Methylene blue@silver nanoprisms conjugates as a strategy against Candida albicans isolated from balanoposthitis using photodynamic inactivation.

Balanoposthitis can affect men in immunocompromised situations, such as HIV infection and diabetes. The main associated microorganism is Candida albicans, which can cause local lesions, such as the development of skin cracks associated with itching. As an alternative to conventional treatment, there is a growing interest in the photodynamic inactivation (PDI). It has been shown that the association of photosensitizers with metallic nanoparticles may improve the effectiveness of PDI via plasmonic effect. We have recently shown that the association of methylene blue (MB), a very known photosensitizer, with silver prismatic nanoplatelets (AgNPrs) improved PDI of a resistant strain of Staphylococcus aureus. To further investigate the experimental conditions involved in PDI improvement, in the present study, we studied the effect of MB concentration associated with AgNPrs exploring spectral analysis, zeta potential measurements, and biological assays, testing the conjugated system against C. albicans isolated from a resistant strain of balanoposthitis. The AgNPrs were synthesized through silver anisotropic seed growth induced by the anionic stabilizing agent poly(sodium 4-styrenesulfonate) and showed a plasmon band fully overlapping the MB absorption band. MB and AgNPrs were conjugated through electrostatic association and three different MB concentrations were tested in the nanosystems. Inactivation using red LED light (660 nm) showed a dose dependency in respect to the MB concentration in the conjugates. Using the highest MB concentration (100 µmol⋅L-1) with AgNPr, it was possible to completely inactivate the microorganisms upon a 2 min irradiation exposure. Analyzing optical changes in the conjugates we suggest that these results indicate that AgNPrs are enhancers of MB photodynamic action probably by a combined mechanism of plasmonic effect and reduction of MB dimerization. Therefore, MBAgNPrs can be considered a suitable choice to be applied in PDI of resistant microorganisms.

UV Light as an Efficient Tool for Reducing Surface Defects of ZnSe-MSA Quantum Dots.

Defects in ZnSe quantum dots are responsible for increasing the trap states, which can lead to the drastic reduction of their fluorescence output, being one of the major drawbacks of these materials. As surface atoms become more relevant in these nanoscale structures, energy traps due to surface vacancies, play a very definite role in the final emission quantum yield. In the present study, we report the use of photoactivation procedures to decrease surface defects of ZnSe QDs stabilized with mercaptosuccinic acid (MSA), in order to improve the radiative pathways. We applied the colloidal precipitation procedure in a hydrophilic medium and evaluated the role of Zn/Se molar ratios as well as the Zn2+ precursors (nitrate and chloride salts) on their optical properties. Best results (i.e. increment of 400% of the final fluorescence intensity) were obtained for nitrate precursor and a Zn/Se = 1.2 ratio. Thus, we suggest that the chloride ions may compete more efficiently than nitrate ions with MSA molecules decreasing the passivation capability of this molecule. The improvement in ZnSe QDs fluorescence can potentialize their use for biomedical applications.

A fluorescent glyconanoprobe based on quantum dots and thiolated glucose: Applications in monolayers and spheroids of cancer cells.

The differential energy metabolism of cancer cells has stimulated the development of tools that can be applied to better understand the complex biological interaction involved in the uptake of glucose analogs at the cellular level in this disease. Herein, we explored the outstanding optical properties of quantum dots (QDs) to develop a new fluorescent glyconanoprobe using the 1-thio-ß-d-glucose (Glc). Then, monolayers and spheroids of HeLa cells were applied to probe the biological interaction with the conjugate through fluorescence techniques. Spheroids have been gaining prominence for better mimicking the tumor microenvironment. The Glc-QDs conjugate was prepared by a facile and direct procedure based on the affinity of the Glc thiol group by the QD semiconductor surface. The conjugation was evaluated and confirmed by Zeta potential (ζ) measurements, FTIR spectroscopy, and fluorescence correlation spectroscopy (FCS). Moreover, a biological assay using Candida albicans yeasts coated with concanavalin A, by exploring the lectin-carbohydrate affinity, was also developed to further confirm the conjugation, which corroborated the previous analyses. The hanging drop method was used to prepare the spheroids. The fluorescence microscopy analyses indicated an intracellular labeling by the glyconanoprobe, in both cell culture models. Flow cytometry assays revealed effective uptake of the conjugate (above ca. 76%), even by cells cultivated as spheroids, applying short incubation time. Therefore, a new fluorescent glyconanoprobe was developed, which showed potential to be applied for investigating mechanisms involved in the uptake of glucose analogs, both by simpler and complex cancer biological models, as monolayers and spheroids.

