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1.
Ecol Evol ; 14(9): e70236, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39238570

ABSTRACT

An ongoing challenge in evolutionary and ecological research focuses on testing biogeographic hypotheses for the understanding of both species' distributional patterns and of the factors influencing range limits. In this study, we described the climatic niches of Neotropical humid montane forest birds through the analysis of factors driving their evolution at inter- and intraspecific levels; and tested for differences among allopatric lineages within Aulacorhynchus, Chlorospingus, Cardellina, and Eupherusa. We employed ecological niche models (ENMs) along with an ordination approach with kernel smoothing to perform niche overlap analyses and test hypotheses of niche equivalence/similarity among lineages. In addition, we described the potential distributions of each lineage during the Late Pleistocene climate fluctuations, identifying historical range expansions, connectivity, and stability. Overall, we observed differences in environmental variables influencing climatic requirements and distributional patterns for our selected species. We detected the highest values of niche overlap mainly between Eupherusa and some Chlorospingus lineages. At both interspecific and intraspecific levels, sister lineages showed non-identical environmental niches. Our results offer weak support to a moist forest model, in which populations followed the expansion and contraction cycles of montane forests, leading to a lack of niche conservatism among lineages (they tend to occupy not identical climatic environments) throughout Mesoamerica. Therefore, historical climatic conditions may act as ecological barriers determining the distributional ranges of these species.

2.
Article in English | MEDLINE | ID: mdl-39250735

ABSTRACT

OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

3.
Hum Genomics ; 18(1): 94, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39227859

ABSTRACT

BACKGROUND: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients. METHODS: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR ß chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19. RESULTS: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs. CONCLUSIONS: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.


Subject(s)
COVID-19 , Complementarity Determining Regions , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Male , Middle Aged , Female , SARS-CoV-2/immunology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Adult , Aged , Complementarity Determining Regions/genetics , Complementarity Determining Regions/immunology , Spain , T-Lymphocytes/immunology , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Alleles
4.
Am J Trop Med Hyg ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39288760

ABSTRACT

The New World screwworm, Cochliomyia hominivorax Coquerel (Diptera: Calliphoridae), was officially eliminated from Costa Rica in 2000, but it was reintroduced in 2023. A myiasis by C. hominivorax in a 71-year-old man with a 4-month history of foot hyperkeratosis and interdigital ulcers is reported. The myiasis was detected before sampling for bacterial culture. Approximately 160 first- and second-instar larvae were recovered and identified as C. hominivorax. Morphological identification was based mainly on characteristics of the cephalopharyngeal skeleton, spiracles, and pigmented dorsal tracheal trunks. Sequencing of a cytochrome c oxidase subunit I gene fragment confirmed the identity. The ulcers healed after extraction of the larvae and ciprofloxacin treatment of a concurrent Staphylococcus aureus and Pseudomonas aeruginosa infection. Given the reintroduction of C. hominivorax in Costa Rica and the risk of northward expansion, this report highlights its impact on public health and calls for awareness among clinicians and healthcare practitioners.

5.
Int J Mol Sci ; 25(17)2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39273702

ABSTRACT

This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified. Additionally, we observed overexpression of L1 cell adhesion molecule (L1CAM), Cdc37, GPX1, and GPX4 and lower expression of ceruloplasmin in the patient compared to the control. We also found changes in sphingolipid, inositol, and inositol phosphate metabolism. These findings help to clarify the mechanisms of JP and suggest that the etiology of JP in the patient may be multifactorial. This is the first report of the rs2254562 mutation in the SYNJ gene identified in a JP patient with seizures and cognitive impairment.


