Is micronucleus assay a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage induced by chemical, physical, and biological agents in vivo? A systematic review with meta-analysis.

The present systematic review (SR) aims to evaluate manuscripts in order to help further elucidate the following question: is the micronucleus assay (MA) also a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage in vivo? A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to December 2023. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CIs) were established. Full manuscripts from 34 studies were carefully selected and reviewed in this setting. Our results demonstrate that the MA may be a useful biomarker of gingival tissue damage in vivo, and this tissue could be a useful alternative to the buccal mucosa. The meta-analysis analyzing the different sites regardless of the deleterious factor studied, the buccal mucosa (SMD = 0.69, 95% CI, - 0.49 to 1.88, p = 0.25) and gingiva (SMD = 0.31, 95% CI, - 0.11 to 0.72, p = 0.15), showed similar results and different outcome for the tongue (SMD = 1.19, 95% CI, 0.47 to 1.91, p = 0.001). In summary, our conclusion suggests that the MA can be a useful marker for detecting DNA damage in gingiva in vivo and that this tissue could be effective site for smearing.

In vitro and In vivo Activity of a New N-Oxide Derivative for Acne Vulgaris Treatment.

INTRODUCTION: Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 µg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-ß) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 µg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.

Computer-aided drug design supporting sunscreen research: a showcase study using previously synthesized hybrid UV filter-antioxidant compounds.

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.

Globe-shaped central incisors in a patient with otodental syndrome.

Hearing impairments and dental anomalies are found in many genetic syndromes. Otodental syndrome is a rare combination of hearing loss and the presence of a pathognomonic dental phenotype known as globodontia, in which the tooth exhibits an abnormal globe shape. There is no histologic evidence of structural anomalies in the enamel, dentin, or pulp. This report describes the case of a 12-year-old boy who had hearing loss and 2 supernumerary globe-shaped teeth in the sites of the permanent maxillary central incisors. The diagnosis of otodental syndrome was established based on the clinical, radiographic, and histologic features, but other conditions, including dens evaginatus, talon cusp, dens invaginatus, and compound odontoma, should be included in the differential diagnosis. Dental treatment consisted of the extraction of both anomalous teeth, allowing spontaneous eruption of the impacted permanent central incisors. Early diagnosis of otodental syndrome permits a multidisciplinary approach to prevent other pathologic conditions, reduce functional damage, and avoid social problems.

Tolerance Mitigates Gall Effects When Susceptible Plants Fail to Elicit Induced Defense.

Variations in plant genotypes and phenotypes are expressed in ways that lead to the development of defensive abilities against herbivory. Induced defenses are mechanisms that affect herbivore insect preferences and performance. We evaluated the performance of resistant and susceptible phenotypes of Bauhinia brevipes (Fabaceae) against attacks by the gall-inducing insect Schizomyia macrocapillata (Diptera). We hypothesized that there is a positive relationship between resistance to S. macrocapillata and host plant performance because resistance can have a high adaptive value. We evaluated plant architecture, nutritional leaf quality, leaf fluctuating asymmetry, and reproductive capacity between phenotypes. Plant performance was evaluated at three ontogenetic stages: seed, seedling, and juvenile. Overall, there were no differences in vegetative and reproductive performance or asymmetry between the resistant and susceptible mature plants. We found no relationship between leaf nutritional quality and resistance to S. macrocapillata. Plant performance was consistent across ontogeny for both phenotypes, except for five variables. Contrary to our expectations, the susceptible plants performed equally well or better than the resistant plants, suggesting that tolerance and overcompensation to herbivory in B. brevipes may be mediated by induced defense. Our study highlights the importance of multiple layers of plant defense against herbivory, where plant tolerance acts as a secondary barrier in plants susceptible to gall-inducing insects.

Endothelial dysfunction in Sickle Cell Disease: Strategies for the treatment.

Sickle Cell Anemia (SCA), is an inherited hemoglobinopathy characterized by the presence of an abnormal hemoglobin (HbS), being the most prevalent sickle cell disease (SCD). SCA is characterized by vascular endothelial dysfunction, which contributes significantly to various clinical conditions, including but not limited to pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke. The pathophysiology of endothelial dysfunction (ED) in SCA is a multifaceted process involving a chronic inflammatory and hypercoagulable state. Key factors include hemolysis-associated elements like reduced arginine and nitric oxide (NO) availability, elevated levels of vascular adhesion molecules, the uncoupling effect of NO synthase, heightened arginase activity, an environment characterized by oxidative stress with the production of reactive oxygen and nitrogen species, and occurrences of ischemia-reperfusion injury, along with apolipoprotein A-1 depletion. The urgency for novel interventions addressing ED is evident. Presently, there is a focus on investigating small molecules that disrupt the arginine-nitric oxide pathway, exhibiting anti-inflammatory and antioxidant properties while diminishing levels of cellular and vascular adhesion molecules. In this mini-review article, we delve into the progress made in strategies for treating ED in SCD with the aim of cultivating insights for drug design.

