Does waterpipe smoke induce genotoxicity (DNA damage) in mammalian cells in vivo? A systematic review.

The waterpipe works by placing tobacco in a bowl with holes at the bottom, which is connected to a tube leading to a water-filled container. Upon heating the tobacco product with hot charcoal placed atop it, the emanating smoke is inhaled by the user via a hose linked to the water receptacle. The aim of this literature review is to evaluate whether the use of waterpipes can indeed induce genotoxicity in mammalian cells in vivo. Additionally, the study aims to assess the quality of the included research articles on this topic to ensure the reliability of the findings. We performed comprehensive searches in PubMed, SCOPUS, and Web of Science to identify relevant articles published until July 2024. The findings confirmed that waterpipe smoke induces genetic damage. This assertion is supported by the fact that 11 studies (out of 15) received a Strong or Moderate assessment categorization, suggesting that the majority of studies adhered to most technical standards, thereby enhancing the reliability of the research findings. Regarding the types of DNA damage reported, DNA strand breaks, chromosome damage and oxidative DNA damage were found in this review. Taken together, this study holds significant importance in assessing the efficacy of genotoxicity assays in detecting DNA damage due to waterpipe smoke and the comet and micronucleus assays are suitable biomarkers for biomonitoring people who use waterpipe.

Gamma-Decanolactone Increases Stress Resistance and Improves Toxicity Parameters on the Caenorhabditis elegans Alternative Model.

Gamma-decanolactone (GD) is a monoterpene compound with anticonvulsant, antiparkinsonian, and neuroprotective effects in preclinical trials. This study aimed to evaluate the toxicity and antioxidant profile of GD in silico and in the Caenorhabditis elegans (C. elegans) experimental model. The C. elegans was used to determine the median lethal concentration (LC50) of GD, as well as its effect on survival, development, reproduction, pharyngeal pumping, and stress resistance assays. The in silico study did not indicate hepatotoxic, cardiotoxic, or mutagenic potential to GD. It reduced the worms' survival, both at the L1 and L4 stages, in a concentration-dependent manner with an LC50 value of 212.16 ± 5.56 µmol/mL. GD did not alter the development, reproduction, and pharyngeal pumping under normal experimental conditions in the three concentrations tested (25, 50, and 100 µmol/mL). In the thermal stress assay, GD did not change the survival pattern of the worms. Hydrogen peroxide (H2O2) reduced the survival of C. elegans and decreased the number of pharyngeal pumping, with these effects being reversed by GD. Also, GD presents an antioxidant activity by modulation the expression of the stress response genes such as sod-3, ctl-1,2,3, and gst-4. In conclusion, GD showed low toxicity in the C. elegans model and antioxidant profile both in the in silico study and in vivo assays.

Synergistic Antifungal Effect and In Vivo Toxicity of a Monoterpene Isoespintanol Obtained from Oxandra xylopioides Diels.

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.

XP-Endo Finisher behaviour and irrigant temperature in intracanal environment: Clinical measurements.

AIM: To evaluate the behaviour of the XP-Endo Finisher and the variation in the intracanal temperature of the irrigant at rest and when activated over time. METHODOLOGY: Differential scanning calorimetry (DSC) determined the transformation temperatures of XP-Endo Finisher instruments. A digital thermocouple was used to measure the temperature of the irrigant inside the pulp chamber. Two measurements were performed for each tooth (n = 12): with the irrigant at rest and during XP-Endo agitation for 60 s to observe the temperature evolution. The data were statistically analysed using a t-test with a confidence level of 95%. RESULTS: DSC results suggested that the XP-Endo Finisher had a mixed R-phase and austenitic structure at room temperature. The temperature values at predetermined time points (0, 10, 40, 70, 120 and 240 s) were measured, and no statistical difference was observed between the values of the resting and activated solutions at any of the selected points (p > .05). For the protocol performed with the XP-Endo file, the mean irrigant temperature observed at instrument insertion inside the root canal was 28.65°C. After 60 s of agitation, the temperature was 34.02°C. The solution temperature stabilized inside the canal only after 211 s at 35.5°C. The mean maximum irrigation solution temperature recorded inside the canal was 35.5°C without agitation and after XP-endo agitation (p > .05). CONCLUSIONS: Although the XP-Endo Finisher system does not promote heating of the irrigation solution, file expansion responsible for improved instrument cleaning starts at a temperature below the expected value.

