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Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r² adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95% CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Discussion: Findings regarding humoral and cellular response are consistent with previous reports [ABSTRACT FROM AUTHOR]

Purpose: Studies have recently shown a correlation between the elemental components of coal dusts, including potassium aluminosilicates, and the lung response as a potential driver for lung diseases associated with inhalation of coal dust. Here we aimed to systematically review the evidence for the association between exposure to potassium bearing dusts and lung outcomes in human studies as well as adverse cellular response in animal/cell culture studies. Methods: A systematic search of the National Library of Medicine (PubMed), Embase and Web of Science was conducted in May 2024. Studies regarding exposure to potassium bearing dusts and aluminosilicates and respiratory consequence were included in the search. Articles were screened, with a secondary assessment for relevance and extraction of key information using a systematic review process. Results: We identified 64 studies, of which 35 were human studies, 22 involved animal experiments and 12 were in vitro studies with 5 papers having both in vivo and in vitro studies. Our review found some evidence that a range of potassium rich dusts increased incidence of respiratory symptoms and lung diseases, although the effect on radiological changes in the lung and pulmonary function loss was not consistent. The in vivo animal and in vitro studies consistently demonstrated an inflammatory response and cytotoxic effect after exposure to these dusts. Conclusion: Given complexity in the dust compositions and lack of direct evidence attributing these specific responses to potassium, we are not able to conclude the effect of potassium minerals in coal on development of respiratory diseases, warranting further research. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis (GPS) can cause severe systemic inflammation in pigs, resulting in huge economic losses to the pig industry. At present, no effective method is available for the prevention and control of GPS infection. Molecular breeding for disease resistance is imminent, but disease-resistance genes have not been identified. To study the mechanism of systemic acute inflammation caused by GPS, we established three in vitro infection models (3D4/21 cells, PK15 cells, and PAVEC cells) according to its infection path. There was no significant difference in apoptosis among the three kinds of cells after 12 h of continuous GPS stimulation, while inflammatory factors were significantly upregulated. Subsequent transcriptome analysis revealed 1969, 1207, and 3564 differentially expressed genes (DEGs) in 3D4/21 cells, PK15 cells, and PAVEC cells, respectively, after GPS infection. Many of the DEGs were predicted to be associated with inflammatory responses (C3, CD44, etc.); cell proliferation, growth and apoptosis; gene expression; and protein phosphorylation. Key signaling pathways, including S100 family signaling, bacteria and virus recognition, and pathogen-induced cytokine storm signaling, were enriched based on Ingenuity Pathway Analysis (IPA). Furthermore, a total of three putative transmembrane receptors and two putative G-protein-coupled receptors, namely F3, ICAM1, PLAUR, ACKR3, and GPRC5A, were identified by IPA among the three types of cells. ACKR3 and GPRC5A play pivotal roles in bacterial adhesion, invasion, host immune response and inflammatory response through the S100 family signaling pathway. Our findings provide new insights into the pathological mechanisms underlying systemic inflammation caused by GPS infection in pigs, and they lay a foundation for further research on disease-resistance breeding to GPS. [ABSTRACT FROM AUTHOR]

The improvement of the capability of poly(N-isopropylacrylamide) (PNIPAAm) hydrogel coating in cell adhesion and detachment is critical to efficiently prepare cell sheets applied in cellular therapies and tissue engineering. To enhance cell response on the surface, the amine group-modified PNIPAAm (PNIPAAm-APTES) nanohydrogels were synthesized and deposited spontaneously on tannic acid (TA)-modified polyethylene (PE) plates. Subsequently, TA was introduced onto PNIPAAm-APTES nanohydrogels to fabricate coatings composed of TA-modified PNIPAAm-APTES (PNIPAAm-APTES-TA). Characterization techniques, including TEM, SEM, XPS, and UV-Vis spectroscopy, confirmed the effective deposition of hydrogels of PNIPAAm as well as the morphologies, content of chemical bonding-TA, and stability of various coatings. Importantly, the porous hydrogel coatings exhibited superhydrophilicity at 20 °C and thermo-responsive behavior. The fluorescence measurement demonstrated that the coating's stability effectively regulated protein behavior, influencing cell response. Notably, cell response tests revealed that even without precise control over the chain length/thickness of PNIPAAm during synthesis, the coatings enhanced cell adhesion and detachment, facilitating efficient cell culture. This work represented a novel and facile approach to preparing bioactive PNIPAAm for cell culture. [ABSTRACT FROM AUTHOR]

Zirconia-based dental implants are in direct contact with living tissues and any improvements in their bioactivity and adhesion to the tissues are highly welcome. In this study, different ratios of barium titanate (BT) were added to 3 mol% yttria-stabilized zirconia (3YSZ) through conventional sintering. The laser-texturing technique was also conducted to improve the biological performance of 3YSZ ceramics. The composition and the surface of the prepared composites were characterized by X-ray diffraction and scanning electron microscopy (SEM), respectively. The roughness and surface wettability of the composites were also measured. Furthermore, MC3T3-E1 pre-osteoblast cells were used for the in vitro experiments. Cell viability was evaluated using a commercial resazurin-based method. Morphology and cellular adhesion were observed using SEM. Based on the results, the laser texturing and the barium titanate content influenced the surface characteristics of the prepared composites. The laser-textured 3YSZ/7 mol% BT composites showed a lower water contact angle compared to the other samples, which indicated superior surface hydrophilicity. The cell viability and cell adhesion of 3YSZ/BT composites increased with the rise in the barium titanate content and laser power. An elongated cell morphology and apatite nucleation were also observed by the BT content. Overall, the laser-treated 3YSZ/5 and 7 mol% BT composites may be promising candidates in hard tissue repair due to their good cell response. [ABSTRACT FROM AUTHOR]

