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1.
PLoS Negl Trop Dis ; 18(6): e0012137, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38848319

ABSTRACT

A group of children with clinical suspicion of dengue were assessed to determine if there was an overestimation of dengue compared with that of leptospirosis and leishmaniasis. This descriptive and analytical cross-sectional study, based on the active search of participants with acute febrile illness, was conducted at two pediatric hospitals. The collection of clinical and epidemiological data was performed using questionnaires, and laboratory tests specific for dengue were performed using immunochromatographic, serological, and molecular methods. Dengue-negative samples were assessed for Leptospira and Leishmania spp. using molecular tests. Data were assessed using analysis of variance (ANOVA), the chi-square test, and Fisher's exact test. In total, 86 participants were evaluated, of whom 39 (45%) were positive for dengue fever, 4 (5%) for leptospirosis, and 1 (1%) for leishmaniasis. Forty-two participants (49%) presented dengue-like symptoms. The predominant age range for the virus was 3-10 years. Most clinical manifestations were nonspecific, with frequent concomitant gastrointestinal and respiratory symptoms. Furthermore, we found that the acute febrile syndrome in childhood persists as a challenge for health professionals, especially in the early days of the disease, due to a plurality of diagnostic hypotheses, associated with the difficulty of establishing well-defined symptoms in children, especially in infants. Dengue fever continues to be a frequent pathology with acute febrile infections in childhood; however, there is an overestimation of the disease, especially in endemic regions, when one considers only the clinical epidemiological diagnosis.


Subject(s)
Dengue , Fever , Humans , Dengue/epidemiology , Dengue/complications , Dengue/diagnosis , Male , Female , Cross-Sectional Studies , Child, Preschool , Child , Infant , Leptospirosis/epidemiology , Leptospirosis/diagnosis , Leptospirosis/complications , Adolescent
2.
J Cell Mol Med ; 28(12): e18482, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38899556

ABSTRACT

Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover novel approaches to overcome this. In this study, we investigated the underlying mechanisms contributing to x-ray radioresistance in HPV-negative HNSCC cells under mild hypoxic conditions (1% oxygen) and explored the potential for autophagy modulation as a promising therapeutic strategy. Our findings show that HNSCC cells exposed to mild hypoxic conditions exhibit increased radioresistance, which is largely mediated by the hypoxia-inducible factor (HIF) pathway. We demonstrate that siRNA knockdown of HIF-1α and HIF-1ß leads to increased radiosensitivity in HNSCC cells under hypoxia. Hypoxia-induced radioresistance was not attributed to differences in DNA double strand break repair kinetics, as these remain largely unchanged under normoxic and hypoxic conditions. Rather, we identify autophagy as a critical protective mechanism in HNSCC cells following irradiation under mild hypoxia conditions. Targeting key autophagy genes, such as BECLIN1 and BNIP3/3L, using siRNA sensitizes these cells to irradiation. Whilst autophagy's role in hypoxic radioresistance remains controversial, this study highlights the importance of autophagy modulation as a potential therapeutic approach to enhance the effectiveness of radiotherapy in HNSCC.


Subject(s)
Autophagy , Cell Hypoxia , Radiation Tolerance , Squamous Cell Carcinoma of Head and Neck , Humans , Autophagy/radiation effects , Autophagy/genetics , Radiation Tolerance/genetics , Cell Line, Tumor , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Cell Hypoxia/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Beclin-1/metabolism , Beclin-1/genetics , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , DNA Repair/radiation effects , DNA Repair/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , X-Rays , DNA Breaks, Double-Stranded/radiation effects , Tumor Suppressor Proteins
3.
Int J Biochem Cell Biol ; 172: 106599, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797495

ABSTRACT

Elevated levels of prostaglandin E2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E2, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E2in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.


