Pd(II)/diphosphine/curcumin complexes as potential anticancer agents.

Palladium(II) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells. Thus, in this work, we combined Pd(II)/phosphine systems with the natural product curcumin as a ligand, obtaining a series of complexes, [Pd(cur)(PPh3)2]PF6 (A1), [Pd(cur)(dppe)]PF6 (A2), [Pd(cur)(dppp)]PF6 (A3), [Pd(cur)(dppb)]PF6 (A4) and [Pd(cur)(dppf)]PF6 (A5), where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1'-bis(diphenylphosphino)ferrocene (P-P), which were characterized by elemental analysis, molar conductivity analysis, and mass, NMR (1H, 13C, 31P{1H}), UV-vis, and IR spectroscopies, and four of them (A1, A2, A4, and A5) by X-ray crystallography. The in vitro cell viability of the complexes A1-A5, cisplatin, and the free ligand curcumin against MDA-MB-231 (human triple-negative breast tumor cells), SK-BR-3 (human breast tumor cells), A549 (human lung tumor cells), MRC-5 (non-tumor human lung cells), A2780 (human ovarian carcinoma cells), and A2780cis (cisplatin-resistant human ovarian carcinoma cells), was evaluated by the MTT colorimetric assay. For the tumor cell lines tested, the complexes showed good anticancer activities. The results showed that in general the complexes had lower IC50 values than free curcumin and the precursors [PdCl2(P-P)]. IC50 results obtained for the A1-A5 complexes, in the MCF-7 cell line, are similar to those that had already been observed for some Pd/bipy/curcumin complexes. In the MDA-MB-231 cell line, complexes A1 and A5 stood out, with their lowest IC50 values, around 5 µmol L-1, and the complexes appeared to be more active (lower IC50 values) against the ovarian cell lines. Complex A1 was 23 and 22-fold more cytotoxic than cisplatin, against the A2780 and A2780cis cells, respectively. The complex A1 was studied on A2780cis cells and it was found that this complex inhibits colony formation and induces cell cycle arrest in the sub-G1 phase in a concentration-dependent manner and leads to cell death by apoptosis. The DCFDA assay revealed a potent ROS induction for complex A1.

The effect of light irradiation on a nitro-ruthenium porphyrin complex in the induced death of lung cancer cells in two- and three-dimensional cultures: Insights into the effect of nitric oxide.

Efforts to find compounds selectively affecting cancer cells while sparing normal ones have continued to grow. Nitric oxide (NO) is critical in physiology and pathology, including cancer. It influences cellular processes like proliferation, apoptosis, and angiogenesis. The intricate interaction of NO with cancer cells offers innovative treatment possibilities, but its effects can vary by concentration and site. Ruthenium complexes capable of releasing NO upon stimulation show for this purpose. These versatile compounds can also enhance photodynamic therapy (PDT), a light-activated approach, which induces cellular damage. Ruthenium-based photosensitizers (PSs), delivering NO and producing reactive oxygen species (ROS), offer a novel strategy for improved cancer treatments. In this study, a nitro-ruthenium porphyrin conjugate: {TPyP[Ru(NO2)(bpy)2]4}(PF6)4, designated RuNO2TPyP, which releases NO upon irradiation, was investigated for its effects on lung cells (non-tumor MRC-5 and tumor A549) in 2D and 3D cell cultures. The findings suggest that this complex has potential for PDT treatment in lung cancer, as it exhibits photocytotoxicity at low concentrations without causing cytotoxicity to normal lung cells. Moreover, treatment of cells with RuNO2TPyP followed by light irradiation (4 J cm-2) can induce apoptosis, generate ROS, promote intracellular NO formation, and has anti-migratory effects. Additionally, the complex can modify tumor cell structures and induce photocytotoxicity and apoptosis in a 3D culture. These outcomes are attributed to the internalization of the complex and its subsequent activation upon light irradiation, resulting in NO release and singlet oxygen production.

Plasma ADAM10 Levels and Their Association with Alzheimer's Disease Diagnosis in Older Adults with Fewer Years of Formal Education.

INTRODUCTION: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment. METHODS: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination - Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis. RESULTS: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment. CONCLUSION: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis.

Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer's disease.

An inverse association between Alzheimer's disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.

Present and Future of Blood-Based Biomarkers of Alzheimer's Disease: Beyond the Classics.

