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Dina Farinha,1,2 Ana Bela Sarmento-Ribeiro,2– 4 Henrique Faneca1,2 1CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; 2CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; 3Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 4Clinical Hematology Department, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, PortugalCorrespondence: Henrique Faneca, CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal, Tel +351-239-820-190, Fax +351-239-853-607, Email henrique@cnc.uc.ptPurpose: Hepatocellular carcinoma is the most frequent liver cancer and constitutes one of the main causes of cancer mortality. The combination of targeted therapy drugs, such as selumetinib and perifosine that inhibit cell signaling pathways involved in cell survival and proliferation, with the expression of tumor suppressor transgenes, such as PTEN, may result in an efficient therapeutic approach against HCC. Thus, the main objective of this work was to develop a new lipid-polymer hybrid nanosystem (HNP), composed of a PLGA core coated with a pH-sensitive lipid bilayer functionalized with the targeting ligand GalNAc, in order to specifically and efficiently deliver this novel combination of therapeutic agents in HCC cells.Methods: Transmission electron microscopy, zeta potential, Fourier transform infrared spectroscopy, and dynamic light scattering were used to determine the physicochemical properties of hybrid nanosystems and their components. The biological activity and specificity of nanosystems were evaluated using luminescence and flow cytometry. A variety of techniques were used to assess the therapeutic activity of hybrid nanosystems, including the Alamar Blue assay for cell viability; flow cytometry for cell death mechanisms, mitochondrial membrane potential and cell cycle; luminescence for caspase activity; flow cytometry and fluorescence microscopy for cell proliferation; and Western blot for molecular targets levels.Results: The obtained results showed that this new hybrid nanosystem not only has a high loading capacity of both drugs, but also allows for substantial expression of the PTEN transgene. In addition, the developed formulation has high stability, adequate physicochemical properties and high specificity to HCC cells. Moreover, the achieved data revealed that this innovative nanosystem presents a high antitumor effect, demonstrated not only by the enhancement on the programmed cell death, but also by the reduction in cell proliferation capacity.Conclusion: The generated formulation shows a high anticancer effect, demonstrating a high translational potential for future clinical application in HCC treatment. Keywords: hybrid nanosystem, gene and drug delivery, chemotherapy, gene therapy, hepatocellular carcinoma

Hyperuricemia is a common finding in hypertensive patients, especially among those who are on diuretic therapy. However, its clinical relevance regarding cardiovascular and chronic kidney disease (CKD) has not clearly been established. The authors assessed whether, in a population of 385 hypertensive women categorized according to diuretic therapy, the stratification in quartiles by uric acid levels would identify a gradient of changes in renal function and in risk factors for cardiovascular disease. The following were evaluated: serum uric acid, glycemia, total and fractional cholesterol, triglycerides, apolipoprotein (Apo) B, Apo A-I, and C-reactive protein. Renal function was assessed by serum creatinine, albuminuria, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation, whereas cardiovascular risk was estimated through the Framingham score. A total of 246 women were on diuretic therapy; 139 were taking other antihypertensive medications. There was a reduction in eGFR parallel to the increase in uric acid levels, regardless of diuretic use and without a concomitant increase in albuminuria. In both groups, higher uric acid levels translated into an increase in metabolic syndrome components, in markers of insulin resistance, triglyceride / high-density lipoprotein levels, and Apo B/Apo A-I ratios, as well as in Framingham scores. Hyperuricemia was associated with an increase in inflammatory markers only in patients on diuretic therapy. In a binary logistic regression, hyperuricemia (uric acid >6.0 mg/ dL) was independently associated with CKD (eGFR <60 mL/ min / 1.73 m(2)) (odds ratio, 2.63; 95% confidence interval, 1.61-4.3; P<.001). In hypertensive women, the presence of hyperuricemia indicated a substantial degree of kidney dysfunction as well as a greater cardiovascular risk profile. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Western and Asian countries. Effective antihypertensive therapy reduces the rate of decline in renal function and postpones ESRD in patients with diabetic nephropathy. OBJECTIVE: This review presents evidence from studies on how blood pressure control, plasma glucose control, and the presence of proteinuria determine outcomes in diabetic patients. The role of angiotensin II (All) in the development of diabetic nephropathy and the reno- and cardiobeneficial effects of AII antagonism in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy also are addressed. METHODS: Articles included in this review were found using a MEDLINE search for studies published from 1991 to 2001 and including the search terms diabetic nephropathy, type 2 diabetes mellitus, microalbuminuria, proteinuria, angiotensin receptor blockade, angiotensin-converting enzyme inhibition, and cardiovascular disease. Articles reporting new data, new mechanisms, major clinical trials, and our own data were included. RESULTS: Recently, the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL) trial provided sufficient data to conclude that the blockade of the All AT1 receptor with losartan confers renoprotection in patients with DM-2 and nephropathy. Similar results were obtained with irbesartan in the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study (IRMA 2). The results of RENAAL indicate that the renoprotective effects of losartan were attributable to effects beyond blood pressure control. In addition to the favorable impact of the All blockade on blood pressure and renal hemodynamics, the blockade of the growth-promoting, profibrotic, nonhemodynamic actions of AII also may be important for renoprotection. Intensive blood pressure control also confers cardiovascular protection in pa- tients with DM-2. Some studies suggest that the blockade of the renin-angiotensin system confers superior cardioprotective effects in patients with DM-2. The RENAAL study also showed cardioprotection with losartan, with an important reduction in the risk for first hospitalization for heart failure. CONCLUSION: Evidence supports the importance of an effective blockade of AII action for both reno- and cardioprotection in patients with DM-2. [ABSTRACT FROM AUTHOR]

We have studied repositioning of carvedilol (an antihypertensive drug) incorporated into MCM-41 mesoporous silica. The repositioning proposes a reduction in the slow pace of discovery of new drugs, as well as toxicological safety and a significant reduction in high research costs, making it an attractive strategy for researchers and large pharmaceutical companies. We obtained MCM-41 by template synthesis and functionalized it by post-synthesis grafting with aminopropyltriethoxysilane (APTES) only or with folic acid (FA), which gave MCM-41-APTES and MCM-41-APTES-FA, respectively. We characterized the materials by scanning and transmission electron microscopy, zeta potential (ZP) measurements, Fourier transform infrared absorption spectroscopy, x-ray diffractometry, nitrogen gas adsorption, and CHNS elemental analysis. We quantified the percentage of drug that was incorporated into the MCM-41 materials by thermogravimetric analysis and evaluated their cytotoxic activity in non-tumor human lung fibroblasts and the tumor human melanoma and human cervical adenocarcinoma cell lines by XTT salt reduction (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-arboxanilide). The x-ray diffractograms of the MCM-41 materials displayed low-angle peaks in the 2 θ range between 2° and 3°, and the materials presented type IV nitrogen adsorption isotherms and H2 hysteresis typical of the MCM-41hexagonal network. The infrared spectra, the charge changes revealed by ZP measurements, and the CHN ratios obtained from elemental analysis showed that MCM-41 was amino-functionalized, and that carvedilol was incorporated into it. MCM-41-APTES incorporated 23.80% carvedilol, whereas MCM-41 and MCM-41-APTES-FA incorporated 18.69% and 12.71% carvedilol, respectively. Incorporated carvedilol was less cytotoxic to tumor and non-tumor cells than the pure drug. Carvedilol repositioning proved favorable and encourages further studies aimed at reducing its cytotoxicity to non-tumor cells. Such studies may allow for larger carvedilol incorporation into drug carriers or motivate the search for a new drug nanocarrier to optimize the carvedilol antitumoral activity., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Bacterial peritonitis infections comprise a life-threatening clinical condition in domestic animals that commonly lead to sepsis and high mortality. A set of bacterial pathogens have been identified in septic peritonitis in livestock and companion