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1.
J Nat Prod ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255387

RESUMO

Three new dihydroflavonols, gloverinols A-C (1-3), a new flavon-3-ol, gloverinol D (4), two new isoflavans, gloveriflavan A (5) and B (6), and seven known compounds were isolated from the root bark of Dalbergia gloveri. The structures of the isolates were elucidated by using NMR, ECD, and HRESIMS data analyses. Among the isolated compounds, gloverinol B (2), gloveriflavan B (6), and 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl)-1-propanone (10) were the most active against Staphylococcus aureus, with MIC values of 9.2, 18.4, and 14.2 µM, respectively.

2.
Eur Urol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39242323

RESUMO

BACKGROUND AND OBJECTIVE: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177Lu-PSMA-617. METHODS: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline. KEY FINDINGS AND LIMITATIONS: Patients randomised to 177Lu-PSMA-617 with the best PSA declines of ≥0-<50% (96/551 [17%]), ≥50-<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer. CONCLUSIONS AND CLINICAL IMPLICATIONS: The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177Lu-PSMA-617 treatment in this population.

3.
Sci Total Environ ; 952: 175895, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39218090

RESUMO

We assessed the concentrations of metals and other trace elements in two of the most common seabird species breeding on Svalbard, the black-legged kittiwake (Rissa tridactyla) and the Brünnich's guillemot (Uria lomvia). Both of these species feed mostly on fish and crustaceans but have different foraging strategies, kittiwakes being surface feeders while guillemots are divers. We investigated the concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), lead (Pb), selenium (Se) and zinc (Zn) in the plasma and body feathers of black-legged kittiwakes (n = 17), as well as in the body feathers of Brünnich's guillemots (n = 13). Samples were collected from adult birds at two time points, one week apart during July 2017 in Kongsfjorden, Svalbard. Of the non-essential trace elements, As was found at the highest median concentration at both the first (56.23 ng/g ww) and second (39.99 ng/g ww) sampling timepoints in the kittiwake plasma. When separating for the sexes, as well as sampling time, males sampled at the first sampling time point had significantly higher concentrations of As (median at 0.087 ng/g versus 0.039 ng/g) and Se (median 0.26 ng/g versus 0.16 ng/g) compared to males sampled at the second time point. There was no significant difference in plasma concentrations between females at first and second sampling time points. Kittiwake feathers contained significantly higher concentrations of As, Cd and Hg than guillemot feathers, while guillemot feathers had significantly higher concentrations of Cu, Pb and Zn. However, of the non-essential elements in both kittiwake and guillemot feathers Hg was found with the highest median concentrations at 5160 and 1080 ng/g, respectively, thus in kittiwakes exceeding the level of 5000 ng/g associated with adverse effect (e.g., impaired reproduction). Levels of Hg and Se found in the kittiwake feathers were higher than previous studies on seabirds in the Arctic.


Assuntos
Charadriiformes , Monitoramento Ambiental , Plumas , Oligoelementos , Animais , Plumas/química , Oligoelementos/análise , Svalbard , Charadriiformes/metabolismo , Poluentes Ambientais/metabolismo , Poluentes Ambientais/sangue , Masculino , Feminino , Metais/análise , Metais/sangue , Selênio/análise , Selênio/sangue
4.
Sci Total Environ ; 950: 175303, 2024 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-39127197

