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The primary objective of this systematic review study was to investigate the effectiveness, durability, and adverse events of PLLA treatment for aesthetic indications. The search strategy was performed in MEDLINE (Ovid). The electronic literature search of five databases was performed, from the inception of the databases until the 12th of February 2024. This was to identify randomized clinical trials that assessed PLLA treatment in adult individuals exhibiting facial aging and/or facial lipoatrophy. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). Eleven RCTs out of 1467 identified citations were included. Four studies showed increased dermal thickness, significant improvement in facial lipoatrophy severity and aesthetic clinical scores, after PLLA treatment with its effects sustained for at least 25 months. Two studies demonstrated the superiority of PLLA over injectable human collagen. Also, three studies showed positive results favoring PLLA when compared with PH gel in lipoatrophy severity, transepidermal water loss, skin quality, elasticity, and patient satisfaction. All adverse events were mild-to-moderate in intensity, and the main ones worth noting were bruising, hematoma, tenderness, nodules, and edema. Five out of eleven studies were considered having high risk of bias. The evidence on the effectiveness and safety of PLLA for facial rejuvenation is of low quality; thus, the reported high effectiveness, safety, and long-lasting effects for this purpose should be further investigated.

SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection. Our methodology is based on a genetic algorithm performing systematic steps of random mutation, protein-peptide docking (using the PyRosetta library) and selecting the best-optimized peptides based on the contacts made at the peptide-protein interface. We performed three case studies to evaluate the tool parameters and compared our results with proposals presented in the literature. Additionally, we performed molecular dynamics (MD) simulations (three systems, 200 ns each) to probe whether our suggested peptides could interact with the spike protein. Our results suggest that our methodology could be a good strategy for designing peptides.

We investigated three calcium silicate-based sealers with respect to their chemical characterization, cytotoxicity, and attachment to RAW264.7 cells. BioRoot RCS (BR), Bio-C Sealer (BC), and Sealer Plus BC (SPBC) were assessed using Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), and energy-dispersive X-ray spectroscopy (EDX) (n = 4) for elemental characterization, and using scanning electron microscopy (SEM) to evaluate cell morphology and adhesion. Cytotoxicity was determined at different dilutions (1:1, 1:2, and 1:5) using the succinate dehydrogenase activity (MTT assay). Statistical analysis was performed for normal distribution using the Shapiro-Wilk test and for homoscedasticity using Levene's test, and one-way ANOVA, Tukey's/Dunnett's post hoc tests for cell viability and XRF (α = 0.05). Calcium silicate hydrate and calcium hydroxide were detected by FTIR in all groups. EDX detected a higher calcium content for BR and SPBC and aluminum only in the premixed sealers. XRF detected the highest calcium release in BR ( p < 0.05). The surface morphology showed irregular precipitates for all the sealers. SPBC at a 1:2 dilution resulted in the lowest cell viability compared to BR ( p < 0.05) and BC ( p < 0.05). The calcium silicate-based sealers produced a statistically significant reduction in cellular viability at a 1:1 dilution compared to the control group ( p < 0.0001). All the sealers maintained viability above 70%.

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March-April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG's 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks.

Exosome-liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.

Mesenchymal stromal cells (MSCs) have long been used in research for bone regeneration, with evidence of their beneficial properties. In the segmental area of MSC-based therapies, MSC-derived extracellular vesicles (EVs) have also shown great therapeutic effects in several diseases, including bone healing. This study aimed to assess whether the conditioning of MSCs improves the therapeutic effects of their derived extracellular vesicles for bone regeneration. Electronic research was performed until February 2021 to recover the studies in the following databases: PubMed, Scopus, and Web of Science. The studies were screened based on the inclusion criteria. Relevant information was extracted, including in vitro and in vivo experiments, and the animal studies were evaluated for risk of bias by the SYRCLE tool. A total of 463 studies were retrieved, and 18 studies met the inclusion criteria (10 studies for their in vitro analysis, and 8 studies for their in vitro and in vivo analysis). The conditioning methods reported included: osteogenic medium; dimethyloxalylglycine; dexamethasone; strontium-substituted calcium silicate; hypoxia; 3D mechanical microenvironment; and the overexpression of miR-375, bone morphogenetic protein-2, and mutant hypoxia-inducible factor-1α. The conditioning methods of MSCs in the reported studies generate exosomes able to significantly promote bone regeneration. However, heterogeneity regarding cell source, conditioning method, EV isolation and concentration, and defect model was observed among the studies. The different conditioning methods reported in this review do improve the therapeutic effects of MSC-derived EVs for bone regeneration, but they still need to be addressed in larger animal models for further clinical application.