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1.
Physiol Plant ; 176(1): e14183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38343301

RESUMEN

Roots are the main sensing organ, initiating multiple signaling pathways in response to abiotic factors, including nutrients, drought, and salt stress. A focus on improving the root system architecture is a key strategy to mitigate these stresses in wheat crop. In the present study, a diversity panel comprising indigenous landraces and historical cultivars from Pakistan was characterized for the root system architecture (RSA) and important loci were identified using a genome-wide association study (GWAS). RSA of the diversity panel was characterized 30 days after sowing in brunch tubes, and root images were taken. A high-throughput root imaging analysis using Rhizovision software was performed by setting the scale to extract the eight RSA traits and four plant biomass-related traits. GWAS identified 323 association signals for 12 root and biomass traits present on all wheat chromosomes, while the most important and reliable genetic loci (based on pleotropic loci and candidate genes) were identified on chromosomes 2A, 2B, 5A, 5D, 6A, 7B, and 7D for RSA. SNP annotation and transcriptome profiling identified nine candidate genes regulating the RSA and plant biomass traits, including ROOTLESS WITH UNDETECTABLE MERISTEM1, MYB TRANSCRIPTION FACTOR4, BRASSINOSTEROID INSENSITIVE1, SLENDER RICE1, AUXIN-RESPONSIVE FACTOR25, SCARECROW, NARROW LEAF2, PIN-FORMED1 AND PHOSPHATE TRANSCRIPTION FACTOR1. This study provided pre-breeding information for deep-rooting genotypes and associated markers that will accelerate the incorporation of such traits in breeding.


Asunto(s)
Sitios de Carácter Cuantitativo , Triticum , Sitios de Carácter Cuantitativo/genética , Triticum/genética , Estudio de Asociación del Genoma Completo , Fenotipo , Genotipo , Polimorfismo de Nucleótido Simple
2.
Bioorg Med Chem ; 98: 117540, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38134663

RESUMEN

Global challenges with treatment failures and/or widespread resistance in parasitic worms against commercially available anthelmintics lend impetus to the development of new anthelmintics with novel mechanism(s) of action. The free-living nematode Caenorhabditis elegans is an important model organism used for drug discovery, including the screening and structure-activity investigation of new compounds, and target deconvolution. Previously, we conducted a whole-organism phenotypic screen of the 'Pandemic Response Box' (from Medicines for Malaria Venture, MMV) and identified a hit compound, called ABX464, with activity against C. elegans and a related, parasitic nematode, Haemonchus contortus. Here, we tested a series of 44 synthesized analogues to explore the pharmacophore of activity on C. elegans and revealed five compounds whose potency was similar or greater than that of ABX464, but which were not toxic to human hepatoma (HepG2) cells. Subsequently, we employed thermal proteome profiling (TPP), protein structure prediction and an in silico-docking algorithm to predict ABX464-target candidates. Taken together, the findings from this study contribute significantly to the early-stage drug discovery of a new nematocide based on ABX464. Future work is aimed at validating the ABX464-protein interactions identified here, and at assessing ABX464 and associated analogues against a panel of parasitic nematodes, towards developing a new anthelmintic with a mechanism of action that is distinct from any of the compounds currently-available commercially.


Asunto(s)
Antihelmínticos , Nematodos , Quinolinas , Animales , Humanos , Caenorhabditis elegans , Antihelmínticos/farmacología , Antihelmínticos/química , Relación Estructura-Actividad
3.
Planta Med ; 90(12): 959-970, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079700