Subject(s)
Cyclooxygenase 1 , Cyclooxygenase 2 , Dinoprostone , Leukocytes , Pyrazoles , Respiratory Burst , Humans , Pyrazoles/pharmacology , Pyrazoles/chemistry , Dinoprostone/metabolism , Respiratory Burst/drug effects , Leukocytes/drug effects , Leukocytes/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 1/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Structure-Activity Relationship , Cyclooxygenase Inhibitors/pharmacology
4.
Syst Parasitol ; 101(3): 37, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700664

ABSTRACT

A synopsis of Ortholinea Shulman, 1962 (Cnidaria: Myxosporea: Ortholineidae) is presented and identifies 26 nominal species presently allocated within this genus. Species morphological and morphometric features, tissue tropism, type-host, and type-locality are provided from original descriptions. Data from subsequent redescriptions and reports is also given. Accession numbers to sequences deposited in GenBank are indicated when available, and the myxospores were redrawn based on original descriptions. The information gathered shows that Ortholinea infect a wide taxonomic variety of freshwater and marine fish. Nonetheless, the broad host specificity reported for several species is not fully supported by morphological descriptions and requires molecular corroboration. The members of this genus are coelozoic and mainly parasitize the urinary system, with few species occurring in the gallbladder. Ortholinea visakhapatnamensis is the only exception, being histozoic in the visceral peritoneum. Molecular data of the small subunit ribosomal RNA gene (SSU rDNA) is available for about one third of Ortholinea species, with genetic interspecific variation ranging between 1.65% and 29.1%. Phylogenetic analyses reveal Ortholinea to be polyphyletic, with available SSU rDNA sequences clustering within the subclades of the highly heterogenous freshwater urinary clade of the oligochaete-infecting lineage. The life cycles of two Ortholinea species have been clarified based on molecular inferences and identify triactinomyxon actinospores as counterparts, and marine oligochaetes of the family Naididae as permissive hosts to this genus.


Subject(s)
Myxozoa , Species Specificity , Animals , Myxozoa/classification , Myxozoa/genetics , Myxozoa/anatomy & histology , Phylogeny , Host Specificity , Fishes/parasitology , DNA, Ribosomal/genetics
5.
Trends Biochem Sci ; 49(7): 573-582, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38599898

ABSTRACT

Investigating how cells and organisms sense and respond to O2 levels is essential to our understanding of physiology and pathology. This field has advanced considerably since the discovery of the major transcription factor family, hypoxia-inducible factor (HIF), and the enzymes that control its levels: prolyl hydroxylases (PHDs). However, with its expansion, new complexities have emerged. Herein we highlight three main areas where, in our opinion, the research community could direct some of their attention. These include non-transcriptional roles of HIFs, specificity and O2 sensitivity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), and new tools and methods to detect O2 concentrations in cells and organs. A greater understanding of these areas would answer big questions and help drive our knowledge of cellular responses to hypoxia forward.


Subject(s)
Oxygen , Humans , Animals , Oxygen/metabolism , Hypoxia/metabolism , Hypoxia-Inducible Factor 1/metabolism
6.
Proteomics ; : e2300393, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38430206

ABSTRACT

Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.

7.
Pharmaceutics ; 16(2)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38399315

ABSTRACT

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

8.
Clin Transl Radiat Oncol ; 44: 100695, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37961749

ABSTRACT

Introduction: Neoadjuvant radiotherapy is successfully used in rectal cancer to improve overall survival. However, treatment response is both unpredictable and variable. There is strong evidence to show that the phenomenon of tumour hypoxia is associated with radioresistance, however the mechanism(s) behind this are poorly understood. Consequently, there have only been a small number of studies evaluating methods targeting hypoxia-induced radioresistance. The purpose of this systematic review is to evaluate the potential effectiveness of targeting hypoxia-induced radioresistance in rectal cancer and provide recommendations for future research in this area. Methods: A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983). Results: Eight articles met the inclusion criteria. All studies identified were in vitro or in vivo studies, there were no clinical trials. Of the 8 studies identified, 5 assessed the efficacy of drugs which directly or indirectly targeted hypoxia and three that identified potential targets. There was conflicting in vivo evidence for the use of metformin to overcome hypoxia induced radioresistance. Vorinostat, atovaquone, and evofosfamide showed promising preclinical evidence that they can overcome hypoxia-induced radioresistance. Discussion: The importance of investigating hypoxia-induced radioresistance in rectal cancer is crucial. However, to date, only a small number of preclinical studies exist evaluating this phenomenon. This systematic review highlights the importance of further research to fully understand the mechanism behind this radioresistance. There are promising targets identified in this systematic review however, substantially more pre-clinical and clinical research as a priority for future research is needed.

