ADAM10 isoforms: Optimizing usage of antibodies based on protein regulation, structural features, biological activity and clinical relevance to Alzheimer's disease.

A Disintegrin and Metalloproteinase 10 (ADAM10) is a crucial transmembrane protein involved in diverse cellular processes, including cell adhesion, migration, and proteolysis. ADAM10's ability to cleave over 100 substrates underscores its significance in physiological and pathological contexts, particularly in Alzheimer's disease (AD). This review comprehensively examines ADAM10's multifaceted roles, highlighting its critical function in the non-amyloidogenic processing of the amyloid precursor protein (APP), which mitigates amyloid beta (Aß) production, a critical factor in AD development. We summarize the regulation of ADAM10 at multiple levels: transcriptional, translational, and post-translational, revealing the complexity and responsiveness of its expression to various cellular signals. A standardized nomenclature for ADAM10 isoforms is proposed to improve clarity and consistency in research, facilitating better comparison and replication of findings across studies. We address the challenges in detecting ADAM10 isoforms using antibodies, advocating for standardized detection protocols to resolve discrepancies in results from different biological matrices. By highlighting these issues, this review underscores the potential of ADAM10 as a biomarker for early diagnosis and a therapeutic target in AD. By consolidating current knowledge on ADAM10's regulation and function, we aim to provide insights that will guide future research and therapeutic strategies in the AD context.

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.

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.

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.

A systematic review and meta-analysis on cognitive frailty in community-dwelling older adults: risk and associated factors.

OBJECTIVES: To identify which factors are associated with cognitive frailty (CF), as well as the impact of CF on the incidence of dementia and mortality. METHODS: A systematic review with meta-analysis was carried out using papers that enrolled a total of 75,379 participants and were published up to January 2020. RESULTS: Of the 558 identified records, 28 studies met the inclusion criteria and were included in the review. The meta-analysis of cross-sectional studies showed that CF has a significant association of having an older age and a history of falls. In longitudinal studies, the analysis showed a significant increase in risk of mortality and dementia for those with CF. DISCUSSION: This is the first systematic review and meta-analysis on CF, which addressed a wide variety of factors associated with the theme and which pointed out some as a potential target for prevention or management with different interventions or treatments, showing the clinical importance of its identification in the most vulnerable and susceptible groups.

Phenylalanine and COVID-19: Tracking disease severity markers.

BACKGROUND: Although there are several severity predictors for COVID-19, none are specific. Serum levels of phenylalanine were recently associated with increased inflammation, higher SOFA scores, ICU admission, and mortality rates among non-COVID-19 patients. Here, we investigated the relationship between phenylalanine and inflammatory markers in adults with COVID-19. METHODS: We assessed adults with COVID-19 at hospital admission for clinical and laboratory data. Nuclear magnetic resonance spectroscopy measured serum levels of phenylalanine and other amino acids of its metabolomic pathway. Flow Cytometry measured serum levels of IL-2, IL-4, IL-6, Il-10, TNF-α, and IFN-γ. Linear regression models adjusted for potential confounders assessed the relationship between serum levels of phenylalanine and inflammatory cytokines. RESULTS: Phenylalanine and tyrosine were significantly lower in mild disease as compared to moderate and severe groups. Linear regression models showed that phenylalanine is independently and positively associated with disease severity regardless of the cytokine analyzed and after adjustment for potential confounders. In addition, mild cases showed consistently lower serum phenylalanine levels within the first ten days from disease onset to hospital admission. CONCLUSIONS: Phenylalanine is a marker of disease severity. This association is independent of the time between the onset of symptoms and the magnitude of the inflammatory state.

Elevations in Liver Transaminases in COVID-19: (How) Are They Related?

Liver involvement in COVID-19 is not yet well-understood, but elevations in liver transaminases have been described to occur in 14-53% of the cases and are more frequently seen in severe disease. This cross-sectional study explored the relationship between the elevations in liver transaminases and inflammatory parameters in 209 adults with COVID-19. Demographic and clinical data, serum levels of inflammatory cytokines and liver aminotransferases were analyzed. Three groups were formed according to the liver transaminase abnormalities: (I) Normal transaminases, (II) Borderline transaminases elevation, and (III) Mild to severe transaminases elevation. Altered liver transaminases were directly related to disease severity, showing association with the NEWS2 score at admission and greater need for ICU or death. Moreover, higher levels of IL-2 and CRP were associated with borderline transaminases elevations, whereas higher levels of IL-10 and Neutrophil to Lymphocyte ratio were associated with mild to severe transaminases elevation. These results reinforce the importance of liver transaminases in patients with COVID-19 as a complementary marker for disease severity and also point to them as a parameter reflecting the continuous dynamics between viral infection and the immune response.

