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2.
Mediterr J Hematol Infect Dis ; 16(1): e2024064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258185

RESUMO

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring the t(9;22)(q34;q11)/BCR::ABL1 rearrangement represent a category with previously dismal prognosis whose management and outcome dramatically changed thanks to the use of tyrosine kinase inhibitors (TKIs) usage and more recently full chemo-free approaches. The prompt identification of these cases represents an important clinical need. Objectives: We sought to identify an optimized cytofluorimetric diagnostic panel to predict the presence of Philadelphia chromosome (Ph) in B-ALL cases by the introduction of CD146 in our multiparametric flow cytometry (MFC) panels. Methods: We prospectively evaluated a total of 245 cases of newly diagnosed B-ALLs with a CD146 positivity threshold >10% referred to the Division of Hematology of 'Sapienza' University of Rome. We compared the results of CD146 expression percentage and its mean fluorescence intensity (MFI) between Ph+ ALLs, Ph-like ALLs, and molecularly negative ALLs. Results: Seventy-nine of the 245 B-ALL cases (32%) did not present mutations at molecular testing, with 144/245 (59%) resulting in Ph+ ALL and 19/245 (8%) Ph-like ALLs. Comparing the 3 groups, we found that Ph+ B-ALLs were characterized by higher expression percentage of myeloid markers such as CD13, CD33, and CD66c and low expression of CD38; Ph+ B-ALL showed a higher CD146 expression percentage and MFI when compared with both molecular negative B-ALL and Ph-like ALLs; neither the mean percentage of CD146 expression neither CD146 MFI were statically different between molecular negative B-ALL and Ph-like ALLs. Conclusions: Our data demonstrate the association between CD146 expression and Ph+ ALLs. CD146, along with myeloid markers, may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in the diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39187445

RESUMO

Reconstruction of extrahepatic bile ducts is a staple procedure of HPB surgery. The current standard for most cases is a nonanatomical bilioenteric reconstruction, a satisfactory option for the majority of patients. However, it cannot be used for a small number of selective cases (short bowel syndrome, severe abdominal adhesions), where an anatomical reconstruction with or without an interponate can be used. This review summarizes current knowledge about tissue and material usage for experimental and clinical anatomical bile duct reconstruction in the last 100 years. A Pubmed database was searched for published articles about anatomical extrahepatic bile duct reconstruction in experimental and clinical settings ranging from 1920 to 2022. To date, the truly optimal interponate material has not yet been found. However, evidence reveals important properties of such material, most importantly its biodegradability and neovascularization in the recipient's body. The role of internal bile duct stenting for anatomical reconstruction seems important for the outcome. Anatomical reconstruction of extrahepatic bile ducts is an uncommon but usable technique in unique cases when a nonanatomical reconstruction cannot be done. The optimal properties of interponate material for anatomical bile duct reconstruction have been more clarified, although further research is required.

5.
Foods ; 13(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38998660

RESUMO

Since ancient times, Aloe vera L. (AV) has attracted scientific interest because of its multiple cosmetic and medicinal properties, attributable to compounds present in leaves and other parts of the plant. The collected literature data show that AV and its products have a beneficial influence on human health, both by topical and oral use, as juice or an extract. Several scientific studies demonstrated the numerous biological activities of AV, including, for instance, antiviral, antimicrobial, antitumor, and antifungal. Moreover, its important antidepressant activity in relation to several diseases, including skin disorders (psoriasis, acne, and so on) and prediabetes, is a growing field of research. This comprehensive review intends to present the most significant and recent studies regarding the plethora of AV's biological activities and an in-depth analysis exploring the component/s responsible for them. Moreover, its morphology and chemical composition are described, along with some studies regarding the single components of AV available in commerce. Finally, valorization studies and a discussion about the metabolism and toxicological aspects of this "Wonder Plant" are reported.