Honey and Aloe vera Solution Increases Survival and Modulates the Tumor Size In Vivo.

SCOPE: The combination of honey and Aloe vera is used as a popular complementary treatment for cancer due to their nutraceutical properties. This study aims to investigate the anticancer activity of honey and A. vera solution and its ethanolic extraction through in vitro and in vivo approaches. METHODS AND RESULTS: After comparisons of honey and A. vera (HA) solution and its ethanolic extraction solution (E) samples by UPLC-ESI-MS/MS, the study verifies HA-treatment affected only Walker tumor cells viability at the highest dose, and E-treatment has a more cytotoxic/antiproliferative effect in MCF-7 and Walker-256 cells. The in vivo results show a higher survival rate in Walker-256 tumor-bearing rats (WHA), with higher NK cell infiltration in tumor tissue and a tendency in the WE group. These results are possible due to decreased mannose-based immunomodulatory polysaccharides and aloin-A contents in the ethanolic extract solution compared to HA solution. CONCLUSION: The current study provides compelling evidence of selectively cytotoxic against tumor cells under honey and A. vera solution and ethanolic extraction solution treatment, due to the cytotoxic/antiproliferative compounds. Therefore, the use of honey and A. vera solution could be used as a basis for coadjuvant therapy in cancer treatment.

Isolation of Monocrotophos degrading bacterial consortium from agricultural soil for in vivo analysis of pesticide degradation.

Extensive Monocrotophos (MCP) application in agricultural soils has led to its ubiquitous accumulation in the environment. Human health can be adversely affected by chronic exposure to produce and water from such areas, causing endocrine dysfunction, birth defects, blood and nervous disorders. This study investigated the possibility of detecting Monocrotophos-degrading bacteria in soil samples taken from a cotton cultivation field in a local area. We isolated a consortium that could tolerate and neutralize Monocrotophos upto a concentration of 2000 ppm. The consortium on 16 S rRNA sequencing were identified as Micrococcus luteus SBR2, Rhodococcus SBR5, Bacillus aryabhattai SBR8, Ochrobactrum intermedium SBK2. Significant tolerance of individual strains in the range of 500-5000 ppm was observed when incubating them in vitro with Monocrotophos in minimal salt medium. An analysis of the degrading genes opdA, mpd, and opd revealed plasmid borne opdA and mpd in the O.intermedium strain and B.aryabhattai strain. All the strains indicated genomic opdA and mpd whereas opd was not detected in plasmid or genomic DNA. The HPLC showed no peak at 2.5 min, when individual strains were incubated with Monocrotophos. The HPLC analysis of soil samples incubated with the consortium for two weeks showed complete degradation of Monocrotophos. GC-MS analysis confirmed that Monocrotophos and its solvent cyclohexamide were degraded into non-toxic compounds such as cyclotrisiloxane compounds, acetic acid, and others. This study indicates that the expression of organophosphate hydrolyzing enzymes in the consortium can greatly contribute to the neutralization of organophosphorus compounds and also serve as a bioremediation method for agricultural soils.

In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones.