The field of blood-based biomarkers for Alzheimer's disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more sophisticated diagnostic methods are scarce and expensive. Thus, blood-based biomarkers can potentially reduce diagnosis inequities among populations from different socioeconomic contexts. This large-scale screening can be performed so that older adults at risk of cognitive decline assessed using these methods can then undergo more complete assessments with classic biomarkers, increasing diagnosis efficiency and reducing costs to the health systems. Blood-based biomarkers can also aid in assessing the effect of new disease-modifying treatments. This paper reviews recent advances in the area, focusing on the following leading candidates for blood-based biomarkers: amyloid-beta (Aß), phosphorylated tau isoforms (p-tau), neurofilament light (NfL), and glial fibrillary acidic (GFAP) proteins, as well as on new candidates, Neuron-Derived Exosomes contents (NDEs) and Transactive response DNA-binding protein-43 (TDP-43), based on data from longitudinal observational cohort studies. The underlying challenges of validating and incorporating these biomarkers into routine clinical practice and primary care settings are also discussed. Importantly, challenges related to the underrepresentation of ethnic minorities and socioeconomically disadvantaged persons must be considered. If these challenges are overcome, a new time of cost-effective blood-based biomarkers for AD could represent the future of clinical procedures in the field and, together with continued prevention strategies, the beginning of an era with a lower incidence of dementia worldwide.

The Brain Health Diplomat's Toolkit: supporting brain health diplomacy leaders in Latin America and the Caribbean.

Maintaining and improving brain health, one of the most critical global challenges of this century, necessitates innovative, interdisciplinary, and collaborative strategies to address the growing challenges in Latin America and the Caribbean. This paper introduces Brain Health Diplomacy (BHD) as a pioneering approach to bridge disciplinary and geographic boundaries and mobilize resources to promote equitable brain health outcomes in the region. Our framework provides a toolkit for emerging brain health leaders, equipping them with essential concepts and practical resources to apply in their professional work and collaborations. By providing case studies, we highlight the importance of culturally sensitive, region-specific interventions to address unique needs of vulnerable populations. By encouraging dialogue, ideation, and cross-sector discussions, we aspire to develop new research, policy, and programmatic avenues. The novel BHD approach has the potential to revolutionize brain health across the region and beyond, ultimately contributing to a more equitable global cognitive health landscape.

Do the oxidative stress biomarkers predict COVID-19 outcome? An in-hospital cohort study.

In SARSCoV-2 infections, excessive activation of the immune system dramatically elevates reactive oxygen species levels, harms cell structures, and directly increases disease severity and mortality. We aimed to evaluate whether plasma oxidative stress biomarker levels could predict mortality in adults admitted with Coronavirus Disease 2019 (COVID-19), considering potential confounders. We conducted a cohort study of 115 adults (62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Serum levels of α-tocopherol, glutathione, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and advanced oxidation protein products were quantified at COVID-19 diagnosis using real-time polymerase chain reaction. Serum levels of α-tocopherol, glutathione, superoxide dismutase, and advanced oxidation protein products differed significantly between survivors and non-survivors. Serum glutathione levels below 327.2 µmol/mL were associated with a significant risk of death in COVID-19 patients, even after accounting for other factors (adjusted hazard ratio = 3.12 [95% CI: 1.83-5.33]).

New ruthenium(II) complexes with cyclic thio- and semicarbazone: evaluation of cytotoxicity and effects on cell migration and apoptosis of lung cancer cells.

We describe the synthesis, physicochemical characterization, and in vitro antitumor assays of four novel analogous ruthenium(II) complexes with general formula cis-[RuII(N-L)(P-P)2]PF6, where P-P = bis(diphenylphosphine)methane (dppm, in complexes 1 and 2) or bis(diphenylphosphine)ethane (dppe, in complexes 3 and 4) and N-L = 5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (Btsc, in complexes 1 and 3) or 5,6-diphenyltriazine-3-one (Bsc, in complexes 2 and 4). The data were consistent with cis arrangement of the biphosphine ligands. For the Btsc and Bsc ligands, the data pointed to monoanionic bidentate coordination to ruthenium(II) through N,S and N,O, respectively. Single-crystal X-ray diffraction showed that complex 1 crystallized in the monoclinic system, space group P21/c. Determination of the cytotoxicity profiles of complexes 1-4 gave SI values ranging from 1.19 to 3.50 against the human lung adenocarcinoma cell line A549 and the non-tumor lung cell line MRC-5. Although the molecular docking studies suggested that the interaction between DNA and complex 4 was energetically favorable, the experimental results showed that they interacted weakly. Overall, our results demonstrated that these novel ruthenium(II) complexes have interesting in vitro antitumor potential and this study may contribute to further studies in medicinal inorganic chemistry.