IntroductionThere are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2.MethodsIgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.ResultsMultivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p

The advancement of metal additive manufacturing has recently enabled the integration of porous lattice regions into orthopaedic devices. Despite the increased utilisation of various metamaterials there remains limited understanding of how to optimise laser process specifically for these geometries. Selective laser melting (SLM) of representative single struts is focused on this study from the perspective of surface properties, mechanical performance, and in-vitro biological response. Specifically, the influence of laser power (100 – 200 W) and speed (2250 – 900 mm/s) and struts angle (20–90°) for a 250μ m strut diameter was explored. Struts built below 45° to the substrate using optimal laser parameters (150 W and 1125 mm/s) were found to exhibit a surface topography that facilitated the highest level of cell adhesion (84.3 cells/mm2) after 24 hrs (p ≤ 0.001). To support this finding, a novel image analysis method was developed to characterise the average roughness across the complete strut profile. An opposite trend was observed for mechanical strength with struts built at above 45° without failure. These findings were brought together in a parameter design map was to guide stakeholders in producing customised biomedical devices, enabling control of key physiochemical properties with the aim of maximising osseointegration.

In this study, multi‐scale triply periodic minimal surface (TPMS) porous scaffolds with uniform and radial gradient distribution on pore size were printed based on the selective laser melting technology, and the influences of porosity, pore size and radial pore size distribution on compression mechanical properties, cell behavior, and bone regeneration behavior were analyzed. The results showed that the compression performance of the uniform porous scaffolds with high porosity was similar to that of cancellous bone of pig tibia, and the gradient porous scaffolds have higher elastic modulus and compressive toughness. After 4 days of cell culture, cells were distributed on the surface of scaffolds mostly, and the number of adherent cells was higher on the small pore size porous scaffolds; After 7 days, the area and density of cell proliferation on the scaffolds were improved; After 14 days, the cells on the small pore size scaffolds tended to migrate to adjacent pores. Animal implantation experiments showed that collagen fiber osteoid was intermittent on scaffolds with high porosity and large pore size, which was not conducive to bone formation. The appropriate pore size and porosity of bone regeneration were 792 um and 83%, respectively, and the regenerative ability of gradient pore size was better than that of uniform pore size. Our study explains the rules of TPMS gyroid structure parameters on compression performance, cell response and bone regeneration, and provides a reference value for the design of bone repair scaffolds for clinical orthopedics. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others. In this study, we apply time-resolved analysis of a human macrophage model (differentiated THP-1-ASC-GFP cells) to commonly accessible methods. This approach yields the additional quantifiable metrics time-resolved absolute change and acceleration, allowing comparisons between readouts. Using this methodological approach, we reveal (potential) discrepancies between inflammasome-related readouts that otherwise might go undiscovered. The study highlights the importance of time-resolved data in general and may be further extended as well as incorporated into other areas of research.

Essential oils are complex mixtures of volatile organic substances obtained from medicinal plants, their structural diversity determines their pharmacological bioactivity, including their therapeutic applications. Clinical studies have reported favorable health benefits to patients using medicinal plants for ulcerative skin lesions, reducing the discomfort, pain, and duration of ulcers. Chitosan (CHT) is a polymer with potential as a drug carrier in ulcer disease; also has antibacterial, anti-inflammatory, wound-healing, and hemostatic properties, proposed for its use in gels, biofilms, and sponges to cover the ulcerative lesion in the oral mucosa for both drug delivery and physical protection. The objective of this study was to evaluate the biological properties and enzymatic activity of sponges from CHT and Oregano essential oil (OEs). CHT sponges were incubated in OEs eluates (0.01, 0.02 and 0.03 mg/mL). The cell response and enzymatic activity of Super Oxide Dismutase (SOD) and Catalase (CAT) were evaluated in human periodontal ligament fibroblasts (hPLFs). The results showed that CHT-OEs at 0.02 mg/mL and at 0.03 mg/mL significantly increased hPLFs proliferation (p < 0.05). Micrographs demonstrated that the viability and mitochondrial activity of hPLFs were not affected by the eluates from CHT and OEs. SOD activity increased with eluates from OEs and CHT and CAT was significantly increased with CHT+OEs 0.01 mg/mL (p < 0.05). The synergy of CHT with OEs at a concentration of 0.02 mg/mL and 0.03 mg/mL in culture medium increases the proliferative response and stimulates SOD and CAT activity. [ABSTRACT FROM AUTHOR]

Wheat bran has high nutritional values and is also cheaper than yeast nitrogen base as an important component of a medium. Although its use in microbial cultivations is expected, research and development has hardly progressed so far. In this study, with experimental Saccharomyces cerevisiae BY4741, the cell responses to wheat bran as a nutrient were evaluated by analyses of cell growth, ethanol production, and comprehensive gene transcription levels. Comparing wheat bran and yeast nitrogen base, BY4741 showed specific growth rates of 0.277 ± 0.002 and 0.407 ± 0.035 as a significant difference. Additionally, wheat bran could be used as a restricted media component like yeast nitrogen base. However, in 24 h of cultivation with wheat bran and yeast nitrogen base, although conversion ratios of ethanol productions showed no significant difference at 63.0 ± 7.2% and 62.5 ± 8.2%, the ratio of cell production displayed a significant difference at 7.31 ± 0.04% and 4.90 ± 0.16%, indicating a different cell response. In fact, the comprehensive evaluation of transcription levels strongly suggested major changes in glucose metabolism. This study indicated that BY4741 could switch transcription levels efficiently to use wheat bran. [ABSTRACT FROM AUTHOR]