RESUMO

Marine and freshwater mammalian predators and fish samples, retrieved from environmental specimen banks (ESBs), natural history museum (NHMs) and other scientific collections, were analysed by LIFE APEX partners for a wide range of legacy and emerging contaminants (2545 in total). Network analysis was used to visualize the chemical occurrence data and reveal the predominant chemical mixtures for the freshwater and marine environments. For this purpose, a web tool was created to explore these chemical mixtures in predator-prey pairs. Predominant chemicals, defined as the most prevalent substances detected in prey-predator pairs were identified through this innovative approach. The analysis established the most frequently co-occurring substances in chemical mixtures from AP&P in the marine and freshwater environments. Freshwater and marine environments shared 23 chemicals among their top 25 predominant chemicals. Legacy chemical, including perfluorooctanesulfonic acid (PFOS), brominated diphenyl ethers (BDEs), polychlorinated biphenyls (PCBs), hexachlorobenzene and mercury were dominant chemicals in both environments. Furthermore, N-acetylaminoantipyrine was a predominant pharmaceutical in both environments. The LIFE APEX chemical mixture application (https://norman-data.eu/LIFE_APEX_Mixtures) was proven to be useful to establish most prevalent compounds in terms of number of detected counts in prey-predator pairs. Nonetheless, further research is needed to establish food chain associations of the predominant chemicals.


Assuntos
Monitoramento Ambiental , Peixes , Cadeia Alimentar , Água Doce , Mamíferos , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/análise , Europa (Continente) , Água do Mar/química
5.
Heliyon ; 10(15): e35638, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170453

RESUMO

This literature review offers an extensive exploration of Chaga mushrooms (Inonotus obliquus), focusing on their phytochemical composition, health-promoting attributes, and mechanisms of action. The aim was to provide an up-to-date overview of Chaga's significance in the medicinal sector, emphasizing its potential role in diverse health benefits. The review highlights Chaga's remarkable anticancer, antioxidant, anti-diabetic, anti-inflammatory, antimicrobial, and immunomodulating properties. By synthesizing recent findings, this work underscores Chaga's importance in the medicinal industries and provides valuable insights into its pharmacological potential.

6.
Life (Basel) ; 14(8)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39202669

RESUMO

Guideline-recommended screening programs exist for only a few cancer types. Although all these programs are understood to lead to reductions in cancer-related mortality, standard-of-care screening tests vary in accuracy, adherence and effectiveness. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer cancer early detection (MCED) tests. MCED tests are positioned to be complementary to standard-of-care screening and they may broaden screening availability, especially for individuals who are not adherent with current screening programs and for individuals who may harbor cancers with no available screening options. In this article, we outline some key features that should be considered for study design and MCED test development, provide an example of the developmental pathway undertaken for an emerging multi-biomarker class MCED test and propose a clinical algorithm for an imaging-based diagnostic resolution strategy following MCED testing.

7.
Clin Transl Sci ; 17(9): e70016, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39206679

RESUMO

In the United States, 2.0 million new cancer cases and around 600,000 cancer deaths are estimated to occur in 2024. Early detection gives cancer patients the best chance for treatment success. Currently, cancer screening in the general population is recommended for a limited set of cancers; as a result, most cancer types are not regularly screened. Thus, in recent years, we have seen a wave of novel, non-invasive, single- and multi-cancer detection tests (SCD and MCD), promising detection of cancer signals prior to the onset of symptoms and/or clinical diagnosis. To accelerate the development, access, and adoption of these tests, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices, established the Early Detection & Screening (ED&S) Working Group. The early detection space is in need of consensus around definitions for SCD and MCD tests that harmonize terminology across diverse stakeholders, thereby reducing communication barriers and ultimately advancing the discipline. To this end, the ED&S Working Group compiled a lexicon of terms, chosen based on perceived importance, frequency of use, lack of clarity, and unique challenges in the context of SCD and MCD tests. This lexicon was submitted to the FDA for their feedback, which was incorporated. In this work, we present the first installment of the lexicon, consisting of 14 primary terms, that will be part of an online dictionary and provide a foundation for future projects of BLOODPAC's ED&S Working Group.


