases. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. There was delayed membrane healing after laser injury in patient-derived myogenic cells, and a knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality. INTERPRETATION: The identification of specific GGPS1 mutations defines the cause of a unique form of muscular dystrophy with hearing loss and ovarian insufficiency and points to a novel pathway for this clinical constellation. ANN NEUROL 2020;88:332-347.


Asunto(s)
Dimetilaliltranstransferasa/genética , Farnesiltransferasa/genética , Geraniltranstransferasa/genética , Pérdida Auditiva/genética , Distrofias Musculares/genética , Mutación/genética , Insuficiencia Ovárica Primaria/genética , Adolescente , Adulto , Animales , Femenino , Técnicas de Sustitución del Gen/métodos , Pérdida Auditiva/diagnóstico por imagen , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Distrofias Musculares/diagnóstico por imagen , Linaje , Insuficiencia Ovárica Primaria/diagnóstico por imagen , Estructura Secundaria de Proteína , Análisis de Secuencia de ADN/métodos , Secuenciación del Exoma/métodos , Adulto Joven
14.
J Inherit Metab Dis ; 43(5): 1082-1101, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32279353

RESUMEN

Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease (LSD) caused by inactivating mutations in the CLN1 gene. CLN1 encodes palmitoyl-protein thioesterase-1 (PPT1), a lysosomal enzyme that catalyzes the deacylation of S-palmitoylated proteins to facilitate their degradation and clearance by lysosomal hydrolases. Despite the discovery more than two decades ago that CLN1 mutations causing PPT1-deficiency underlies INCL, the precise molecular mechanism(s) of pathogenesis has remained elusive. Here, we report that autophagy is dysregulated in Cln1-/- mice, which mimic INCL and in postmortem brain tissues as well as cultured fibroblasts from INCL patients. Moreover, Rab7, a small GTPase, critical for autophagosome-lysosome fusion, requires S-palmitoylation for trafficking to the late endosomal/lysosomal membrane where it interacts with Rab-interacting lysosomal protein (RILP), essential for autophagosome-lysosome fusion. Notably, PPT1-deficiency in Cln1-/- mice, dysregulated Rab7-RILP interaction and preventing autophagosome-lysosome fusion, which impaired degradative functions of the autolysosome leading to INCL pathogenesis. Importantly, treatment of Cln1-/- mice with a brain-penetrant, PPT1-mimetic, small molecule, N-tert (butyl)hydroxylamine (NtBuHA), ameliorated this defect. Our findings reveal a previously unrecognized role of CLN1/PPT1 in autophagy and suggest that small molecules functionally mimicking PPT1 may have therapeutic implications.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Lisosomas/enzimología , Lipofuscinosis Ceroideas Neuronales/genética , Tioléster Hidrolasas/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Animales , Autofagia , Células Cultivadas , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Lipofuscinosis Ceroideas Neuronales/patología , Tioléster Hidrolasas/genética , Proteínas de Unión a GTP rab7
15.
J Neurochem ; 153(5): 545-548, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32128827

RESUMEN

Kessler et al. in this current issue have attempted to discern biomarker(s) for spinal muscular atrophy (SMA) by assessing alterations in cerebrospinal fluid (CSF) proteomics profile. Recently, antisense oligonucleotide (nusinersen) therapy is shown to mitigate pathologies and provide behavioral improvements in patients. This Editorial highlights the study by Kessler et al on the proteomics of CSF from adult and young patients prior to, and 10 months after nusinersen intrathecal therapy. Although the study by Kessler et al. suffers from small sample size and mixed results that deterred a strong conclusion, yet is a strong case-control study that is contemporary and important to the patients, clinicians and care-takers alike. Since identifying biomarker and characterizing the pathology in SMA are imminent necessity to advance this promising therapy, the high-throughput CSF proteomics data prior and after nusinersen therapy provide possible biomarkers that may help in identification of positive responders, the disease course, efficacy of treatment, and more accurate prognosis.


