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PloS One 2024Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current...
Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current chemotherapy for CCA often fails due to drug resistance, necessitating novel anticancer agents. This study investigates the potential of 5'-deoxy-5'-methylthioadenosine (MTA), a naturally occurring nucleoside, against CCA. While MTA has shown promise against various cancers, its effects on CCA remain unexplored. We evaluated MTA's anticancer activity in CCA cell lines and drug-resistant sub-lines, assessing cell viability, migration, invasion, and apoptosis. The potential anticancer mechanisms of MTA were explored through proteomic analysis using LC-MS/MS and bioinformatic analysis. The results show a dose-dependent reduction in CCA cell viability, with enhanced effects on cancer cells compared to normal cells. Moreover, MTA inhibits growth, induces apoptosis, and suppresses cell migration and invasion. Additionally, MTA enhanced the anticancer effects of gemcitabine on drug-resistant CCA cells. Proteomics revealed the down-regulation of multiple proteins by MTA, affecting various molecular functions, biological processes, and cellular components. Network analysis highlighted MTA's role in inhibiting proteins related to mitochondrial function and energy derivation, crucial for cell growth and survival. Additionally, MTA suppressed proteins involved in cell morphology and cytoskeleton organization, important for cancer cell motility and metastasis. Six candidate genes, including ZNF860, KLC1, GRAMD1C, MAMSTR, TANC1, and TTC13, were selected from the top 10 most down-regulated proteins identified in the proteomics results and were subsequently verified through RT-qPCR. Further, KLC1 protein suppression by MTA treatment was confirmed through Western blotting. Additionally, based on TCGA data, KLC1 mRNA was found to be upregulated in the tissue of CCA patients compared to that of normal adjacent tissues. In summary, MTA shows promising anticancer potential against CCA by inhibiting growth, inducing apoptosis, and suppressing migration and invasion, while enhancing gemcitabine's effects. Proteomic analysis elucidates possible molecular mechanisms underlying MTA's anticancer activity, laying the groundwork for future research and development of MTA as a treatment for advanced CCA.
Topics: Cholangiocarcinoma; Humans; Proteomics; Cell Line, Tumor; Deoxyadenosines; Bile Duct Neoplasms; Apoptosis; Cell Movement; Thionucleosides; Antineoplastic Agents; Gemcitabine; Deoxycytidine; Cell Survival; Cell Proliferation; Drug Resistance, Neoplasm
PubMed: 38923999
DOI: 10.1371/journal.pone.0306060 -
The FEBS Journal Jun 2024Trichomonas vaginalis, the causative agent of trichomoniasis, is a prevalent anaerobic protozoan parasite responsible for the most common nonviral sexually transmitted...
Trichomonas vaginalis, the causative agent of trichomoniasis, is a prevalent anaerobic protozoan parasite responsible for the most common nonviral sexually transmitted infection globally. While metronidazole and its derivatives are approved drugs for this infection, rising resistance necessitates the exploration of new antiparasitic therapies. Protein posttranslational modifications (PTMs) play crucial roles in cellular processes, and among them, hypusination, involving eukaryotic translation factor 5A (eIF5A), has profound implications. Despite extensive studies in various organisms, the role of hypusination in T. vaginalis and its potential impact on parasite biology and pathogenicity remain poorly understood. This study aims to unravel the structural basis of the hypusination pathway in T. vaginalis using X-ray crystallography and cryo-electron microscopy. The results reveal high structural homology between T. vaginalis and human orthologs, providing insights into the molecular architecture of eIF5A and deoxyhypusine synthase (DHS) and their interaction. Contrary to previous suggestions of bifunctionality, our analyses indicate that the putative hydroxylation site in tvDHS is nonfunctional, and biochemical assays demonstrate exclusive deoxyhypusination capability. These findings challenge the notion of tvDHS functioning as both deoxyhypusine synthase and hydroxylase. The study enhances understanding of the hypusination pathway in T. vaginalis, shedding light on its functional relevance and potential as a drug target, and contributing to the development of novel therapeutic strategies against trichomoniasis.
PubMed: 38923395
DOI: 10.1111/febs.17207 -
JMIR Public Health and Surveillance Jun 2024A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures.
OBJECTIVE
This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings.
METHODS
The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders.
RESULTS
In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community.
CONCLUSIONS
pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets.
TRIAL REGISTRATION
Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.