9.
J Invertebr Pathol ; 203: 108043, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38104963

ABSTRACT

Three new aurantiactinomyxon types are described from the oligochaete Ilyodrilus templetoni (Southern, 1909) (Naididae) collected from a northern Portuguese estuary, based on light microscopy and sequencing of the 18S rDNA. The addition of I. templetoni to the group of freshwater annelids known to be permissive for aurantiactinomyxon development reinforces the crucial role of naidids in the evolution and settlement of myxozoans in estuarine environments. Maximum likelihood and Bayesian inference analyses of a comprehensive 18S rDNA dataset placed the novel types within the Paramyxidium clade. This positioning suggests them as probable life cycle counterparts to Paramyxidium spp. that most likely infect the European eel Anguilla anguilla, as the sole representative of Elopomorpha in Portuguese rivers. Although distance estimation revealed a genetic difference of only 0.4 % between Aurantiactinomyxon types 1 and 3, this value was determined to be representative of interspecific variability based on the consistent matching of both genotypes with distinct actinospore morphologies, and potential richness of closely related species of Paramyxidium infecting the European eel in Portuguese waters. The clustering of aurantiactinomyxon types within distinct myxosporean lineages, representative of the suborders Variisporina and Platysporina, demonstrates that the aurantiactinomyxon morphotype is highly functional in promoting myxozoan infections in estuarine environments.


Subject(s)
Cnidaria , Dog Diseases , Fish Diseases , Myxozoa , Oligochaeta , Dogs , Animals , Myxozoa/genetics , Cnidaria/genetics , Phylogeny , Bayes Theorem , DNA, Ribosomal/genetics , Oligochaeta/genetics
10.
EMBO Rep ; 24(12): e57849, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37877678

ABSTRACT

Oxygen is essential for viability in mammalian organisms. However, cells are often exposed to changes in oxygen availability, due to either increased demand or reduced oxygen supply, herein called hypoxia. To be able to survive and/or adapt to hypoxia, cells activate a variety of signalling cascades resulting in changes to chromatin, gene expression, metabolism and viability. Cellular signalling is often mediated via post-translational modifications (PTMs), and this is no different in response to hypoxia. Many enzymes require oxygen for their activity and oxygen can directly influence several PTMS. Here, we review the direct impact of changes in oxygen availability on PTMs such as proline, asparagine, histidine and lysine hydroxylation, lysine and arginine methylation and cysteine dioxygenation, with a focus on mammalian systems. In addition, indirect hypoxia-dependent effects on phosphorylation, ubiquitination and sumoylation will also be discussed. Direct and indirect oxygen-regulated changes to PTMs are coordinated to achieve the cell's ultimate response to hypoxia. However, specific oxygen sensitivity and the functional relevance of some of the identified PTMs still require significant research.


Subject(s)
Lysine , Oxygen , Animals , Humans , Oxygen/metabolism , Lysine/metabolism , Protein Processing, Post-Translational , Chromatin , Hypoxia/metabolism , Mammals/metabolism
11.
Radiother Oncol ; 189: 109951, 2023 12.
Article in English | MEDLINE | ID: mdl-37838322

ABSTRACT

Radiotherapy is a widely used treatment modality against cancer, and although survival rates are increasing, radioresistant properties of tumours remain a significant barrier for curative treatment. Tumour hypoxia is one of the main contributors to radioresistance and is common in most solid tumours. Hypoxia is responsible for many molecular changes within the cell which helps tumours to survive under such challenging conditions. These hypoxia-induced molecular changes are predominantly coordinated by the hypoxia inducible factor (HIF) and have been linked with the ability to confer resistance to radiation-induced cell death. To overcome this obstacle research has been directed towards autophagy, a cellular process involved in self degradation and recycling of macromolecules, as HIF plays a large role in its coordination under hypoxic conditions. The role that autophagy has following radiotherapy treatment is conflicted with evidence of both cytoprotective and cytotoxic effects. This literature review aims to explore the intricate relationship between radiotherapy, hypoxia, and autophagy in the context of cancer treatment. It provides valuable insights into the potential of targeting autophagy as a therapeutic strategy to improve the response of hypoxic tumours to radiotherapy.