Nanoencapsulation of Ruthenium Complex Ru(ThySMet): A Strategy to Improve Selective Cytotoxicity Against Breast Tumor Cells in 2D and 3D Culture Models.

BACKGROUND: Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans-[Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested in vivo. AIMS: Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its in vitro effects. METHODS: The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)ME, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDA-MB-231, MCF-10A, 4T1.13ch5T1 and Balb/C 3T3 fibroblasts. RESULTS: An increased selective cytotoxicity of the Ru(ThySMet)ME for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)ME presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells. CONCLUSION: These results demonstrate that the Ru(ThySMet)ME is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.

Cytotoxic activity of Ru(II)/DPEPhos/N,S-mercapto complexes (DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether).

We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)]PF6 (Ru1), [Ru(DPEPhos)(mmi)(bipy)]PF6 (Ru2) and [Ru(DPEPhos)(dmp)(bipy)]PF6 (Ru3). DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether, mtz = 2-mercapto-2-thiazoline, mmi = 2-mercapto-1-methylimidazole, dmp = 4,6-diamino-2-mercaptopyrimidine and bipy = 2,2'-bipyridine. The compounds were characterized by several spectroscopic techniques, and the molecular structure of Ru1 complex was determined by single-crystal X-ray diffraction. The cytotoxicity of Ru1 - Ru3 complexes were tested against the A549 (human lung) and the MDA-MB-231 (human breast) cancer cell lines and against MRC-5 (non-tumor lung) and MCF-10A (non-tumor breast) cell lines through the MTT assay. All three complexes are cytotoxic against the cell lines studied, with IC50 values lower than those found for the cisplatin. Among them, the Ru2 complex has shown the best selectivity against MDA-MB-231 cancer cell lines, with an IC50 value 12 times lower than that on MCF-10A. The complex Ru2 was capable to induce changes in MDA-MB-231 cells morphology, with loss of cellular adhesion, inhibited colony formation and induce an accumulation of cells at the sub-G1 phase, with an increase in S-phase and decrease of cells at G2 phase. Viscosity, electrochemical and Hoechst 33258 displacement experiments for Ru1 - Ru3 complexes with calf thymus DNA (CT-DNA) showed an electrostatic and groove binding mode of interaction. Additionally, the complexes interact with the protein Human Serum Albumin (HSA) by static mechanism. The negative values for ΔH and ΔS indicate that van der Waals forces and hydrogen bonding may occurs between the complexes and HSA. Therefore, this class of complexes are promising anticancer candidates and may be selected to further detailed studies.

Protecting cognitive function in older adults with age-related hearing loss: Insights from The Irish Longitudinal Study on Ageing (TILDA) and the role of hearing aids.

BACKGROUND: Age-related hearing loss (ARHL) is prevalent in adults over 70, impairing hearing sensitivity and speech perception. ARHL has been linked to an increased risk of cognitive decline and dementia. However, most affected adults are not receiving adequate treatment, including hearing aids. OBJECTIVE: This study aimed to evaluate the impact of ARHL on cognitive decline in older adults participating in the Irish Longitudinal Study on Aging (TILDA). DESIGN: METHODS: Data from four TILDA waves, a 6-year follow-up, was collected and analyzed using zero-inflated Poisson regression. The primary outcome, cognitive function, was assessed using Mini-Mental State Examination (MMSE) total score and error counts. RESULTS: Our analysis revealed that age, education, use of aids to help with hearing, and history of stroke were significantly associated with error counts at baseline. Additionally, poor hearing was associated with a negative change in MMSE score from wave 4, indicating the potential role of ARHL in cognitive decline. When further adjusted for age, sex, history of stroke, hypertension, any emotional, nervous, or psychiatric problem, polypharmacy, and hearing aids, the zero-inflated Poisson model indicated that poor hearing, use of hearing aids, stroke, hypertension, and polypharmacy all predicted MMSE error counts in follow-up assessments. Moreover, the use of hearing aids was associated with a decreased likelihood of cognitive decline. CONCLUSION: ARHL was independently associated with cognitive decline, underscoring the importance of addressing hearing loss in older adults. Future research should explore the potential of hearing aids to protect cognitive functioning in older adults.