Assuntos
Consenso , Detecção Precoce de Câncer , Neoplasias , Humanos , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Neoplasias/diagnóstico , Neoplasias/sangue , Estados Unidos , Biomarcadores Tumorais/sangue , Terminologia como Assunto
8.
Pharm Stat ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978387

RESUMO

During the drug development process, testing potency plays an important role in the quality assessment required for the manufacturing and marketing of biologics. Due to multiple operational and biological factors, higher variability is usually observed in bioassays compared with physicochemical methods. In this paper, we discuss different sources of bioassay variability and how this variability can be statistically estimated. In addition, we propose an algorithm to estimate the variability of reportable results associated with different numbers of runs and their corresponding OOS rates under a given specification. Numerical experiments are conducted on multiple assay formats to elucidate the empirical distribution of bioassay variability.

9.
J Med Chem ; 67(13): 11053-11068, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38952152

RESUMO

Metastable binding sites (MBS) have been observed in a multitude of molecular dynamics simulations and can be considered low affinity allosteric binding sites (ABS) that function as stepping stones as the ligand moves toward the orthosteric binding site (OBS). Herein, we show that MBS can be utilized as ABS in ligand design, resulting in ligands with improved binding kinetics. Four homobivalent bitopic ligands (1-4) were designed by molecular docking of (S)-alprenolol ((S)-ALP) in the cocrystal structure of the ß2 adrenergic receptor (ß2AR) bound to the antagonist ALP. Ligand 4 displayed a potency and affinity similar to (S)-ALP, but with a >4-fold increase in residence time. The proposed binding mode was confirmed by X-ray crystallography of ligand 4 in complex with the ß2AR. This ligand design principle can find applications beyond the ß2AR and G protein-coupled receptors (GPCRs) as a general approach for improving the pharmacological profile of orthosteric ligands by targeting the OBS and an MBS simultaneously.


Assuntos
Simulação de Acoplamento Molecular , Receptores Adrenérgicos beta 2 , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/química , Ligantes , Humanos , Sítios de Ligação , Cristalografia por Raios X , Alprenolol/química , Alprenolol/farmacologia , Alprenolol/metabolismo , Antagonistas de Receptores Adrenérgicos beta 2/química , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/metabolismo , Simulação de Dinâmica Molecular , Desenho de Fármacos
10.
Materials (Basel) ; 17(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998187

RESUMO

The inherent brittleness of polyhydroxybutyrate (PHB), a well-studied polyhydroxyalkanoate (PHA), limits its applicability in flexible and impact-resistant applications. This study explores the potential of blending PHB with a different PHA to overcome brittleness. The synthesis of PHA polymers, including PHB and an amorphous medium-chain-length PHA (aPHA) consisting of various monomers, was achieved in previous works through canola oil fermentation. Detailed characterization of aPHA revealed its amorphous nature, as well as good thermal stability and shear thinning behavior. The blending process was carried out at different mass ratios of aPHA and PHB, and the resulting blends were studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The blends exhibited complex DSC curves, indicating the presence of multiple crystalline forms of PHB. SEM images revealed the morphology of the blends, with PHB particles dispersed within the aPHA matrix. TGA showed similar thermal degradation patterns for the blends, with the residue content decreasing as the PHB content increased. The crystallinity of the blends was influenced by the PHB content, with higher PHB ratios resulting in an increased degree of crystallinity. XRD confirmed the presence of both α and ß crystals of PHB in the blends. Overall, the results demonstrate the potential of PHB+aPHA blends to enhance the mechanical properties of biopolymer materials, without com-promising the thermal stability, paving the way for sustainable material design and novel application areas.