6.
Anticancer Res ; 44(8): 3507-3514, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060087

RESUMO

BACKGROUND/AIM: Surgical resection with a minimally invasive approach is the standard for diagnosing and treating solitary pulmonary nodules. A computed tomography (CT)-guided technetium99m-macroaggregated albumin (99mTc-MAA) injection-based procedure has been employed for small and non-palpable lung nodule radio-guided preoperative localization (ROLL). This procedure is usually followed by video-assisted thoracoscopic surgery (VATS). This study retrospectively evaluated the feasibility, clinicopathologic outcomes, and complications of this localization radio-guided procedure followed by uniportal VATS. PATIENTS AND METHODS: This retrospective study included 63 patients with suspicious lung nodules who underwent 99mTc-MAA CT-guided localization before uniportal VATS. The analysis examined the imaging and procedure characteristics, procedural risks, successful intra-operative localization, wedge resection, conversion from VATS to open thoracotomy, the reason, and histological diagnosis for each nodule. Also, it was evaluated how nodule and procedure features affected successful intra-operative localization. RESULTS: All patients were diagnosed using a CT scan, and 90.4% had a PET scan at basal staging. A round-glass morphology was present in 9.6% of cases, whereas most had a solid appearance. The mean nodule size was 9.78 mm (maximal tumoral diameter) with a 1-23 mm range. The mean distance from the pleural surface was 15.6 mm (range=1-117 mm). The detection rate of the 99mTc-MAA CT-guided localization procedure was 100%. Surgical procedures were uniportal VATS and transpleural thoracoscopy in 52 (82.5%) and 11 (17.5%) patients, respectively. The intraoperative localization rate was 98.4%. Pneumothorax represented the most frequent complication (6.3%), with one case clinically significant and three only with minimal radiological evidence. Pathology confirmed radical excision in all cases. CONCLUSION: Lung nodule localization with CT-guided 99mTc-MAA followed by uniportal VATS is feasible with a high success rate and low complication rate.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Agregado de Albumina Marcado com Tecnécio Tc 99m , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X , Humanos , Cirurgia Torácica Vídeoassistida/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/cirurgia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Compostos Radiofarmacêuticos/administração & dosagem , Idoso de 80 Anos ou mais
7.
Foods ; 13(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38891002

RESUMO

Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and prion disease, due to its potent anti-inflammatory, antioxidant potential, anticancerous, immunomodulatory, neuroprotective, antiproliferative, and antibacterial activities. Traditionally, curcumin has been used for medicinal and dietary purposes in Asia, India, and China. However, low water solubility, poor stability in the blood, high rate of metabolism, limited bioavailability, and little capability to cross the blood-brain barrier (BBB) have limited the clinical application of curcumin, despite the important pharmacological activities of this drug. A variety of nanocarriers, including liposomes, micelles, dendrimers, cubosome nanoparticles, polymer nanoparticles, and solid lipid nanoparticles have been developed with great success to effectively deliver the active drug to brain cells. Functionalization on the surface of nanoparticles with brain-specific ligands makes them target-specific, which should significantly improve bioavailability and reduce harmful effects. The aim of this review is to summarize the studies on curcumin and/or nanoparticles containing curcumin in the most common neurodegenerative diseases, highlighting the high neuroprotective potential of this nutraceutical.

8.
Acta Trop ; 257: 107306, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38944407

RESUMO

Colpodella species are close relatives of Apicomplexan protozoa. Although most species of this genus are free-living organisms that feed on other protists and algae, reports indicate their occurence in ticks and human patients, including an individual with a history of tick bite manifesting neurological symptoms. During an investigation of tick-borne pathogens (TBPs) in blood samples of cattle, goats, and in ticks collected on them, Colpodella sp. DNA was detected in a Rhipicephalus bursa tick collected from cattle, while of Theileria sergenti/buffeli/orientalis, Babesia bigemina, Sarcocystis cruzi, Babesia spp., and Rickettsia spp. were molecularly detected in cattle, goats, and ticks in southern Italy. Data herein reported highlight the unprecedented presence of Colpodella sp. in ticks in Italy, raising concern due to the potential pathogenic role of this less known protozoan. This finding advocates for performing routine epidemiological surveys to monitor potential emerging vector-borne pathogens.