Septic shock is a life‐threatening clinical condition characterized by a robust immune inflammatory response to disseminated infection. Little is known about its impact on the transcriptome of distinct human tissues. To address this, we performed RNA sequencing of samples from the prefrontal cortex, hippocampus, heart, lung, kidney and colon of seven individuals who succumbed to sepsis and seven uninfected controls. We identified that the lungs and colon were the most affected organs. While gene activation dominated, strong inhibitory signals were also detected, particularly in the lungs. We found that septic shock is an extremely heterogeneous disease, not only when different individuals are investigated, but also when comparing different tissues of the same patient. However, several pathways, such as respiratory electron transport and other metabolic functions, revealed distinctive alterations, providing evidence that tissue specificity is a hallmark of sepsis. Strikingly, we found evident signals of accelerated ageing in our sepsis population. [ABSTRACT FROM AUTHOR]

The mechanical stimulation induced by poking cells with a glass needle activates Piezo1 receptors and the adenosine triphosphate (ATP) autocrine pathway, thus increasing intracellular Ca2+ concentration. The differences between the increase in intracellular Ca2+ concentration induced by cell poking and by ATP‐only stimulation have not been investigated. In this study, we investigated the Ca2+ signaling mechanism induced by autocrine ATP release during Madin–Darby Canine Kidney cell membrane deformation by cell poking. The results suggest that the pathways for supplying Ca2+ into the cytoplasm were not identical between cell poking and conventional ATP stimulation. The functions of the G protein‐coupled receptor (GPCR) subunits (Gα $\alpha $q, Gβγ $\beta \gamma $), ATP‐activated receptor and the upstream Ca2+ release signal from the intracellular endoplasmic reticulum Ca2+ store, were investigated. The results show that Gα $\alpha $q plays a major role in the Ca2+ response evoked by ATP‐only stimulation, while cell poking induces a Ca2+ response requiring the involvement of both Gα $\alpha $q and Gβγ $\beta \gamma $ units simultaneously. These results suggest that GPCR are not only activated by ATP‐only stimulation or autocrine ATP release during Ca2+ signaling, but also activated by the mechanical effects of cell poking. Significance statement: This paper investigated the mechanosensitivity of P2Y receptors and the role of the heterotrimeric G protein subunits in the process of elevation of intracellular Ca2+ concentration in Madin–Darby Canine Kidney cells mechanically deformed by poking. Results showed that the Ca2+ concentration increase triggered through P2Y receptors occurs independently of autocrine signaling triggered by released adenosine triphosphate. [ABSTRACT FROM AUTHOR]

The importance of Saccharomyces cerevisiae yeast cells is known worldwide, as they are the most used microorganisms in biotechnology for bioethanol and biofuel production. Also, they are analyzed and studied for their similar internal biochemical processes to human cells, for a better understanding of cell aging and response to cell stressors. The special ability of S. cerevisiae cells to develop in both aerobic and anaerobic conditions makes this microorganism a viable model to study the transformations and the way in which cellular metabolism is directed to face the stress conditions due to environmental changes. Thus, this review will emphasize the effects of oxidative, ethanol, and osmotic stress and also the physiological and genetic response of stress mitigation in yeast cells. [ABSTRACT FROM AUTHOR]

The improvement of the capability of poly(N-isopropylacrylamide) (PNIPAAm) hydrogel coating in cell adhesion and detachment is critical to efficiently prepare cell sheets applied in cellular therapies and tissue engineering. To enhance cell response on the surface, the amine group-modified PNIPAAm (PNIPAAm-APTES) nanohydrogels were synthesized and deposited spontaneously on tannic acid (TA)-modified polyethylene (PE) plates. Subsequently, TA was introduced onto PNIPAAm-APTES nanohydrogels to fabricate coatings composed of TA-modified PNIPAAm-APTES (PNIPAAm-APTES-TA). Characterization techniques, including TEM, SEM, XPS, and UV-Vis spectroscopy, confirmed the effective deposition of hydrogels of PNIPAAm as well as the morphologies, content of chemical bonding-TA, and stability of various coatings. Importantly, the porous hydrogel coatings exhibited superhydrophilicity at 20 °C and thermo-responsive behavior. The fluorescence measurement demonstrated that the coating’s stability effectively regulated protein behavior, influencing cell response. Notably, cell response tests revealed that even without precise control over the chain length/thickness of PNIPAAm during synthesis, the coatings enhanced cell adhesion and detachment, facilitating efficient cell culture. This work represented a novel and facile approach to preparing bioactive PNIPAAm for cell culture.

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered micro-array. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications. [ABSTRACT FROM AUTHOR]

Arranged patterns obtained via ultrafast laser processing on the surface of Ti/Cu/Ti/Si and Ti/Zr/Ti/Si thin-film systems are reported. Two differently designed multilayer thin films Ti/Cu/Ti/Si and Ti/Zr/Ti/Si were deposited on silicon using the ion sputtering method. The bioactive surfaces of these systems involve the formation of laser-induced periodic surface structures (LIPSS) in each of the laser-written lines of mesh patterns on 5 × 5 mm areas. The formation of nano- and micro-patterns with an ultra-thin oxide film on the surfaces was used to observe the effects of morphology and proliferation of the MRC-5 cell culture line. To determine whether Ti-based thin films have a toxic effect on living cells, an MTT assay was performed. The relative cytotoxic effect, as a percentage of surviving cells, showed that there was no difference in cell number between the Ti-based thin films and the control cells. There was also no difference in the viability of the MRC-5 cells, except for the Ti/Cu/Ti/Si system, where there was a slight 10% decrease in cell viability. [ABSTRACT FROM AUTHOR]