Strengthening collaborations at the Biology-Physics interface: trends in antimicrobial photodynamic therapy.

The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and effective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT field involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an effective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat different infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers.

A fluorescent quantum dot conjugate to probe the interaction of Enterolobium contortisiliquum trypsin inhibitor with cancer cells.

Serine proteases play crucial biological roles and have their activity controlled by inhibitors, such as the EcTI, a serine protease inhibitor purified from Enterolobium contortisiliquum seeds, which has anticancer activity. This study aimed to conjugate EcTI with quantum dots (QDs), fluorophores with outstanding optical properties, and investigate the interaction of QDs-EcTI nanoprobe with cancer cells. The conjugation was evaluated by fluorescence correlation spectroscopy (FCS) and fluorescence microplate assay (FMA). EcTI inhibitory activity after interaction with QDs was also analyzed. From FCS, the conjugate presented a hydrodynamic diameter about 4× greater than bare QDs, suggesting a successful conjugation. This was supported by FMA, which showed a relative fluorescence intensity of ca. 3815% for the nanosystem, concerning bare QDs or EcTI alone. The EcTI inhibitory activity remained intact after its interaction with QDs. From flow cytometry analyses, approximately 62% of MDA-MB-231 and 90% of HeLa cells were labeled with the QD-EcTI conjugate, suggesting that their membranes have different protease levels to which EcTI exhibits an affinity. Concluding, the QD-EcTI represents a valuable nanotool to study the interaction of this inhibitor with cancer cells using fluorescence-based techniques with the potential to unravel the intricate dynamics of interplays between proteases and inhibitors in cancer biology.

New Insights in Phenothiazinium-Mediated Photodynamic Inactivation of Candida Auris.

In recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) combined with a red LED against C. auris. To evaluate the photoinactivation of yeasts, we quantified colony-forming units and monitored ROS production. To gain some insights into the differences between MB and DMMB, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm). After, we verified the effectiveness of DMMB against biofilms by measuring metabolic activity and biomass, and the structures were analyzed through scanning electron microscopy and optical coherence tomography. We also evaluated the cytotoxicity in mammalian cells. DMMB-PDI successfully eradicated C. auris yeasts at 3 µM regardless of the light dose. In contrast, MB (100 µM) killed cells only when exposed to the highest dose of light. DMMB-PDI promoted higher ROS, LPO and ΔΨm levels than those of MB. Furthermore, DMMB-PDI was able to inhibit biofilm formation and destroy mature biofilms, with no observed toxicity in fibroblasts. We conclude that DMMB-PDI holds great potential to combat the global threat posed by C. auris.

Emerging biomedical tools for biomarkers detection and diagnostics in schistosomiasis.

Schistosomiasis is a neglected disease that strikes many people from tropical and subtropical countries where there are not satisfactory sanitation and wide access to clean water. Schistosoma spp., the causative agents of schistosomiasis, exhibit a quite complex life cycle that involves two hosts (humans and snails, respectively, the definitive and the intermediate), and five evolutive forms: cercariae (human infective form), schistosomula, adult worms, eggs, and miracidia. The techniques to diagnose schistosomiasis still have various limitations, mainly regarding low-intensity infections. Although various mechanisms associated with schistosomiasis have already been evidenced, there is still a need to fulfill the comprehension of this disease, especially to prospect for novel biomarkers to improve its diagnosis. Developing methods with more sensitivity and portability to detect the infection is valuable to reach schistosomiasis control. In this context, this review has gathered information not only on schistosomiasis biomarkers but also on emerging optical and electrochemical tools proposed in selected studies from about the last ten years. Aspects of the assays regarding the sensibility, specificity, and time needed for detecting diverse biomarkers are described. We hope this review can guide future developments in the field of schistosomiasis, contributing to improving its diagnosis and eradication.