animals. Nonetheless, most descriptions are restricted to case reports or limited to only one domestic species, and a restrict number of comprehensive studies involving this infection has focused on a great number of domestic animals. Here, we retrospectively investigated selected epidemiological data (with an emphasis in outcome), clinical signs, bacteriological culturing, and in vitro antimicrobial susceptibility patterns of microorganisms isolated of peritoneal fluid from 160 domestic animals (2009-2023) compatible with septic peritonitis. Bacteria were isolated from 71.9% (115/160) of the peritoneal fluid from 75 dogs (75/115 = 65.2%), 22 cats (22/115 = 19.1%), 14 horses (14/115 = 12.2%), and 4 cattle (4/115 = 3.5%). Among animals with bacterial isolation, Escherichia coli (34/115 = 29.6%), alfa-hemolytic Streptococcus (12/115 = 10.4%), Staphylococcus aureus (8/115 = 6.9%), beta-hemolytic Streptococcus (7/115 = 6.1%), and Pasteurella multocida (6/115 = 5.2%) were predominant in pure culture, in addition to a miscellaneous of other bacteria isolated in minor frequency, e.g., Pseudomonas sp., Trueperella pyogenes, Klebsiella pneumoniae, and Salmonella sp. In general, in vitro susceptibility tests of isolates revealed that florfenicol, chloramphenicol, and amoxicillin/clavulanic acid showed moderate effectivity (≥ 60%). Conversely, most of isolates exhibited resistance mainly to trimethoprim/sulfamethoxazole, enrofloxacin, and penicillin (> 60%). Additionally, multidrug resistance was found in 42.6% (49/115) of the isolates. Data related to the outcome were available in 37.4% (43/115) of animals that had bacterial isolation and, from these, the mortality rate was 79.1% (34/43), with a significant association (p < 0.036) between mortality and septic peritonitis by gram-negative bacteria. Neoplasia (7/43 = 16.3%), pneumonia/pulmonary abscess (5/43 = 11.6%), hepatitis (5/43 = 11.6%), metritis/pyometra (4/43 = 9.3%), and gall bladder rupture (3/43 = 7%) represented the probable main sources of septic peritonitis. Anorexia (34/115 = 29.6%), emesis (29/115 = 25.2%), lethargy (26/115 = 22.6%), respiratory distress (25/115 = 21.7%), ascites (20/115 = 17.4%), and fever (19/115 = 16.5%) were the most frequent clinical signs among animals with bacterial isolation. A variety of bacteria were isolated in the peritoneal fluid of animals, with a predominance of Enterobacteriaceae, streptococci, and staphylococci, highlighting the opportunistic nature of the pathogens in septic peritonitis. High in vitro multidrug resistance of isolates and high mortality of animals reinforce the need for early diagnosis and therapy based on the in vitro antimicrobial profile of the pathogens involved in septic peritonitis. Our results contribute to the etiological characterization, clinical-epidemiological findings, and vigilance of multidrug-resistant bacteria in septic peritonitis among livestock and companion animals., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: We have previously demonstrated that electrical stimulation of the carotid sinus nerve (CSN) protects the development of periodontitis. In the current study, we evaluated whether periodontitis accelerates the onset of hypertension in spontaneously hypertensive rats (SHR); and whether electrical stimulation of the CSN would delay the onset of hypertension., Methods: Three-week old SHR were implanted with electrodes around the CSN for electrical stimulation for 13 days. Bilateral ligation of the first molar and oral administration of Porphyromonas gingivalis induced periodontitis. The femoral artery of the SHR was cannulated, and 24 h later, in a conscious state, the blood pressure was recorded., Results: Five-week old sham SHR (subjects without electrical stimulation of the CSN) did not demonstrate hypertension. However, when the SHR were submitted to periodontitis they exhibited hypertension at 5 weeks of age. Nevertheless, the stimulation of the CSN prevented the onset of hypertension. Periodontitis promoted alveolar bone loss in SHR; but, electrical stimulation of the CSN prevented this undesirable outcome following the exposure to periodontitis., Conclusion: Periodontitis accelerated the onset of hypertension in SHR; while the electrical stimulation of the CSN delayed the onset of hypertension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7- O -methylvestitol., Methods: BFRP's toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract's effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP's main compounds., Results: BFRP primarily contained vestitol (128.24 ± 1.01 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP., Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties.