BACKGROUND: Schistosomiasis, caused by the parasitic blood fluke Schistosoma mansoni, is a significant global health concern, particularly in tropical and subtropical regions. The available chemotherapeutic drug is restricted to praziquantel with present problems related to efficacy, toxicity and resistance, justifying the search for new drugs. Different natural products, including γ-lactones, have demonstrated anthelmintic activity. Thus, in this study, new γ-lactones from Porcelia ponderosa were investigated for their anti-S. mansoni effects in vitro and in vivo. PURPOSE: To evaluate the therapeutical potential against S. mansoni of the mixture of γ-lactones 1 + 2 obtained from Porcelia ponderosa seeds. STUDY DESIGN AND METHODS: The precipitate formed during the concentration of CH2Cl2 extract from seeds of P. ponderosa showed to be composed by a mixture of the new γ-lactones 1 + 2 (in a ratio 77:23) which were chemically characterized using NMR and ESI-HRMS. This mixture was evaluated in vitro and in vivo against S. mansoni, using a murine model of schistosomiasis. Additionally, toxicity of the mixture of 1 + 2 (77:23) was determined using mammalian cell lines (in vitro) or the model organism Caenorhabditis elegans (in vivo). RESULTS: Seeds of P. ponderosa afforded a mixture of two unreported γ-lactones, 3­hydroxy-4-methylene-2-(tetracosa-17'Z,23'-diene-13',15'-diynyl)­but-2-enolide (1) and 3­hydroxy-4-methylene-2-(tetracos-17'Z-ene-13',15'-diynyl)­but-2-enolide (2). Initially, the antischistosomal activity of the mixture of 1 + 2 (77:23) was investigated in vitro, and obtained results demonstrate reduced activity against Schistosoma mansoni worms (EC50 of 83.3 µg/ml) in comparison to positive control praziquantel (EC50 of 1.5 µg/ml). However, when tested in vivo using oral administration at 400 mg kg-1, the standard dose used in the murine model of schistosomiasis, the mixture of 1 + 2 (77:23) revealed expressive reductions in both worm burden (65.7 %) and egg production (97.2 %), similar of those observed to praziquantel (89.7 % and 91.5 %, respectively). On the other hand, when treated using 200 and 100 mg kg-1, reductions in worm burden (25.7 and 12.4 %) and egg production (33.6 and 13.3 %) were also observed. Importantly, the mixture of 1 + 2 (77:23) exhibited no toxicity using mammalian cell lines (in vitro) or C. elegans (in vivo). CONCLUSION: Considering the promising in vivo activity of γ-lactones from P. ponderosa, the mixture of 1 + 2 (77:23) can be considered as promising candidate for the development of novel antischistosomal therapeutics, underscoring the importance of biodiversity exploration in the search for effective treatments against neglected tropical diseases.

Administration of Lacticaseibacillus casei CSL3 in Swiss Mice with Immunosuppression Induced by Cyclophosphamide: Effects on Immunological, Biochemical, Oxidative Stress, and Histological Parameters.

The study aimed to evaluate the effects of supplementation with Lacticaseibacillus casei CSL3 in Swiss mice immunosuppressed with cyclophosphamide on immunological, biochemical, oxidative stress, and histological parameters. The animals were distributed into four groups (control, CSL3, cyclophosphamide, and CSL3 + cyclophosphamide), where two groups were treated with L. casei CSL3 (10 log CFU mL-1) for 30 days, and two groups received chemotherapy (days 27 and 30-total dose of 250 mg kg-1). Counts of lactic acid bacteria (LAB) and bile-resistant LAB in stool samples; blood count (erythrogram, leukogram, and platelets); serum total cholesterol levels; catalase enzyme activity; and thiobarbituric acid reactive substances (TBARS) levels in liver, kidney, and brain; IL-4 expression; IL-23, TNF-α, NF-κß in the spleen; and histological changes in the liver, kidneys, and intestine were evaluated. The CSL3 + cyclophosphamide group showed a significant increase in bile-resistant LAB counts in feces (p = 0.0001), leukocyte counts, and expression of IL-23, TNF-α, and NF-κß (p < 0.05) significantly reduced total cholesterol levels (p = 0.001) and protected liver damage of supplemented animals. For oxidative stress damage, the bacterium did not influence the results. It is concluded that the bacterium is safe at a concentration of 10 log CFU mL-1 and has probiotic potential due to its positive influence on the immune response and lipid metabolism.

Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection.

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.

Oral Administration of Kaempferol Isolated from Baccharis Mattogrosensis Enables In Vivo Activity Against Schistosoma Mansoni.

