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Parasites & Vectors Jul 2024Abiotic factors play a significant role in the evolution of Leishmania infantum infection due to its vectorial nature. This study aims to assess the evolution in the...
BACKGROUND
Abiotic factors play a significant role in the evolution of Leishmania infantum infection due to its vectorial nature. This study aims to assess the evolution in the detection of new L. infantum infection cases in Valdeorras (Ourense, Northwestern Spain) over a 20-year period and how different climatic variables and preventive measures may have affected it.
METHODS
Indirect immunofluorescence antibody tests (IFAT) were performed on serum samples collected from dogs attending the 'Servicios Veterinarios de Sil' veterinary clinic (Valdeorras, Northwestern Spain) between May 2003 and April 2023 to detect L. infantum exposure. The percentage of new cases of L. infantum infection was calculated from May of one year to April of the following year. Climatic conditions in the region, global sales of ectoparasiticides and the number of vaccines against L. infantum delivered in the veterinary clinic from 2003 to 2022 were recorded. Statistical analyses were conducted to determine the associations between these factors and the percentage of new cases of L. infantum infection.
RESULTS
A total of 2909 dogs were assessed, and 3785 IFAT tests were performed between May 2003 and April 2023. The mean percentage of new seropositive cases over the 20-year period studied was 21.65 ± 10.8%, with a decline from the beginning to the end of the period studied. The percentage was significantly higher between May 2003 and April 2008 compared with the other periods (May 2008 to April 2013, May 2013 to April 2018 and May 2018 to April 2023). There was a positive correlation between the percentage of new cases of L. infantum infection and the maximum relative humidity in winter. Conversely, there was a negative correlation between the percentage of new cases and sales of ectoparasiticides and vaccination against L. infantum.
CONCLUSIONS
This study is one of the longest evaluations of the evolution of L. infantum infection in a fixed location and its association with external factors including climatic conditions and preventive measures. The results confirm that Valdeorras is a high-risk area for L. infantum infection. The use of ectoparasiticides and vaccines against L. infantum has been shown to play a significant role in preventing L. infantum infection, highlighting the crucial role of veterinarians in the fight against this disease.
Topics: Dogs; Animals; Spain; Dog Diseases; Leishmania infantum; Leishmaniasis, Visceral; Climate; Antibodies, Protozoan; Male; Fluorescent Antibody Technique, Indirect; Female
PubMed: 38951858
DOI: 10.1186/s13071-024-06357-8 -
BMC Oral Health Jun 2024Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible... (Comparative Study)
Comparative Study
OBJECTIVE
Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease.
SUBJECTS AND METHODS
The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group.
RESULTS
Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252).
CONCLUSION
These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.
Topics: Humans; Matrix Metalloproteinase 9; Lichen Planus, Oral; Galectin 3; Hypoxia-Inducible Factor 1, alpha Subunit; Female; Male; Middle Aged; Galectins; Adult; Cell Transformation, Neoplastic; Epithelial Cells; Case-Control Studies; Immunohistochemistry; Blood Proteins
PubMed: 38951854
DOI: 10.1186/s12903-024-04457-6 -
Journal of Experimental & Clinical... Jun 2024During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or...
BACKGROUND
During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.
METHODS
aHER2 and sHER2 were assessed by digital PCR and ELISA before and after standard-of-care treatment of advanced HER2-positive breast cancer patients (n=37) with the antibody-drug conjugate (ADC) Trastuzumab-emtansine (T-DM1).
RESULTS
As expected, aHER2 was invariably suppressed by T-DM1, but this loss was surprisingly mirrored by sHER2 gain, sometimes of considerable entity, in most (30/37; 81%) patients. This unorthodox split in HER2 oncogenic dosage was supported by reciprocal aHER2/sHER2 kinetics in two representative cases, and an immunohistochemistry-high status despite copy-number-neutrality in 4/5 available post-T-DM1 tumor re-biopsies from sHER2-gain patients. Moreover, sHER2 was preferentially released by dying breast cancer cell lines treated in vitro by T-DM1. Finally, sHER2 gain was associated with a longer PFS than sHER2 loss (mean PFS 282 vs 133 days, 95% CI [210-354] vs [56-209], log-rank test p=0.047), particularly when cases (n=11) developing circulating HER2-bypass alterations during T-DM1 treatment were excluded (mean PFS 349 vs 139 days, 95% CI [255-444] vs [45-232], log-rank test p=0.009).
CONCLUSIONS
HER2 gain is adaptively selected in tumor tissues and recapitulated in blood by sHER2 gain. Possibly, an increased oncogenic dosage is beneficial to the tumor during anti-HER2 treatment with naked antibodies, but favorable to the host during treatment with a strongly cytotoxic ADC such as T-DM1. In the latter case, HER2-gain tumors may be kept transiently in check until alternative oncogenic drivers, revealed by liquid biopsy, bypass HER2. Whichever the interpretation, HER2-2D might help to tailor/prioritize anti-HER2 treatments, particularly ADCs active on aHER2-low/sHER2-low tumors.
TRIAL REGISTRATION
NCT05735392 retrospectively registered on January 31, 2023 https://www.
CLINICALTRIALS
gov/search?term=NCT05735392.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Liquid Biopsy; Middle Aged; Ado-Trastuzumab Emtansine; Aged; Trastuzumab; Adult; Biomarkers, Tumor
PubMed: 38951853
DOI: 10.1186/s13046-024-03105-9 -
BMC Medicine Jul 2024Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on...
BACKGROUND
Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain.
METHODS
We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models.
RESULTS
Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose.
CONCLUSIONS
In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.