Subject(s)
Parkinsonian Disorders , Humans , Female , Parkinsonian Disorders/genetics , Mutation, Missense , Exome Sequencing , Pedigree , Polymorphism, Single Nucleotide , Nerve Tissue Proteins/genetics , Child , Multiomics
6.
Front Public Health ; 12: 1461630, 2024.
Article in English | MEDLINE | ID: mdl-39234092

ABSTRACT

In most self-determination theory (SDT) research, improving (de)motivating teaching styles provides numerous benefits for students and teachers, although there is less evidence of the latter. Although the recent circumplex model provides a fine-grained picture of the different (de)motivating teaching styles (i.e., autonomy support, structure, control, and chaos) that physical education (PE) teachers can use in their lessons, no previous motivational training programs have been based on this model. Moreover, all SDT-training programs have been implemented through different group sessions, but individual sessions have not been delivered. This study outlines the protocol of a motivational training program, derived from the circumplex model, designed to enhance motivating teaching styles (and prevent or decrease demotivating teaching styles) among PE teachers. Consequently, this program seeks to improve motivational variables and influence (mal)adaptive outcomes in both teachers and students. A randomised controlled trial design with a mixed-method approach. At least 16 secondary PE teachers will be assigned to either an experimental group or a control group, together with some of their students. The training program comprises four face-to-face group sessions and two follow-up sessions (one individual and one group session). PE teachers will learn how to support autonomy and provide structure, as well as to be less controlling and chaotic towards students. Over approximately five months, teachers will implement these motivational strategies during their PE classes. Different (de)motivating teaching styles, motivational variables, and (mal)adaptive outcomes will be assessed in both PE teachers and their students at three distinct points: before the training program (T1), during the intervention (T2), and at the end of the intervention (T3). Additionally, two discussion groups involving all experimental PE teachers will be held (one following the training program and another at the end of the intervention). The results from this study could be useful for developing motivational training programs for in-service PE teachers. Clinical trial registration: ClinicalTrials.gov, identifier [NTC06479369].


Subject(s)
Motivation , Physical Education and Training , School Teachers , Humans , School Teachers/psychology , Personal Autonomy , Students/psychology , Male , Female , Adult , Teacher Training
7.
Lupus ; : 9612033241283551, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259025

ABSTRACT

OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.

8.
Article in English | MEDLINE | ID: mdl-39297205

ABSTRACT

BACKGROUND: Arteriovenous fistulae (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage kidney disease. Chronic kidney disease (CKD) is associated with endothelial injury, impaired AVF maturation, and reduced patency, as well as utilization. Because CKD is characterized by multiple pathophysiological processes that induce endothelial-to-mesenchymal transition (EndMT), we hypothesized that CKD promotes EndMT during venous remodeling and that disruption of endothelial TGF (transforming growth factor)-ß signaling inhibits EndMT to prevent AVF failure even in the end-stage kidney disease environment. METHODS: The mouse 5/6 nephrectomy and aortocaval fistula models were used. CKD was created via 5/6 nephrectomy, with controls of no (0/6) or partial (3/6) nephrectomy in C57BL/6J mice. AVFs were created in mice with knockdown of TGF-ßR1/R2 (TGF-ß receptors type 1/2) in either smooth muscle cells or endothelial cells. AVF diameters and patency were measured and confirmed by serial ultrasound examination. AVF, both murine and human, were examined using Western blot, histology, and immunofluorescence. Human and mouse endothelial cells were used for in vitro experiments. RESULTS: CKD accelerates TGF-ß activation and promotes EndMT that is associated with increased AVF wall thickness and reduced patency in mice. Inhibition of TGF-ß signaling in both endothelial cells and smooth muscle cells decreased smooth muscle cell proliferation in the AVF wall, attenuated EndMT, and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Human AVF also showed increased TGF-ß signaling and EndMT. CONCLUSIONS: CKD promotes EndMT and reduces AVF patency. Inhibition of TGF-ß signaling, especially disruption of endothelial cell-specific TGF-ß signaling, attenuates EndMT and improves AVF patency in mouse AVF. Inhibition of EndMT may be a therapeutic approach of translational significance to improve AVF patency in human patients with CKD.

9.
Cells ; 13(18)2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39329772

ABSTRACT

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs.