Baccharis mattogrosensis is a species from Asteraceae which has been used in Brazilian folk medicine to treatment of several illnesses, including those caused by parasites. In the present work, the MeOH extract of aerial parts of B. mattogrosensis was subjected to chromatographic fractionation to afford three flavonoids: apigenin (1), quercetin (2), and kaempferol (3) as well as a mixture three chlorogenic acids: 3,4-O-dicaffeoylquinic (4), 3,5-O-dicaffeoylquinic (5), and 4,5-O-dicaffeoylquinic (6) acids. When tested in vitro, kaempferol (3) exhibited activity against Schistosoma mansoni with EC50=81.86 µM, whereas compounds 1, 2, 4-6 showed to be inactives. Considering this result, the effects of kaempferol (3) against S. mansoni infection using an experimental approach (in vivo assay) was tested at first time. Using a single oral dose (400 mg/kg) of kaempferol (3) to S. mansoni-infected mice reduced the worm burden by 25.5 %. Similarly, the number of eggs, which are responsible for a variety of pathologies and transmission of schistosomiasis, was decreased by 28.8 % in treated mice. Collectively, although kaempferol (3) is partially active when administered orally in a mouse model of schistosomiasis, our results suggest that this compound could be, in future studies, administered in different forms, such as nanoformulation.

In Vivo Effects of Biosilica and Spongin-Like Collagen Scaffolds on the Healing Process in Osteoporotic Rats.

Due to bioactive properties, introducing spongin-like collagen (SPG) into the biosilica (BS) extracted from marine sponges would present an enhanced biological material for improving osteoporotic fracture healing by increasing bone formation rate. Our aim was to characterize the morphology of the BS/SPG scaffolds by scanning electron microscopy (SEM), the chemical bonds of the material by Fourier transform infrared spectroscopy (FTIR), and evaluating the orthotopic in vivo response of BS/SPG scaffolds in tibial defects of osteoporotic fractures in rats (histology, histomorphometry, and immunohistochemistry) in two experimental periods (15 and 30 days). SEM showed that scaffolds were porous, showing the spicules of BS and fibrous aspect of SPG. FTIR showed characteristic peaks of BS and SPG. For the in vivo studies, after 30 days, BS and BS/SPG showed a higher amount of newly formed bone compared to the first experimental period, observed both in the periphery and in the central region of the bone defect. For histomorphometry, BS/SPG presented higher %BV/TV compared to the other experimental groups. After 15 days, BS presented higher volumes of collagen type I. After 30 days, all groups demonstrated higher volumes of collagen type III compared to volumes at 15 days. After 30 days, BS/SPG presented higher immunostaining of osteoprotegerin compared to the other experimental groups at the same experimental period. The results showed that BS and BS/SPG scaffolds were able to improve bone healing. Future research should focus on the effects of BS/SPG on longer periods in vivo studies.

Tributyltin induces apoptosis in mammalian cells in vivo: a scoping review.

The present review aimed to evaluate the apoptotic effect of tributyltin (TBT) exposure on mammalian tissues and cells in vivo. A search was conducted in specialized literature databases including Embase, Medline, Pubmed, Scholar Google, and Scopus for all manuscripts using the following keywords: "tributyltin", "apoptosis", "mammals", "mammalian cells', "eukaryotic cells", 'rodents', "rats", "mice" and "in vivo" for all data published until September 2023. A total of 16 studies were included. The studies have demonstrated that TBT exposure induces apoptosis in cells from various mammalian organs or tissues in vivo. TBT is capable to increase apoptotic cells, to activate proapoptotic proteins such as calpain, caspases, bax and beclin-1 and to inhibit antiapoptotic protein bcl-2. Additionally, TBT alters the ratio of bcl-2/bax which favor apoptosis. Therefore, the activation of enzymes such as calpain induces apoptosis mediated by ERS and caspases through the intrinsic apoptosis pathway. This review has demonstrated that TBT exposure induces apoptosis in mammalian tissues and cells in vivo.

In Vivo Tracking and 3D Mapping of Cell Death in Regeneration and Cancer Using Trypan Blue.

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl4 intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo "pulse and chase" tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease.

Preclinical evidence of the anti-inflammatory effect and toxicological safety of aryl-cyclohexanone in vivo.