Empathy as a crucial skill in disrupting disparities in global brain health.

Brain health refers to the state of a person's brain function across various domains, including cognitive, behavioral and motor functions. Healthy brains are associated with better individual health, increased creativity, and enhanced productivity. A person's brain health is intricately connected to personal, social and environmental factors. Racial, ethnic, and social disparities affect brain health and on the global scale these disparities within and between regions present a hurdle to brain health. To overcome global disparities, greater collaboration between practitioners and healthcare providers and the people they serve is essential. This requires cultural humility driven by empathy. Empathy is a core prosocial value, a cognitive-emotional skill that helps us understand ourselves and others. This position paper aims to provide an overview of the vital roles of empathy, cooperation, and interdisciplinary partnerships. By consciously integrating this understanding in practice, leaders can better position themselves to address the diverse challenges faced by communities, promote inclusivity in policies and practices, and further more equitable solutions to the problem of global brain health.

Developments in scalable strategies for detecting early markers of cognitive decline.

Effective strategies for early detection of cognitive decline, if deployed on a large scale, would have individual and societal benefits. However, current detection methods are invasive or time-consuming and therefore not suitable for longitudinal monitoring of asymptomatic individuals. For example, biological markers of neuropathology associated with cognitive decline are typically collected via cerebral spinal fluid, cognitive functioning is evaluated from face-to-face assessments by experts and brain measures are obtained using expensive, non-portable equipment. Here, we describe scalable, repeatable, relatively non-invasive and comparatively inexpensive strategies for detecting the earliest markers of cognitive decline. These approaches are characterized by simple data collection protocols conducted in locations outside the laboratory: measurements are collected passively, by the participants themselves or by non-experts. The analysis of these data is, in contrast, often performed in a centralized location using sophisticated techniques. Recent developments allow neuropathology associated with potential cognitive decline to be accurately detected from peripheral blood samples. Advances in smartphone technology facilitate unobtrusive passive measurements of speech, fine motor movement and gait, that can be used to predict cognitive decline. Specific cognitive processes can be assayed using 'gamified' versions of standard laboratory cognitive tasks, which keep users engaged across multiple test sessions. High quality brain data can be regularly obtained, collected at-home by users themselves, using portable electroencephalography. Although these methods have great potential for addressing an important health challenge, there are barriers to be overcome. Technical obstacles include the need for standardization and interoperability across hardware and software. Societal challenges involve ensuring equity in access to new technologies, the cost of implementation and of any follow-up care, plus ethical issues.

New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway.

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF6 and [Ru(L)(dppe)2]PF6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane and bipy = 2,2'-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV-vis and IR spectroscopies, and two by X-ray crystallography. The 31P{1H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)2]PF6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF-7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe)2]PF6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe)2]PF6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death.

Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19.

BACKGROUND & AIMS: Several studies have shown conflicting results for the relationship between vitamin D deficiency and COVID-19 outcomes. Here, we aimed to evaluate whether plasma 25(OH)D levels predict mortality in adults admitted with COVID-19, considering potential confounders. METHODS: We conducted a retrospective cohort study that included 115 adults (age 62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Subjects were classified into two groups according to their plasma levels of 25(OH)D: sufficiency (≥50 nmol/L) and the deficiency (<50 nmol/L). The diagnosis of COVID-19 was performed using real-time polymerase chain reaction (qPCR). In addition, direct competitive chemiluminescence immunoassay assessed serum 25(OH)D levels. RESULTS: The all-cause 30-day mortality was 13.8% (95% CI: 6.5%-21%) in the group of patients with sufficient plasma 25(OH)D levels and 32.1% (95% CI: 14.8%-49.4%) among those with deficient plasma 25(OH)D levels. Cox regression showed that plasma 25(OH)D levels remained a significant predictor of mortality even after adjusting for the covariates sex, age, length of the delay between symptom onset and hospitalization, and disease severity (HR = 0.98, 95% CI: 0.96-1.00; p = 0.02). CONCLUSION: Vitamin D deficiency predicts higher mortality risk in adults with COVID-19.

Cytotoxic and antiparasitic activities of diphosphine-metal complexes of group 10 containing acylthiourea as ligands.