Asunto(s)
Atrofia Muscular Espinal/líquido cefalorraquídeo , Atrofia Muscular Espinal/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Proteómica/métodos , Biomarcadores/líquido cefalorraquídeo , Humanos , Atrofia Muscular Espinal/genética , Proteómica/tendencias
16.
Anal Bioanal Chem ; 412(11): 2505-2516, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32072214

RESUMEN

Infectious diseases caused by bacteria still pose major diagnostic challenges in spite of the availability of various molecular approaches. Irrespective of the type of infection, rapid identification of the causative pathogen with a high degree of sensitivity and specificity is essential for initiating appropriate treatment. While existing methods like PCR possess high sensitivity, they are incapable of identifying the viability status of the pathogen and those which can, like culturing, are inherently slow. To overcome these limitations, we developed a diagnostic platform based on Raman microspectroscopy, capable of detecting biochemical signatures from a single bacterium for identification as well as viability assessment. The study also establishes a decontamination protocol for handling live pathogenic bacteria which does not affect identification and viability testing, showing applicability in the analysis of sputum samples containing pathogenic mycobacterial strains. The minimal sample processing along with multivariate analysis of spectroscopic signatures provides an interface for automatic classification, allowing the prediction of unknown samples by mapping signatures onto available datasets. Also, the novelty of the current work is the demonstration of simultaneous identification and viability assessment at a single bacterial level for pathogenic bacteria. Graphical abstract.


Asunto(s)
Bacterias/aislamiento & purificación , Infecciones Bacterianas/diagnóstico , Espectrometría Raman/métodos , Bacterias/química , Humanos , Sensibilidad y Especificidad , Factores de Tiempo
17.
Biotechnol Lett ; 42(5): 853-863, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32040672

RESUMEN

OBJECTIVE: This study aims to detect pathogenic Escherichia coli (E. coli) bacteria using non-destructive fluorescence microscopy and micro-Raman spectroscopy. RESULTS: Raman vibrational spectroscopy provides additional information regarding biochemical changes at the cellular level. We have used two nanomaterials zinc oxide nanoparticles (ZnO-NPs) and gold nanoparticles (Au-NPs) to detect pathogenic E. coli. The scanning electron microscope (SEM) with energy dispersive X-ray (EDAX) spectroscopy exhibit surface morphology and the elemental composition of the synthesized NPs. The metal NPs are useful contrast agents due to the surface plasmon resonance (SPR) to detect the signal intensity and hence the bacterial cells. The changes due to the interaction between cells and NPs are further correlated to the change in the surface charge and stiffness of the cell surface with the help of the fluorescence microscopic assay. CONCLUSIONS: We conclude that when two E. coli strains (MTCC723 and MTCC443) and NPs are respectively mixed and kept overnight, the growth of bacteria are inhibited by ZnO-NPs due to changes in cell membrane permeability and intracellular metabolic system under fluorescence microscopy. However, SPR possessed Au-NPs result in enhanced fluorescence of both pathogens. In addition, with the help of Raman microscopy and element analysis, significant changes are observed when Au-NPs are added with the two strains as compared to ZnO-NPs due to protein, lipid and DNA/RNA induced conformational changes.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/aislamiento & purificación , Oro/farmacología , Óxido de Zinc/farmacología , Antibacterianos/química , Permeabilidad de la Membrana Celular , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Proteínas de Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/metabolismo , Oro/química , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Microscopía Fluorescente , Propiedades de Superficie , Óxido de Zinc/química
18.
J Vector Borne Dis ; 57(4): 295-300, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-34856708