RESUMEN

The present study endeavored to design and develop a self-nanoemulsifying drug delivery system to improve the solubility and dermatological absorption of curcumin and naringin. Curcumin and naringin-loaded self-nanoemulsifying drug delivery system formulations were developed using aqueous phase titration. Phase diagrams were used to pinpoint the self-nanoemulsifying drug delivery system zones. Tween 80 and Labrasol (surfactants), Transcutol (cosurfactant), and cinnamon oil were chosen from a large pool of surfactants, cosurfactants, and oils based on their solubility and greatest nano-emulsion region. Fourier transform infrared spectroscopy, zeta sizer, and atomic force microscopy were used to characterize the optimized formulations and test for dilution and thermodynamic stability. The optimized curcumin-naringin-self-nanoemulsifying drug delivery system demonstrated the following characteristics: polydispersity index (0.412 ± 0.03), % transmittance (97%), particle size (212.5 ± 05 nm), zeta potential (- 25.7 ± 1.80 mV) and having a smooth and spherical droplet shape, as shown by atomic force microscopy. The ability of their combined formulation to cure wounds was tested in comparison to pure curcumin suspension, empty self-nanoemulsifying drug delivery system, and standard fusidic acid. Upon topical administration, the optimized curcumin-naringin-self-nanoemulsifying drug delivery system demonstrated significant wound healing activity in comparison with a pure curcumin suspension, empty self-nanoemulsifying drug delivery system, and standard fusidic acid. Based upon this result, we assume that skin penetration was increased by using the optimized curcumin-naringin-self-nanoemulsifying drug delivery system with enhanced solubility.


Asunto(s)
Curcumina , Sistemas de Liberación de Medicamentos , Emulsiones , Flavanonas , Polisorbatos , Tensoactivos , Cicatrización de Heridas , Curcumina/administración & dosificación , Curcumina/química , Curcumina/farmacología , Curcumina/farmacocinética , Animales , Flavanonas/química , Flavanonas/administración & dosificación , Flavanonas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Polisorbatos/química , Tensoactivos/química , Solubilidad , Ratas , Tamaño de la Partícula , Glicéridos/química , Masculino , Nanopartículas/química , Espectroscopía Infrarroja por Transformada de Fourier , Ratas Wistar , Glicoles de Etileno
4.
Exp Appl Acarol ; 92(3): 479-506, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38457048

RESUMEN

Tick-borne pathogens (TBPs) represent a substantial threat to cattle globally, exerting adverse impacts on production, health, and economic viability. This study delves into the prevalence and implications of TTBPs in cattle sourced from resource-limited smallholder livestock farms situated in southeastern Iran, proximate to Afghanistan and Pakistan. Blood and tick specimens were systematically collected from a cohort of 230 cattle, comprising 150 asymptomatic and 80 symptomatic individuals. Genomic DNA isolated from blood samples underwent rigorous examination for the presence of key TBPs, including Anaplasma marginale, A. phagocytophilum, A. bovis, A. centrale, Babesia bigemina, and Theileria annulata, utilizing multiple genetic markers. Nucleotide sequence analysis facilitated the reconstruction of phylogenetic relationships. The study also evaluated various potential risk factors, such as clinical status, gender, age, breed, tick infestation, and management practices, to elucidate their associations with TTBPs. Among the cattle cohort, a staggering 87.8% (202/230) tested positive for at least one pathogen. Prevalence statistics encompassed A. marginale (72.2%), T. annulata (68.3%), A. phagocytophilum/A. platys-like complex (66.1%), A. centrale (16.7%), B. bigemina (10.0%), and A. bovis (6.1%). Remarkably, mixed infections involving two, three, and four pathogens were detected in 23%, 52.1%, and 2.2% of animals, respectively. Notably, all asymptomatic cattle were positive for at least one TBP. Tick infestation was observed in 62.2% (143/230) of cattle, predominantly caused by Hyalomma anatolicum (82.5%), Rhipicephalus (Boophilus) annulatus (13.1%), and R. sanguineus sensu lato (4.4%). Risk factors linked to TBPs encompassed tick infestation, older age, and crossbred animals. Clinical presentations among symptomatic cattle encompassed fever, anemia, weight loss, anorexia, jaundice, and enlarged superficial lymph nodes. This study underscores the pivotal role of asymptomatic carriers in the propagation of TTBPs within endemic regions. Furthermore, it emphasizes the potential for the implementation of molecular diagnostics to unmask subclinical infections, thereby affording the opportunity for targeted interventions aimed at ameliorating the burden of TTBPs in resource-constrained smallholder dairy farms.