Assuntos
Cabras , Animais , Itália/epidemiologia , Cabras/parasitologia , Bovinos , DNA de Protozoário/genética , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/parasitologia , Doenças Transmitidas por Carrapatos/veterinária , Rickettsia/isolamento & purificação , Rickettsia/genética , Rickettsia/classificação , Babesia/isolamento & purificação , Babesia/genética , Babesia/classificação , Rhipicephalus/microbiologia , Rhipicephalus/parasitologia , Theileria/genética , Theileria/isolamento & purificação , Theileria/classificação , Análise de Sequência de DNA , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Eucoccidiida/genética , Eucoccidiida/isolamento & purificação , Eucoccidiida/classificação , Dados de Sequência Molecular , Carrapatos/microbiologia , Carrapatos/parasitologia , Filogenia
9.
New Phytol ; 243(2): 620-635, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38812269

RESUMO

In natural systems, different plant species have been shown to modulate specific nitrogen (N) cycling processes so as to meet their N demand, thereby potentially influencing their own niche. This phenomenon might go beyond plant interactions with symbiotic microorganisms and affect the much less explored plant interactions with free-living microorganisms involved in soil N cycling, such as nitrifiers and denitrifiers. Here, we investigated variability in the modulation of soil nitrifying and denitrifying enzyme activities (NEA and DEA, respectively), and their ratio (NEA : DEA), across 193 Arabidopsis thaliana accessions. We studied the genetic and environmental determinants of such plant-soil interactions, and effects on plant biomass production in the next generation. We found that NEA, DEA, and NEA : DEA varied c. 30-, 15- and 60-fold, respectively, among A. thaliana genotypes and were related to genes linked with stress response, flowering, and nitrate nutrition, as well as to soil parameters at the geographic origin of the analysed genotypes. Moreover, plant-mediated N cycling activities correlated with the aboveground biomass of next-generation plants in home vs away nonautoclaved soil, suggesting a transgenerational impact of soil biotic conditioning on plant performance. Altogether, these findings suggest that nutrient-based plant niche construction may be much more widespread than previously thought.


Assuntos
Arabidopsis , Biomassa , Ciclo do Nitrogênio , Microbiologia do Solo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Nitrogênio/metabolismo , Solo/química , Genótipo , Nitrificação , Desnitrificação , Ecossistema
10.
ChemMedChem ; 19(15): e202400147, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713763

RESUMO

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several biological processes. They show a wide diversity in tissue distribution and their subcellular localization. Twenty-two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms: hCA I, hCA II, hCA IX, and hCA XII. Compounds appeared to be very active mostly against hCA IX (7) and hCA I (6) isoforms being more potent than reference drug acetazolamide (AAZ). Some compounds appeared to be very selective with a selectivity index up to 13.8. Furthermore, docking was performed for some of these compounds on all isoforms to understand the possible interactions with the active site. Additionally, the most active compounds against hCA IX were subjected to cell viability assay. The anticancer activity of the compounds (3 a-d, 5 d, 5 i, and 5 m) was investigated using two human breast cancer cell lines, i. e. MCF-7 and MDA-MB-231 cells, and the normal counterpart, namely MCF10-A cells.


Assuntos
Antineoplásicos , Inibidores da Anidrase Carbônica , Simulação de Acoplamento Molecular , Ftalazinas , Sulfonamidas , Humanos , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Ftalazinas/farmacologia , Ftalazinas/síntese química , Ftalazinas/química , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Anidrases Carbônicas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Domínio Catalítico , Células MCF-7 , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Proliferação de Células/efeitos dos fármacos
11.
Biofactors ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801155

RESUMO

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether Limosilactobacillus reuteri DSM 17938 (L. reuteri)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but L. reuteri neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by L. reuteri administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of L. reuteri DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.

12.
Psychol Sport Exerc ; 73: 102635, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38575103

RESUMO

Anxiety has been the primary focus of emotion research in sport psychology. Most of the existing anxiety measures focus on the competition related anxiety. Little is known about the way in which anxiety affects athletic outcomes in extreme sports. We contribute to the literature on anxiety in extreme sports by: (1) developing and providing a preliminary validation for a novel, theoretically anchored sport climbing inventory, Climbing Anxiety Scale (CAS-20), among an international sample of rock-climbers (N = 153); and (2) providing preliminary evidence on its factorial and criterion-related validity. Our investigation includes two phases. The first phase (6 clinical and sport psychology experts) included the development and expert review of a climbing specific anxiety scale. The second phase (N = 153) offers preliminary evidence pertaining to the measure's reliability, factorial, convergent and criterion related validity. Factorial validity was investigated by deploying a series of confirmatory factorial analyses. Convergent and discriminatory validity were examined by comparing the scale's associations with a general anxiety measure, a sport anxiety measure, as well as climbing self-efficacy. Criterion-related validity was estimated by examining its relationship with rock-climbing performance. We contribute to the general domain of sport and athletic research by developing a sport-specific anxiety measure, investigating whether and how anxiety comes into play in rock-climbing, a high-risk sport. This scale can be used for assessing anxiety in climbing and monitoring the impact of an interventions designed to reduce these symptoms.