Subject(s)
Cell Nucleolus , Viral Proteins , Cell Nucleolus/metabolism , Cell Nucleolus/virology , Humans , Viral Proteins/metabolism , Animals
11.
Biomedicines ; 12(9)2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39335610

ABSTRACT

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

12.
J Cyst Fibros ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39327194

ABSTRACT

Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine. In light of these advances, it is appropriate to re-evaluate the CF care team structure. This position paper offers guidance for the structure of a CF care center designed to meet the evolving needs of the CF community. Fundamental to the proposed center structure is recognition of pwCF and their families as integral members of their care teams, underpinning the necessity for shared decision making, awareness of social determinants of health, and active partnership between all healthcare professionals involved in the care of pwCF.

13.
J Leukoc Biol ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39327799

ABSTRACT

Viral RNA and miRNAs released by immune cells contribute to inflammation in COVID-19 patients. Here, we investigated the role of SARS-CoV2 RNA and host miRNAs carried within extracellular vesicles (EVs) in modulating inflammation. EVs were classified as positive or negative depending on their viral RNA cargo. To assess the function of viral RNA, EVs, and LPS were used to stimulate whole blood samples from healthy subjects, and the secretion of 27 serum analytes was measured. EVs alone did not induce cytokines, chemokines, or growth factors. However, under LPS stimulation, (SARS-CoV2+) EVs increased IL-12 and decreased IL-13 secretion, while (SARS-CoV2-) EVs increased MIP-1α and IL-1ß secretion. Host miR-19a-3p, -192-5p, -let-7c-5p, and -92b-3a were differentially expressed in association with viral RNA. EVs from COVID-19 patients exhibited differences in viral RNA and miRNA expression profiles that modulate LPS responses. This knowledge sheds light on the immunopathology of COVID-19.

14.
J Thromb Haemost ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39173878

ABSTRACT

BACKGROUND: Anticoagulation and antiplatelet therapy effectively inhibit neointimal hyperplasia (NIH) in both arterial and venous systems but not in arteriovenous fistulae (AVF). The main site of AVF failure is the juxta-anastomotic area that is characterized by disturbed flow compared with laminar flow in the arterial inflow and the venous outflow. OBJECTIVES: We hypothesized that early thrombus formation is required for eccentric and heterogeneous NIH in the presence of disturbed flow. METHODS: Needle puncture and sutured AVF were created in C57BL/6 mice, in PF4-Cre × mT/mG reporter mice, and in Wistar rats. Human AVF samples were second-stage basilic vein transpositions. The tissues were examined by histology, immunofluorescence, immunohistochemistry, and en face staining. RESULTS: In the presence of disturbed flow, both mouse and human AVF showed eccentric and heterogeneous NIH. Maladapted vein wall was characterized by eccentric and heterogeneous neointima that was composed of a different abundance of thrombus and smooth muscle cells. PF4-cre × mT/mG reporter mice AVF showed that green fluorescent protein-labeled platelets deposit on the wall directly facing the fistula exit with endothelial cell loss and continue to accumulate in the presence of disturbed flow. Neither disturbed flow with limited endothelial cell loss nor nondisturbed flow induced heterogeneous neointima in different animal models. CONCLUSION: Early thrombus contributes to late heterogeneous NIH in the presence of disturbed flow. Disturbed flow, large area of endothelial cell loss, and thrombus formation are critical to form eccentric and heterogeneous NIH. Categorization of adapted or maladapted walls may be helpful for therapy targeting heterogeneous NIH.

15.
J Craniofac Surg ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39212303

ABSTRACT

ABSTRACT: Disk perforation can result in degenerative changes within the joint structures. While discectomy has demonstrated enduring benefits, it has traditionally been described using an open approach, with the disadvantages inherent to this method. This study aims to present a series of patients who underwent arthroscopic discectomy technique and to report the outcomes. METHODS: Patients diagnosed with internal disorders of the temporomandibular joint underwent arthroscopic arthroscopic discectomy technique. Surgical outcomes were assessed by changes in pain using a visual analog scale and the maximum incisal opening. RESULTS: One hundred seventy-eight joints from 106 patients who underwent arthroscopic surgery were included. Discectomy was performed on 22 joints. Prior to surgery, patients reported an average visual analog scale pain score of 6.5, which decreased to an average of 0.5 at 6 months postsurgery (P<0.001). Before surgery, the average maximum incisal opening was 30 mm, which increased to 41 mm at 6 months postsurgery (P<0.001). CONCLUSIONS: The described technique represents an excellent alternative for managing patients with disk perforations.