A Novel Strategy Based on Zn(II) Porphyrins and Silver Nanoparticles to Photoinactivate Candida albicans.

Background: Photodynamic inactivation (PDI) is an attractive alternative to treat Candida albicans infections, especially considering the spread of resistant strains. The combination of the photophysical advantages of Zn(II) porphyrins (ZnPs) and the plasmonic effect of silver nanoparticles (AgNPs) has the potential to further improve PDI. Here, we propose the novel association of polyvinylpyrrolidone (PVP) coated AgNPs with the cationic ZnPs Zn(II) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin or Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin to photoinactivate C. albicans. Methods: AgNPs stabilized with PVP were chosen to allow for (i) overlap between the NP extinction and absorption spectra of ZnPs and (ii) favor AgNPs-ZnPs interaction; prerequisites for exploring the plasmonic effect. Optical and zeta potential (ζ) characterizations were performed, and reactive oxygen species (ROS) generation was also evaluated. Yeasts were incubated with individual ZnPs or their respective AgNPs-ZnPs systems, at various ZnP concentrations and two proportions of AgNPs, then irradiated with a blue LED. Interactions between yeasts and the systems (ZnP alone or AgNPs-ZnPs) were evaluated by fluorescence microscopy. Results: Subtle spectroscopic changes were observed for ZnPs after association with AgNPs, and the ζ analyses confirmed AgNPs-ZnPs interaction. PDI using ZnP-hexyl (0.8 µM) and ZnP-ethyl (5.0 µM) promoted a 3 and 2 log10 reduction of yeasts, respectively. On the other hand, AgNPs-ZnP-hexyl (0.2 µM) and AgNPs-ZnP-ethyl (0.6 µM) systems led to complete fungal eradication under the same PDI parameters and lower porphyrin concentrations. Increased ROS levels and enhanced interaction of yeasts with AgNPs-ZnPs were observed, when compared with ZnPs alone. Conclusion: We applied a facile synthesis of AgNPs which boosted ZnP efficiency. We hypothesize that the plasmonic effect combined with the greater interaction between cells and AgNPs-ZnPs systems resulted in an efficient and improved fungal inactivation. This study provides insight into the application of AgNPs in PDI and helps diversify our antifungal arsenal, encouraging further developments toward inactivation of resistant Candida spp.

Optics in South America: introduction.

South American optics research has seen remarkable growth over the past 50 years, with significant contributions in areas such as quantum optics, holography, spectroscopy, nonlinear optics, statistical optics, nanophotonics and integrated photonics. The research has driven economic development in sectors like telecom, biophotonics, biometrics, and agri-sensing. This joint feature issue between JOSA A and JOSA B exhibits cutting-edge optics research from the region, fostering a sense of community and promoting collaboration among researchers.

Fluorescent nanoprobes based on quantum dots conjugated to Cramoll to assess surface carbohydrates of Aeromonas spp.

The association of quantum dots (QDs) to carbohydrate-binding proteins - lectins - has revealed novel biotechnological strategies for glycobiology studies. Herein, carboxyl-coated QDs were conjugated by adsorption to Cramoll, a glucose/mannose lectin obtained from Cratylia mollis seeds. Then, the conjugates were optically characterized and used to evaluate the surface carbohydrate profiles of four Aeromonas species isolated from the tambaqui fish (Colossoma macropomum). All the Aeromonas cells were labeled by the conjugate. Inhibition assays with methyl-α-D-mannopyranoside and mannan were performed to confirm the labeling specificity. Cramoll-QDs conjugates presented high brightness and showed similar absorption and emission profiles compared to bare QDs. According to the labeling pattern of Aeromonas spp. by the conjugate, results suggested that A. jandaei and A. dhakensis strains may harbor a higher content of more complex glucose/mannose surface glycans, with more available sites for Cramoll-QDs interaction, than A. hydrophila and A. caviae. Noteworthy, the Cramoll-QDs conjugates demonstrated to be potential tools for bacterial characterization based on superficial carbohydrate detection.

Influence of metformin on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS). METHODS: A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies. RESULTS: Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment. CONCLUSION: We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761).