Asunto(s)
Enfermedades de los Bovinos , Filogenia , Animales , Bovinos , Irán/epidemiología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Femenino , Masculino , Factores de Riesgo , Enfermedades por Picaduras de Garrapatas/veterinaria , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/parasitología , Babesia/aislamiento & purificación , Babesia/genética , Prevalencia , Anaplasmosis/epidemiología , Anaplasmosis/microbiología , Theileriosis/epidemiología , Theileriosis/parasitología , Babesiosis/epidemiología , Infestaciones por Garrapatas/veterinaria , Infestaciones por Garrapatas/epidemiología , Infestaciones por Garrapatas/parasitología
5.
Mol Ecol ; 32(13): 3733-3746, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37009964

RESUMEN

Individual animals in natural populations tend to host diverse parasite species concurrently over their lifetimes. In free-living ecological communities, organismal life histories shape interactions with their environment, which ultimately forms the basis of ecological succession. However, the structure and dynamics of mammalian parasite communities have not been contextualized in terms of primary ecological succession, in part because few datasets track occupancy and abundance of multiple parasites in wild hosts starting at birth. Here, we studied community dynamics of 12 subtypes of protozoan microparasites (Theileria spp.) in a herd of African buffalo. We show that Theileria communities followed predictable patterns of succession underpinned by four different parasite life history strategies. However, in contrast to many free-living communities, network complexity decreased with host age. Examining parasite communities through the lens of succession may better inform the effect of complex within host eco-evolutionary dynamics on infection outcomes, including parasite co-existence through the lifetime of the host.


Asunto(s)
Interacciones Huésped-Parásitos , Rasgos de la Historia de Vida , Parásitos , Animales , Evolución Biológica , Biota , Mamíferos
6.
Parasitology ; 150(10): 894-900, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37621007

RESUMEN

Four methods were compared for the diagnosis of human taeniasis caused by Taenia solium. Fecal samples from persons living in a T. solium endemic region of Madagascar were examined for taeniid eggs by the Kato­Katz method. Subsequently, samples positive (n = 16) and negative (n = 200) for T. solium eggs were examined by (i) amplification of the fragment of small subunit of the mitochondrial ribosomal RNA (rrnS) gene using conventional polymerase chain reaction (PCR) and (ii) a nested PCR of a fragment of the T. solium Tso31 gene. Additionally, 12 egg-positive and all egg-negative samples were tested for coproantigen detection. A further 9 egg-positive fecal samples were examined using both PCRs. Of the 12 egg-positive samples tested by PCRs and coproantigen methods, 9 (75%) were positive by rrnS PCR, 3 (25%) using Tso31-nested PCR and 9 (75%) by coproantigen testing. None of the 200 egg-negative fecal samples was positive in either rrnS or Tso31-nested PCR. Twenty of the 25 egg-positive samples (80%) were positive in rrnS PCR, and DNA sequencing of PCR amplicons was obtained from 18 samples, all confirmed to be T. solium. Twelve of the 25 egg-positive samples (48%) were positive in the Tso31-nested PCR, all of which were also positive by rrnS PCR. It is suggested that species-specific diagnosis of T. solium taeniasis may be achieved by either coprological examination to detect eggs or coproantigen testing, followed by rrnS PCR and DNA sequencing to confirm the tapeworm species in egg-positive or coproantigen-positive samples.