Purpose: Several vaccines against respiratory syncytial virus (RSV) are being developed. The objective of this systematic review is to determine the efficacy of these vaccines in preventing RSV disease in adults over 60 years of age, especially regarding severe illness., Methods: We researched MEDLINE, CENTRAL, Scopus, medRxiv, bioRxiv and ClinicalTrials.gov until April/2024. Randomized controlled trials studying an anti-RSV vaccine in adults above 60 years and reporting RSV-related acute respiratory infection/disease (ARI/ARD), lower respiratory tract infection/disease (LRTI/LRTD) and severe LRTI/LRTD were included. Vaccine efficacy was calculated as ([1 - risk ratio] × 100). Risk of bias and certainty of evidence were assessed by RoB2 tool and GRADE approach. The meta-analytical relative risk of ARI/ARD and LRTI/LRTD was estimated, with a subgroup analysis performed according to the vaccine type. The random effects model was used., Results: We included seven studies, five addressing prefusion vaccines and two regarding non-prefusion ones. The number of RSV-related LRTI/LRTD cases was reduced by vaccination, with a relative risk of 0.39 [CI 95% 0.22 to 0.69] and a vaccine efficacy of 61%. Considering the subgroup of prefusion vaccines alone, there is a relative risk of 0.27 [CI 95% 0.19 to 0.36] for LRTI/LRTD and a vaccine efficacy of 73%. ARI/ARD incidence presented a similar pattern. Only one trial reports results for severe LRTI/LRTD, with a vaccine efficacy of 94.1% [95% CI 62.4 to 99.9]., Conclusions: Prefusion anti-RSV vaccines are efficacious in the prevention of LTRI/LTRD and ARI/ARD cases. More studies regarding severe LTRI/LTRD are necessary in the future., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Lycium barbarum L. berries have a remarkable chemical composition and extensive biological activities, being a valuable component of health and nutraceutical practices. Nevertheless, a deep insight on the intestinal permeation of the pro-healthy bioactive compounds is urgently needed to predict the real effects on human body. This study attempted, for the first time, to optimize the Ultrasound-Assisted Extraction (UAE) of goji berries using a Response Surface Methodology approach and establish the intestinal permeation of the principal pro-healthy compounds. The optimal extraction conditions were a solid:liquid ratio of 8.75 % for 56.21 min, using an intensity of 59.05 W/m 2 . The optimal extract displayed a remarkable antioxidant capacity, with LC/DAD-ESI-MS analysis unveiled a diverse phytochemical profile, encompassing different compounds (e.g. glu-lycibarbarspermidine F, 2-glu-kukoamine, rutin, 3,5-dicaffeoylquinic acid). The intestinal co-culture model demonstrated that glu-lycibarbarspermidine F (isomer 2) (73.70 %), 3,5-dicaffeoylquinic acid (52.66 %), and isorhamnetin-3-O-rutinoside (49.31 %) traversed the intestinal cell layer, exerting beneficial health-promoting effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Melanoma, an aggressive and potentially fatal skin cancer, is constrained by immunosuppression, resistance, and high toxicity in its treatment. Consequently, there is an urgent need for innovative antineoplastic agents. Therefore, this study investigated the antimelanoma potential of guttiferone E (GE). In an allogeneic murine B16 melanoma model, GE was administered subcutaneously and intraperitoneally. Antitumor evaluation included tumor volume/weight measurements and histopathological and immunohistochemical analysis. Furthermore, the toxicity of the treatments was evaluated through body/organ weights, biochemical parameters, and genotoxicity. Subcutaneous administration of 20 mg/kg of GE resulted in a significant reduction in both tumor volume and weight, effectively suppressing melanoma cell proliferation as evidenced by a decrease in mitotic figures. The tumor growth inhibition rate was equivalent to 54%. This treatment upregulated cleaved caspase-3, indicating apoptosis induction. On the other hand, intraperitoneal administration of GE showed no antimelanoma effect. Remarkably, GE treatments exhibited no toxicity, evidenced by non-significant differences in body weight gain, as well as organ weight, biochemical parameters of nephrotoxicity and hepatotoxicity, and genotoxic damage. This study revealed, for the first time, the efficacy of subcutaneous administration of GE in reducing melanoma, in the absence of toxicity. Furthermore, it was observed that the apoptotic signaling pathway is involved in the antimelanoma property of GE. These findings offer valuable insights for further exploring GE's therapeutic applications in melanoma treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hematological neoplasias are among the most common cancers worldwide, and the number of new cases has been on the rise since 1990, reaching 1 [...].