Sensitive Zika biomarker detection assisted by quantum dot-modified electrochemical immunosensing platform.

We report the development of a new nanostructured electrochemical immunosensing platform for the detection of the Zika virus envelope protein (EP-ZIKV). For this, quantum dots (QDs) were explored in combination with screen-printed carbon electrodes (SPCEs) functionalized with a conductor polymeric film, formed from 2-(1H-pyrrol-1-yl)ethanamine (Pyam), and anti-EP DIII ZIKV antibodies. Carboxylated CdTe QDs were synthesized, characterized by optical and structural techniques, and covalently immobilized onto the SPCE/PPyam surface. Then, anti-EP ZIKV antibodies were also covalently conjugated to QDs. All stages of platform assembly were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The detection of EP-ZIKV was performed by differential pulse voltammetry (DPV). Results indicated that QDs were efficiently immobilized, and did not show oxidation, under the conditions evaluated, for at least 7 months. Anti-EP ZIKV antibodies were effectively immobilized on the PPyam/QDs surface, even after 2 months of electrode storage. The platform enabled the detection of EP-ZIKV with high sensitivity using minimal sample volumes (LOD = 0.1 ng mL-1 and LOQ = 0.4 ng mL-1). The platform was also able to detect EP-ZIKV in spiked serum samples. Moreover, the platform showed specificity, not detecting the EP-DENV 3 nor a mixture of four DENV serotypes antigens. Thus, the proposed combination favored the development of a sensitive immunosensing platform, promising for the detection of Zika in the viremic phase, which also holds potential for transposition to other arboviruses.

Photoinactivation of Yeast and Biofilm Communities of Candida albicans Mediated by ZnTnHex-2-PyP4+ Porphyrin.

Candida albicans is the main cause of superficial candidiasis. While the antifungals available are defied by biofilm formation and resistance emergence, antimicrobial photodynamic inactivation (aPDI) arises as an alternative antifungal therapy. The tetracationic metalloporphyrin Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (ZnTnHex-2-PyP4+) has high photoefficiency and improved cellular interactions. We investigated the ZnTnHex-2-PyP4+ as a photosensitizer (PS) to photoinactivate yeasts and biofilms of C. albicans strains (ATCC 10231 and ATCC 90028) using a blue light-emitting diode. The photoinactivation of yeasts was evaluated by quantifying the colony forming units. The aPDI of ATCC 90028 biofilms was assessed by the MTT assay, propidium iodide (PI) labeling, and scanning electron microscopy. Mammalian cytotoxicity was investigated in Vero cells using MTT assay. The aPDI (4.3 J/cm2) promoted eradication of yeasts at 0.8 and 1.5 µM of PS for ATCC 10231 and ATCC 90028, respectively. At 0.8 µM and same light dose, aPDI-treated biofilms showed intense PI labeling, about 89% decrease in the cell viability, and structural alterations with reduced hyphae. No considerable toxicity was observed in mammalian cells. Our results introduce the ZnTnHex-2-PyP4+ as a promising PS to photoinactivate both yeasts and biofilms of C. albicans, stimulating studies with other Candida species and resistant isolates.

Aeromonas and Human Health Disorders: Clinical Approaches.

The genus Aeromonas comprises more than 30 Gram-negative bacterial species and naturally inhabitants from aquatic environments. These microorganisms, commonly regarded as pathogens of fish and several other animals, have been gaining prominence on medical trial due to its ability to colonize and infect human beings. Besides water, Aeromonas are widely spreaded on most varied sources like soil, vegetables, and food; Although its opportunistic nature, they are able to cause infections on immunocompromised or immunocompetent patients. Aeromonas species regarded as potential human pathogens are usually A. hydrophila, A. caviae, and A. veronii biovar sobria. The main clinical manifestations are gastrointestinal tract disorders, wound, and soft tissue infections, as well as septicemia. Regarding to antibiotic responses, the bacteria present a diversified susceptibility profile and show inherence resistance to ampicillin. Aeromonas, as an ascending genus in microbiology, has been carefully studied aiming comprehension and development of methods for detection and medical intervention of infectious processes, not fully elucidated in medicine. This review focuses on current clinical knowledge related to human health disorders caused by Aeromonas to contribute on development of efficient approaches able to recognize and impair the pathological processes.