Subject(s)
Neoplasms , Radiation Tolerance , Humans , Neoplasms/radiotherapy , Hypoxia , Cell Hypoxia , Autophagy , Cell Line, Tumor , Hypoxia-Inducible Factor 1, alpha Subunit
12.
Life Sci Alliance ; 6(11)2023 11.
Article in English | MEDLINE | ID: mdl-37684043

ABSTRACT

Prostate cancer (PCa) poses a significant health threat to males, and research has shown that fish oil (FO) can impede PCa progression by activating multiple mitochondria-related pathways. Our research is focused on investigating the impact of FO on succinylation, a posttranslational modification that is closely associated with mitochondria in PCa cells. This study employed a mass spectrometry-based approach to investigate succinylation in PCa cells. Bioinformatics analysis of these succinylated proteins identified glutamic-oxaloacetic transaminase 2 (GOT2) protein as a key player in PCa cell proliferation. Immunoprecipitation and RNA interference technologies validated the functional data. Further analyses revealed the significance of GOT2 protein in regulating nucleotide synthesis by providing aspartate, which is critical for the survival and proliferation of PCa cells. Our findings suggest that FO-dependent GOT2 succinylation status has the potential to inhibit building block generation. This study lays a solid foundation for future research into the role of succinylation in various biological processes. This study highlights the potential use of FO as a nutrition supplement for managing and slowing down PCa progression.


Subject(s)
Lysine , Prostatic Neoplasms , Male , Humans , Fish Oils/pharmacology , Prostate , Mitochondria
13.
Article in English | MEDLINE | ID: mdl-37711123

ABSTRACT

INTRODUCTION: Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, leading to decreased/absent α-galactosidase activity. In clinical practice, enzyme activity and substrate/byproduct accumulation play a role in diagnosis and disease-monitoring biomarkers. However, interpreting biomarker levels is not straightforward and can change according to the underlying GLA protein abnormality. OBJECTIVE: Our goals were to understand how disrupting specific protein regions changes biomarker behaviour and to establish specific patterns for individual variants. METHODOLOGY: We analysed data from the Biochemical Genetics Laboratory regarding GLA variants, GLA enzyme activity (in dried blood spots, plasma or white blood cells), plasma LysoGb3 accumulation, and urinary Gb3 excretion. We assessed correlations, trends, and potential predictor models of biomarker behaviour. RESULTS: We assessed 169 hemizygous male and 255 heterozygous female patients. For both groups, substrate accumulation correlates inversely with GLA activity. Variants affecting residues buried within the protein core or the active site were associated with more severe biomarker changes, while those affecting residues that establish disulfide bonds or are glycosylated were similar to other variants. For each non-truncating variant, we also established specific profiles of biomarker behaviour. Finally, we also designed predictor models of biomarker behaviour based on structural variant information. This study provides the groundwork for the impact of GLA protein variation on GLA activity and substrate accumulation. CONCLUSION: This knowledge is of extreme relevance for diagnostic labs and clinicians, as some genetic variants are challenging to interpret regarding pathogenicity. Assessing whether biomarker changes are in the expected range for a specific variant may help diagnostic evaluation. This study also contributes to recognising non-disease-causing variants, considering their overall biochemical impact, and providing a comparative reference for biomarker discovery studies. In the future, the correlation of these findings with disease severity may be of great relevance for diagnosis and monitoring progression.