Assuntos
Ansiedade , Psicometria , Humanos , Masculino , Feminino , Adulto , Ansiedade/psicologia , Ansiedade/diagnóstico , Reprodutibilidade dos Testes , Adulto Jovem , Psicometria/métodos , Análise Fatorial , Inquéritos e Questionários , Pessoa de Meia-Idade , Montanhismo/psicologia , Desempenho Atlético/psicologia , Autoeficácia , Adolescente
13.
J Clin Microbiol ; 62(6): e0010424, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38661386

RESUMO

Leishmaniasis is a vector-borne disease caused by many Leishmania spp. which infect humans and other mammalian hosts. Leishmania infantum is the main agent of canine leishmaniasis (CanL) whose diagnosis is usually confirmed by serological and molecular tests. This study aimed to evaluate the clinical and analytical sensitivities of a lab-on-chip (LOC) real-time PCR applied on the portable Q3-Plus V2 platform (Q3 qPCR) in the detection of L. infantum. The Q3 qPCR performance was assessed by comparing the quantification cycle (Cq) values with those obtained using the qPCR run on a CFX96 Real-Time System (CFX96 qPCR). A total of 173 DNA samples (extracted from bone marrow, lymph node, blood, buffy coat, conjunctival swab, and skin) as well as 93 non-extracted samples (NES) (bone marrow, lymph node, blood, and buffy coat) collected from dogs were tested with both systems. Serial dilutions of each representative DNA and NES sample were used to assess the analytical sensitivity of the Q3 qPCR system. Overlapping Cq values were obtained with the Q3 qPCR and CFX96 qPCR, both using DNA extracted from L. infantum promastigotes (limit of detection, <1 promastigote per milliliter) and from biological samples as well as with NES. However, the Q3 qPCR system showed a higher sensitivity in detecting L. infantum in NES as compared with the CFX96 qPCR. Our data indicate that the Q3 qPCR system could be a reliable tool for detecting L. infantum DNA in biological samples, bypassing the DNA extraction step, which represents an advance in the point-of-care diagnostic of CanL.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Cães , Animais , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/parasitologia , Dispositivos Lab-On-A-Chip , Técnicas de Diagnóstico Molecular/métodos , DNA de Protozoário/genética
14.
Biomolecules ; 14(4)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38672460

RESUMO

A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.


Assuntos
Antioxidantes , Edaravone , Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Animais , Humanos , Camundongos , Antioxidantes/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Tumoral , Edaravone/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/metabolismo
15.
Foods ; 13(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611284

RESUMO

Heavy metals (HMs) are natural elements present in the Earth's crust, characterised by a high atomic mass and a density more than five times higher than water. Despite their origin from natural sources, extensive usage and processing of raw materials and their presence as silent poisons in our daily products and diets have drastically altered their biochemical balance, making them a threat to the environment and human health. Particularly, the food chain polluted with toxic metals represents a crucial route of human exposure. Therefore, the impact of HMs on human health has become a matter of concern because of the severe chronic effects induced by their excessive levels in the human body. Chelation therapy is an approved valid treatment for HM poisoning; however, despite the efficacy demonstrated by chelating agents, various dramatic side effects may occur. Numerous data demonstrate that dietary components and phytoantioxidants play a significant role in preventing or reducing the damage induced by HMs. This review summarises the role of various phytochemicals, plant and herbal extracts or probiotics in promoting human health by mitigating the toxic effects of different HMs.

16.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473851

RESUMO

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A3-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated.


Assuntos
Complexos de Coordenação , Compostos Heterocíclicos , Metano/análogos & derivados , Neoplasias , Humanos , Prata/química , Ouro/química , Cafeína , Antibacterianos/farmacologia , Metano/química , Compostos Heterocíclicos/química , Complexos de Coordenação/química
17.
Mediterr J Hematol Infect Dis ; 16(1): e2024018, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468826