Topics: Humans; Primaquine; Thailand; Mass Drug Administration; Male; Female; Adult; Adolescent; Malaria, Vivax; Antimalarials; Middle Aged; Young Adult; Proof of Concept Study; Child; Cross-Over Studies; Cross-Sectional Studies; Patient Acceptance of Health Care
PubMed: 38922648
DOI: 10.2196/51993 -
Planta Jun 2024Integrated management strategies, including novel nematicides and resilient cultivars, offer sustainable solutions to combat root-knot nematodes, crucial for... (Review)
Review
Integrated management strategies, including novel nematicides and resilient cultivars, offer sustainable solutions to combat root-knot nematodes, crucial for safeguarding global agriculture against persistent threats. Root-knot nematodes (RKN) pose a significant threat to a diverse range of host plants, with their obligatory endoparasitic nature leading to substantial agricultural losses. RKN spend much of their lives inside or in contact by secreting plant cell wall-modifying enzymes resulting in the giant cell development for establishing host-parasite relationships. Additionally, inflicting physical harm to host plants, RKN also contributes to disease complexes creation with fungi and bacteria. This review comprehensively explores the origin, history, distribution, and physiological races of RKN, emphasizing their economic impact on plants through gall formation. Management strategies, ranging from cultural and physical to biological and chemical controls, along with resistance mechanisms and marker-assisted selection, are explored. While recognizing the limitations of traditional nematicides, recent breakthroughs in non-fumigant alternatives like fluensulfone, spirotetramat, and fluopyram offer promising avenues for sustainable RKN management. Despite the success of resistance mechanisms like the Mi gene, challenges persist, prompting the need for integrative approaches to tackle Mi-virulent isolates. In conclusion, the review stresses the importance of innovative and resilient control measures for sustainable agriculture, emphasizing ongoing research to address evolving challenges posed by RKN. The integration of botanicals, resistant cultivars, and biological controls, alongside advancements in non-fumigant nematicides, contributes novel insights to the field, laying the ground work for future research directions to ensure the long-term sustainability of agriculture in the face of persistent RKN threats.
Topics: Animals; Plant Diseases; Plant Roots; Agriculture; Tylenchoidea; Host-Parasite Interactions; Disease Resistance; Crops, Agricultural; Antinematodal Agents
PubMed: 38922545
DOI: 10.1007/s00425-024-04464-5 -
Tomography (Ann Arbor, Mich.) Jun 2024Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas.... (Review)
Review
Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas. With a peculiar clinical presentation that ranges from paucisymptomatic illness to severe and possibly fatal complications, quality imaging and serological studies are required for diagnosis. The mainstay of treatment to date is surgery combined with antiparasitic agents. The surgical armamentarium consists of open and laparoscopic procedures for selected cases with growing confidence in parenchyma-sparing interventions. Endoscopic retrograde cholangiopancreatography (ERCP) is extremely useful for the diagnosis and treatment of biliary fistulas. Recent relevant studies in the literature are reviewed, and two complex cases are presented. The first patient underwent open surgery to treat 11 liver cysts, and during the follow-up, a right pulmonary cyst was diagnosed that was treated by minimally invasive surgery. The second case is represented by the peritoneal rupture of a giant liver cyst in a young woman who underwent laparoscopic surgery. Both patients developed biliary fistulas that were managed by ERCP. Both patients exhibited a non-specific clinical presentation and underwent several surgical procedures combined with antiparasitic agents, highlighting the necessity of customized treatment in order to decrease complications and successfully cure the disease.
Topics: Female; Humans; Biliary Fistula; Cholangiopancreatography, Endoscopic Retrograde; Echinococcosis, Hepatic; Laparoscopy; Liver; Tomography, X-Ray Computed
PubMed: 38921947
DOI: 10.3390/tomography10060070 -
Pathogens (Basel, Switzerland) Jun 2024Babesiosis is a growing concern due to the increased prevalence of this infectious disease caused by protozoan parasites, affecting various animals and humans. With...