14.
Microb Pathog ; 184: 106366, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37734487

ABSTRACT

The introduction of new fish species to the aquaculture industry is essential to halt the progressive decline of natural fish stocks. The sheepshead Archosargus probatocephalus is a commercially valuable sparid fish with potential for breeding in captivity, but with limited information regarding parasitic infections that could pose a significant threat for its sustainable production. Thus, the present study aimed to study the myxozoan diversity infecting A. probatocephalus. A novel Henneguya sp. was detected forming plasmodia in the gill lamellae of specimens inhabiting the Brazilian coast, and is characterized based on morphological, histopathological, ultrastructural, molecular, and phylogenetic data. Myxospore total length was 21.3 ± 0.8 µm, with myxospore body 10.0 ± 0.5 µm long, 6.2 ± 0.3 µm wide, and 4.8 ± 0.5 µm thick. Caudal appendages were 10.3 ± 0.5 µm long and did not present any type of coating. Two pyriform polar capsules, 3.4 ± 0.3 µm long and 1.5 ± 0.2 µm wide, each containing an isofilar polar tubule with 4-5 coils. Histopathological analyses showed large intralamellar polysporic plasmodia associated with vascular congestion of the gill filament and gill lamellae, as well as epithelial hyperplasia causing partial or total fusion of gill lamellae. Maximum likelihood and Baysesian inference SSU rDNA-based phylogenetic analyses showed the novel sequence grouped within the marine clade of Henneguya spp. that mostly parasitize fishes belonging to Eupercaria incertae sedis.


Subject(s)
Cnidaria , Fish Diseases , Myxozoa , Parasitic Diseases, Animal , Perciformes , Animals , Myxozoa/genetics , Phylogeny , Brazil , Fish Diseases/parasitology , Fishes , Parasitic Diseases, Animal/parasitology , Gills/parasitology
15.
Cancer Gene Ther ; 30(11): 1554-1568, 2023 11.
Article in English | MEDLINE | ID: mdl-37582934

ABSTRACT

Acquired platinum resistance poses a significant therapeutic impediment to ovarian cancer patient care, accounting for more than 200,000 deaths annually worldwide. We previously identified that overexpression of the antioxidant superoxide dismutase 1 (SOD1) in ovarian cancer is associated with a platinum-resistant phenotype via conferring oxidative stress resistance against platinum compounds. We further demonstrated that enzymatic inhibition using small-molecule inhibitors or silencing of SOD1 via RNA interference (RNAi) increased cisplatin sensitivity and potency in vitro. We launched this study to explore the potential therapeutic applications of SOD1 silencing in vivo in order to reverse cisplatin resistance using a graphene-based siRNA delivery platform. PEGylated graphene oxide (GO) polyethyleneimine (GOPEI-mPEG) nanoparticle was complexed with SOD1 siRNA. GOPEI-mPEG-siSOD1 exhibited high biocompatibility, siRNA loading capacity, and serum stability, and showed potent downregulation of SOD1 mRNA and protein levels. We further observed that cisplatin and PEI elicited mitochondrial dysfunction and transcriptionally activated the mitochondrial unfolded protein response (UPRmt) used as a reporter for their respective cytotoxicities. SOD1 silencing was found to augment cisplatin-induced cytotoxicity resulting in considerable tumour growth inhibition in cisplatin-sensitive A2780 and cisplatin-resistant A2780DDP subcutaneous mouse xenografts. Our study highlights the potential therapeutic applicability of RNAi-mediated targeting of SOD1 as a chemosensitizer for platinum-resistant ovarian cancers.


Subject(s)
Antineoplastic Agents , Graphite , Nanoparticles , Ovarian Neoplasms , Humans , Female , Animals , Mice , Cisplatin/pharmacology , Cisplatin/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , RNA Interference , Superoxide Dismutase-1/genetics , Superoxide Dismutase-1/metabolism , Superoxide Dismutase-1/therapeutic use , Graphite/metabolism , Graphite/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Polyethylene Glycols , RNA, Small Interfering/genetics , Carcinoma, Ovarian Epithelial/genetics
16.
Healthcare (Basel) ; 11(15)2023 Aug 06.
Article in English | MEDLINE | ID: mdl-37570450