RESUMO

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring rearrangements of the histone lysine [K]-Methyltransferase 2A (KMT2A) gene on chromosome 11q23 (KMT2A-r) represent a category with dismal prognosis. The prompt identification of these cases represents an urgent clinical need. Considering the correlation between rat neuron glial-antigen 2 (NG2) chondroitin-sulfate-proteoglycan molecule expression and KMT2A-r, we aimed to identify an optimized cytofluorimetric diagnostic panel to predict the presence of KMT2A-r. Materials and Methods: We evaluated 88 NG2+ B-ALL cases identified with an NG2 positivity threshold >10% from a cohort of 1382 newly diagnosed B-ALLs referred to the Division of Hematology of 'Sapienza' University of Rome. Results: Eighty-five of 88 (96.6%) NG2+ B-ALLs harbored KMT2A-r and were mainly pro-B ALL (77/85; 91%). Only 2 B-ALLs with KMT2A-r showed NG2 expression below 10%, probably due to the steroid therapy administered prior to cytofluorimetric analysis.Compared to KMT2A-r-cases, KMT2A r+ B-ALLs showed a higher blast percentage, significantly higher mean fluorescence intensity (MFI) of CD45, CD38, and CD58, and significantly lower MFI of CD34, CD22, TdT, and CD123.The study confirmed differences in CD45, CD34, CD22, and TdT MFI within the same immunologic EGIL group (European Group for the immunological classification of leukemias), indicating no influence of the B-ALLs EGIL subtype on the KMT2A-r+ B-ALLs immunophenotype. Conclusions: Our data demonstrate the association between NG2 and KMT2A-r in B-ALLs identify a distinctive immunophenotypic pattern, useful for rapid identification in diagnostic routines of these subtypes of B-ALLs with a poor prognosis that benefits from a specific therapeutic approach.

18.
Glob Med Genet ; 11(1): 59-68, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38348157

RESUMO

Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

19.
Sci Rep ; 14(1): 3348, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336818

RESUMO

Onchocerca lupi is a zoonotic filarioid parasite of dogs and cats with widespread distribution. A specific non-invasive diagnostic assay for the detection of O. lupi infections remains unavailable. This study aimed to assess the accuracy, specificity, and sensitivity of an ELISA test designed using nine peptides from two O. lupi proteins. Sera (n = 54) collected from O. lupi infected dogs from endemic areas (Portugal and USA), alongside sera from dogs positive for Dirofilaria immitis, D. repens, Cercopithifilaria bainae, and Acanthocheilonema reconditum (n = 53) from a non-endemic area for O. lupi, as well as from helminth-free dogs (n = 60), were tested. The checkerboard titration method was applied for the optimization of peptide concentrations and conjugate anti-dog dilutions. Sensitivity, specificity, and optimal cut-off values were calculated using ROC curve analysis. All peptides reacted against sera of O. lupi, with no correlation between optic density (OD) values and microfilariae (mfs) loads. Sensitivity and specificity values ranging from 85.45 to 100%, and 88.89% to 100%, respectively, were recorded for all peptides examined, with 100% specificity and sensitivity observed for peptides 40_3, 40_5, 130_3, 120_3 and 40_1, 130_5, respectively. The maximum cut-off value was observed for peptides 40_5 (0.765) and 40_3 (0.708). Testing of sera from dogs positive for other filarioids resulted in lower OD values (up to 1.565) for peptides 40_3 and 40_5 when compared with O. lupi (up to 2.929). The availability of this assay will be of value in epidemiological studies of canine O. lupi infection in both endemic and non-endemic areas, and in assessing the risk for zoonotic transmission.


Assuntos
Doenças do Gato , Doenças do Cão , Animais , Cães , Gatos , Onchocerca , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia , Ensaio de Imunoadsorção Enzimática/veterinária , Testes Sorológicos/veterinária , Peptídeos
20.
Pediatr Rep ; 16(1): 135-150, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391001

RESUMO

In the developed world, pediatric obesity (PO) has been a major health concern since the last century, and this condition may lead to detrimental life-long physical and mental comorbidities. Currently, its prevalence has increased in low- and middle-income countries and in many high-income countries. Thus, the provision of effective and tailored care for children and their families has become vital. The social consequences of the COVID-19 pandemic are known everywhere, and among these, it has been argued that the COVID-19 pandemic has had a major impact on PO. Overall, the growth of PO over the last decade has been enhanced by the pandemic. During the COVID-19 pandemic, children, adolescents and young adults gained weight as the pediatric population dealt with sedentary lifestyles and changes in food habits. In this review, we want to highlight the impact that the COVID-19 pandemic had on PO.

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