COVID-19 pandemic health restrictions affected the theoretical and practical teaching of anatomy. This review aims to analyze studies about teaching anatomy in this period. A search through the PubMed/Medline, Scopus, Lilacs, Web of Science, and Google Scholar databases found 1607 articles. After removing duplicates and excluding articles by reading the title/abstract, and then after full reading, 43 articles were included. The remote synchronous and asynchronous active methodologies employ virtual reality, 3D models, and web conferencing platforms to enable audio-visual interaction. While synchronous remote teaching emerged as an important opportunity, its efficacy in imparting knowledge and practical skills remains under scrutiny., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort., (© 2024. The Author(s).)

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer., Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease., Results and Discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vβ 5.1 in CD4+ CD20+ T cells in CLL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodrigues, Laranjeira, Pinho, Silva, Silva, Coucelo, Oliveira, Simões, Damásio, Silva, Urbano, Sarmento-Ribeiro, Geraldes, Domingues, Almeida, Criado, Orfao and Paiva.)

Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to novel agents, sometimes in combination with conventional therapies, makes this management even more challenging. A careful balance between treatment efficacy and its tolerability should be considered for every patient. During treatment, a close monitoring of comorbidities, disease-related manifestations and treatment side effects is recommended, as well as a proactive approach, with reinforcement of information and patient awareness for the early recognition of adverse events, allowing prompt therapeutic adjustments. In this review, we discuss various issues that must be considered in the treatment of MM patients, while giving practical guidance for monitoring, prevention and management of myeloma-related manifestations and treatment-related toxicities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Geraldes, Roque, Sarmento-Ribeiro, Neves, Ionita, Gerivaz, Tomé, Afonso, Silveira, Sousa, Bergantim and João.)

Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. Bibliographic research was conducted, looking at PubMed, Embase, Web of Science, and Scopus, where 935 articles were found. After removing duplicates and excluding articles by reading the title and abstract, 131 articles were selected for full reading and 104 articles were included. Another 38 articles were added from the gray literature. This review followed the PRISMA-ScR guidelines. The historical period described ranges from 1969 to 2023, in which, during the 21st century, in vitro and in vivo studies became more common and, from 2010 to 2023, the number of randomized controlled trials increased. Among the various approaches tested are the incorporation of antimicrobial products into prosthetic materials, the improvement of oral and denture hygiene protocols, the development of synthetic and natural products for the chemical control of microorganisms, and intervention with local or systemic antimicrobial agents. Studies report good results with brushing combined with sodium hypochlorite, and new disinfectant solutions and products incorporated into prosthetic materials are promising.

Cutaneous pythiosis is a life-threatening infectious disease. Low-level laser therapy (LLLT) and ozone (O 3 ) have been used individually in the treatment of infected wounds. The goals of the study were a) to characterize the antimicrobial action of the photo-ozone therapy (LLLT-O 3 ) against equine Pythium insidiosum, and b) to assess the cytotoxic potential of the LLLT-O 3 in keratinocytes. Specimens of pathogen were isolated from 10 horses. After culturing, 120 hyphae plugs were distributed among four groups (n=30 hyphae plugs/group): LLLT (laser irradiation for 160 sec;), O 3 (exposition to O 3 for 15 min;), LLLT-O 3 (LLLT and O 3 treatments in sequence) and control (untreated plugs). The hyphae growth was measured during the first 14 days post-treatment. Where there was an absence of hyphae growth, the plug was recultured for an additional 7 days. The cytotoxic potential of the treatments against HaCaT keratinocytes was assessed by colorimetric assays. The LLLT-O 3 and O 3 treatments inactivated, respectively, 92.3% (28/30) and 30% (9/30) of the samples. No growth was detected after 7 days reculture of inactivated hyphae plugs on new media. Hyphae growth was visualized in 100% of the control and LLLT hyphae plugs. The viability of HaCaT cells was not affected by the isolated treatments (LLLT and O 3 ), while the LLLT-O 3 showed slight cytotoxic effect (20%) when compared to the control