ABSTRACT

(1) Background: Non-Hodgkin Lymphoma is a neoplasm that can significantly compromise the immune system, but timely assessment can change the patient outcome. In cancer, the activation of the immune system could lead to the secretion of autoantibodies. (2) Methods: A retrospective cohort study was performed from 2017 to 2019 in patients with Non-Hodgkin Lymphoma diagnosed with a biopsy. (3) Results: We included 39 patients who were newly diagnosed, untreated, and without any autoimmune disease previously reported. Thirty patients had the presence of autoantibodies (antiphospholipid antibodies, anti-cytoplasmic neutrophils antibodies, antinuclear antibodies), and nine were without autoantibodies. There were no statistical differences among groups regarding clinical, demographic, staging, and prognosis characteristics. Also, there were no differences in the outcomes of the patients after finishing chemotherapy and one year after initiating treatment. (4) Conclusions: Further investigations must be conducted regarding an extended panel of autoantibodies because the panel of autoantibodies in this study did not show a relationship between the presence and the clinical outcome of the patients.

17.
Parasite ; 30: 26, 2023.
Article in English | MEDLINE | ID: mdl-37401858

ABSTRACT

A myxozoan survey was performed on specimens of thicklip grey mullet Chelon labrosus (Risso) captured from the Douro River estuary, northern Portugal. Eleven new species, all belonging to the genus Myxobolus Bütschli, 1882 (M. abdominalis n. sp., M. aestuarium n. sp., M. caudalis n. sp., M. chelonari n. sp., M. cucurbitiformis n. sp., M. douroensis n. sp., M. intestinicola n. sp., M. invictus n. sp., M. labicola n. sp., M. peritonaei n. sp., and M. pinnula n. sp.) are described based on microscopic and molecular data, confirming the known high radiation of these myxozoans in mullets. Additionally, Myxobolus pupkoi Gupta et al., 2022 is reported for the first time from C. labrosus, bringing forth a novel case of morphological plasticity between geographic isolates. We consider that molecular-based comparisons are imperative for the description of mugiliform-infecting Myxobolus, with distance estimation further matching two of the novel Myxobolus spp. with sphaeractinomyxon types previously reported from another Portuguese estuary. This finding supports sphaeractinomyxon as specific life cycle counterparts of Myxobolus that infect mullets. Phylogenetic analyses of 18S rDNA retrieved a monophyletic clade of mugiliform-infecting myxobolids comprising well-supported lineages of species parasitizing mullets from the genera Chelon, Mugil, Crenimugil, and Planiliza. The existence of more than one Chelon- and Planiliza-infecting lineage reveals that myxobolids parasitized members of these genera multiple times during their evolution. Lastly, the elevated number of unmatched sphaeractinomyxon sequences included in the Chelon-infecting lineages clearly shows that Myxobolus diversity hosted by this genus remains underrated.


Title: Un inventaire des myxozoaires du mulet lippu Chelon labrosus confirme le rayonnement réussi de Myxobolus chez les hôtes mugiliformes. Abstract: Un inventaire des myxozoaires a été réalisé sur des spécimens de mulets lippus Chelon labrosus (Risso) capturés dans l'estuaire du fleuve Douro, au nord du Portugal. Onze nouvelles espèces, toutes appartenant au genre Myxobolus Bütschli, 1882 (M. abdominalis n. sp., M. aestuarium n. sp., M. caudalis n. sp., M. chelonari n. sp., M. cucurbitiformis n. sp., M. douroensis n. sp., M. intestinicola n. sp., M. invictus n. sp., M. labicola n. sp., M. peritonaei n. sp. et M. pinnula n. sp.) sont décrites sur la base de données microscopiques et moléculaires, confirmant le rayonnement connu de ces myxozoaires chez les mulets. De plus, Myxobolus pupkoi Gupta et al., 2022 est signalé pour la première fois chez C. labrosus, démontrant un nouveau cas de plasticité morphologique entre des isolats géographiques. Nous considérons que les comparaisons moléculaires sont impératives pour la description des Myxobolus infectant les mugiliformes, l'estimation de la distance correspondant en outre à deux des nouveaux Myxobolus spp. avec des types de sphaeractinomyxons précédemment signalés dans un autre estuaire portugais. Cette découverte soutient les sphaeractinomyxons en tant que contreparties spécifiques du cycle de vie de Myxobolus qui infectent les mulets. Les analyses phylogénétiques de l'ADNr 18S ont montré un clade monophylétique de Myxobolidae infectant les mugiliformes, comprenant des lignées robustes d'espèces parasitant les mulets des genres Chelon, Mugil, Crenimugil et Planiliza. L'existence de plusieurs lignées infectant Chelon et Planiliza révèle que les Myxobolidae ont parasité des membres de ces genres plusieurs fois au cours de leur évolution. Enfin, le nombre élevé de séquences de sphaeractinomyxons non appariées incluses dans les lignées infectant Chelon montre clairement que la diversité de Myxobolus hébergée par ce genre reste sous-estimée.