Due to affordability, and the ability to parametrically control the vital processing parameters, material extrusion is a widely accepted technology in tissue engineering. Material extrusion offers sufficient control over pore size, geometry, and spatial distribution, and can also yield different levels of in-process crystallinity in the resulting matrix. In this study, an empirical model based on four process parameters—extruder temperature, extrusion speed, layer thickness, and build plate temperature—was used to control the level of in-process crystallinity of polylactic acid (PLA) scaffolds. Two sets of scaffolds were fabricated, with low- and high-crystallinity content, and subsequently seeded with human mesenchymal stromal cells (hMSC). The biochemical activity of hMSC cells was tested by examining the DNA content, lactate dehydrogenase (LDH) activity, and alkaline phosphatase (ALP) tests. The results of this 21-day in vitro experiment showed that high level crystallinity scaffolds performed significantly better in terms of cell response. Follow-up tests revealed that the two types of scaffolds were equivalent in terms of hydrophobicity, and module of elasticity. However, detailed examination of their micro- and nanosurface topographic features revealed that the higher crystallinity scaffolds featured pronounced nonuniformity and a larger number of summits per sampling area, which was the main contributor to a significantly better cell response. [ABSTRACT FROM AUTHOR]

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered microarray. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications. [ABSTRACT FROM AUTHOR]

Late in-stent thrombus and restenosis still represent two major challenges in stents’ design. Surface treatment of stent is attracting attention due to the increasing importance of stenting intervention for coronary artery diseases. Several surface engineering techniques have been utilised to improve the biological response in vivo on a wide range of biomedical devices. As a tailorable, precise, and ultra-fast process, laser surface engineering offers the potential to treat stent materials and fabricate various 3D textures, including grooves, pillars, nanowires, porous and freeform structures, while also modifying surface chemistry through nitridation, oxidation and coatings. Laser-based processes can reduce the biodegradable materials' degradation rate, offering many advantages to improve stents’ performance, such as increased endothelialisation rate, prohibition of SMC proliferation, reduced platelet adhesion and controlled corrosion and degradation. Nowadays, adequate research has been conducted on laser surface texturing and surface chemistry modification. Laser texturing on commercial stents has been also investigated and a promotion of performance of laser-textured stents has been proved.In this critical review, the influence of surface texture and surface chemistry on stents performance is firstly reviewed to understand the surface characteristics of stents required to facilitate cellular response. This is followed by the explicit illustration of laser surface engineering of stents and/or related materials. Laser induced periodic surface structure (LIPSS) on stent materials is then explored, and finally the application of laser surface modification techniques on latest generation of stent devices is highlighted to provide future trends and research direction on laser surface engineering of stents.

Wheat bran has high nutritional values and is also cheaper than yeast nitrogen base as an important component of a medium. Although its use in microbial cultivations is expected, research and development has hardly progressed so far. In this study, with experimental Saccharomyces cerevisiae BY4741, the cell responses to wheat bran as a nutrient were evaluated by analyses of cell growth, ethanol production, and comprehensive gene transcription levels. Comparing wheat bran and yeast nitrogen base, BY4741 showed specific growth rates of 0.277 ± 0.002 and 0.407 ± 0.035 as a significant difference. Additionally, wheat bran could be used as a restricted media component like yeast nitrogen base. However, in 24 h of cultivation with wheat bran and yeast nitrogen base, although conversion ratios of ethanol productions showed no significant difference at 63.0 ± 7.2% and 62.5 ± 8.2%, the ratio of cell production displayed a significant difference at 7.31 ± 0.04% and 4.90 ± 0.16%, indicating a different cell response. In fact, the comprehensive evaluation of transcription levels strongly suggested major changes in glucose metabolism. This study indicated that BY4741 could switch transcription levels efficiently to use wheat bran.

The importance of Saccharomyces cerevisiae yeast cells is known worldwide, as they are the most used microorganisms in biotechnology for bioethanol and biofuel production. Also, they are analyzed and studied for their similar internal biochemical processes to human cells, for a better understanding of cell aging and response to cell stressors. The special ability of S. cerevisiae cells to develop in both aerobic and anaerobic conditions makes this microorganism a viable model to study the transformations and the way in which cellular metabolism is directed to face the stress conditions due to environmental changes. Thus, this review will emphasize the effects of oxidative, ethanol, and osmotic stress and also the physiological and genetic response of stress mitigation in yeast cells.

The repair of segmental bone defects caused by traumatic injury or pathological diseases remains a substantial challenge in clinic. Poly-l-lactic acid (PLLA) is recognized as one potential bone substitute material due to its natural biodegradability and excellent biocompatibility. Nevertheless, it still faces several fundamental puzzles including insufficient mechanical properties, slow degradation and poor osteogenic activity. To address these issues, the corresponding strategies were thoroughly explored in this review. Regulation of molecular weight and crystallization, as well as the control of crack propagation were the mainstream methods to improve the mechanical properties of PLLA, whereas surface medication and polymer blending was commonly adopted to regulate the degradation behavior. To achieve desirable tissue regeneration ability, the combination of physical stimulation (electric and magnetic) brings about a new and attractive solution, since it is able to mimic the electro-magnetic microenvironment of human body. Furthermore, future research directions are proposed from the prospects of fabrication process, dynamic degradation and multifunctional application. This review aims to offer deep insights and meaningful guidelines for future study of PLLA as implants.