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Structural variety of glucans from Ganoderma lucidum fruiting bodies.

Ganoderma lucidum, widely used in traditional medicine, has several biological properties. Polysaccharides, mainly glucans, are known as one of its main bioactive compounds. Consequently, the achievement and chemical investigation of such molecules are of pharmaceutical interest. Herein, we obtained water-insoluble and water-soluble polysaccharides from G. lucidum by alkaline extraction. Fractionation process yielded three fractions (GLC-1, GLC-2, and GLC-3). All samples showed to be composed mainly of glucans. GLC-1 is a linear (1 â†’ 3)-linked ß-glucan; GLC-2 is a mixture of three different linear polysaccharides: (1 â†’ 3)-ß-glucan, (1 â†’ 3)-α-glucan, and (1 â†’ 4)-α-mannan; while GLC-3 is a branched ß-glucan with a (1 â†’ 4)-linked main chain, which is branched at O-3 or O-6 by (1 â†’ 3)- or (1 â†’ 6)-linked side chains. This research reports the variability of glucans in Ganoderma lucidum fruiting bodies and applicable methodologies to obtain such molecules. These polysaccharides can be further applied in biological studies aiming to investigate how their chemical differences may affect their biological properties.

Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line.

BACKGROUND: Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process. METHODS: Cholesterol depletion was induced on SCC-9 cells by methyl-ß-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence. RESULTS: Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-ß-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-ß-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-ß-cyclodextrin (p = 0.02, Kruskal-Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1. CONCLUSION: These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.

Description of the female of Leptagrion jeromei Lencioni, Vilela & Furieri, 2021 (Odonata: Coenagrionidae) with taxonomic notes on the male.

The female of Leptagrion jeromei Lencioni, Vilela & Furieri, 2021 is described, illustrated, and diagnosed based on a specimen collected in epiphytic bromeliads at the Federal University of Sergipe ( (B0545), BRAZIL, Federal University of Sergipe, So Cristvo, -10.92707, -37.10100, 30 m asl, 6.x.2023, A.B.S. Farias & J.C. Santos leg.). Additionally, we provide information on its biology, ecology, and taxonomic notes, along with illustrations of the collected males.

Survival analysis of dental implants placed in horizontally severely resorbed maxillae after reconstruction with xenogeneic graft: a case series.

PURPOSE: To evaluate the survival rates of dental implants with a hybrid macrostructure and the surface biomimetically coated with nanohydroxyapatite, placed in horizontally atrophic maxillae previously submitted to the guided bone regeneration (GBR) procedure, associated with the use of a deproteinized bovine bone graft (DBB). METHODS: Twenty-five patients who received 196 implants were involved in this study. First, these patients were submitted to GBR procedures and maxillary sinus lift, where DBB was used as the grafting material. The dental implants were placed after a minimum period of 6 months of the grafting procedures. The patients were followed up every six months and clinical/radiographic examinations were performed to assess the implants, using the following indicators as a reference: (1) Absence of mobility; (2) Absence of pain. Data about the age, surgery time, smoking status, implant size, and time between the grafting procedure and implant placement were correlated with implant failures. RESULTS: Twelve implants failed, generating a survival rate of 94.23%. None of the variables analysed correlated with the implant failures. CONCLUSION: Implants with a hybrid macrostructure and surface biomimetically coated with nanohydroxyapatite present good survival rates in horizontally atrophic maxillae grafted with DBB.

Evaluation of the photoprotective and antioxidant potential of an avobenzone derivative.

Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can generate photoproducts and reactive oxygen species (ROS). Adding antioxidants, such as resveratrol, to enhance the action of UV filters in sunscreens is an interesting strategy for reducing the damage caused by UV radiation exposure. However, new compounds must have their stability, safety and efficacy guaranteed. Avobenzone, a commonly used UV filter, stands out as a promising candidate for structural modification to enhance its stability. Its molecular hybridization with other UV filters and antioxidants can lead to safer and more effective compounds. In this study, the photoprotective and antioxidant potential of a derivative of avobenzone, hybridized with resveratrol's molecule, was evaluated using in vitro models of cells in monolayer and reconstructed human skin (RHS). Phototoxic potential was assessed using fibroblasts, while the antioxidant activity was measured using the DCFH2-DA probe in HaCaT keratinocytes and in-house RHS. The derivative exhibited UV absorption and demonstrated photostability. It did not exhibit any phototoxic nor photoreactivity potential. Additionally, it was able to photo stabilize a combination of photounstable UV filters, avobenzone and octyl methoxycinnamate, and to reduce their phototoxic potential. In terms of antioxidant activity, the derivative successfully protected against UVA-induced ROS production in the HaCaT keratinocytes model, showing statistical equivalence to the antioxidant control, quercetin (10 µg/mL). Furthermore, experiments conducted in the RHS model demonstrated a significant reduction of 30.7% in ROS generation compared to the irradiated control. This study demonstrated that structural modifications of avobenzone can lead to the development of a broad spectrum (absorbing UVB and UVA II radiation, as well as a portion of the UVA I radiation), non-phototoxic, non-photoreactive and photostable derivative for sunscreen and anti-aging formulations. This derivative enhances protection against oxidative stress induced by UV radiation and improves the effectiveness of sun protection. In addition to the monolayer model, the use of a standardized in-house RHS model was highly relevant for evaluating the effects of UV radiation and skin aging. This model closely mimics human physiological conditions and enables the testing of new compounds and the investigation of protective mechanisms against skin damage.

Occupational Exposure to Domestic Waste and Oral Mucosal Lesions: a Cross-Sectional Study / Exposição Ocupacional a Resíduos Domésticos e Lesões de Mucosa Oral: Estudo Transversal

This study aimed to evaluate the occurrence of oral mucosal lesions (OML) in domestic waste collectors and their association with occupational exposure to domestic waste. This cross-sectional study included 295 adult men who worked in a waste management company: 129 men were exposed to domestic waste during their labor of waste collection, and 166 were not. The waste collectors used personal protective equipment. The lips, buccal mucosa and sulcus, gum, alveolar ridge, tongue, the floor of the mouth, and soft and hard palate were evaluated. The chi-square or Fisher's exact test assessed the variables associated with OML (P ≤ 0.05). Twenty-five OMLs were observed in 22 volunteers, 8 in the exposed and 17 in the non-exposed group. Actinic cheilitis in the lips and candidiasis were the most common lesions in both groups. OML was not associated with waste exposure (OR= 0.72, 95% CI = 0.29-1.77, P = 0.47). There was no association between domestic waste exposure and actinic cheilitis (OR = 0.70, 95% CI= 0.23-2.15, P = 0.37), candidiasis (OR = 0.42, 95% CI= 0.08-2.12, P = 0.24) or leukoplakia (OR = 0.99, 95% CI= 0.97-1.01, P = 0.32). Actinic cheilitis in the lips and candidiasis were the most common lesions in both exposed and non-exposed groups. Occupational exposure to domestic waste was not related to OML. Proper use of personal protective equipment may have prevented the development of OML in domestic waste collectors. (AU)

Este estudo teve como objetivo avaliar a ocorrência de lesões de mucosa oral (LMO) em coletores de lixo doméstico e sua associação com a exposição ocupacional a resíduos domésticos. Este estudo transversal incluiu 295 homens adultos que trabalhavam numa empresa de gestão de resíduos: 129 homens foram expostos a resíduos domésticos durante o seu trabalho de coleta de resíduos e 166 não. Os coletores de lixo usavam equipamentos de proteção individual. Foram avaliados lábios, mucosa bucal e vesticulo, gengiva, rebordo alveolar, língua, assoalho da boca e palato mole e duro. O teste qui-quadrado ou exato de Fisher avaliou as variáveis associadas à LMO (P ≤ 0,05). Vinte e cinco LMO foram observadas em 22 voluntários, 8 no grupo exposto e 17 no grupo não exposto. Queilite actínica nos lábios e candidíase foram as lesões mais comuns em ambos os grupos. A LMO não foi associada à exposição a resíduos (OR = 0,72, IC 95% = 0,29-1,77, P = 0,47). Não houve associação entre exposição a resíduos domésticos e queilite actínica (OR = 0,70, IC 95% = 0,23-2,15, P = 0,37), candidíase (OR = 0,42, IC 95% = 0,08-2,12, P = 0,24) ou leucoplasia ( OR = 0,99, IC 95% = 0,97-1,01, P = 0,32). A queilite actínica nos lábios e a candidíase foram as lesões mais comuns nos grupos expostos e não expostos. A exposição ocupacional a resíduos domésticos não esteve relacionada com LMO. O uso adequado de equipamentos de proteção individual pode ter evitado o desenvolvimento de LMO em coletores de lixo doméstico. (AU)

Genotoxicity induced by endodontic sealers: A systematic review.