Asunto(s)
Taenia solium , Taenia , Teniasis , Humanos , Animales , Taenia solium/genética , Teniasis/diagnóstico , Teniasis/epidemiología , Reacción en Cadena de la Polimerasa , Heces , Especificidad de la Especie , Taenia/genética
7.
BMC Public Health ; 23(1): 2084, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875875

RESUMEN

BACKGROUND: Following the mass influx of Rohingya refugees into Cox's Bazaar, Bangladesh in 2017, makeshift settlement camps in Ukhiya and Teknaf have been overburdened, leading to livelihood challenges for both Rohingya and host communities. The humanitarian crisis has had adverse effects on vulnerable populations, which include older people, persons with disabilities, adolescents, and single female household heads. Using a subset of a larger dataset on households with most vulnerable groups in both communities, we analysed the effect of the pandemic and lockdown on the livelihood of single female household (HH) heads. METHODS: A cross-sectional household roster survey was designed to collect data from households with most vulnerable groups (MVGs) of host and Rohingya communities from December 2020 to March 2021; 11 host community villages and 10 Rohingya camps purposively selected as per the affiliated intervention of the project. The paper analysed quantitative and qualitative data from the sub-group of single female household heads without any income/low income. Participants were surveyed for their socio-demographic characteristics, COVID-19 experiences and knowledge, food security situation, social experiences and mental health using PHQ-2 test for depression. RESULTS: We surveyed 432 single female HH heads. Support during the pandemic was reported to be low, with less than 50% of HHs reporting relief meeting their needs; only 36% and 15% of these HHs received rations in camps and host communities respectively. Loan facilities were mostly unavailable and there were reported insufficiencies in food consumption. Over 50% of respondents tested positive on the PHQ-2, a scale used to screen for depression. Further analyses indicates that having a chronic health issue (OR 2.2, 95% CI 1.33-3.66) was positively associated with the PHQ-2 score for Rohingya single females. For host single females, having an ill member in the HH (OR 1.46, 95% CI 1.02-2.08) and the inability to save before the pandemic (OR 1.57 95% CI 1.11-2.23) increased the odds of screening positive for depression. CONCLUSION: Our study findings revealed insufficiencies with economic opportunities and food security for single female-headed households, as well as a high rate of positive screening for depression amongst this population. These findings call for a more in-depth understanding of the needs of this group.


Asunto(s)
COVID-19 , Refugiados , Adolescente , Humanos , Femenino , Anciano , Pandemias , Bangladesh/epidemiología , Estudios Transversales , COVID-19/epidemiología , Control de Enfermedades Transmisibles
8.
Sensors (Basel) ; 22(5)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35270898

RESUMEN

To address the problem of automatically detecting and removing the mask without user interaction, we present a GAN-based automatic approach for face de-occlusion, called Automatic Mask Generation Network for Face De-occlusion Using Stacked Generative Adversarial Networks (AFD-StackGAN). In this approach, we decompose the problem into two primary stages (i.e., Stage-I Network and Stage-II Network) and employ a separate GAN in both stages. Stage-I Network (Binary Mask Generation Network) automatically creates a binary mask for the masked region in the input images (occluded images). Then, Stage-II Network (Face De-occlusion Network) removes the mask object and synthesizes the damaged region with fine details while retaining the restored face's appearance and structural consistency. Furthermore, we create a paired synthetic face-occluded dataset using the publicly available CelebA face images to train the proposed model. AFD-StackGAN is evaluated using real-world test images gathered from the Internet. Our extensive experimental results confirm the robustness and efficiency of the proposed model in removing complex mask objects from facial images compared to the previous image manipulation approaches. Additionally, we provide ablation studies for performance comparison between the user-defined mask and auto-defined mask and demonstrate the benefits of refiner networks in the generation process.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Cara/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos
9.
Sensors (Basel) ; 22(7)2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35408303