12.
Psychiatr Pol ; 58(1): 7-24, 2024 Feb 28.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-38852182

RESUMO

OBJECTIVES: Anxiety disorders are significant predictors of suicidality and are proposed to be independent risk factors for suicide attempts. They are common in people with type 2 diabetes (T2DM) and are associated with longer duration of diabetes and poorer treatment outcomes. The aim was to examine associations between anxiety disorders and suicidal thoughts and behaviour in people with T2DM, to establish the prevalence of suicidality among people with T2DM in the selected European countries and to examine whether anxiety disorders were predictive of current outcomes of suicidality in this population using data from the International Prevalence and Treatment of Diabetes and Depression study. METHODS: The study sample comprised 1063 adults with T2DM from 6 European countries. The presence of anxiety disorders and suicidality was assessed with the MINI International Neuropsychiatric Interview. The group of participants with current suicidal risk was compared with the group of participants with no suicidal risk. RESULTS: The participants from Germany were more likely to report suicidality than those from other countries, whereas people from Serbia and Ukraine were less likely to report it. Depression and anxiety disorders significantly contributed to the increased presence of suicidality among people with T2DM. Agoraphobia was a significant predictor of suicidality when controlling for depression. The participants with T2DM and comorbid agoraphobia had 4.86 times higher odds to report suicidality than those without agoraphobia. CONCLUSIONS: Agoraphobia was a significant predictor of suicidality in people with T2DM.


Assuntos
Transtornos de Ansiedade , Diabetes Mellitus Tipo 2 , Ideação Suicida , Humanos , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Adulto , Europa (Continente)/epidemiologia , Fatores de Risco , Comorbidade , Idoso , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia , Prevalência , Ucrânia/epidemiologia , Alemanha/epidemiologia
13.
Cancer Prev Res (Phila) ; : OF1-OF5, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853442

RESUMO

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

14.
Materials (Basel) ; 17(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38893822

RESUMO

Pomegranate peel extract is known for its potent antibacterial, antiviral, antioxidant, anti-inflammatory, wound healing, and probiotic properties, leading to its use in treating oral infections. In the first stage of this work, for the first time, using the Design of Experiment (DoE) approach, pomegranate peel extract (70% methanol, temperature 70 °C, and three cycles per 90 min) was optimized and obtained, which showed optimal antioxidant and anti-inflammatory properties. The optimized extract showed antibacterial activity against oral pathogenic bacteria. The second part of this study focused on optimizing an electrospinning process for a combination of polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) nanofibers loaded with the optimized pomegranate peel extract. The characterization of the nanofibers was confirmed by using SEM pictures, XRPD diffractograms, and IR-ATR spectra. The composition of the nanofibers can control the release; in the case of PVP-based nanofibers, immediate release was achieved within 30 min, while in the case of PCL/PVP, controlled release was completed within 24 h. Analysis of the effect of different scaffold compositions of the obtained electrofibers showed that those based on PCL/PVP had better wound healing potential. The proposed strategy to produce electrospun nanofibers with pomegranate peel extract is the first and innovative approach to better use the synergy of biological action of active compounds present in extracts in a patient-friendly pharmaceutical form, beneficial for treating oral infections.

15.
World J Biol Psychiatry ; 25(6): 342-351, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38905131

RESUMO

OBJECTIVES: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. METHODS: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed. RESULTS: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). DISCUSSION: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.


Assuntos
Antipsicóticos , Atitude do Pessoal de Saúde , Monitoramento de Medicamentos , Psiquiatria , Humanos , Antipsicóticos/uso terapêutico , Feminino , Masculino , Estudos Transversais , Inquéritos e Questionários , Adulto , Internato e Residência , Europa (Continente) , Padrões de Prática Médica/estatística & dados numéricos , Sociedades Médicas , Psiquiatras
16.
Eur Psychiatry ; 67(1): e41, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38778031

RESUMO

BACKGROUND: Climate change is one of the greatest threats to health that societies face and can adversely affect mental health. Given the current lack of a European consensus paper on the interplay between climate change and mental health, we signal a need for a pan-European position paper about this topic, written by stakeholders working in mental health care. METHODS: On behalf of the European Psychiatric Association (EPA), we give recommendations to make mental health care, research, and education more sustainable based on a narrative review of the literature. RESULTS: Examples of sustainable mental healthcare comprise preventive strategies, interdisciplinary collaborations, evidence-based patient care, addressing social determinants of mental health, maintaining health services during extreme weather events, optimising use of resources, and sustainable facility management. In mental health research, sustainable strategies include investigating the impact of climate change on mental health, promoting research on climate change interventions, strengthening the evidence base for mental health-care recommendations, evaluating the allocation of research funding, and establishing evidence-based definitions and clinical approaches for emerging issues such as 'eco-distress'. Regarding mental health education, planetary health, which refers to human health and how it is intertwined with ecosystems, may be integrated into educational courses. CONCLUSIONS: The EPA is committed to combat climate change as the latter poses a threat to the future of mental health care. The current EPA position paper on climate change and mental health may be of interest to a diverse readership of stakeholders, including clinicians, researchers, educators, patients, and policymakers.