In this work, group 10 transition metal complexes bearing dppe [1,2-bis(diphenylphosphino)ethane] and acylthiourea ligands were evaluated for their cytotoxic and antiparasitic activities. Six new complexes with a general formula [M(Ln)(dppe)]BF4 [where M = NiII, PdII or PtII; Ln = N, N'-dimethyl-N-benzoyl thiourea (L1) or N, N'-dimethyl-N-tiofenyl thiourea (L2) were synthesized and characterized by infrared, NMR (31P{1H}, 1H and 13C{1H}) spectroscopies, elemental analysis and molar conductivity. The structures of the complexes were confirmed by X-ray diffraction technique. The biological activity of the complexes was evaluated on breast cancer cells (MDA-MB-231 and MCF-7) and causative agents of chagas disease and leishmaniasis. The complexes presented higher cytotoxicity for breast cancer cell lines compared to non-tumor cells. Nickel complexes stood out when evaluated against the triple-negative breast cancer line (MDA-MB-231), presenting considerably lower IC50 values (about 10 to 22×), when compared to palladium and platinum complexes, and the cisplatin drug. When evaluated on the triple-negative line (MDA-MB-231), the complexes [Ni(L2)(dppe)]BF4(2), [Pd(L2)(dppe)]BF4(4) and [Pt(L2)(dppe)]BF4(6) were able to induce cell morphological changes, influence on the cell colony formation and the size of the cells. The complexes inhibit cell migration and cause changes to the cell cytoskeleton and nuclear arrangement. In the same cell line, the compounds caused cell arrest in the Sub-G1 phase of the cell cycle. The compounds were also tested against the Trypanosom Cruzi (T. cruzi) and Leishmania sp. parasites, which cause Chagas and leishmaniasis disease, respectively. The compounds showed good anti-parasitic activity, mainly for T. cruzi, with lower IC50 values, when compared to the commercial drug, benznidazole. The compounds interact with CT-DNA, indicating that interaction occurs by the minor groove of the biomolecule.

Hearing handicap and frailty in community-dwelling older adults living. / Handicap auditivo e fragilidade em idosos da comunidade.

PURPOSE: To verify the relationship between hearing handicap and frailty in community-dwelling older adults. METHODS: A cross-sectional study was carried out with 238 older adults (aged ≥ 60 years) in 2018. The Hearing Handicap Inventory for the Elderly - Screening version - HHIE-S was applied to assess the hearing handicap. To assess frailty, the Frailty Phenotype proposed for Fried and co-workers was adopted, objectively evaluating 5 criteria: unintentional weight loss, reported fatigue, reduced grip strength, reduced walking speed and low physical activity. It was investigated whether the hearing handicap were related with frailty using Kruskal-Wallis and Spearman test. RESULTS: Worse perception of the hearing handicap was found in pre-frail and frail individuals, compared to non-frail individuals. In addition, hearing handicap showed a positive and statistically significant correlation with frailty. CONCLUSION: Hearing handicap is related to frailty in community-dwelling older adults.

OBJETIVO: Verificar a relação entre o handicap auditivo e fragilidade em idosos residentes da comunidade. MÉTODO: Estudo transversal realizado com 238 idosos (idade ≥ 60 anos), no ano de 2018. O questionário Hearing Handicap Inventory for the Elderly - Screening version - HHIE-S, foi aplicado para quantificar o handicap auditivo. A fragilidade foi avaliada segundo o Fenótipo de Fragilidade proposto por Fried e colaboradores, utilizando os 5 critérios: perda de peso não intencional, fadiga relatada, redução da força de preensão, redução da velocidade de caminhada e baixa atividade física. A relação entre o handicap auditivo e a fragilidade foi realizada por meio dos Testes Kruskal-Wallis e Spermann. RESULTADOS: Maior percepção do handicap auditivo foi verificado nos indivíduos pré-frágeis e frágeis, comparados aos não frágeis. O handicap auditivo apresentou correlação positiva e estatisticamente significante com maiores níveis de fragilidade. CONCLUSÃO: O handicap auditivo está relacionado a fragilidade em idosos da comunidade.

Potential Protein Blood-based Biomarkers in Different Types of Dementia: A Therapeutic Overview.