Advances in the study of spheroids as versatile models to evaluate biological interactions of inorganic nanoparticles.

Spheroids are in vitro three-dimensional multicellular microstructures able to mimic the biological microenvironment, including the complexity of tumor architecture. Therefore, results closer to those expected for in vivo organisms can be reached using spheroids compared to the cell culture monolayer model. Inorganic nanoparticles (NPs) have also been playing relevant roles in the comprehension of biological processes. Moreover, they have been probed as novel diagnostic and therapeutical nanosystems. In this context, in this review, we present applications, published in the last five years, which show that spheroids can be versatile models to study and evaluate biological interactions involving inorganic NPs. Applications of spheroids associated with (i) basic studies to assess the penetration profile of nanostructures, (ii) the evaluation of NP toxicity, and (iii) NP-based therapeutical approaches are described. Fundamentals of spheroids and their formation methods are also included. We hope that this review can be a reference and guide future investigations related to this interesting three-dimensional biological model, favoring advances to Nanobiotechnology.

Does Oncocalyxone A (oncoA) have intrinsic fluorescence?

BACKGROUND: Oncocalyxone A (oncoA) is a quinone extracted from the Cordia oncocalyx plant. This compound has pharmacological properties, such as anti-inflammatory, analgesic, and cytotoxic activities, among others. OncoA presents a similar chemical structure to doxorubicin, a drug used in cancer treatment, which possesses an intrinsic fluorescence explored in various studies, including those using doxorubicin-loaded nanoparticles. Thus, due to the chemical structural similarity, the question arose whether oncoA could also show autofluorescence. Therefore, this study proposed to characterize the absorption and emission spectral profiles of oncoA and analyze if this compound could be used as a fluorescent probe. METHODS: For this, fucoidan-coated polyisobutylcyanoacrylate (PIBCA) nanoparticles containing oncoA were prepared, and an uptake study was performed using a human metastatic breast cancer cell line (MDA-MB-231 cells). RESULTS: OncoA presented a maximum emission wavelength in the blue region, near 430 nm, at 350 nm excitation, compatible with standard microscope optics. Fluorescence microscopy analyses showed that oncoA-loaded PIBCA nanoparticles were internalized by MDA-MB-231 cells under incubation times as shorter as 15 min. CONCLUSION: According to these findings, oncoA-encapsulated nanoparticles are promising fluorescent probes and could be useful for cellular uptake studies.

Myracrodruon urundeuva leaf lectin damages exochorionic cells and binds to the serosal cuticle of Aedes aegypti eggs.

In recent years, lectins have been identified as alternative agents against Aedes aegypti during the aquatic phases of its life cycle. For example, chitin-binding lectin from Myracrodruon urundeuva leaf (MuLL) can function as a larvicide. In this study, we investigated whether MuLL can also act as an ovicide against this insect. Aedes aegypti eggs were incubated with MuLL for 72 h to determine the concentration at which the hatching rate reduces by 50% (EC50). The effects of MuLL on the egg surface structure were evaluated using scanning electron microscopy (SEM), and the possible interaction of MuLL with the internal structures of eggs and embryos was investigated using MuLL-fluorescein isothiocyanate (FITC) conjugate. MuLL acted as an ovicidal agent with an EC50 of 0.88 mg/mL. The SEM analysis revealed that eggs treated with MuLL for 24 and 48 h no longer had tubercles and did not show a well-defined exochorionic network. In addition, deformation and degeneration of the surface were observed after 72 h. Fluorescence microscopy showed that MuLL penetrated the eggs 48 h after incubation and was detected in the upper portion of the embryo's gut. After 72 h, MuLL was observed in the serosal cuticle and digestive tract. In conclusion, MuLL can function as an ovicidal agent against A. aegypti through damage to the surface and internal structures of the eggs.

New Insights into Hemolytic Anemias: Ultrastructural and Nanomechanical Investigation of Red Blood Cells Showed Early Morphological Changes.