Babesiosis is a growing concern due to the increased prevalence of this infectious disease caused by protozoan parasites, affecting various animals and humans. With rising worries over medication side effects and emerging drug resistance, there is a notable shift towards researching babesiacidal agents. Antimicrobial peptides, specifically cathelicidins known for their broad-spectrum activity and immunomodulatory functions, have emerged as potential candidates. Aquiluscidin, a cathelicidin from , and its derivative Vcn-23, have been of interest due to their previously observed antibacterial effects and non-hemolytic activity. This work aimed to characterize the effect of these peptides against three species. Results showed Aquiluscidin's significant antimicrobial effects on species, reducing the . growth rate and exhibiting IC values of 14.48 and 20.70 μM against . and . , respectively. However, its efficacy was impacted by serum presence in culture, and it showed no inhibition against a strain grown in serum-supplemented medium. Conversely, Vcn-23 did not demonstrate babesiacidal activity. In conclusion, Aquiluscidin shows antibabesia activity in vitro and its efficacy is affected by the presence of serum in the culture medium. Nevertheless, this peptide represents a candidate for further investigation of its antiparasitic properties and provides insights into potential alternatives for the treatment of babesiosis.
PubMed: 38921794
DOI: 10.3390/pathogens13060496 -
Biosensors Jun 2024Agricultural products are vitally important for sustaining life on earth and their production has notably grown over the years worldwide in general and in Brazil...
Agricultural products are vitally important for sustaining life on earth and their production has notably grown over the years worldwide in general and in Brazil particularly. Elevating agricultural practices consequently leads to a proportionate increase in the usage of pesticides that are crucially important for enhanced crop yield and protection. These compounds have been employed excessively in alarming concentrations, causing the contamination of soil, water, and air. Additionally, they pose serious threats to human health. The current study introduces an innovative tool for producing appropriate materials coupled with an electrochemical sensor designed to measure carbendazim levels. The sensor is developed using a molecularly imprinted polymer (MIP) mounted on a glassy carbon electrode. This electrode is equipped with multi-walled carbon nanotubes (MWCNTs) for improved performance. The combined system demonstrates promising potential for accurately quantifying carbendazim. The morphological characteristics of the synthesized materials were investigated using field emission scanning electron microscopy (FESEM) and the Fourier-transform infrared (FTIR) technique. The analytical curve was drawn using the electrochemical method in the range of 2 to 20 ppm while for HPLC 2-12 ppm; the results are presented as the maximum adsorption capacity of the MIP (82.4%) when compared with NIP (41%) using the HPLC method. The analysis conducted using differential pulse voltammetry (DPV) yielded a limit of detection (LOD) of 1.0 ppm and a repeatability of 5.08% ( = 10). The results obtained from the analysis of selectivity demonstrated that the proposed electrochemical sensor is remarkably efficient for the quantitative assessment of carbendazim, even in the presence of another interferent. The sensor was successfully tested for river water samples for carbendazim detection, and recovery rates ranging from 94 to 101% were obtained for HPLC and 94 to 104% for the electrochemical method. The results obtained show that the proposed electrochemical technique is viable for the application and quantitative determination of carbendazim in any medium.
Topics: Carbamates; Benzimidazoles; Pesticides; Nanotubes, Carbon; Electrochemical Techniques; Biosensing Techniques; Electrodes; Biomimetic Materials; Limit of Detection
PubMed: 38920608
DOI: 10.3390/bios14060304 -
ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on mA modification.BMC Genomics Jun 2024Previous studies have demonstrated the role of N6-methyladenosine (mA) RNA methylation in various biological processes, our research is the first to elucidate its...
BACKGROUND
Previous studies have demonstrated the role of N6-methyladenosine (mA) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry.
RESULTS
The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential mA modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis.
CONCLUSIONS
In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.
Topics: Animals; Adipogenesis; RNA Stability; Chickens; Phosphatidylcholine-Sterol O-Acyltransferase; AlkB Homolog 5, RNA Demethylase; Female; Adenosine; RNA, Messenger; Methylation
PubMed: 38918701
DOI: 10.1186/s12864-024-10537-2 -
The Korean Journal of Gastroenterology... Jun 2024Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral... (Review)
Review
Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by . Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a -induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.
Topics: Humans; Toxocara canis; Larva Migrans, Visceral; Male; Animals; Young Adult; Albendazole; Tomography, X-Ray Computed; Dogs; Liver; Antibodies, Helminth; Ultrasonography; Liver Abscess; Toxocariasis; Immunoglobulin E; Anthelmintics
PubMed: 38918038
DOI: 10.4166/kjg.2024.051 -
QJM : Monthly Journal of the... Jun 2024
Review
Topics: Humans; Trypanosomiasis, African; Trypanocidal Agents
PubMed: 38917478
DOI: 10.1093/qjmed/hcae106