Subject(s)
Fish Diseases , Myxobolus , Myxozoa , Parasitic Diseases, Animal , Smegmamorpha , Animals , Myxobolus/genetics , Phylogeny , Rivers , Gills
18.
Methods Mol Biol ; 2675: 261-269, 2023.
Article in English | MEDLINE | ID: mdl-37258769

ABSTRACT

Hypoxia and its signalling pathway play a key role in human physiology and a variety of diseases. Alterations in histone methylation coordinate transcriptional responses to hypoxia. Here, we detail a fixed cell immunofluorescence method for quantifying hypoxia-induced changes in histone methylation, exemplified by the measurement of H3K27me3.


Subject(s)
Histones , Hypoxia , Humans , Methylation , Histones/metabolism , Hypoxia/metabolism , Protein Processing, Post-Translational , Fluorescent Antibody Technique , DNA Methylation
19.
Syst Parasitol ; 100(3): 291-305, 2023 06.
Article in English | MEDLINE | ID: mdl-37020081

ABSTRACT

The genus Henneguya Thélohan, 1892 (Cnidaria: Myxosporea: Myxobolidae) encompasses a large number of species that mostly infect freshwater fish belonging to 71 families of Actinopterygii. A synopsis of Henneguya species described between 2012 and 2022 is herein presented. It includes 57 species described during the last decade, and one species missing from the previous synopses, adding to a total of 254 species that have been formally described within this genus. Biological characters and myxospore morphometry are presented for each species record.


Subject(s)
Cnidaria , Fish Diseases , Myxozoa , Parasitic Diseases, Animal , Animals , Species Specificity , Fishes , Fresh Water , Phylogeny
20.
Syst Parasitol ; 100(3): 307-323, 2023 06.
Article in English | MEDLINE | ID: mdl-37060426

ABSTRACT

Aurantiactinomyxon is one of the most diverse myxozoan collective groups, comprising types that mostly infect freshwater and marine oligochaetes belonging to the family Naididae Ehrenberg, 1828, but also Lumbriculidae Claus, 1872. In this study, a comprehensive revision of all known aurantiactinomyxon types is performed and highlights the fallibility of using the form and length of the valvular processes as main criterion for differentiating among style-less actinospore morphotypes. The demise of the guyenotia collective group is proposed based on the ambiguous features of several types that allow conformity with both the aurantiactinomyxon and guyenotia definitions. Nonetheless, the information presently available clearly shows that a general shift is needed in our approach to actinospore grouping, which should probably be based on actinospore functionality relative to environment and host ecology, rather than on morphology. Life cycle studies based on experimental transmission and molecular inferences of the 18S rDNA have linked aurantiactinomyxon (including former guyenotia) to myxozoans belonging to a diverse array of genera, including Chloromyxum, Henneguya, Hoferellus, Myxobolus, Paramyxidium, Thelohanellus and Zschokkella. This undoubtedly shows a high capacity of the aurantiactinomyxon morphotype to promote infection in intrinsically distinct vertebrate hosts and environmental habitats, consequently increasing interest in its study for attaining a better understanding of myxozoan-host interactions. The identification of novel and known types, however, is impeded by the lack of concise information allowing a comprehensive analysis of biological, morphological, and molecular criteria. In this sense, the compilation of data presented in this study will ultimately help researchers seeking to perform reliable identifications.


Subject(s)
Cnidaria , Myxobolus , Myxozoa , Oligochaeta , Animals , Cnidaria/genetics , Myxozoa/genetics , Species Specificity , Myxobolus/genetics , DNA, Ribosomal/genetics , Oligochaeta/genetics , Phylogeny
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