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Neuro-Chirurgie Jun 2024
PubMed: 38943701
DOI: 10.1016/j.neuchi.2024.101580 -
Plant & Cell Physiology Jun 2024Root parasitic plants in the Orobancheceae, such as Striga and Orobanche, cause significant damage to crop production. The germination step of these root parasitic...
Root parasitic plants in the Orobancheceae, such as Striga and Orobanche, cause significant damage to crop production. The germination step of these root parasitic plants is induced by host-root-derived strigolactones (SLs). After germination, the radicles elongate toward the host and invade the host root. We have previously discovered that a simple amino acid, tryptophan (Trp), as well as its metabolite, the plant hormone indole-3-acetic acid (IAA), can inhibit radicle elongation of Orobanche minor. These results suggest that auxin plays a crucial role in the radicle elongation step in root parasitic plants. In this report, we used various auxin chemical probes to dissect the auxin function in the radicle growth of O. minor and Striga hermonthica. We found that synthetic auxins inhibited radicle elongation. In addition, auxin receptor antagonist, auxinole, rescued the inhibition of radicle growth by exogenous IAA. Moreover, a polar transport inhibitor of auxin, N-1-naphthylphthalamic acid (NPA), affected radicle bending. We also proved that exogenously applied Trp is converted into IAA in O. minor seeds, and auxinole partly rescued this radicle elongation. Our data demonstrate a pivotal role of auxin in radicle growth. Thus, manipulation of auxin function in root parasitic plants should offer a useful approach to combat these parasites.
PubMed: 38943636
DOI: 10.1093/pcp/pcae071 -
Molekuliarnaia Biologiia 2024CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification...
CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification of epigenome etc. While CRISPR/Cas systems proved to be highly effective for correcting genetic disorders and treating infectious diseases and cancers in experimental settings, clinical translation of these results is hampered by the lack of efficient CRISPR/Cas delivery vehicles. Modern synthetic nanovehicles based on organic and inorganic polymers have many disadvantages, including toxicity issues, the lack of targeted delivery, and complex and expensive production pipelines. In turn, exosomes are secreted biological nanoparticles that exhibit high biocompatibility, physico-chemical stability, and the ability to cross biological barriers. Early clinical trials found no toxicity associated with exosome injections. In the recent years, exosomes have been considered as perspective delivery vehicles for CRISPR/Cas systems in vivo. The aim of this study was to analyze the efficacy of CRISPR/Cas stochastic packaging into exosomes for several human cell lines. Here, we show that Cas9 protein is effectively localized into the compartment of intracellular exosome biogenesis, but stochastic packaging of Cas9 into exosomes turns to be very low (~1%). As such, stochastic packaging of Cas9 protein is very ineffective and cannot be used for gene editing purposes. Developing novel tools and technologies for loading CRISPR/Cas systems into exosomes is needed.
Topics: Exosomes; Humans; CRISPR-Cas Systems; Gene Editing; CRISPR-Associated Protein 9
PubMed: 38943588
DOI: No ID Found -
Iranian Journal of Immunology : IJI Jun 2024Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease...
Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with β-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.
PubMed: 38943529
DOI: 10.22034/iji.2024.101584.2752 -
Journal of Fish Diseases Jun 2024Alternatives to conventional chemical treatments for parasitic diseases in fish are needed. Microalgal-sourced fatty acid ethyl esters (FAEEs) have shown an...
Alternatives to conventional chemical treatments for parasitic diseases in fish are needed. Microalgal-sourced fatty acid ethyl esters (FAEEs) have shown an antiparasitic effect against Gyrodactylus turnbulli infection in guppies. Here, we tested a range of commercial FAEEs of various carbon chain lengths and unsaturation levels against two fish parasites. Guppies and barramundi infected with G. turnbulli and Trichodina sp., respectively, were used. The most effective FAEE, after excluding those toxic to fish, was ethyl laurate (12:0). For both parasites, the LD50 was 18.75 μM within 250 min of incubation. Ethyl eicosapentaenoate (20:5n3) was the next most effective FAEE against G. turnbulli, and dihomo-γ-linolenic acid ethyl ester (20:3n6) and ethyl α-linolenate (18:3n3) were the next most effective against Trichodina sp. In addition, FAEEs prepared from the microalga Phaeodactylum tricornutum residue, after fucoxanthin extraction, were examined against Trichodina sp. infection in barramundi for the first time. LD85 and LD100 was achieved at 2.5 and 5 μL mL of the FAEE preparation, respectively. In vivo, immersion of infected barramundi in 1.25 μL mL of this preparation for 24 h reduced infection prevalence from 100% to 53% and was non-toxic to fish.
PubMed: 38943443
DOI: 10.1111/jfd.13991 -
Pest Management Science Jun 2024Root-knot nematodes (RKNs), Meloidogyne spp., are one of the most destructive polyphagous plant-parasitic nematodes. They pose a serious threat to global food security...
BACKGROUND
Root-knot nematodes (RKNs), Meloidogyne spp., are one of the most destructive polyphagous plant-parasitic nematodes. They pose a serious threat to global food security and are difficult to control. Entomopathogenic nematodes (EPNs) show promise in controlling RKNs. However, it remains unclear whether the volatile organic compounds (VOCs) emitted from EPN-infected cadavers can control RKNs.