RESUMEN

Industry 4.0 is a new paradigm of digitalization and automation that demands high data rates and real-time ultra-reliable agile communication. Industrial communication at sub-6 GHz industrial, scientific, and medical (ISM) bands has some serious impediments, such as interference, spectral congestion, and limited bandwidth. These limitations hinder the high throughput and reliability requirements of modern industrial applications and mission-critical scenarios. In this paper, we critically assess the potential of the 60 GHz millimeter-wave (mmWave) ISM band as an enabler for ultra-reliable low-latency communication (URLLC) in smart manufacturing, smart factories, and mission-critical operations in Industry 4.0 and beyond. A holistic overview of 60 GHz wireless standards and key performance indicators are discussed. Then the review of 60 GHz smart antenna systems facilitating agile communication for Industry 4.0 and beyond is presented. We envisage that the use of 60 GHz communication and smart antenna systems are crucial for modern industrial communication so that URLLC in Industry 4.0 and beyond could soar to its full potential.


Asunto(s)
Redes de Comunicación de Computadores , Tecnología Inalámbrica , Comunicación , Industrias , Reproducibilidad de los Resultados
10.
Trop Anim Health Prod ; 54(2): 107, 2022 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-35187616

RESUMEN

BACKGROUND: Haemonchosis is a fatal disease of small ruminants caused by the parasite Haemonchus contortus (H. contortus). The most common drugs used in the treatment of H. contortus include albendazole, oxfendazole, and ivermectin. However, as previously reported in the treatment of haemonchosis, these medicines have acquired drug resistance problems over time. Interestingly, natural plant compounds have demonstrated promising effects in the treatment of H. contortus. Therefore, the current study evaluated the effects of plant extract, Ferula asafetida, against common drugs such as albendazole, oxfendazole, ivermectin, and closantel for the treatment of haemonchosis in small ruminants. METHODOLOGY: The current study was conducted on different small ruminant farms in Kasur District, Punjab, Pakistan. The positive animals (n = 720) after coprological examination were selected in this study and divided into two major groups (n = 360 goats and n = 360 sheep). Further, animals were divided into five treatment groups (A-E) and one control group with no treatment (F). Albendazole, oxfendazole, ivermectin, closantel, and Ferula asafetida were administered orally to groups A-E, respectively. The eggs per gram feces (EPG) were determined through the McMaster technique on days 0, 7th, and 14th of treatment. RESULTS: The results showed a significantly higher efficacy of closantel and Ferula asafetida against H. contortus in both goats (100% and 70%; p < 0.05) and sheep (99% and 87%; p < 0.05), respectively. No correlation was observed between EPG reduction with age and gender in both goats and sheep. CONCLUSION: Allopathic drug closantel and herbal drug, Ferula asafetida, have been proved an effective dewormer against H. contortus in small ruminants.


Asunto(s)
Antihelmínticos , Ferula , Enfermedades de las Cabras , Hemoncosis , Haemonchus , Enfermedades de las Ovejas , Albendazol/farmacología , Albendazol/uso terapéutico , Animales , Antihelmínticos/uso terapéutico , Bencimidazoles , Resistencia a Medicamentos , Enfermedades de las Cabras/tratamiento farmacológico , Cabras , Hemoncosis/tratamiento farmacológico , Hemoncosis/parasitología , Hemoncosis/veterinaria , Ivermectina/farmacología , Ivermectina/uso terapéutico , Óvulo , Recuento de Huevos de Parásitos/veterinaria , Salicilanilidas , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológico , Enfermedades de las Ovejas/parasitología
11.
Pak J Med Sci ; 38(1): 297-301, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35035443

RESUMEN

OBJECTIVE: To determine the frequency of place of delivery and person detecting the anomaly among newborn babies presenting with delayed diagnosis of anorectal malformation (ARM). METHODS: This is a Descriptive Cross-Sectional Study, conducted at Department of Paediatric Surgery, National Institute of Child Health (NICH) Karachi, from February 19, 2019 to August 18, 2019. All patients with ARM who were diagnosed beyond two hours of life (Delayed diagnosis) were included in the study. Chi square test was applied for comparison of categorical variables. RESULTS: Total 110 patients were enrolled in this study. Nineteen (17.3%) patients were delivered at home, while 91 (82.7%) were delivered at the hospital. The first person detecting the anomaly was grandmother (n=25) or a non-medical person in 58 patients (52.7%), 52 were diagnosed by a medical personal either primarily in 31 cases (28.2%) or secondarily by a neonatologist in 21 cases (19.1%). CONCLUSION: It is concluded that Non-medical person detected ARM mainly despite the babies being delivered mostly at the hospital, indicating the need for meticulous neonatal examination.