[10]-Gingerol-Loaded Nanoemulsion and its Biological Effects on Triple-Negative Breast Cancer Cells.

The apoptotic, cytotoxic, and cytostatic activities for [10]-gingerol in triple-negative breast cancer cells (TNBCs) were already reported. However, despite these important antitumor activities, the compound has the disadvantage to have a hydrophobic characteristic, hindering in vivo administration. To surpass this issue, in this study we have created a [10]-gingerol-loaded nanoemulsion (10GNE) in order to increase the stability and solubility of the compound. The nanoemulsion was characterized and tested for its cytotoxic, cytostatic, and apoptotic effects on a panel of murine and human TNBC cell lines, as well as non-tumor cells, and compared with a [10]-gingerol-free nanoemulsion (NE) and with [10]-gingerol itself. Except for the murine 4T1.13 cell line, the IC50 of the free 10G molecule, after 72 h of incubation, was higher in all cell lines tested, both murine and human, demonstrating therefore the efficacy of the 10GNE regarding cytotoxicity. In murine tumor cells, 60 µM 10GNE was able to arrest cell cycle at sub-G0 phase and induce apoptosis, leading to 48% and 78% of total cell death in 4T1.13 and 4T1Br4 murine tumor cells, respectively. This represents an improvement compared to 10G-free molecule that only induced 74% of total apoptosis at 100 µM in 4T1Br4 cells. Taken together, our results show that nanoformulation preserved the [10]-gingerol cytotoxic and cytostatic properties and improved its apoptotic function on murine TNBC cell lines. These data open new perspectives to a more suitable drug-delivery approach for [10]-gingerol for TNBC treatment that should be further demonstrated using in vivo assays.

ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease.

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of ß-amyloid peptide (Aß) in Alzheimer's disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

ADAM10: Biomarker of mild cognitive impairment but not of cognitive frailty.

Mild cognitive impairment (MCI) associated with physical frailty gave rise to the new concept of cognitive frailty. Previous studies have suggested that MCI may represent a condition that precedes Alzheimer's disease (AD), in view of its higher conversion rate to dementia, when compared with the conversion rate of cognitively healthy older adults. Therefore, and considering that MCI represents a reversible condition, the identification of biomarkers for this condition is imperative to early diagnosis. Accordingly, this study aimed to assess whether the platelet and plasma levels of ADAM10 could be related with the concomitant conditions of MCI and physical frailty, in order to support a new blood-based biomarker for the construct of cognitive frailty. Sixty-one adults aged 60 years or older participated in this study. The results showed that ADAM10 levels are reduced in platelets (p < 0.05) and increased in plasma (p < 0.05) of older adults with MCI compared to healthy controls, regardless of the physical frailty condition. The analysis of the ROC curve of ADAM10 in platelets showed sensitivity and specificity of 72.7 and 73.9%, respectively, to correct differentiate between participants with preserved cognition from those with MCI. For plasma samples, ADAM10 presented 62.5 and 90.0%, sensitivity and specificity respectively, to differentiate the aforementioned conditions. Together with other clinical criteria blood ADAM10 could be a relevant, low-invasive, low-cost and fast processing biomarker tool to help in the early and accurate diagnosis of MCI, however this marker was not able to identify cognitive frailty.

Are body fat and inflammatory markers independently associated with age-related muscle changes?

BACKGROUND & AIMS: A growing number of studies have shown that body fat and inflammation are associated with age-related changes in body muscle composition. However, most of these studies did not control for potential confounders. The aim was to determine whether there is an association between body fat and inflammatory cytokines with muscle mass/strength decline in community-dwelling older adults. METHODS: Anthropometric, physical and functionality variables were collected. Nutritional status was assessed by the MNA form. Dynapenia was assessed with handgrip strength on the dominant hand using a dynamometer. Sarcopenia was determined using adapted criteria from the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Inflammatory cytokines were evaluated in plasma using a multiplex assay. Associations to muscle mass/strength decline were analyzed using a multinominal logistic regression, adjusted for potential confounders. RESULTS: We recruited a convenience sample of 311 adults aged 60 years or older. Most of subjects were sufficiently active females with a median age of 68 years (interquartile range [IQR], 64-74 years), whereas about a half (46.3%) were at risk of malnutrition. The prevalence of dynapenia was 38.3%, whereas sarcopenia was 13.2%. After controlling for potential confounders, we found that relative fat mass index is independently associated with sarcopenia. Loss of strength was independently associated only with female sex, lower physical activity, worse nutrition and IL-10/TNF-α ratio, whereas female sex, an insufficiently active lifestyle and relative fat mass index were the key determinants of sarcopenia. CONCLUSIONS: These findings highlight the importance of physical activity and healthy diet as effective interventions to prevent muscle mass/strength decline, and points to IL-10/TNF-α ratio and body fat as independently associated factors for dynapenia and sarcopenia, respectively.

Lycium barbarum polysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage.

Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The polysaccharide fraction (LBPF) isolated from Lycium Barbarum fruits (goji berry) contains several active ingredients with antioxidant, immune system modulation, and antitumor effects. In addition, the photobiomodulation (PBM) is widely applied in photoaging treatment. This study investigated the effects of LBPF and PBM against the UVR-induced photodamage in the skin of hairless mice. The mice were photoaged for 6 weeks in a chronic and cumulative exposure regimen using a 300-W incandescent lamp that simulates the UVR effects. From the third to the sixth week of photoaging induction, the animals received topical applications of LBPF and PBM, singly or combined, in different orders (first LBPF and then PBM and inversely), three times per week after each session of photoaging. After completion of experiments, the dorsal region skin was collected for the analysis of thickness, collagen content, and metalloproteinases (MMP) levels. A photoprotective potential against the increase of the epithelium thickness and the fragmentation of the collagen fibers was achieved in the skin of mice treated with LBPF or PBM singly, as well as their combination. All treatments maintained the skin collagen composition, except when PBM was applied after the LBPF. However, no treatment protected against the UVR-induced MMP increase. Taken together, we have shown that the LBPF and PBM promote a photoprotective effect in hairless mice skin against epidermal thickening and low collagen density. Both strategies, singly and combined, can be used to reduce the UVR-induced cutaneous photoaging.

A Systematic Review of Altered P300 Event-Related Potential in Apolipoprotein E4 (APOE4) Carriers.

BACKGROUND: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for Alzheimer's disease and seems to be related to cognitive decline and damaged event-related potential P300, which is a sensitive measure to assess cognitive processing. OBJECTIVE: This research aims to critically review the existing scientific evidence regarding the association between APOE4 and P300. METHODS: A systematic review was carried out up to January 2020 on the following databases: Web of Science, Scopus and Medline/PubMed. Articles were considered for inclusion if they are original research that provided information regarding the association between APOE4 and P300, available in English, Spanish, or Portuguese, and available in full text. The methodological quality of the studies selected was evaluated using the quality assessment tool for observational cohort and cross-sectional studies recommended by Cochrane. RESULTS: Out of 993 studies, 14 met the inclusion criteria. The results obtained showed that APOE4 is related to a longer P300 latency. However, the data supplied do not allow us to confirm if this relationship also occurs in amplitude measures. Moreover, it was observed that APOE genotype may influence P300 in different ages, from younger individuals to demented older people. CONCLUSION: Evidence shows that APOE4 negatively influences cortical activities related to cognitive functions, as indicated by P300.

Treino cognitivo em idosos participantes de uma oficina gerontológica: melhorias no tempo de reação / Cognitive training in the elderly from a gerontological group: improvement in reaction time

Frente ao crescente aumento da prevalência de doenças crônicas na população, demência e comprometimento cognitivo tornam-se demandas preocupantes na saúde pública. Estudos sugerem que a prática de atividades cognitivas contribui para preservar e proteger a cognição de idosos, entretanto poucos estudos brasileiros avaliam tais efeitos por meio de testes digitais. Objetivo: avaliar os efeitos do treino cognitivo em idosos participantes de uma oficina gerontológica por meio de um teste digital e um teste tradicional. Métodos: trata-se de um estudo quase experimental, cuja amostra foi composta por 10 participantes (poder amostral = 0,89). O estudo teve duração de 20 semanas, cada com uma hora de treino cognitivo, e realizaram-se avaliações pré-intervenção e pós-intervenção. Foram utilizados um questionário sociodemográfico, o Addenbrooke's Cognitive Examination ­ Revised, e um teste digital de detecção de mudanças. Resultados: nove idosas eram do sexo feminino, a média de idade foi de 71,5 anos (± 8,2) e de escolaridade de 11,3 anos de estudo (±4,8). Não foram encontradas diferenças estatisticamente significativas quando comparadas as avaliações pré-intervenção e pós-intervenção para o ACE-R (t=2,083/p=0,067), nem para o número de acertos no teste digital (t=0,335; p=0,745). Contudo, observou-se uma diferença significativa no tempo de reação dos idosos (t=2,597; p=0,029), cuja média reduziu de 5,9s (±3,35) para 3,7s (±1,18). Conclusão: os resultados sugerem que o teste digital de detecção de mudanças tem potencial para monitoramento das alterações longitudinais advindas de treino cognitivo.(AU)

Due to the increasing number of chronic conditions among the population, dementia and mild cognitive impairment have become worrying demands for the field of public health. Research suggests that the practice of cognitive activities contributes to preserving and protecting cognitive functioning in the elderly, however, few Brazilian studies have evaluated such effects with digital tests. Purpose: evaluate the effects of cognitive training in elderly participants of a gerontological group with both digital and traditional cognitive tests. Methods: this is a quasi-experimental study, whose sample was 10 older adults (sampling power = 0.89). The intervention was given for 20 weeks, with one hour of cognitive training each. Pre- and post-intervention evaluation was conducted. In addition to a sociodemographic questionnaire, Addenbrooke's Cognitive Examination-Revised and a digital task were used to access participants' cognition. Results: nine participants were female; the mean age was 71.5 years (± 8.2); the mean years of education was 11.3 (±4.8). No statistical difference was observed, between pre- and post-evaluations, for ACE-R (t=2.083/p=0.067) or performance in the digital task (t=0.335; p=0.745). However, a significant difference was obtained for older adults' reaction time (t=2.597; p=0.029), whose mean decreased from 5.9s (±3.35) to 3.7s (±1.18). Conclusion: our results suggest that the change detection task has the potential for monitoring longitudinal changes caused by cognitive training.(AU)

[10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models.

PURPOSE: Although doxorubicin is widely used to treat cancer, severe side effects limit its clinical use. Combination of standard chemotherapy with natural products can increase the efficacy and attenuate the side effects of current therapies. Here we studied the anticancer effects of a combined regimen comprising doxorubicin and [10]-gingerol against triple-negative breast cancer, which does not respond to hormonal or targeted therapies. METHODS: Cytotoxicity was evaluated by MTT assay, cell cycle progression and apoptosis were analyzed by flow cytometry and signaling pathways were analyzed by Western blotting in human and murine triple negative breast cancer cell systems. The anticancer/antimetastatic and toxic effects of the combined regimen was evaluated using syngeneic and xenograft orthotopic models. RESULTS: The combination of doxorubicin and [10]-gingerol significantly increased the number of apoptotic cells, compared to each compound alone. In 4T1Br4 cells, the combined regimen was the only condition able to increase the levels of active caspase 3 and γH2AX and to decrease the level of Cdk-6 cyclin. In vivo, doxorubicin (3 mg/Kg, D3) and [10]-gingerol (10 mg/Kg, G10) resulted in a significant reduction in the volume of primary tumors and a decrease in the number of circulating tumor cells (CTCs). Interestingly, only the combined regimen led to decreased tumor burdens to distant organs (i.e., metastasis) and reduced chemotherapy-induced weight loss and hepatotoxicity in tumor-bearing animals. Likewise, in a xenograft model, only the combined regimen was effective in significantly reducing the primary tumor volume and the prevalence of CTCs. CONCLUSIONS: Our data indicate that [10]-gingerol has potential to be used as a neoadjuvant or in combined therapy with doxorubicin, to improve its anticancer activity.

Factors associated with depressive symptoms in older adults in context of social vulnerability.

OBJECTIVE: To identify factors associated with depressive symptoms in the elderly inserted in a context of high social vulnerability. METHODS: A cross-sectional study was carried out with 302 elderly people enrolled in Primary Care. We used a sociodemographic questionnaire, Geriatric Depression Scale, Mini Nutritional Assessment, Shor-form-6D Quality of Life Questionnaire and Medical Outcome Study Scale. For data analysis, a logistic regression was performed considering two groups, with and without depressive symptoms. RESULTS: A good perception of the quality of life (OR: 0.21) and receiving emotional support (OR: 0.98) were presented as protective factors for depression, have risks of malnutrition (OR: 4.87), belong to the female sex OR: 1.88) and living alone (OR: 2.34), indicated a predictor factor for depression. CONCLUSION: Quality of life and social support were identified as protective factors for depressive symptoms while being at risk of malnutrition, living alone, reporting pain and being female are predictors.

Copper transporter 1 affinity as a delivery strategy to improve the cytotoxic profile of rationally designed copper(II) complexes for cancer treatment.

Cisplatin is widely used to treat different types of cancer, but its severe side effects are the major disadvantage of this treatment. Therefore, other metals are currently the subject of research in the rational development of anticancer drugs, such as copper, that has been demonstrated to be promising in this scenario. Here, we evaluated the effects of two novel copper complexes against breast cancer cell lines, and also examined the influence of overexpressing copper transporter 1 (CTR1) on the cytotoxicity of these complexes. Complex (1) [Cu(sdmx-)2(phen)] showed low IC50 values, induced intense cell morphological changes and arrested the cell cycle at the sub-G1 phase in cancer cells. Complex (1) was tested in transfected cells overexpressing the CTR1 receptor in order to compare its steric effects with a less bulky ligand and more labile complex (2) [CuCl2(impy)]. A significant reduction of IC50 value was observed in CTR1 overexpressing cells for complex (2) (32 µM to 20 µM) as compared to (1) (2.78 µM to 3.41 µM), evidencing a possible uptake through copper reduction (Cu+2 â†’ Cu+1) mediated by CTR1. Thus, considering that CTR1 is a mediator of metallodrugs uptake, the development of strategies that use rational drug design is important in order to improve the therapeutic efficacy through greater specificity and consecutive reduction of side effects. Here we show the example for the case of copper(II) complexes.

Polysaccharide-rich hydrogel formulation combined with photobiomodulation repairs UV-induced photodamage in mice skin.

Prolonged skin exposure to ultraviolet radiation (UVR) induces premature aging in both the epidermis and the dermis. Chronic exposure to UVR induces the activation of mitogen-activated protein kinase (MAPK) signaling pathway, activating c-Jun, c-Fos expression, and transcription factor of AP-1 activating protein. AP-1 activation results in the positive induction of matrix metalloproteinase (MMP) synthesis, which degrade skin collagen fibers. Polysaccharides from the fruit of Lycium barbarum (LBP fraction) have a range of activities and have been demonstrate to repair the photodamage. In different approaches, laser application aims to recover the aged skin without destroying the epidermis, promoting a modulation, called photobiomodulation (PBM), which leads to protein synthesis and cell proliferation, favoring tissue repair. Here we developed a topical hydrogel formulation from a polysaccharide-rich fraction of Lycium barbarum fruits (LBP). This formulation was associated with PBM (red laser) to evaluate whether the isolated and combined treatments would reduce the UVR-mediated photodamage in mice skin. Hairless mice were photoaged for 6 weeks and then treated singly or in combination with LBP and PBM. Histological, immunohistochemistry, and immunofluorescence analyses were used to investigate the levels of c-Fos, c-Jun, MMP-1, -2, and -9, collagen I, III, and FGF2. The combined regimen inhibited UVR-induced skin thickening, decreased the expression of c-Fos and c-Jun, as well as MMP-1, -2, and -9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation.

Vitamin D Deficient Older Adults Are More Prone to Have Metabolic Syndrome, but Not to a Greater Number of Metabolic Syndrome Parameters.

This study investigated the relationship between metabolic parameters and low serum 25-hydroxyvitamin D (25(OH)D) levels in older adults (n = 265). They were assessed for anthropometrics and metabolic measurements, including 25(OH)D, insulin, glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and other inflammatory markers. Vitamin D deficiency was defined as a 25(OH)D level below 50 nmol/L. Comparisons between groups were performed using Wilcoxon-Mann-Whitney or Pearson's Chi-squared test. A multivariate adjusted Poisson regression was used to model the number of metabolic parameters as a function of a set of explanatory variables. Subjects with 25(OH)D deficiency were predominantly females and presented higher body weight, body mass index, waist circumference, triglycerides and Tumor Necrosis Factor-α (TNF-α), and higher insulin resistance. Metabolic syndrome was also more prevalent among 25(OH)D-deficient subjects. In those without metabolic syndrome, 25(OH)D deficiency was related only to obesity and higher insulin resistance. Female sex, hypertension, higher waist circumference and higher levels of hemoglobin A1C (%), HDL-C, and TG were significantly associated with an increased number of metabolic syndrome parameters after adjusting for covariates, but 25(OH)D was not. The fact that serum 25(OH)D concentration was inversely associated with metabolic syndrome and insulin resistance not only reaffirms the relevance to consider serum 25(OH)D concentration as an influencing factor for insulin resistance, but also the need to actively screen for hypovitaminosis D in all patients with this condition.