Carica papaya leaf has a potentially well-known therapeutic effect in accelerating human blood platelet counts against dengue fever and dengue haemorrhagic fever. However, consuming the extract was considered troublesome due to its bitter taste. The fresh papaya leaves were extracted into two types of preparation: a) Fresh Papaya Leaves Extract (FPL) and b) Papaya Leaves with Saponin Reduction Extract (PLSR). This was followed by the determination of the best edible O/W emulsion formulation of both different extracts with virgin coconut oil (VCO) and whey protein (WP) as surfactant. Through Ternary Phase Diagram (TPD), the optimum ratio (w/w) of FPL/PLSR: VCO: WP were 63: 16: 21 and 65: 16: 19 respectively. Both formulas were examined for their physicochemical properties including pH, creaming index (CI), contact angle and droplet size measurement. The human bronchial epithelium cell (BEAS-2B) was treated using both emulsions for 72 hrs of cell growth response (EC50). The result shows that both FPL and PLSR formulations were slightly acidic and exhibited stable emulsion with no creaming formation (CI) up to 24 hrs of storage (25 ℃). Next, FPL emulsion shows 3 times higher wettability and 4 times bigger nanoparticle size than PLSR. These properties can affect the emulsion absorptivity in the targeted cell microenvironment. Remarkably, the BEAS-2B cell viability (%) for each emulsion was relatively elevated within 24 hrs and increased to more than 100 % at 48 and 72 hrs of exposure. This might hugely represent its potential in repairing damaged blood vessels due to dengue haemorrhagic fever. Besides, the EC50 value also indicated low levels of concentration needed to exponentially increase cell growth and safe for dengue fever treatment. For that reason, the recommended effective dosage by the Ministry of Health (Malaysia) (MOH) for both FPL and PLSR emulsions is two tablespoons twice a day for three consecutive days of treatment (equally to the effective dosage of 102 g extract).

Porous hydroxyapatite (HAp) ceramics with macropores of more than 200 μm were fabricated via our new method comprising chemical synthesis and heat treatment. In this study, four types of porous Zn-doped HAp ceramics were produced by adding 0.1, 0.5, 1.0 and 5.0 g of zinc acetate dehydrate to 50 g of a HAp nanoparticle slurry during chemical synthesis and then calcining the mixtures at 1200 °C. Three samples fabricated by adding 0.5, 1.0 and 5.0 g of zinc acetate dehydrate showed a ZnO phase as a byproduct. In contrast, the sample fabricated by adding 0.1 g of zinc acetate dehydrate did not show it. As the additive amounts of Zn ions increased, lattice parameters a and c of the HAp phase increased. By inserting Zn ions into OH channels within HAp lattices, the hydroxyl groups within them decreased, and consequently, the lattice parameter c increased by forming linear O—Zn—O units within them. On the other hand, the lattice parameter a increased because the HAp lattices were disordered owing to the insertion of Zn ions. Moreover, upon examining the cell behavior of our samples, the cells adhered well to and spread widely on the sample without the ZnO phase, similar to porous undoped HAp ceramics 48 h after cell culture. Namely, Zn ions that were themselves inserted into the HAp lattice did not significantly influence cell adhesion. In contrast, the number of adhering cells on the samples with the ZnO phase decreased compared to that without it. [ABSTRACT FROM AUTHOR]

Ideal osteoporotic bone defect repair materials are capable of enhancing osteogenesis and simultaneously restraining osteoclastogenesis. Gallium has a potent effect on inhibiting osteoclastogenesis, but it cannot promote osteogenesis. Zinc is a well-documented osteostimulative element. In this work, zinc/gallium co-doped β-tricalcium phosphate (ZG-TCP) ceramic blocks and scaffolds were prepared through mold forming and extrusion-type 3D printing technology, respectively. The zinc/gallium dual doping promoted densification of β-tricalcium phosphate ceramics, thereby affecting the compressive strength. The ZG-TCP ceramic scaffolds showed 3D interconnected uniform pore structure. The zinc and gallium released from ZG-TCP compromised cell proliferation, increased the alkaline phosphatase activity of bone marrow stromal cells, and restrained the osteoclastogenesis of RAW264.7 cells. The ZG-TCP ceramic scaffolds doped with 0.5 mol% zinc and 2.5 mol% gallium possessed the most favorable comprehensive properties, including considerable compressive strength, enhanced osteoblastogenesis and suppressed osteoclastogenesis, so they are suitable for regenerating osteoporotic bone defects. [ABSTRACT FROM AUTHOR]

The electrical properties of bone implant scaffolds are a pivotal factor in regulating cellular behavior and promoting osteogenesis. The previous study shows that built-in electric fields established between electropositive nanofilms and electronegative bone defect walls are beneficial for promoting bone defect healing. Considering that the physiological electrical microenvironment is spatially distributed in 3D, it is imperative to establish a 3D spatial charged microenvironment on bone scaffolds to optimize the efficacy of osseointegration. Nevertheless, this still poses a formidable challenge. Here, a bone repair strategy that utilizes micro-scale 3D topography is developed on a piezoelectric BaTiO 3 (BTO) substrate to provide 3D spatial electrical stimulation. The BTO micropillar arrays, especially with a height of 50 µm and positive-charge distribution (50 µm positive), promote the spreading, cytoskeletal reorganization, focal adhesion maturation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). They enhanced the clustering of mechanosensing integrin α5 in BMSCs. The biomimetic 3D spatial electrical microenvironment accelerated bone repair and osseointegration in a rat femoral diaphysis defect repair model. The study thus reveals that implants with a 3D spatial electrical microenvironment can significantly enhance osseointegration, thereby providing a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies., (© 2024 Wiley‐VCH GmbH.)

Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets. [ABSTRACT FROM AUTHOR]

Background We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Methods This prospective study included patients with coronavirus disease 2019 (COVID-19) with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of reverse transcription–polymerase chain reaction or vaccination was considered as the reference standard. Results A total of 239 individuals were included (152 convalescent, 54 vaccinated, and 33 uninfected unvaccinated). Overall sensitivity, specificity, and positive- and negative-predictive values (95% confidence interval) of the IGRA were 81.1% (74.9–86%), 90.9% (74.5–97.6%), 98.2% (94.5–99.5%), and 43.5% (31.8–55.9%), respectively. All vaccinated SARS-CoV-2-naive subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3 months and the worst in those with mild disease at 12 months. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). Conclusions The IGRA was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients, the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections. [ABSTRACT FROM AUTHOR]

Cells sense their environment through the cell membrane receptors. Interaction with extracellular ligands induces receptor clustering at the nanoscale, assembly of the signaling complexes in the cytosol and activation of downstream signaling pathways, regulating cell response. Nanoclusters of receptors can be further organized hierarchically in the cell membrane at the meso- and micro-levels to exert different biological functions. To study and guide cell response, cell culture substrates have been engineered with features that can interact with the cells at different scales, eliciting controlled cell responses. In particular, nanoscale features of 1–100 nm in size allow direct interaction between the material and single cell receptors and their nanoclusters. Since the first “contact guidance” experiments on parallel microstructures, many other studies followed with increasing feature resolution and biological complexity. Here we present an overview of the advances in the field summarizing the biological scenario, substrate fabrication techniques and applications, highlighting the most recent developments.

Surface structures and physicochemical properties critically influence osseointegration of titanium (Ti) implants. Previous studies have shown that the surface with both micro- and nanoscale roughness may provide multiple features comparable to cell dimensions and thus efficiently regulate cell-material interaction. However, less attention has been made to further optimize the physicochemical properties (e.g., crystalline phase) and to further improve the bioactivity of micro/nanostructured surfaces. Herein, micro/nanostructured titania surfaces with different crystalline phases (amorphous, anatase and anatase/rutile) were prepared and hydroxyapatite (HA) nanorods were deposited onto the as-prepared surfaces by a spin-assisted layer-by-layer assembly method without greatly altering the initial multi-scale morphology and wettability. The effects of crystalline phase, chemical composition and wettability on osteoblast response were investigated. It is noted that all the micro/nanostructured surfaces with/without HA modification presented superamphiphilic. The activities of MC3T3-E1 cells suggested that the proliferation trend on the micro/nanostructured surfaces was greatly influenced by different crystalline phases, and the highest proliferation rate was obtained on the anatase/rutile surface, followed by the anatase; but the cell differentiation and extracellular matrix mineralization were almost the same among them. After ultrathin HA modification on the micro/nanostructured surfaces with different crystalline phases, it exhibited similar proliferation trend as the original surfaces; however, the cell differentiation and extracellular matrix mineralization were significantly improved. The results indicate that the introduction of ultrathin HA to the micro/nanostructured surfaces with optimized crystalline phase benefits cell proliferation, differentiation and maturation, which suggests a favorable biomimetic microenvironment and provides the potential for enhanced implant osseointegration in vivo.

[Display omitted] • This study investigated individual and combined effects of geometries and selective laser melting parameters on physiochemical properties of lattice struts to develop fundamental understanding of 3D scaffolds. • Significant superiority of mechanical properties without visible failure and defects was observed on struts built above 45° and linear energy density of 0.13 J/mm. • Remarkable increasing of in vitro pre-osteoblast response was found on struts built below 45°. • A comprehensive parameter map towards geometric design was developed to potentially improve and predict mechanical and biological properties of lattices. The advancement of metal additive manufacturing has recently enabled the integration of porous lattice regions into orthopaedic devices. Despite the increased utilisation of various metamaterials there remains limited understanding of how to optimise laser process specifically for these geometries. Selective laser melting (SLM) of representative single struts is focused on this study from the perspective of surface properties, mechanical performance, and in-vitro biological response. Specifically, the influence of laser power (100 – 200 W) and speed (2250 – 900 mm/s) and struts angle (20–90°) for a 250 μ m strut diameter was explored. Struts built below 45° to the substrate using optimal laser parameters (150 W and 1125 mm/s) were found to exhibit a surface topography that facilitated the highest level of cell adhesion (84.3 cells/mm2) after 24 hrs (p ≤ 0.001). To support this finding, a novel image analysis method was developed to characterise the average roughness across the complete strut profile. An opposite trend was observed for mechanical strength with struts built at above 45° without failure. These findings were brought together in a parameter design map was to guide stakeholders in producing customised biomedical devices, enabling control of key physiochemical properties with the aim of maximising osseointegration. [ABSTRACT FROM AUTHOR]

Metallic materials have been widely used as orthopedic implants in clinics for their good mechanical, physical, and chemical properties, but their slow osseointegration rate is still one of the main issues causing implantation failure. Grain refinement has recently attracted wide attention for its effective improvement of cell–material interaction for biometals. In this review, the surface and bulk grain refinement mode and the influence of grain size reduction of various metallic materials including titanium, stainless steel, magnesium, zirconium, tantalum, and their alloys as well as NiTi shape memory alloys on the cell responses is summarized in detail. It is hoped that this review could help biomaterials-related researchers to understand the grain refinement of metallic materials in a timely manner, thus boosting the development of biomedical metals for clinical use. [ABSTRACT FROM AUTHOR]

Cells live in dynamic environments that necessitate perpetual adaptation. Since cells have limited resources to monitor external inputs, they are required to maximize the information content of perceived signals. This challenge is not unique to microscopic life: Animals use senses to perceive inputs and adequately respond. Research showed that sensory-perception is actively shaped by learning and expectation allowing internal cognitive models to "fill in the blanks" in face of limited information. We propose that cells employ analogous strategies and use internal models shaped through the long process of evolutionary adaptation. Given this perspective, we postulate that cells are prone to "misperceptions," analogous to visual illusions, leading them to incorrectly decode patterns of inputs that lie outside of their evolutionary experience. Mapping cellular misperception can serve as a fundamental approach for dissecting regulatory networks and could be harnessed to modulate cell behavior, a potentially new avenue for therapy.