Introduction: This systematic review aimed to help further elucidate the following question: are endodontics sealers able to induce DNA damage in vitro or in vivo? Methods: This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 2020 criteria. A total of 23 studies were carefully selected by the authors. Results: Regarding the general characteristics, most studies evaluated, on average, 3-5 types of sealers (resin epoxy, salicylate, salicylate + MTA, zinc oxide-eugenol, bioceramic products, calcium hydroxide), performing comparisons between them. Our results demonstrate that endodontic sealers may be a genotoxic agent since most studies demonstrated positive findings, with the resin-based ones being the most potentially genotoxic. Conclusion: The type of genotoxicity assay, material evaluated, and dilution concentration levels influenced the outcome. This study clarifies whether and to what extent endodontic sealers are capable of inducing DNA injury in oral tissues.

Is the carotenoid production from Phaffia rhodozyma yeast genuinely sustainable? a comprehensive analysis of biocompatibility, environmental assessment, and techno-economic constraints.

Microorganisms, such as yeasts, filamentous fungi, bacteria, and microalgae, have gained significant attention due to their potential in producing commercially valuable natural carotenoids. In recent years, Phaffia rhodozyma yeasts have emerged as intriguing non-conventional sources of carotenoids, particularly astaxanthin and ß-carotene. However, the shift from academic exploration to effective industrial implementation has been challenging to achieve. This study aims to bridge this gap by assessing various scenarios for carotenoid production and recovery. It explores the use of ionic liquids (ILs) and bio-based solvents (ethanol) to ensure safe extraction. The evaluation includes a comprehensive analysis involving Life Cycle Assessment (LCA), biocompatibility assessment, and Techno-Economic Analysis (TEA) of two integrated technologies that utilize choline-based ILs and ethanol (EtOH) for astaxanthin (+ß-carotene) recovery from P. rhodozyma cells. This work evaluates the potential sustainability of integrating these alternative solvents within a yeast-based bioeconomy.

E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST contribute to epithelial-mesenchymal transition in salivary gland tumors.

BACKGROUND: Transcription factors are important in the epithelial-mesenchymal transition process and are possibly related to the development of a more invasive tumor phenotype. Thus, the objective of this study was to analyze the expression and identify the localization of cellular markers related to the epithelial-mesenchymal transition process in salivary gland tumors. STUDY DESIGN: The expression and localization of E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST were evaluated, using immunohistochemistry, in 48 salivary gland tumors, being 17 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). these proteins were compared to clinical and histopathologic parameters. normal gland tissues were included for immunohistochemical comparisons. RESULTS: ACC and MEC cases showed higher expression of SNAIL compared to PA. MEC showed high expression of SLUG and TWIST. Low expression of N-CADHERIN, SNAIL, and TWIST in ACC was frequent in T3 and T4. High expression of TWIST in MEC was more frequent at age ≥ 40 years A positive correlation was only observed between N-cadherin/SNAIL in ACC, between SNAIL/TWIST in MEC, and between SLUG/TWIST in PA. CONCLUSION: This study provided insight into EMT-related proteins (E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST) and their contribution to the maintenance of morphogenesis and the development of the salivary gland tumors and showed a positive correlation among N-CADHERIN/SNAIL in ACC and SNAIL/TWIST in MEC.

In silico drug design strategies for discovering novel tuberculosis therapeutics.

INTRODUCTION: Tuberculosis remains a significant concern in global public health due to its intricate biology and propensity for developing antibiotic resistance. Discovering new drugs is a protracted and expensive endeavor, often spanning over a decade and incurring costs in the billions. However, computer-aided drug design (CADD) has surfaced as a nimbler and more cost-effective alternative. CADD tools enable us to decipher the interactions between therapeutic targets and novel drugs, making them invaluable in the quest for new tuberculosis treatments. AREAS COVERED: In this review, the authors explore recent advancements in tuberculosis drug discovery enabled by in silico tools. The main objectives of this review article are to highlight emerging drug candidates identified through in silico methods and to provide an update on the therapeutic targets associated with Mycobacterium tuberculosis. EXPERT OPINION: These in silico methods have not only streamlined the drug discovery process but also opened up new horizons for finding novel drug candidates and repositioning existing ones. The continued advancements in these fields hold great promise for more efficient, ethical, and successful drug development in the future.

BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterial drug discovery.

Tuberculosis (TB) has claimed more lives over the course of two millennia than any other infectious disease worldwide. In 2021, the World Health Organization (WHO) estimated that 10.6 million people were diagnosed with TB, resulting in the deaths of 1.4 million HIV-negative individuals. The emergence of multidrug-resistant TB (MDR-TB), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), and extensively drug-resistant TB (XDR-TB), poses the primary challenge to overcome in the coming years. We have recently conducted an extensive analysis of investments and research endeavours in the field, with the overarching objective of achieving the established milestone of TB eradication by the year 2030. Over the past several years, there has been notable progress in advancing a multitude of promising compounds, each possessing distinct mechanisms of action, into clinical phases of development. However, it is worth noting that strains of mycobacteria resistant to current antitubercular drugs have already emerged for some of these compounds The exploration of the innovative Proteolytic Target Chimeras (PROTACs) protein degradation approach has emerged as a viable avenue for the discovery of novel antimicrobials. While the ubiquitin system is exclusive to eukaryotic cells, certain bacteria use a similar degradation system that relies on the recognition of phosphorylated arginine residues (pArg) by the ClpC:ClpP (ClpCP) protease, thereby leading to protein degradation. In this opinion article, we have described and analized the advances in the use of PROTACs that leverage bacterial proteolytic machinery (BacPROTACs) to design new antitubercular agents. Scope Statement. The development of novel pharmaceuticals for tuberculosis treatment is deemed urgently necessary due to the emergence of resistant strains. In this context, the introduction of new technologies capable of alleviating the disease and attaining the objectives outlined by the World Health Organization is imperative. Among the innovative strategies, the degradation of proteins that are crucial for the survival of the bacillus holds promise for generating new medications, particularly those that are effective at treating latent (non-replicating) Mycobacterium tuberculosis. Within this perspective, we present the advancements and obstacles encountered in the exploration of new BacPROTAC compounds, with the intention of encouraging research and illuminating challenges associated with the implementation of BacPROTACs to address to the global tuberculosis crisis.

Effective adsorption of cadmium and nickel ions in mono and bicomponent systems using eco-friendly adsorbents prepared from peanut shells.

The work investigates the potential of peanut shells, an abundant agro-industrial waste, to serve as an adsorbent precursor for the effective and simple treatment of effluents loaded with cadmium and nickel ions. Among the adsorbents prepared, carbonized peanut shell (CCarb), due to its higher adsorption capacity, proved to be the most effective compared to carbonized and activated peanut shell (CATQ). The carbonization process led to structural changes, which resulted in an increase in surface area (around 6 times more in CATQ) and pore volume (around 3 times more in CATQ). Even so, the amount of H+ acid sites due to acid activation produced unfavorable effects for adsorption. Hydroxyl, carboxyl and carbonyl groups were identified on the adsorbent surface which presented favorable charges for metal adsorption. This improvement propels the carbonized variant to the forefront, demonstrating the highest adsorption capacity and reaching equilibrium in less than 90 and 60 min for cadmium and nickel ions, respectively. In both monocomponent and bicomponent systems concentrations greater than 40 ppm signify an increase in adsorption capacity for Ni2+. The experimental data best fit the Freundlich model, showing maximum adsorption capacities of 17.04 mg g-1 for cadmium and 31.28 mg g-1 for nickel. Despite the antagonistic effect observed in the bicomponent system, this study concludes by underlining the promise of activated carbon from peanut shells to harmonize technical and environmental concerns.

Exploring Parkinson's Disease-Associated Depression: Role of Inflammation on the Noradrenergic and Serotonergic Pathways.

Parkinson's disease (PD) is a multifactorial disease, with genetic and environmental factors contributing to the disease onset. Classically, PD is a movement disorder characterized by the loss of dopaminergic neurons in the nigrostriatal pathway and intraneuronal aggregates mainly constituted of the protein α-synuclein. However, PD patients also display non-motor symptoms, including depression, which have been linked to functional abnormalities of non-dopaminergic neurons, including serotonergic and noradrenergic ones. Thus, through this comprehensive literature review, we shed light on the noradrenergic and serotonergic impairment linked to depression in PD, focusing on the putative involvement of inflammatory mechanisms.