16.
World J Diabetes ; 15(7): 1398-1403, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39099820

ABSTRACT

Diabetic kidney disease (DKD) is one of the complications of diabetes, affecting millions of people worldwide. The relentless progression of this condition can lead to kidney failure, requiring life-altering interventions such as dialysis or transplants. Accumulating evidence suggests that immunologic and inflammatory elements play an important role in initiating and perpetuating the damage inflicted on renal tissues, exacerbating the decline in organ function. Toll-like receptors (TLRs) are a family of receptors that play a role in the activation of the innate immune system by the recognition of pathogen-associated molecular patterns. Recent data from in vitro and in vivo studies have highlighted the critical role of TLRs, mainly TLR2 and TLR4, in the pathogenesis of DKD. In the diabetic milieu, these TLRs recognize diabetic-associated molecular signals, triggering a proinflammatory cascade that initiates and perpetuates inflammation and fibrogenesis in the diabetic kidney. Emerging non-traditional strategies targeting TLR signaling with potential therapeutic implications in DKD have been pro-posed. One of these approaches is the use of microRNAs, small non-coding RNAs that can regulate gene expression. This editorial comments on the results of this approach carried out in a rat model of diabetes by Wu et al, published in this issue of the World Journal of Diabetes. The results of the experimental study by Wu et al shows that microRNA-630 decreased levels compared to non-diabetic rats. Additionally, microRNA-630 exerted anti-inflammatory effects in the kidneys of diabetic rats through the modulation of TLR4. These findings indicate that the microRNA-630/TLR4 axis might represent a pathological mechanism of DKD and a potential therapeutic target capable of curbing the destructive inflammation characteristic of DKD.

17.
J Clin Med ; 13(15)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39124800

ABSTRACT

Androgenetic alopecia, the most common cause of hair loss affecting both men and women, is typically treated using pharmaceutical options, such as minoxidil and finasteride. While these medications work for many individuals, they are not suitable options for all. To date, the only non-pharmaceutical option that the United States Food and Drug Administration has cleared as a treatment for androgenetic alopecia is low-level laser therapy (LLLT). Numerous clinical trials utilizing LLLT devices of various types are available. However, a myriad of other physical treatments for this form of hair loss have been reported in the literature. This review evaluated the effectiveness of microneedling, pulsed electromagnetic field (PEMF) therapy, low-level laser therapy (LLLT), fractional laser therapy, and nonablative laser therapy for the treatment of androgenetic alopecia (AGA). It also explores the potential of multimodal treatments combining these physical therapies. The majority of evidence in the literature supports LLLT as a physical therapy for androgenetic alopecia. However, other physical treatments, such as nonablative laser treatments, and multimodal approaches, such as PEMF-LLLT, seem to have the potential to be equally or more promising and merit further exploration.

19.
Cardiovasc Diabetol ; 23(1): 314, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182114

ABSTRACT

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.


Subject(s)
Carotid Intima-Media Thickness , Diabetes Mellitus, Type 2 , Disease Progression , Pentoxifylline , Renal Insufficiency, Chronic , Humans , Pilot Projects , Male , Middle Aged , Pentoxifylline/therapeutic use , Female , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Prospective Studies , Aged , Treatment Outcome , Time Factors , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/drug therapy , Glucuronidase/blood , Glucuronidase/genetics , Biomarkers/blood , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/drug therapy , Asymptomatic Diseases , Inflammation Mediators/blood , Phosphodiesterase Inhibitors/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/diagnosis , Osteocalcin
20.
Mar Drugs ; 22(8)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39195485

ABSTRACT

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.


Subject(s)
Antiviral Agents , Dengue Virus , Microalgae , Dengue Virus/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Animals , Protein Hydrolysates/pharmacology , Protein Hydrolysates/chemistry , Dengue/drug therapy , Dengue/virology , Peptides/pharmacology , Peptides/chemistry , Serogroup , Chlorocebus aethiops , Humans , Aedes/drug effects , Vero Cells
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