Assuntos
Mudança Climática , Saúde Mental , Humanos , Europa (Continente) , Psiquiatria , Sociedades Médicas , Serviços de Saúde Mental/organização & administração
17.
Cancer Prev Res (Phila) ; 17(8): 349-353, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819783

RESUMO

In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multiyear outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred at a median of 4.4 years (IQR: 4.1-4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All eight treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multiyear outcomes (P = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants. Prevention Relevance: This study provides preliminary evidence of the potential of multicancer early detection testing as an effective screening tool for detecting cancers without standard-of-care (SoC) screening modalities and complementing SoC cancer screening.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Estudos Prospectivos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Seguimentos , Adulto
18.
J Med Chem ; 67(11): 8481-8501, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38769934

RESUMO

Metallacarboranes, exemplified by cobalt bis(dicarbollide) ([COSAN]-), have excelled their historical metallocene analogue label to become promising in drug design, medical studies, and fundamental biological research. Serving as a unique platform for conjugation with biomolecules, they also constitute an auspicious building block for biologically active derivatives and a carrier for cellular transport of membrane-impermeable cargos. Modified [COSAN]- exhibits specific antimicrobial, antiviral, and anticancer actions showing promise for preclinical trials. Contributing to the ongoing development in medicinal chemistry, metallacarboranes offer desirable physicochemical properties and low acute toxicity. This article presents a critical look at metallacarboranes in the context of their application in medicinal chemistry, emphasizing [COSAN]- as a potential game-changer in drug design and biomedical sciences. As medicinal chemistry seeks innovative building blocks, metallacarboranes emerge as an important novelty with versatile solutions and promising implications.


Assuntos
Química Farmacêutica , Cobalto , Humanos , Química Farmacêutica/tendências , Cobalto/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Boranos/química , Boranos/farmacologia , Boranos/síntese química , Desenho de Fármacos , Animais , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Compostos Organometálicos/síntese química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antivirais/química , Antivirais/farmacologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-38705577

RESUMO

Guideline recommended standard of care (SoC) screening is available for four cancer types; most cancer-related deaths are caused by cancers without SoC screening. DETECT-A is the first prospective interventional trial evaluating an MCED blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within one year of enrollment (n=98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% CI: 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years.

20.
Heliyon ; 10(9): e30254, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707308

RESUMO

This literature review provides an up-to-date exploration of the multifaceted attributes of maitake mushrooms (Grifola frondosa), elucidating their bioactive phytochemicals and diverse health advantages, including their substantial role in supporting human health and potential incorporation into the medicinal industry. Carbohydrates and protein are the major constituents contributing to the dry weight of G. frondosa, taking up around 70-80 % and 13-21 %, respectively, with emerging research linking these constituents to various health benefits. By synthesising current research findings, this review emphasises the substantial role of maitake mushrooms in supporting human health and underscores their potential incorporation into the medicinal industry. To further advance our understanding, future research should delve into the mechanisms underlying their health-promoting effects, with a focus on conducting quantitative studies to elucidate physiological pathways and potential drug interactions. Additionally, exploring their integration into functional foods or nutraceuticals through quantitative assessments of bioavailability and efficacy will be crucial for maximising their therapeutic benefits. This review aims to provide comprehensive insights, catalysing further research and innovation in utilising maitake mushrooms for improved well-being and industry advancement.

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