group (P<0.05). Photo-ozone therapy inactivated equine P. insidiosum hyphae with minimal cytotoxicity in skin cells in vitro., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Melanoma is the most aggressive and lethal type of skin cancer due to its characteristics such as high metastatic potential and low response rate to existing treatment modalities. In this way, new drug prototypes are being studied to solve the problem of treating patients with melanoma. Among these, ruthenium-based metallopharmaceuticals may be promising alternatives due to their antitumor characteristics and low systemic toxicity. In this context, the present study evaluated the antineoplastic effect of the ruthenium complex [Ru(mtz)(dppe) 2 ]PF 6 -2-mercaptothiazoline-di-1,2-bis(diphenylphosphine) ethaneruthenium(II), namely RuMTZ, on human melanoma (A-375) and murine (B16-F10) cells, considering different approaches. Through XTT colorimetric and clonogenic efficiency assays, the complex revealed the selective cytotoxic activity, with the lowest IC 50 (0.4 µM) observed for A375 cells. RuMTZ also induced changes in cell morphology, increased cell population in the sub-G0 phase and inhibiting cell migration. The levels of γH2AX and cleaved caspase 3 proteins were increased in both cell lines treated with RuMTZ. These findings indicated that the cytotoxic activity of RuMTZ on melanoma cells is related, at least in part, to the induction of DNA damage and apoptosis. Therefore, RuMTZ exhibited promising antineoplastic activity against melanoma cells., (© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 μg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

Pterodon pubescens Benth is a Brazilian medicinal plant ( sucupira , in Brazilian Portuguese). This paper aims to determine the volatile composition and antibacterial activities of hexane extract from P. pubescens seeds (HE-PP). Antibacterial activities were screened by the microdilution broth method in 96-well culture plates and MIC values were expressed as µg/mL. HE-PP was active against several oral bacteria whose MIC values ranged between 12.5 µg/mL and 50 µg/mL and against three mycobacterial strains (MIC = 125 µg/mL and 500 µg/mL). In addition, HE-PP was active against Xanthomonas citri strain (MIC = 100 µg/mL). Cytotoxic activity of the extract was evaluated in human tumour and non-tumour cell lines. HE-PP showed selective cytotoxicity to cervical adenocarcinoma (HeLa cells - IC 50 = 53.47 µg/mL). Its major constituents were identified by GC-MS and GC-FID: E -caryophyllene, vouacapane, E -geranylgeraniol and dehydroabietol. Results reinforce the biological potential of HE-PP against a broad spectrum of pathogenic and phytopathogenic bacteria.

Objective: To assess the association between risk factors for developing denture stomatitis (DS) and oral health-related quality of life (OHRQoL) in complete denture wearers., Methodology: Participants of both sexes, wearing complete dentures, were classified using the modified Newton classification for the absence or the severity of DS and allocated to groups Normal or zero, IA, IB, II, and III. Lifestyle, oral and denture history, and medication use were assessed using specific questionnaires; clinical parameters such as anatomical characteristics of support were evaluated with the Kapur classification; salivary flow (SF) was calculated by the volume of unstimulated saliva per minute; and microbial load was determined by counting colony forming units (CFU) of target microorganisms present in the biofilm collected from dentures and palate. OHIP-EDENT assessed the OHRQoL. Kendall's tau&#95;b and Spearman tests were applied with a significance level of 5%., Results: 184 patients (143 female and 41 male) aged 65.5 ± 6.8 years were evaluated. Positive correlations were found for sex (women; p=0.013, r=0.16), individuals who started to consume alcoholic beverages as a young adult (18-27 years) (p=0.008, r=0.22), CFU of Candida spp. (p<0.001, r=0.27 denture; p<0.001, r=0.31 palate); Candida albicans (p=0.004, r=0.22 denture; p=0.003, r=0.25 palate), and Candida glabrata (p=0.004, r=0.22 denture; p=0.001, r=0.27 palate). Moreover, negative correlations with DS were found for CFU of Staphylococcus spp. (p=0.004, r=-0.20 palate) and enterobacteria (p=0.002, r=-0.24 palate), as well as a negative correlation between SF (p=0.009, r=-0.193) and DS. The CFU of Staphylococcus spp. and enterobacteria on the palate significantly correlated with OHRQoL., Conclusion: Being female, consuming alcoholic beverages as a young adult, CFU of Candida spp., Candida albicans, Candida glabrata, and salivary flow may be the most significant risk factors for DS. The microbial load of Staphylococcus spp. and enterobacteria seems to influence the quality of life for complete denture wearers.