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2., Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2 nd dose (Sputnik V or AZD1222) and 3 nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed., Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r 2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population., Discussion: Findings regarding humoral and cellular response are consistent with previous reports., Competing Interests: The authors declare that this study received funding from Novartis and donations from Merck Argentina and Synthon Bagó. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Author Berenice Anabel Silva, as principal investigator, received a 2-year research grant from the Research Council of the Ministry of Health of the Government of the City of Buenos Aires, Argentina., (Copyright © 2024 Silva, Miglietta, Casabona, Wenker, Eizaguirre, Alonso, Casas, Lázaro, Man, Portuondo, Lopez Bisso, Zavala, Casales, Imhoff, Steinberg, López, Carnero Contentti, Deri, Sinay, Hryb, Chiganer, Leguizamon, Tkachuk, Bauer, Ferrandina, Giachello, Henestroza, Garcea, Pascuale, Heitrich, Podhajcer, Vinzón, D’Alotto-Moreno, Benatar, Rabinovich, Pitossi and Ferrari.)

Engineered nanomaterials (ENMs) are increasingly produced and used today, but health risks due to their occupational airborne exposure are incompletely understood. Traditionally, nanoparticle (NP) toxicity is tested by introducing NPs to cells through suspension in the growth media, but this does not mimic respiratory exposures. Different methods to introduce aerosolized NPs to cells cultured at the air-liquid-interface (ALI) have been developed, but require specialized equipment and are associated with higher cost and time. Therefore, it is important to determine whether aerosolized setups induce different cellular responses to NPs than traditional ones, which could provide new insights into toxicological responses of NP exposure. This study evaluates the response of human alveolar epithelial cells (A549) to zinc oxide (ZnO) NPs after dry aerosol exposure in the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) system as compared to conventional, suspension-based exposure: cells at ALI or submerged. Similar to other studies using nebulization of ZnO NPs, we found that dry aerosol exposure of ZnO NPs via the NACIVT system induced different cellular responses as compared to conventional methods. ZnO NPs delivered at 1.0 µg/cm2 in the NACIVT system, mimicking occupational exposure, induced significant increases in metabolic activity and release of the cytokines IL-8 and MCP-1, but no differences were observed using traditional exposures. While factors associated with the method of exposure, such as differing NP aggregation, may contribute toward the different cellular responses observed, our results further encourage the use of more physiologically realistic exposure systems for evaluating airborne ENM toxicity. [ABSTRACT FROM AUTHOR]

Metallic materials have been widely used as orthopedic implants in clinics for their good mechanical, physical, and chemical properties, but their slow osseointegration rate is still one of the main issues causing implantation failure. Grain refinement has recently attracted wide attention for its effective improvement of cell–material interaction for biometals. In this review, the surface and bulk grain refinement mode and the influence of grain size reduction of various metallic materials including titanium, stainless steel, magnesium, zirconium, tantalum, and their alloys as well as NiTi shape memory alloys on the cell responses is summarized in detail. It is hoped that this review could help biomaterials-related researchers to understand the grain refinement of metallic materials in a timely manner, thus boosting the development of biomedical metals for clinical use.

One of the main goals of quantitative proteomics is molecular profiling of cellular response to stress at the protein level. To perform this profiling, statistical analysis of experimental data involves multiple testing of a hypothesis about the equality of protein concentrations between the cells under normal and stress conditions. This analysis is then associated with the multiple testing problem dealing with the increased chance of obtaining false positive results. A number of solutions to this problem are known, yet, they may lead to the loss of potentially important biological information when applied with commonly accepted thresholds of statistical significance. Using the proteomic data obtained earlier for the yeast samples containing proteins at known concentrations and the biological models of early and late cellular responses to stress, we analyzed dependences of distributions of false positive and false negative rates on the protein fold changes and thresholds of statistical significance. Based on the analysis of the density of data points in the volcano plots, Benjamini–Hochberg method, and gene ontology analysis, visual approach for optimization of the statistical threshold and selection of the differentially regulated proteins has been suggested, which could be useful for researchers working in the field of quantitative proteomics. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others. In this study, we apply time-resolved analysis of a human macrophage model (differentiated THP-1-ASC-GFP cells) to commonly accessible methods. This approach yields the additional quantifiable metrics time-resolved absolute change and acceleration, allowing comparisons between readouts. Using this methodological approach, we reveal (potential) discrepancies between inflammasome-related readouts that otherwise might go undiscovered. The study highlights the importance of time-resolved data in general and may be further extended as well as incorporated into other areas of research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:co-author affiliated to Nanoxis Consulting AB - R.K. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Several studies have been carried out to develop new materials for biomedical applications. Material surfaces that present biomimetic morphology like nanotubes or nanofibers that provides nanoscale architectures have been shown to alter cell/biomaterial interactions. The coated surface biomaterial with biocompatible polymers and nanotubes of TiO2 is an alternative to improve osseointegration. The anodization process was performed to obtain nanotubes of TiO2 covering the Ti-30Ta alloy surface and the electrospinning process has been used for producing polymer fibers. Characterization techniques such as scanning electron microscopy (SEM - FEG), X-ray diffraction analysis (X-rays), thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC) and contact angle were used for samples analyses. Adult human adipose-derived stem cells (ADSCs) were used to investigate the cellular response and S. aureus antimicrobial activity on these coated surfaces. The results indicated that both surface modification treatment showed a favorable micro-environment for cells growth and proliferation such as adhesion, viability and morphology which is a desire property for an implant. In addition, the antimicrobial activity study presented both materials with similar growth of S. aureus. So, it can conclude nanotubes and nanofibers can be used at biomedical field and both present similar cell evaluation and antimicrobial activity results.