12.
Pak J Pharm Sci ; 35(4(Special)): 1281-1286, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36218108

RESUMEN

Hertia intermedia is a traditional medicinal plant of Balochistan, used for pain management and stomach problems. Current research work was intended to evaluate the anti-inflammatory and analgesic activities of crude ethanolic extract of H. intermedia. Anti-inflammatory activity was determined by the carrageenan-induced and histamine-induce Rat paw edema in rats, analgesic activity was determined by acetic acid-Induced writhing test, formalin-induced hind paw licking in mice and Tail immersion test. H. intermedia crude ethanolic extract showed significant (p<0.05) effect in both carrageenan and histamine-induced rat paw edema at both 250 and 500 mg/kg oral doses. There were significant analgesic activities in comparison with standard drug and control (p<0.05). It is concluded that H. intermedia crude ethanolic extract possesses significant anti-inflammatory and analgesic effects. However further studies may be carried out to isolate the phytochemicals responsible for anti-inflammatory and analgesic activities.


Asunto(s)
Asteraceae , Histamina , Acetatos , Ácido Acético , Analgésicos/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Carragenina , Edema/inducido químicamente , Edema/tratamiento farmacológico , Etanol/uso terapéutico , Histamina/efectos adversos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Ratones , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ratas
13.
Pak J Pharm Sci ; 35(6(Special)): 1739-1746, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36861237

RESUMEN

Grewia asiatica L. is a potential medicinal plant used for various diseases in traditional medicine. Current study was aimed to evaluate the cardio protective, anti-inflammatory, analgesic and CNS depressant activities of Grewia asiatica L. fruit extract. In cardio protective activity myocardial injury was produced by injection of Isoproterenol (200 mg/kg, s.c), G. asiatica 250 and 500mg/kg treated groups significantly (p<0.05) decreased the level of serum AST, ALT, LDH and CKMB, hence produced cardio protective effect. In analgesic activities G. asiatica produced significant (p<0.05) analgesic effects in acetic acid induced writhing, formalin, paw pressure and tail immersion test. G. asiatica at 250 and 500mg/kg oral dose, significantly (p<0.05) reduced the rat paw edema in carrageen an induced rat paw edema test. G. asiatica extract also produced significant CNS depressant effects in open field, hole board and thiopental sodium induced sleeping time. Findings of the current study suggest that G. asiatica fruit extract showed potential pharmacological effects and can be utilized in alternative medicine.


Asunto(s)
Depresores del Sistema Nervioso Central , Grewia , Animales , Ratas , Frutas , Antiinflamatorios no Esteroideos , Extractos Vegetales/farmacología
14.
Crit Rev Eukaryot Gene Expr ; 31(5): 67-78, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34591392

RESUMEN

The junk DNA "pseudogenes," known as genomic fossils, are characterized by their ubiquitousness and abundance within the genomic structure. These genomics sets are recognized by the potential activity of meta-regulating the parent genes; these are transcribed into interfering RNA, consequently acting on miRNA concentration, thereby shedding light on the crosstalk of the pseudogenes' miRNA, siRNA, lncRNA/tumor therapy co-relationship. Moreover, an upcoming visualization regarding pseudogenes is under investigation, which describes the potentiality of pseudogenes as a fundamental component of cancerous evolutionary processing tools. Accordingly, here is a systematic review covering pseudobirth, pseudosignatures, and functional properties of pseudogenes, concluding that these pseudogenes are hypothetically predictive tumor therapies.