Several diseases are characterized by changes in the mechanical properties of erythrocytes. Hemolytic anemias are an example of these diseases. Among the hemolytic anemias, Sickle Cell Disease and Thalassemia are the most common, characterized by alterations in the structure of their hemoglobin. Sickle cell disease has a pathological origin in synthesizing abnormal hemoglobin, HbS. In contrast, thalassemia results in extinction or decreased synthesis of α and ß hemoglobin chains. This work presents a detailed study of biophysical and ultrastructural early erythrocytes membrane alterations at the nanoscale using Atomic Force Microscopy (AFM). Cells from individuals with sickle cell anemia and thalassemia mutations were studied. The analysis methodology in the AFM was given by blood smear and exposure of the inner membrane for ghost analysis. A robust statistic was used with 65,536 force curves for each map, ten cells of each type, with three individuals for each sample group. The results showed significant differences in cell rigidity, adhesion, volume, and roughness at early morphological alterations, bringing new perspectives for understanding pathogenesis. The sickle cell trait (HbAS) results stand out. Significant alterations were observed in the membrane properties, bringing new perspectives for the knowledge of this mutation. This work presents ultrastructural and biomechanical signatures of sickle cell anemia and thalassemia genotypes, which may help determine a more accurate biophysical description and clinical prognosis for these diseases.

Mannose-binding lectin conjugated to quantum dots as fluorescent nanotools for carbohydrate tracing.

Quantum dots (QDs) have stood out as nanotools for glycobiology due to their photostability and ability to be combined with lectins. Mannose-binding lectin (MBL) is involved in the innate immune system and plays important roles in the activation of the complement cascade, opsonization, and elimination of apoptotic and microbial cells. Herein, adsorption and covalent coupling strategies were evaluated to conjugate QDs to a recombinant human MBL (rhMBL). The most efficient nanoprobe was selected by evaluating the conjugate ability to labelCandida albicansyeasts by flow cytometry. The QDs-rhMBL conjugate obtained by adsorption at pH 6.0 was the most efficient, labelingca.100% of cells with the highest median fluorescence intensity. The conjugation was also supported by Fourier transform infrared spectroscopy, zeta potential, and size analyses.C. albicanslabeling was calcium-dependent; 12% and <1% of cells were labeled in buffers without calcium and containing EDTA, respectively. The conjugate promoted specific labeling (based on cluster effect) since, after inhibition with mannan, there was a reduction of 80% in cell labeling, which did not occur with methyl-α-D-mannopyranoside monosaccharide. Conjugates maintained colloidal stability, bright fluorescence, and biological activity for at least 8 months. Therefore, QDs-rhMBL conjugates are promising nanotools to elucidate the roles of MBL in biological processes.

Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Alzheimer's disease (AD) comprises 60-70% of diagnosed dementia cases, and is characterized by the deposition of ß-amyloid peptide and the formation of neurofibrillary tangles of tau protein. Resveratrol is a neuroprotective agent acting in the prevention of redox impairment in addition to exerting anti-apoptotic actions on brain cells. An ability to reduce neuronal damage in patients with AD has been suggested by preclinical studies. OBJECTIVES: The aim of this systematic review was to investigate the evidence in the published literature from studies that evaluated the effects of supplementation with resveratrol, alone or in a solution with glucose and malate (RGM), on the functional and cognitive performance of patients with AD, as assessed by validated instruments. METHODS: A systematic literature search was performed in MEDLINE, CENTRAL, Embase, CINAHL, Web of Science, and Scopus databases including articles published up to August 2021. Randomized, placebo-controlled, clinical trials that reported cognitive and functional performance, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Cooperative Study of Alzheimer's Disease-Activities of Daily Living (ADCS-ADL), or the Mini Mental State Examination (MMSE), in AD patients treated with resveratrol, alone or as RGM, were included. RESULTS: After 1855 studies were identified, 24 RCTs underwent full-text review, with 20 studies excluded because they did not meet the inclusion criteria. Thus, four RCTs were included in the qualitative analyses. The findings demonstrate that there are still few studies in humans, but they showed that this polyphenol acts in the delay of cognitive impairment in patients with AD, when administered alone or in combination with glucose and malate. CONCLUSIONS: Supplementation with resveratrol seems to influence the progressive cognitive and functional decline in AD patients, when compared with a placebo group. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021229234.