Topics: Humans; Female; Dementia; Male; Aged; Benzodiazepines; Middle Aged; Magnetic Resonance Imaging; Netherlands; Aged, 80 and over; Neuroimaging; Brain; Prospective Studies; Neurodegenerative Diseases; Hypnotics and Sedatives; Risk Factors
PubMed: 38951846
DOI: 10.1186/s12916-024-03437-5 -
BMC Oral Health Jun 2024Oral cancer, including malignancies of the tongue, lips, floor of the mouth, cheek mucosa, gums, palate, and oropharynx, is life-threatening. Early diagnosis and...
BACKGROUND/PURPOSE
Oral cancer, including malignancies of the tongue, lips, floor of the mouth, cheek mucosa, gums, palate, and oropharynx, is life-threatening. Early diagnosis and appropriate treatment are crucial for long-term survival. Dentists frequently encounter oral cancers due to the nature of their work. This study aimed to evaluate the knowledge and experience of dentists in Turkey regarding oral cancers.
MATERIALS AND METHODS
A total of 361 participants were included in the study, and survey questions were sent via email. The survey consisted of 16 questions measuring demographic data and knowledge about oral cancerous lesions. Participants were grouped based on their specialization and knowledge level, and differences in responses among groups were examined.
RESULTS
Only 21.3% of the participants felt they had sufficient knowledge and experience about oral cancerous lesions. Overall, the correct answer rates indicated a moderate level of knowledge and experience. When grouped by specialization, oral surgeons had the highest accuracy in their responses (p < 0.05).
CONCLUSION
Dentists are the professional group that most frequently encounters clinically oral cancerous lesions. Therefore, it is critically important for them to be knowledgeable and experienced to reduce morbidity and mortality through early diagnosis. This study evaluated the knowledge status of dentists in Turkey regarding oral cancer and highlighted the need for improved education.
Topics: Humans; Turkey; Mouth Neoplasms; Dentists; Female; Male; Adult; Middle Aged; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Clinical Competence; Mouth Mucosa
PubMed: 38951844
DOI: 10.1186/s12903-024-04533-x -
Journal of Nanobiotechnology Jul 2024Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently,...
BACKGROUND
Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear.
RESULTS
Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs.
CONCLUSIONS
These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.
Topics: Animals; Extracellular Vesicles; Mice; Myocardial Reperfusion Injury; Myocytes, Cardiac; Male; Mice, Inbred C57BL; Mitochondrial Proton-Translocating ATPases; Mitochondria; Myocardium; Reactive Oxygen Species; Ferroptosis; Disease Models, Animal
PubMed: 38951822
DOI: 10.1186/s12951-024-02618-x -
BMC Veterinary Research Jun 2024Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant...
BACKGROUND
Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples.
RESULTS
Out of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted.
CONCLUSION
The presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.
Topics: Animals; Female; Cat Diseases; Cats; Tandem Mass Spectrometry; Mammary Neoplasms, Animal; Biomarkers, Tumor; Chromatography, Liquid; Cross-Sectional Studies; Neoplasm Metastasis; Proteomics
PubMed: 38951817
DOI: 10.1186/s12917-024-04148-y -
BMC Cancer Jul 2024Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying...
INTRODUCTION
Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa.
METHODS
A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients.
DISCUSSION
If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community.
TRIAL REGISTRATION
The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
Topics: Humans; Male; Extracellular Vesicles; Cross-Over Studies; Prostatic Neoplasms; Exercise; Muscle, Skeletal; Exercise Therapy; Cytokines; Aged; Middle Aged; Myokines
PubMed: 38951803
DOI: 10.1186/s12885-024-12530-0 -
Journal of Translational Medicine Jul 2024The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic...
BACKGROUND
The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic value of the TIIC spatial distribution is unknown. Thus, we aimed to investigate the association between TIICs in situ and patient prognosis in a large CRC sample.
METHODS
We implemented multiplex immunohistochemistry staining technology in 190 CRC samples to quantify 14 TIIC subgroups in situ. To delineate the spatial relationship of TIICs to tumor cells, tissue slides were segmented into tumor cell and microenvironment compartments based on image recognition technology, and the distance between immune and tumor cells was calculated by implementing the computational pipeline phenoptr.
RESULTS
MPO neutrophils and CD68IDO1 tumor-associated macrophages (TAMs) were enriched in the epithelial compartment, and myeloid lineage cells were located nearest to tumor cells. Except for CD68CD163 TAMs, other cells were all positively associated with favorable prognosis. The prognostic predictive power of TIICs was highly related to their distance to tumor cells. Unsupervised clustering analysis divided colorectal cancer into three subtypes with distinct prognostic outcomes, and correlation analysis revealed the synergy among B cells, CD68IDO1TAMs, and T lineage cells in producing an effective immune response.
CONCLUSIONS
Our study suggests that the integration of spatial localization with TIIC abundance is important for comprehensive prognostic assessment.
Topics: Humans; Colorectal Neoplasms; Prognosis; Male; Female; Middle Aged; Tumor Microenvironment; Cluster Analysis; Aged; Lymphocytes, Tumor-Infiltrating; Immunohistochemistry; Macrophages; Spatial Analysis
PubMed: 38951801
DOI: 10.1186/s12967-024-05418-x -
World Journal of Surgical Oncology Jul 2024The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy...
PURPOSE
The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model.
METHODS
All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model.
RESULTS
A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients.
CONCLUSION
A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.
Topics: Humans; Male; Female; Colorectal Neoplasms; SEER Program; Neoadjuvant Therapy; Nomograms; Middle Aged; Survival Rate; Follow-Up Studies; Prognosis; Aged; Lymphatic Metastasis; Neoplasm Staging; Adult; Retrospective Studies
PubMed: 38951795
DOI: 10.1186/s12957-024-03458-7