Asunto(s)
Evolución Biológica , Genómica , Neoplasias/genética , Seudogenes , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Terapia Genética/métodos , Humanos
15.
Microb Pathog ; 152: 104754, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33508415

RESUMEN

Mitochondria is a cellular source of energy, appears to play an essential role in dealing with cellular stress induced by environmental stimuli. The genetic diversity of mitochondrial genes involved in oxidative phosphorylation affecting the production of cellular energy and regional adaptation to various ecological (climatic) pressures affecting amino acid sequences (variants of protein). However, little is known about the combined effect of protein changes on cell-level metabolic alterations in simultaneous exposure to various environmental conditions, including mitochondrial dysfunction and oxidative stress induction. The present study was designed to address this issue by analyzing the mitochondrial proteins in Fasciola species including Cytochrome oxidase (COX1, COX2, COX3, and CYTB) and NADH dehydrogenase (ND1, ND2, ND3, ND4, ND5, and ND6). Mitochondrial proteins were used for detailed computational investigation, using available standard bioinformatics tools to exploit structural and functional relationships. These proteins in Fasciola hepatica, Fasciola gigentica, and Fasciola jacksoni were functionally annotated using public databases. The results showed that the protein of COX1 of F. hepatica, F. gigantica, and F. jacksoni consist of 510, 513, and 517 amino acids, respectively. The alignment of proteins showed that these proteins are conserved in the same regions at ten positions in COX and CYTB proteins while at twelve locations in NADH. Three-dimensional structure of COX, CYTB, and NADH proteins were compared and showed differences in additional conserved and binding sites in COX and CYTB proteins as compared to NADH in three species of Fasciola. These results based on the amino acid diversity pattern were used to identify sites in the enzyme and the variations in mitochondrial proteins among Fasciola species. Our study provides valuable information for future experimental studies, including identification of therapeutic, diagnostic, and immunoprophylactic interests with novel mitochondrial proteins.


Asunto(s)
Fasciola hepatica , Fasciola , Fascioliasis , Animales , Fasciola hepatica/genética , Variación Genética , Proteínas Mitocondriales/genética
16.
Mar Drugs ; 19(12)2021 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-34940697

RESUMEN

High-throughput screening of the NatureBank marine extract library (n = 7616) using a phenotypic assay for the parasitic nematode Haemonchus contortus identified an active extract derived from the Australian marine sponge Citronia sp. Bioassay-guided fractionation of the CH2Cl2/MeOH extract from Citronia sp. resulted in the purification of two known hexachlorinated peptides, dysidenin (1) and dysideathiazole (2). Compound 1 inhibited the growth/development of H. contortus larvae and induced multiple phenotypic changes, including a lethal evisceration (Evi) phenotype and/or somatic cell and tissue destruction. This is the first report of anthelmintic activity for these rare and unique polychlorinated peptides.


Asunto(s)
Antinematodos/farmacología , Haemonchus/efectos de los fármacos , Poríferos , Tiazoles/farmacología , Animales , Antinematodos/química , Organismos Acuáticos , Ensayos Analíticos de Alto Rendimiento , Larva/efectos de los fármacos , Tiazoles/química
17.
Molecules ; 26(14)2021 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-34299431

RESUMEN

In the present study, we established a practical and cost-effective high throughput screening assay, which relies on the measurement of the motility of Caenorhabditis elegans by infrared light-interference. Using this assay, we screened 14,400 small molecules from the "HitFinder" library (Maybridge), achieving a hit rate of 0.3%. We identified small molecules that reproducibly inhibited the motility of C. elegans (young adults) and assessed dose relationships for a subset of compounds. Future work will critically evaluate the potential of some of these hits as candidates for subsequent optimisation or repurposing as nematocides or nematostats. This high throughput screening assay has the advantage over many previous assays in that it is cost- and time-effective to carry out and achieves a markedly higher throughput (~10,000 compounds per week); therefore, it is suited to the screening of libraries of tens to hundreds of thousands of compounds for subsequent evaluation and development. The present phenotypic whole-worm assay should be readily adaptable to a range of socioeconomically important parasitic nematodes of humans and animals, depending on their dimensions and motility characteristics in vitro, for the discovery of new anthelmintic candidates. This focus is particularly important, given the widespread problems associated with drug resistance in many parasitic worms of livestock animals globally.