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection caused by thermally dimorphic fungi of the genus Paracoccidioides. Endemic in Latin America, PCM presents with high incidence in Brazil, Colombia, and Venezuela, especially among rural workers. The main clinical types are acute/subacute (AF) form and chronic form (CF). Even after effective antifungal treatment, patients with CF usually present sequelae, such as pulmonary fibrosis. In general, pulmonary fibrosis is associated with dysregulation wound healing and abnormal fibroblast activation. Although fibrogenesis is recognized as an early process in PCM, its mechanisms remain unknown. In the current study, we addressed the role of Paracoccidioides spp. exoantigens in pulmonary fibroblast proliferation and responsiveness. Human pulmonary fibroblasts (MRC-5) and pulmonary fibroblasts isolated from BALB/c mice were cultivated with 2.5, 5, 10, 100, and 250 µg/ml of exoantigens produced from P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334, and Pb66) isolates. Purified gp43, the immunodominant protein of P. brasiliensis exoantigens, was also evaluated at concentrations of 5 and 10 µg/ml. After 24 h, proliferation and production of cytokines and growth factors by pulmonary fibroblasts were evaluated. Each exoantigen concentration promoted a different level of interference of the pulmonary fibroblasts. In general, exoantigens induced significant proliferation of both murine and human pulmonary fibroblasts (p < 0.05). All concentrations of exoantigens promoted decreased levels of IL-6 (p < 0.05) and VEGF (p < 0.05) in murine fibroblasts. Interestingly, decreased levels of bFGF (p < 0.05) and increased levels of TGF-β1 (p < 0.05) and pro-collagen I (p < 0.05) were observed in human fibroblasts. The gp43 protein induced increased TGF-β1 production by human cells (p = 0.02). In conclusion, our findings showed for the first time that components of P. brasiliensis and P. lutzii interfered in fibrogenesis by directly acting on the biology of pulmonary fibroblasts.

The aim of this study was to evaluate the potential protective role of Agrimonia eupatoria L. in heavy metal induced nephrotoxicity. Rabbit kidney epithelial cells (RK13) were used as the model cell line. They were exposed to three different heavy metal compounds: cadmium chloride dihydrate CdCl2.2H2O (15 and 20 mg.l−1), potassium dichromate K2Cr2O7 (1, 10 mg.l−1), and zinc sulfate heptahydrate ZnSO4.7H2O (50, 150 mg.l−1) simultaneously with agrimony (ethanolic extract, 100 mg.l−1). The cell response was recorded using the xCELLigence system or real-time cell analysis (RTCA) as a cell index (CI) and expressed as cell adherence (%) compared to control cells without treatment. The potential nephroprotective effects were recorded in cells treated with chromium (1 a 10 mg.l−1) and agrimony, where the cell adherence increased from 95.11 ± 11.25 % and 7.24 ± 0.33 % to 103.26 ± 1.23 % and 68.54 ± 4.89 % (P < 0.05) respectfully and also with a combination of agrimony and zinc (150 mg.l−1), where the adherence increased from 57.45 ± 1.98 % to 95.4 ± 6.95 %. During the cell exposure to cadmium in combination with agrimony, the protective effect was not recorded; the adherence of cells was even decreased (P < 0.05).

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection caused by thermally dimorphic fungi of the genus Paracoccidioides. Endemic in Latin America, PCM presents with high incidence in Brazil, Colombia, and Venezuela, especially among rural workers. The main clinical types are acute/subacute (AF) form and chronic form (CF). Even after effective antifungal treatment, patients with CF usually present sequelae, such as pulmonary fibrosis. In general, pulmonary fibrosis is associated with dysregulation wound healing and abnormal fibroblast activation. Although fibrogenesis is recognized as an early process in PCM, its mechanisms remain unknown. In the current study, we addressed the role of Paracoccidioides spp. exoantigens in pulmonary fibroblast proliferation and responsiveness. Human pulmonary fibroblasts (MRC-5) and pulmonary fibroblasts isolated from BALB/c mice were cultivated with 2.5, 5, 10, 100, and 250 µg/ml of exoantigens produced from P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334, and Pb66) isolates. Purified gp43, the immunodominant protein of P. brasiliensis exoantigens, was also evaluated at concentrations of 5 and 10 µg/ml. After 24 h, proliferation and production of cytokines and growth factors by pulmonary fibroblasts were evaluated. Each exoantigen concentration promoted a different level of interference of the pulmonary fibroblasts. In general, exoantigens induced significant proliferation of both murine and human pulmonary fibroblasts (p < 0.05). All concentrations of exoantigens promoted decreased levels of IL-6 (p < 0.05) and VEGF (p < 0.05) in murine fibroblasts. Interestingly, decreased levels of bFGF (p < 0.05) and increased levels of TGF-β1 (p < 0.05) and pro-collagen I (p < 0.05) were observed in human fibroblasts. The gp43 protein induced increased TGF-β1 production by human cells (p = 0.02). In conclusion, our findings showed for the first time that components of P. brasiliensis and P. lutzii interfered in fibrogenesis by directly acting on the biology of pulmonary fibroblasts. [ABSTRACT FROM AUTHOR]