RESUMEN

BACKGROUND & OBJECTIVES: Lymphatic filariasis (LF) is a neglected parasitic disease of tropics and subtropics including India. Although the disease mostly affects adults, there are evidences that LF infection is often acquired during childhood. This study assessed the filarial epidemiology as well as awareness about the disease among school children in the rural areas of Bankura district, West Bengal, India. METHODS: Night blood samples of 1193 school children were examined to detect microfilariae. They were examined clinically by a physician for filarial manifestations and inquired about their awareness on the disease. RESULTS: Microfilaria rate and disease rate among school children of the study area were assessed as 3.69% and 8.97% respectively. Only 12.74% of the school children had proper knowledge about filariasis and 72.09% had filarial patients living nearby. Among those affected children, 53.79% never received proper medical attention and 66.21% were found to be anxious about the fate of their filarial problems. School going males were found to be more affected than the females. Anxiety about the effect of the disease in girls was higher due to societal and medical ignorance among women that might develop psychological concerns. INTERPRETATION & CONCLUSION: This study suggests that, in the present study area, about 12.15% population acquired filarial infection at the stage of schooling. But effort for developing awareness about filariasis among the school children is scanty, which is presumably one of the major causes of high endemicity. To rectify the situation, knowledge about mosquito and mosquito borne diseases, including LF, should be properly incorporated in school curriculum. Control measures like anti-filarial drug administration and morbidity-management can be implemented in schools by the local governments, as it should be.


Asunto(s)
Filariasis Linfática , Animales , Niño , Filariasis Linfática/epidemiología , Femenino , Humanos , India/epidemiología , Masculino , Microfilarias , Prevalencia , Instituciones Académicas , Wuchereria bancrofti
19.
Curr Drug Discov Technol ; 17(4): 523-533, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31702527

RESUMEN

Botanicals have been cultured to flavour food, to treat health disorders and to put a stop to diseases caused by various microorganisms. The awareness of curative features of different medicinal plants has been spread among human communities. The application of herbal products as antimicrobial agents may be a better choice for the extensive and imprudent use of synthetic antibiotics. World Health Organization recommended traditional medicines as the safest remedies for the treatment of diseases of microbial origin. The plant extracts are generally nonhazardous, available in plenty at reasonable prices, biodegradable, eco-friendly and sometimes show broad-spectrum activities against different microorganisms. The current knowledge on plant extracts, phytochemicals and their antibacterial activity, target specific mechanism of action, solvents deployed during extraction, properties of an active ingredient isolated may help in biological control of bacteria. Antimicrobial properties of different plant parts, which act in a low dose, have been organised separately for easy understanding.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Fitoterapia/métodos , Extractos Vegetales/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/uso terapéutico , Infecciones Bacterianas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Fitoterapia/tendencias , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico
20.
Phys Chem Chem Phys ; 21(37): 20791-20804, 2019 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-31513201

RESUMEN

Ionic liquids (ILs) and their aqueous solutions are emerging media for solving and manipulating biochemical molecules such as proteins. Unleashing the full potential however requires a detailed mechanistic understanding of how suitable protic and aprotic ILs behave in the presence of water in the first place. The present work aims at making an important step by performing a combined experimental and computational study of two selected ILs and their mixtures with water: the aprotic cholinium propionate ([Chl][Pro]) and the protic N-methyl-2-pyrrolidonium propionate ([NMP][Pro]). IR and Raman spectroscopy reveal stronger ion-solvent interactions in [Chl][Pro]-H2O systems compared to [NMP][Pro]-H2O mixtures. This can be explained by the tightly packed ion-pair associations in [NMP][Pro] comprising the protic -N+-H counterpart, which allows the establishment of highly directional and strong interionic hydrogen bonds. The spectral decomposition of the O-D stretching band into three sub-peaks showed that the protic [NMP][Pro] favors the self-association of water molecules. On the other hand, the predominant fraction of water-anion/cation aggregates exists in aprotic [Chl][Pro]. These hydrated systems can be envisaged using quantum-chemical calculations in the following way: H2O[Chl]+H2O[Pro]-H2O and H2O[NMP]+[Pro]-H2O, which implied preferable solvent-shared ion-pair (SIP) configurations for [Chl][Pro]-H2O systems, whereas the contact ion-pair (CIP) state prevails for the [NMP][Pro]-H2O systems. The latter holds even in the water-rich regime. In future work, these findings will be the basis for an understanding of the underlying principles that govern the interactions of ions with bio-molecules in aqueous solutions.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA