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OBJECTIVES: The number of people with dementia is on the rise in Kenya and across Africa. Although family carers act as the main providers of dementia care in Kenya, there is still a significant knowledge gap regarding why family members care for someone with dementia. This study explores perceived drivers of care for people with dementia in a rural Kenyan context. METHODS: Participants were recruited in Makueni County, Kenya. Primary data were derived from a focus group discussion (FGD) and five individual interviews with family carers of people with dementia. To complement interpretation, triangulation occurred through using data from FGDs with healthcare workers and members of the general public. All audio recordings were transcribed verbatim and inductive thematic analysis performed using NVIVO 12. RESULTS: Using the Positioning Theory, we sought to generate information pertaining to motivation for becoming a family carer. Five themes emerged from the analysis and included: (i) self-fulfillment, (ii) familial obligation, (iii) cultural and religious beliefs, (iv) reciprocity, and (v) societal pressures. These themes described the nature of care given to people with dementia, based on what the participants perceived as compelling and/or motivating factors. CONCLUSIONS: Our findings describe the unique motivators of family carers for people with dementia in Kenya. The ability to find meaning in the caregiving experience could contribute to development of effective support systems, interventions and policies for dementia carers with the aim of improving the overall quality of dementia care in Kenya.
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Cuidadores , Demencia , Grupos Focales , Motivación , Humanos , Kenia , Cuidadores/psicología , Demencia/enfermería , Demencia/psicología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Población Rural , Familia/psicología , Investigación CualitativaRESUMEN
This research assesses the efficacy of two phosphorus (P) adsorbents as alternative fertilizers in promoting lettuce growth. A synthetic Mg/Al-layered double hydroxide (LDH) and an iron-based recycled water treatment residual (Fe-WTR), both enriched with P from dairy wastewater and added at three dosage levels. We hypothesized that the adsorbents' physicochemical nature will overshadow the biological efforts in the plant ecosystem to increase P solubility, impacting plant growth, nutritional composition, and metabolite profiles. Fe-WTR significantly enhanced lettuce biomass compared to LDH. Yet, elemental analysis revealed higher or equal P concentrations in the low-biomass LDH plants relative to other treatments. Phosphorus uptake appears to influence the assimilation of other nutrients that divided into two groups: calcium, magnesium, zinc, and copper with notable correlations to P and nitrogen, iron, aluminum, vanadium and manganese with low correlations to P. Conversely, P retained poor correlation with most metabolites whereas iron showed a higher correlation with numerous metabolites. Analysis of metabolites, encompassing carbohydrates, the Krebs cycle, amino acids, nucleic acids, and stress and regulatory pathways, revealed diminished levels in the LDH treatments. Overall, carbon assimilation (plant growth) was more effectively predicted by soil P availability (adsorbent type and dose) rather than by cellular P concentration, suggesting root signaling was at play, influencing carbohydrate translocation to the roots. Diminished levels of cellular sugars further affect metabolic pathways and iron uptake, thus restricting photosynthesis. The results illustrate the substantial influence of the P source on the plant's metabolic processes and soil biogeochemistry. The synthetic LDH adsorbent with high sorption capacity, tightly binds its substantial P pool, rendering it inaccessible and potentially disrupting rhizosphere biogeochemical interactions. In contrast, the chemical nature of Fe-WTR enabled efficient nutrients acquisition bioactivity. The study highlights Fe-WTR as a promising sustainable alternative to conventional fertilizers, emphasizing its potential scalability and adaptability in agricultural contexts.
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Agricultura , Lactuca , Fósforo , Suelo , Lactuca/crecimiento & desarrollo , Lactuca/metabolismo , Agricultura/métodos , Suelo/química , Fertilizantes , ReciclajeRESUMEN
Advances in science, medicine and engineering rely on breakthroughs in imaging, particularly for obtaining multiscale, three-dimensional information from functional systems such as integrated circuits or mammalian brains. Achieving this goal often requires combining electron- and photon-based approaches. Whereas electron microscopy provides nanometre resolution through serial, destructive imaging of surface layers1, ptychographic X-ray computed tomography2 offers non-destructive imaging and has recently achieved resolutions down to seven nanometres for a small volume3. Here we implement burst ptychography, which overcomes experimental instabilities and enables much higher performance, with 4-nanometre resolution at a 170-times faster acquisition rate, namely, 14,000 resolution elements per second. Another key innovation is tomographic back-propagation reconstruction4, allowing us to image samples up to ten times larger than the conventional depth of field. By combining the two innovations, we successfully imaged a state-of-the-art (seven-nanometre node) commercial integrated circuit, featuring nanostructures made of low- and high-density materials such as silicon and metals, which offer good radiation stability and contrast at the selected X-ray wavelength. These capabilities enabled a detailed study of the chip's design and manufacturing, down to the level of individual transistors. We anticipate that the combination of nanometre resolution and higher X-ray flux at next-generation X-ray sources will have a revolutionary impact in fields ranging from electronics to electrochemistry and neuroscience.
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Background: Dementia stigma has adverse effects on people with dementia and their carers. These effects can lead to poor quality of life among other negative impacts. Objective: The aim of this study is to develop and pilot a novel dementia stigma reduction intervention in rural Kenya, leveraging existing Community Health Workers (CHWs) for its delivery. Methods: The pre-post pilot study was conducted, utilizing a parallel mixed-methods design. Ten CHWs were trained to deliver a contextually developed dementia anti-stigma intervention. These CHWs delivered four workshops to 59 members of the general public in Makueni County, with each workshop lasting between 1.5 to 2 hours. Focus group discussions and pre/post surveys were used as measures. Results: The intervention was well received amongst the participants, particularly in terms of its format and accessibility. We observed the largest effects in reducing negative beliefs related to treatment (η2â=â0.34), living well with dementia (η2â=â0.98), and care (η2â=â0.56) for the general public post intervention. Improvements to attitudes were also observed in the CHWs, but the effect sizes were typically smaller. Conclusions: The intervention was accessible and feasible in rural Kenya, while also showing preliminary benefits to stigma related outcomes. The findings indicate that culturally sensitive interventions can be delivered in a pragmatic and context specific manner, thus filling an important knowledge gap in addressing stigma in low-resource settings. Future research is needed to ascertain the intervention's long-term benefits and whether it tackles important behavioral outcomes and beliefs deeply ingrained within communities.
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Agentes Comunitarios de Salud , Demencia , Estudios de Factibilidad , Estigma Social , Humanos , Kenia , Demencia/psicología , Demencia/terapia , Femenino , Masculino , Proyectos Piloto , Agentes Comunitarios de Salud/educación , Población Rural , Persona de Mediana Edad , Adulto , Anciano , Grupos Focales , Calidad de Vida , Aceptación de la Atención de Salud/psicología , Cuidadores/psicologíaRESUMEN
In addition to its primary oxygen-atom-transfer function, cysteamine dioxygenase (ADO) exhibits a relatively understudied anaerobic disproportionation reaction (ADO-Fe(III)-SR â ADO-Fe(II) + ½ RSSR) with its native substrates. Inspired by ADO disproportionation reactivity, we employ [Fe(tacn)Cl3] (tacn = 1,4,7-triazacyclononane) as a precursor for generating Fe(III)-thiolate model complexes in buffered aqueous media. A series of Fe(III)-thiolate model complexes are generated in situ using aqueous [Fe(tacn)Cl3] and thiol-containing ligands cysteamine, penicillamine, mercaptopropionate, cysteine, cysteine methyl ester, N-acetylcysteine, and N-acetylcysteine methyl ester. We observe trends in UV-Vis and electron paramagnetic resonance (EPR) spectra, disproportionation rate constants, and cathodic peak potentials as a function of thiol ligand. These trends will be useful in rationalizing substrate-dependent Fe(III)-thiolate disproportionation reactions in metalloenzymes.
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Compuestos Férricos , Compuestos de Sulfhidrilo , Cinética , Compuestos de Sulfhidrilo/química , Concentración de Iones de Hidrógeno , Compuestos Férricos/química , Compuestos Férricos/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Dioxigenasas/metabolismo , Dioxigenasas/química , Técnicas ElectroquímicasRESUMEN
Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.
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OBJECTIVE: To standardize international normalized ratio (INR) measurements and improve data integrity by enabling electronic result transmission for warfarin monitoring, two point-of-care (POC) devices were evaluated against an internal plasma INR reference method. METHODS: A multicenter study was pursued (January 24, 2022, through October 19, 2022) to compare concordance of two commercially available POC devices, Coag-Sense PT2 Meter (Coag-Sense) and CoaguChek XS Pro and Plus devices (CoaguChek), against an internal plasma INR method among patients treated with warfarin. Bias and linear regression analysis were assessed for these devices including dosing decision accuracy compared with plasma INR reference. RESULTS: Two hundred ninety-nine patients treated with warfarin across three Mayo Clinic sites agreed to participate. Atrial fibrillation (n=191, 63.9%), venous thromboembolism (n=65; 21.7%), and heart valve prosthesis (n=46; 15.4%) were common anticoagulant indications with a 2.5 INR target for 280 (93.6%) of patients. For the CoaguChek devices, 243 (81.3%) of values fell within 0.2 INR units with plasma INR referent and 285 (95.3%) within 0.4 units (R2=0.93). For the Coag-Sense device, 102 (34.1%) of values fell within 0.2 INR units and 180 (60.2%) within 0.4 INR units of plasma INR values, (R2=0.83; P<.0001). Using the plasma INR as the gold standard, appropriate dosing recommendations would have occurred for 292 (97.7%) of the CoaguChek and 244 (81.6%) of the Coag-Sense results. CONCLUSION: Compared with a plasma referent, INR values obtained from the CoaguChek devices exhibited less systematic bias compared with Coag-Sense measures. This translates to a greater percentage of concordant management decisions between POC and laboratory INR methods.
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Anticoagulantes , Monitoreo de Drogas , Relación Normalizada Internacional , Sistemas de Atención de Punto , Warfarina , Humanos , Relación Normalizada Internacional/instrumentación , Relación Normalizada Internacional/normas , Masculino , Femenino , Sistemas de Atención de Punto/normas , Anticoagulantes/administración & dosificación , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Monitoreo de Drogas/métodos , Monitoreo de Drogas/instrumentación , Persona de Mediana Edad , Anciano , Fibrilación Atrial/tratamiento farmacológico , Tromboembolia Venosa/sangreRESUMEN
Bone is a frequent site for metastatic development in various cancer types, including breast cancer, with a grim prognosis due to the distinct bone environment. Despite considerable advances, our understanding of the underlying processes leading to bone metastasis progression remains elusive. Here, we applied a bioactive three-dimensional (3D) model capable of mimicking the endosteal bone microenvironment. MDA-MB-231 and MCF7 breast cancer cells were cultured on the scaffolds, and their behaviors and the effects of the biomaterial on the cells were examined over time. We demonstrated that close interactions between the cells and the biomaterial affect their proliferation rates and the expression of c-Myc, cyclin D, and KI67, leading to cell cycle arrest. Moreover, invasion assays revealed increased invasiveness within this microenvironment. Our findings suggest a dual role for endosteal mimicking signals, influencing cell fate and potentially acting as a double-edged sword, shuttling between cell cycle arrest and more active, aggressive states.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Huesos/metabolismo , Línea Celular Tumoral , Materiales Biocompatibles/farmacología , Fenotipo , Proliferación Celular , Microambiente Tumoral/genéticaRESUMEN
INTRODUCTION: In Kenya, there is a lack of data on the number of people with dementia. In this article, we aim to estimate the number of community-dwelling older adults (aged 60 years and above) that are potentially living with dementia in rural Kenya. METHODS: Recruitment of older adults occurred through adopting a convenience approach based on the catchment areas served by ten trained community health workers. Screening was conducted using the Brief Community Screening Instrument for Dementia (CSI-D), in which prevalence ratios were reported. Regression analyses were run to understand the association between screening outcome and wellbeing, social isolation, and employment status (adjusted for age, sex, literacy, geography, and social status). RESULTS: Of the 3,546 older adults who were screened for dementia, 652 screened positive (PR = 0.18, 95% CIs: 0.17-0.20). Back estimating screen positives based on established sensitivity and specificity of the tool against a gold standard (clinical diagnosis), yielded a prevalence of 9.4% (0.09, 95% CIs: 0.08-0.11). Screening positive for dementia was associated with poorer quality of life (B = -0.17, p < 0.001) and loneliness (B = 0.28, p < 0.001). CONCLUSION: There are potentially 258,000 older adults living with dementia in Kenya, who likely have poorer outcomes. We need to encourage a timely diagnosis and develop better ways to support people living with dementia in Kenya and other resource-limited settings.
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Demencia , Tamizaje Masivo , Población Rural , Humanos , Kenia/epidemiología , Demencia/epidemiología , Demencia/diagnóstico , Femenino , Masculino , Anciano , Prevalencia , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Tamizaje Masivo/métodos , Anciano de 80 o más Años , Vida IndependienteRESUMEN
The hippocampus plays a critical role in the formation of declarative memories, and hippocampal damage leads to significant impairments in new memory formation. Drawing can serve as a form of multi-modal encoding that improves declarative memory performance relative to other multimodal encoding strategies such as writing. We examined whether, and to what extent, patients with hippocampal damage could benefit from the mnemonic strategy of drawing. Three patients with focal hippocampal damage, and one patient with both hippocampal and cortical lesions, in addition to 22 age-, sex-, and education-matched controls, were shown a list of words one at a time during encoding and instructed to either draw a picture or repeatedly write each word for 40 s. Following a brief filled delay, free recall and recognition memory for words from both encoding trial types were assessed. Controls showed enhanced recall and recognition memory for words drawn versus those that were written, an effect that was even more pronounced in patients with focal hippocampal damage. By contrast, the patient with both hippocampal and cortical lesions showed no drawing-mediated boost in either recall or recognition memory. These findings demonstrate that drawing is an effective encoding strategy, likely accruing from the engagement of extra-hippocampal processes including the integration of cortical-based motor, visual, and semantic processing, enabling more elaborative encoding.
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We introduce the Individual Differences in Language Skills (IDLaS-NL) web platform, which enables users to run studies on individual differences in Dutch language skills via the Internet. IDLaS-NL consists of 35 behavioral tests, previously validated in participants aged between 18 and 30 years. The platform provides an intuitive graphical interface for users to select the tests they wish to include in their research, to divide these tests into different sessions and to determine their order. Moreover, for standardized administration the platform provides an application (an emulated browser) wherein the tests are run. Results can be retrieved by mouse click in the graphical interface and are provided as CSV file output via e-mail. Similarly, the graphical interface enables researchers to modify and delete their study configurations. IDLaS-NL is intended for researchers, clinicians, educators and in general anyone conducting fundamental research into language and general cognitive skills; it is not intended for diagnostic purposes. All platform services are free of charge. Here, we provide a description of its workings as well as instructions for using the platform. The IDLaS-NL platform can be accessed at www.mpi.nl/idlas-nl .
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Individualidad , Internet , Humanos , Adolescente , Adulto Joven , Adulto , Lenguaje , Cognición , Correo ElectrónicoRESUMEN
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic study in which the duodenum is observed laterally, and the bile duct is instrumented. There are several indications and complications in the procedure. OBJECTIVE: To determine the incidence of duodenal perforations, using the Stapfer classification in the Hospital Juárez de Mexico over a period of 5 years, as well as the management implemented in such cases. METHOD: The study was carried out at the Hospital Juárez de Mexico of the Ministry of Health. All patients who underwent ERCP between January 1, 2017, to May 30, 2022 were included. RESULTS: 485 ERCP were performed in the study period. Incidence of 1.6% post-ERCP duodenal perforation. The average age of the subjects 56.37 years. In-hospital stay of post-ERCP perforations averaged 9.37 days. The time of the endoscopic study at the time of the surgical procedure is 10 h on average. CONCLUSIONS: Post-ERCP duodenal perforation is a complication that occurs with a low incidence, it tends to increase the number of days of in-hospital stay and increases morbimortality of patients; therefore, it is important to be always alert.
ANTECEDENTES: La colangiopancreatografía retrógrada endoscópica (CPRE) es un estudio endoscópico en el cual se observa lateralmente el duodeno y se instrumenta la vía biliar. Existen diversas indicaciones y complicaciones en el procedimiento. OBJETIVO: Determinar la incidencia de perforaciones duodenales utilizando la clasificación Stapfer para ubicación anatómica en el Hospital Juárez de México en un periodo de 5 años, así como el manejo implementado en dichos casos. MÉTODO: El estudio se realizó en el Hospital Juárez de México de la Secretaría de Salud. Se incluyeron todos los pacientes sometidos a CPRE entre el 1 de enero de 2017 y el 30 de mayo de 2022. RESULTADOS: Se realizaron 485 CPRE en el periodo de estudio. Hubo una incidencia del 1.6% de perforación duodenal post-CPRE. El promedio de edad de los sujetos fue de 56.37 años. La estancia hospitalaria de los pacientes con perforación post-CPRE fue en promedio de 9.37 días. El tiempo del estudio endoscópico al momento de realizar el procedimiento quirúrgico fue de 10 h en promedio. CONCLUSIONES: La perforación duodenal post-CPRE es una complicación que ocurre con una baja incidencia, suele aumentar los días de estancia intrahospitalaria y aumenta la morbimortalidad de los pacientes, y por ello es importante estar siempre alerta.
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Úlcera Duodenal , Perforación Intestinal , Úlcera Péptica Perforada , Humanos , Persona de Mediana Edad , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , México/epidemiología , Perforación Intestinal/epidemiología , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Estudios Retrospectivos , Duodeno/cirugía , Úlcera Duodenal/complicacionesRESUMEN
BACKGROUND: Disseminated sporotrichosis is a severe opportunistic infection that often affects immunocompromised patients after a cutaneous inoculation. Here we present a rare case of disseminated sporotrichosis discovered as a solitary intramedullary thoracic spinal cord lesion in an immunocompetent patient. CASE DESCRIPTION: A 37-year-old man presented with progressive lower limb weakness and sensory changes over 1 week. A spinal magnetic resonance imaging (MRI) revealed a contrast-enhancing intramedullary lesion centered at T10. The patient was afebrile and reported no history of trauma or cutaneous lesions. The lesion was unresponsive to a trial of corticosteroids. A thoracic laminectomy was performed and a biopsy obtained. A cutaneous lesion on the arm was concurrently discovered, which was also biopsied. Both the skin and spinal cord biopsies showed Sporothrix schenckii by macroscopic and microscopic morphology which were later confirmed by MALDI-TOF mass spectrometry. CONCLUSION: This is a rare case of intramedullary disseminated sporotrichosis affecting the central nervous system of an immunocompetent patient. This unusual presentation should be taken into consideration when such intramedullary lesions are encountered.
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Sporothrix , Esporotricosis , Masculino , Humanos , Adulto , Esporotricosis/diagnóstico , Esporotricosis/tratamiento farmacológico , Esporotricosis/patología , Antifúngicos/uso terapéutico , Piel/patología , BiopsiaRESUMEN
In an effort to further investigate previously observed activity of indolyl sulfonamides towards pancreatic cancer cell lines, a library of 44â compounds has been synthesized. The biological activity of the compounds has been determined using two different screening assay techniques against 7â pancreatic cancer cell lines and 9â non-pancreatic cancer cell lines. In the first assay, the cytotoxicity of the compounds was evaluated using a traditional (48â hour compound exposure) method. An in silico investigation was conducted to determine if the compounds might be inducing cell death by inhibiting the S100A2-p53 protein-protein interaction. In the second assay, the potential role of the compounds as metabolic inhibitors of ATP production was evaluated using a rapid screening (1-2â hour compound exposure) method. IC50 values of the hit compounds were obtained and four compounds displayed sub-micromolar potency against PANC-1 cells. The investigation has provided several compounds that display selective inâ vitro activity toward pancreatic cancer that warrant further development.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Estructura Molecular , Relación Estructura-Actividad , Antineoplásicos/farmacología , Sulfonamidas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Indoles/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Proliferación Celular , Línea Celular TumoralRESUMEN
ZnT1 is a major zinc transporter that regulates cellular zinc homeostasis. We have previously shown that ZnT1 has additional functions that are independent of its activity as a Zn2+ extruder. These include inhibition of the L-type calcium channel (LTCC) through interaction with the auxiliary ß-subunit of the LTCC and activation of the Raf-ERK signaling leading to augmented activity of the T-type calcium channel (TTCC). Our findings indicate that ZnT1 increases TTCC activity by enhancing the trafficking of the channel to the plasma membrane. LTCC and TTCC are co-expressed in many tissues and have different functions in a variety of tissues. In the current work, we investigated the effect of the voltage-gated calcium channel (VGCC) ß-subunit and ZnT1 on the crosstalk between LTCC and TTCC and their functions. Our results indicate that the ß-subunit inhibits the ZnT1-induced augmentation of TTCC function. This inhibition correlates with the VGCC ß-subunit-dependent reduction in ZnT1-induced activation of Ras-ERK signaling. The effect of ZnT1 is specific, as the presence of the ß-subunit did not change the effect of endothelin-1 (ET-1) on TTCC surface expression. These findings document a novel regulatory function of ZnT1 serving as a mediator in the crosstalk between TTCC and LTCC. Overall, we demonstrate that ZnT1 binds and regulates the activity of the ß-subunit of VGCC and Raf-1 kinase and modulates surface expression of the LTCC and TTCC catalytic subunits, consequently modulating the activity of these channels.
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Canales de Calcio Tipo L , Canales de Calcio Tipo T , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo T/metabolismo , Proteínas Proto-Oncogénicas c-raf/metabolismo , Animales , XenopusRESUMEN
BACKGROUND: In Kenya, there is lack of evidence on existing dementia care pathways, with minimal or no presentation for dementia-related symptoms in health care settings. Understanding the services available for people with dementia as well as how communities access the services could offer a practical pattern for policy makers to identify strategies that encourage early detection, care and support for people with dementia and their families. OBJECTIVES: To elucidate initial responses of individuals and their families to dementia and challenges encountered in help seeking through care pathways to inform dementia care-related policies and practice. METHODS: The Strengthening Responses to dementia in Developing Countries (STRiDE) Kenya team adapted case vignettes (brief hypothetical stories meant to elicit responses on how the characters would behave) developed by the entire STRiDE team. A total of 29 stakeholders were then asked to provide feedback on the completed vignettes and summarize a common pathway to dementia care in Kenya while using the proposed case vignettes. FINDINGS: We found four initial responses to dementia suspicion in Kenya where individuals:(i) Perceive symptoms as normal part of ageing, (ii) Consult a spiritual or traditional healer, (iii) Visit a private clinic or primary health care facilities, or (iv) No action taken. These were the first points within the care pathways which determined the care trajectory the person with dementia would follow. CONCLUSIONS: Identification of dementia care pathways could form a basis for improving the way communities perceive dementia etiology and establish standard pathways to care whilst ensuring that some pathways do not further pose an impediment to care and treatment for dementia.