RESULTS
We investigated the fumigation activity of VOCs released from cadavers infected by five different species of EPNs on RKNs in Petri dishes, and found that VOCs released from Steinernema feltiae (SN strain) and S. carpocapsae (All strain) infected cadavers had a significant lethal effect on second-stage juveniles (J2s) of Meloidogyne incognita. The VOCs released from the cadavers infected with S. feltiae were analyzed using SPME-GC/MS. Dimethyl disulfide (DMDS), tetradecane, pentadecane, and butylated hydroxytoluene (BHT), were selected for a validation experiment with pure compounds. The DMDS compound had significant nematicidal activity and repelled J2s. DMDS also inhibited egg hatching and the invasion of tomato roots by J2s. In a pot experiment, the addition of S. feltiae-infected cadavers and cadavers wrapped with a 400-mesh nylon net also significantly reduced the population of RKNs in tomato roots after 7 days. The number of root knots and eggs was reduced by 58% and 74.34%, respectively, compared to the control.
CONCLUSION
These results suggested that the VOCs emitted by the EPN-infected cadavers affected various developmental stages of M. incognita and thus have the potential to be used in controlling RKNs through multiple methods. © 2024 Society of Chemical Industry.
PubMed: 38943354
DOI: 10.1002/ps.8268 -
Successful treatment of fulminant and recurrent lymphocytic myocarditis with calcineurin inhibitors.ESC Heart Failure Jun 2024Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM...
Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM experience recurrence with a life-threatening fulminant form. Although combining steroids and immunosuppressants, such as azathioprine and mycophenolate mofetil, has demonstrated favourable outcomes in patients with LM, their efficacy is limited to the chronic phase. Indeed, various immunosuppressants have been used for LM with fulminant manifestation; however, their evidence remains lacking. In our case series, two patients with LM experienced fulminant relapses during steroid tapering, and another presented persistent cardiac enzymes elevation despite steroid therapies. Consequently, we initiated calcineurin inhibitors alongside steroids, resulting in well-controlled clinical courses without further recurrence of LM and significant adverse effects. Our cases suggest calcineurin inhibitors as therapeutic options for managing steroid-resistant LM with fulminant relapse.
PubMed: 38943229
DOI: 10.1002/ehf2.14896 -
Parasites & Vectors Jun 2024African swine fever (ASF) is a highly contagious and severe haemorrhagic disease of Suidae, with mortalities that approach 100 percent. Several studies suggested the...
BACKGROUND
African swine fever (ASF) is a highly contagious and severe haemorrhagic disease of Suidae, with mortalities that approach 100 percent. Several studies suggested the potential implication of non-biting dipterans in the spread of ASFV in pig farms due to the identification of the ASFV DNA. However, to our knowledge, no study has evaluated the viral DNA load in non-biting dipterans collected in outbreak farms and no risk factors have been analysed. In this context, our study aimed to analyse the risk factors associated with the presence of non-biting dipterans collected from ASF outbreaks in relation to the presence and load of viral DNA.
METHODS
Backyard farms (BF), type A farms (TAF), and commercial farms (CF), were targeted for sampling in 2020. In 2021, no BF were sampled. Each farm was sampled only once. The identification of the collected flies to family, genus, or species level was performed based on morphological characteristics using specific keys and descriptions. Pools were made prior to DNA extraction. All extracted DNA was tested for the presence of the ASFV using a real-time PCR protocol. For this study, we considered every sample with a CT value of 40 as positive. The statistical analysis was performed using Epi Info 7 software (CDC, USA).
RESULTS
All collected non-biting flies belonged to five families: Calliphoridae, Sarcophagidae, Fanniidae, Drosophilidae, and Muscidae. Of the 361 pools, 201 were positive for the presence of ASFV DNA. The obtained CT values of the positive samples ranged from 21.54 to 39.63, with a median value of 33.59 and a mean value of 33.56. Significantly lower CT values (corresponding to higher viral DNA load) were obtained in Sarcophagidae, with a mean value of 32.56; a significantly higher number of positive pools were noticed in August, mean value = 33.12.
CONCLUSIONS
Our study brings compelling evidence of the presence of the most common synanthropic flies near domestic pig farms carrying ASFV DNA, highlighting the importance of strengthening the biosecurity measures and protocols for prevention of the insect life cycle and distribution.
Topics: Animals; African Swine Fever Virus; African Swine Fever; Swine; Disease Outbreaks; Farms; DNA, Viral; Romania; Diptera; Insect Vectors
PubMed: 38943218
DOI: 10.1186/s13071-024-06346-x -
Parasites & Vectors Jun 2024Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.
BACKGROUND
Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
METHODS
This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS
Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS
A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
Topics: Humans; Child; Praziquantel; Pyrimethamine; Animals; Adolescent; Artesunate; Female; Male; Schistosomiasis mansoni; Schistosoma haematobium; Schistosomiasis haematobia; Schistosoma mansoni; Drug Therapy, Combination; Kenya; Artemisinins; Treatment Outcome; Anthelmintics; Sulfalene; Drug Combinations; Parasite Egg Count
PubMed: 38943214
DOI: 10.1186/s13071-024-06359-6 -
Malaria Journal Jun 2024Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the...
BACKGROUND
Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician's expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan.
METHODS
This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.
RESULTS
Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.
CONCLUSION
When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device's specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.
Topics: Sudan; Microscopy; Humans; Case-Control Studies; Prospective Studies; Point-of-Care Systems; Female; Male; Sensitivity and Specificity; Child; Child, Preschool; Adult; Adolescent; Malaria; Young Adult; Middle Aged
PubMed: 38943203
DOI: 10.1186/s12936-024-05029-3