Asunto(s)
Antihelmínticos/análisis , Evaluación Preclínica de Medicamentos/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Animales , Antihelmínticos/aislamiento & purificación , Antihelmínticos/farmacología , Antiinfecciosos/farmacología , Antinematodos/análisis , Antinematodos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Resistencia a Medicamentos/efectos de los fármacos , Larva/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología
18.
Molecules ; 26(9)2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-34068691

RESUMEN

Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Extending previous work, here we screened a panel of 245 chemically-diverse small molecules for anti-parasitic activity against Haemonchus contortus-an economically important parasitic nematode of livestock. This panel was screened in vitro against exsheathed third-stage larvae (xL3) of H. contortus using an established phenotypic assay, and the potency of select compounds to inhibit larval motility and development assessed in dose-response assays. Of the 245 compounds screened, three-designated MPK18, MPK334 and YAK308-induced non-wildtype larval phenotypes and repeatedly inhibited xL3-motility, with IC50 values of 45.2 µM, 17.1 µM and 52.7 µM, respectively; two also inhibited larval development, with IC50 values of 12.3 µM (MPK334) and 6.5 µM (YAK308), and none of the three was toxic to human liver cells (HepG2). These findings suggest that these compounds deserve further evaluation as nematocidal candidates. Future work should focus on structure-activity relationship (SAR) studies of these chemical scaffolds, and assess the in vitro and in vivo efficacies and safety of optimised compounds against adults of H. contortus.


Asunto(s)
Haemonchus/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Haemonchus/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Fenotipo , Bibliotecas de Moléculas Pequeñas/química
19.
Molecules ; 26(19)2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34641389

RESUMEN

Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature-which assume a diverse 'chemical space'-have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber's pole worm (Haemonchus contortus)-an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall 'hit rate' of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced 'non-wild-type' (abnormal) larval phenotypes with reference to 'wild-type' (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by 1H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein.


Asunto(s)
Antihelmínticos/farmacología , Hemoncosis/tratamiento farmacológico , Haemonchus/crecimiento & desarrollo , Poríferos/química , Extractos de Tejidos/farmacología , Animales , Antihelmínticos/aislamiento & purificación , Hemoncosis/parasitología , Haemonchus/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento , Extractos de Tejidos/aislamiento & purificación
20.
Syst Parasitol ; 98(5-6): 679-695, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34581965

RESUMEN

Rugopharynx australis (Mönnig, 1926) (Nematoda: Strongyloidea) is redescribed based on specimens from the type host, Osphranter rufus (Desmarest), together with matching DNA sequence data. Additional hosts were Macropus giganteus Shaw and Osphranter robustus (Gould) with single occurrences in M. fuliginosus (Desmarest), Notamacropus dorsalis (Gray), Lagorchestes conspicillatus Gould and Petrogale xanthopus Gray. Rugopharynx moennigi n. sp., formerly included within R. australis, is distinguished by shorter but overlapping spicule lengths and in the morphology of the gubernaculum as well as by molecular data. Rugopharynx moennigi n. sp. appears to be primarily parasitic in M. fuliginosus throughout its geographical range, but also infects M. giganteus, O. robustus and O. rufus in areas of host sympatry.


Asunto(s)
Nematodos , Strongyloidea , Animales , Australia , Macropodidae/parasitología , Nematodos/genética , Especificidad de la Especie , Strongyloidea/anatomía & histología , Strongyloidea/genética
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