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Demencia , Humanos , Demencia/terapia , Kenia , Vías Clínicas , Formulación de Políticas , Derivación y ConsultaRESUMEN
A participant in key developmental processes, the adhesion glycoprotein CD44 is also expressed in several types of malignancies and can promote metastasis. In addition, the expression of CD44 isoforms in different types of cancer such as prostate and breast cancers may facilitate bone metastases by enhancing tumorigenicity, osteomimicry, cell migration, homing to bone, and anchorage within the bone specialized domains. Moreover, there is evidence that the CD44-ICD fragments in breast cancer cells may promote the cells' osteolytic nature. Yet the mechanisms by which CD44 and its downstream effectors promote the establishment of these cells within the bone are not fully elucidated. In this review, we summarize the current data on the roles played by CD44 in cancer progression and bone metastasis and the possible effects of its interaction with the different components of the bone marrow milieu.
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Neoplasias Óseas , Neoplasias de la Mama , Masculino , Humanos , Neoplasias Óseas/secundario , Línea Celular Tumoral , Neoplasias de la Mama/patología , Huesos/patología , Movimiento Celular , Receptores de Hialuranos , Metástasis de la Neoplasia/patologíaRESUMEN
Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics was seen. The reduction in proteins involved in vital processes for cell life, such as DNA repair, cell wall turnover, and protein turnover, results in the accumulation of ROS, driving the cell to death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.
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Metal-polysaccharides have recently raised significant interest due to their multifunctional bioactivities. The antimicrobial activity of a complex of Cu2O with the sulfated polysaccharide (PS) of the marine red microalga Porphyridium sp. was previously attributed to spikes formed on the complex surface (roughness). This hypothesis was further examined here using other Cu-PS complexes (i.e., monovalent-Cu2O, CuCl and divalent-CuO, CuCl2). The nanostructure parameters of the monovalent complexes, namely, longer spikes (1000 nm) and greater density (2000-5000 spikes/µm2) were found to be related to the superior inhibition of microbial growth and viability and biofilm formation. When Escherichia coli TV1061, used as a bioluminescent test organism, was exposed to the monovalent Cu-PS complexes, enhanced bioluminescence accumulation was observed, probably due to membrane perforation by the spikes on the surface of the complexes and consequent cytoplasmic leakage. In addition, differences were found in the surface chemistry of the monovalent and divalent Cu-PS complexes, with the monovalent Cu-PS complexes exhibiting greater stability (ζ-potential, FTIR spectra, and leaching out), which could be related to spike formation. This study thus supports our hypothesis that the spikes protruding from the monovalent Cu-PS surfaces, as characterized by their aspect ratio, are responsible for the antimicrobial and antibiofilm activities of the complexes.
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Antiinfecciosos , Microalgas , Porphyridium , Microalgas/química , Metales , Antiinfecciosos/farmacología , Polisacáridos/farmacología , Polisacáridos/química , Cobre/farmacología , Cobre/químicaRESUMEN
Staphylococcus aureus is a human pathogen known to be resistant to antibiotics since the mid-20th century and is constantly associated with hospital-acquired infections. S. aureus forms biofilms, which are complex surface-attached communities of bacteria held together by a self-produced polymer matrix consisting of proteins, extracellular DNA, and polysaccharides. Biofilms are resistance structures responsible for increasing bacterial resistance to drugs by 1000 times more than the planktonic lifestyle. Therefore, studies have been conducted to discover novel antibacterial molecules to prevent biofilm formation and/or degrade preformed biofilms. Synthetic antimicrobial peptides (SAMPs) have appeared as promising alternative agents to overcome increasing antibiotic resistance. Here, the antibiofilm activity of eight SAMPs, in combination with the antibiotic ciprofloxacin, was investigated in vitro. Biofilm formation by S. aureus was best inhibited (76%) by the combination of Mo-CBP3-PepIII (6.2 µg mL-1) and ciprofloxacin (0.39 µg mL-1). In contrast, the highest reduction (60%) of the preformed biofilm mass was achieved with RcAlb-PepII (1.56 µg mL-1) and ciprofloxacin (0.78 µg mL-1). Fluorescence microscopy analysis reinforced these results. These active peptides formed pores in the cellular membrane of S. aureus, which may be related to the enhanced ciprofloxacin's antibacterial activity. Our findings indicated that these peptides may act with ciprofloxacin and are powerful co-adjuvant agents for the treatment of S. aureus infections.