Biomarkers capable of identifying and distinguishing types of dementia, such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (LBD), and frontotemporal dementia (FTD), have become increasingly relentless. Studies on possible biomarker proteins in the blood that can help formulate new diagnostic proposals and therapeutic visions of different types of dementia are needed. However, due to several limitations of these biomarkers, especially in discerning dementia, their clinical applications are still undetermined. Thus, updating biomarker blood proteins that can help in the diagnosis and discrimination of these main dementia conditions is essential to enable new pharmacological and clinical management strategies with specificities for each type of dementia. This paper aimed to review the literature concerning protein bloodbased AD and non-AD biomarkers as new pharmacological targets and/or therapeutic strategies. Recent findings related to protein-based AD, PDD, LBD, and FTD biomarkers are focused on in this review. Protein biomarkers are classified according to the pathophysiology of the dementia types. The diagnosis and distinction of dementia through protein biomarkers is still a challenge. The lack of exclusive biomarkers for each type of dementia highlights the need for further studies in this field. Only after this, blood biomarkers may have a valid use in clinical practice as they are promising to help in the diagnosis and in the differentiation of diseases.

Ruthenium(II)-diphosphine complexes containing acylthiourea ligands are effective against lung and breast cancers.

We have synthesized and characterized three new ruthenium(II) diphosphine complexes containing an acylthiourea ligand, with the general formula [Ru(DPEPhos)(O,S)(bipy)]PF6, where DPEPhos = bis(2-(diphenylphosphino)phenyl)ether, bipy = 2,2'-bipyridine, and O,S = N,N-dimethyl-N'-(benzoyl)thiourea (1), N,N-dimethyl-N'-(furoyl)thiourea (2), and N,N-dimethyl-N'-(thiophenyl)thiourea (3), by several physicochemical techniques. We evaluated the ruthenium complexes for their cytotoxicity against two human cancer cell lines, A549 (lung) and MDA-MB-231 (breast), and two corresponding lines of non-cancer cells, MRC-5 (lung) and MCF-10A (breast). All the complexes are cytotoxic against the cancer cell lines; the IC50 values lie in the micromolar range (0.07-0.70 µM). Ruthenium complex 1 is more selective (7 times more active) toward lung cancer cells (A549) than toward non-cancer cells (MRC-5) and is 160 times more cytotoxic than cisplatin against A549 cells. Investigations of the mechanism of action of complex 1 in A549 cells demonstrated that it inhibits colony formation and promotes cell cycle arrest in the G1 phase and apoptotic cell death. DNA binding studies revealed that complexes 1-3 interact with the biomolecule via minor grooves. These complexes also interact with human serum albumin (HSA) and have affinity for site I by hydrophobic forces. Therefore, this new class of ruthenium complexes can act as cytotoxic agents, mainly for lung cancer treatment.

Apolipoprotein E ε4 allele impairs cortical activity in healthy aging and Alzheimer's disease.

AIM: To investigate the influence of apolipoprotein E (APOE) genotype on cortical activity, using the event-related potential P300 in healthy older adults and individuals with Alzheimer's disease (AD). METHODS: A cohort of 37 healthy older adults and 48 with AD participated in this study and completed an auditory oddball task using electroencephalographic equipment with 21 channels (10-20 system). APOE genotyping was obtained by real-time PCR. RESULTS: AD presented increased P300 latency and lower P300 amplitude, compared to healthy older adults. AD APOE ε4 carriers presented increased P300 latency in F3 (420.7 ± 65.8 ms), F4 (412.0 ± 49.0 ms), C4 (413.0 ± 41.1 ms) and P3 (420.4 ± 55.7 ms) compared to non-carriers (F3 = 382.5 ± 56.8 ms, p < 0.01; F4 = 372.2 ± 56.7 ms, p < 0.01; C4 = 374.2 ± 51.7 ms, p < 0.01; P3 = 384.4 ± 44.4 ms, p < 0.01). Healthy older adults APOE ε4 carriers presented lower Fz amplitude (2.6 ± 1.5 µV) compared to non-carriers (4.9 ± 2.9 µV; p = 0.02). Linear regression analysis showed that being a carrier of APOE ε4 allele remained significantly associated with P300 latency even after adjusting for sex, age, and cognitive grouping. APOE ε4 allele increases P300 latency (95% CI 0.11-0.98; p = 0.02). CONCLUSION: APOE ε4 allele negatively impacts cortical activity in both healthy older adults and AD individuals.