BACKGROUND: Respiratory distress syndrome is a complex inflammatory condition defined by the presence of acute hypoxemia and cellular infiltration with diffuse alveolar injury following a tissue injury, such as acute lung injury. The inflammatory process involved in this pathology is a defense mechanism of the body against infectious agents and/or tissue injuries. However, when the condition is not reversed, it becomes a significant cause of tissue damage, sometimes leading to loss of function of the affected organ. Therefore, it is essential to understand the mechanisms underlying inflammation, as well as the development of new therapeutic agents that reduce inflammatory damage in these cases. Aryl-cyclohexanone derivatives have previously shown significant anti-inflammatory activity linked to an immunomodulatory capacity in vitro and may be good candidates for therapies in which inflammation plays a central role. METHODS: Was evaluated the anti-inflammatory capacity of a synthesized molecule aryl-cyclohexanone in the murine model of lipopolysaccharide (LPS)-induced acute lung injury. The assessment of acute oral toxicity follows the Organization for Economic Co-operation and Development (OECD) guideline 423. RESULTS: The results demonstrated that the studied molecule protects against LPS-induced inflammation. We observed a decrease in the migration of total and differential leukocytes to the bronchoalveolar lavage fluid (BALF), in addition to a reduction in exudation, myeloperoxidase (MPO) activity, nitric oxide metabolites, and the secretion of pro-inflammatory cytokines (alpha tumor necrosis factors [TNF-α], interleukin-6 [IL-6], interferon-gamma [IFN-γ], and monocyte chemoattractant protein-1 [MCP-1]). Finally, aryl cyclohexanone did not show signs of acute oral toxicity (OECD 423). CONCLUSIONS: The results prove our hypothesis that aryl-cyclohexanone is a promising molecule for developing a new, safe anti-inflammatory drug.

Biopolymeric Insulin Membranes for Antimicrobial, Antioxidant, and Wound Healing Applications.

Delayed wound healing increases the wound's vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of S. aureus at 85% and P. aeruginosa at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin's role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials.

Comparison of baseline correction algorithms for in vivo 1H-MRS.

Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short-echo-time MRS data. In short-echo-time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long-echo-time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi-LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm-QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm-QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting.

Potential antitumor effects of short-chain fatty acids in breast cancer models.

The effects of short-chain fatty acids (SCFAs) have been explored against cancer due to the crosstalk between gut microbiota alterations and the immune system as a crucial role in cancer development. We evaluated the SCFAs effects in both in vitro and in vivo breast cancer models. In vitro, the SCFAs displayed contrasting effects on viability index, according to the evaluation of breast cancer cells with different phenotypes, human MCF-7, SK-BR-3, MDA-MD-231, or the mouse 4T1 lineage. Acetate displayed minimal effects at concentrations up to 100 mM. Alternatively, propionate increases or reduces cell viability depending on the concentration. Butyrate and valerate showed consistent time- and concentration-dependent effects on the viability of human or mouse breast cancer cells. The selective FFA2 4-CMTB or FFA3 AR420626 receptor agonists failed to overtake the SCFA actions, except by modest inhibitory effects on MDA-MB-231 and 4T1 cell viability. The FFA2 CATPB or FFA3 and ß-hydroxybutyrate receptor antagonists lacked significant activity on human cell lines, although CATPB reduced 4T1 cell viability. Butyrate significantly affected cell morphology, clonogenicity, and migration, according to the evaluation of MDA-MB-231 and 4T1 cells. A preliminary examination of in vivo oral effects of butyrate, propionate, or valerate, dosed in prophylactic or therapeutic regimens, on several parameters evaluated in an orthotopic breast cancer model showed a reduction of lung metastasis in post-tumor induction butyrate-treated mice. Overall, the present results indicate that in vitro effects of SCFAs did not rely on FFA2 or FFA3 receptor activation, and they were not mirrored in vivo, at least at the tested conditions. Overall, the present results indicate potential in vitro inhibitory effects of SCFAs in breast cancer, independent of FFA2 or FFA3 receptor activation, and, in the metastatic breast cancer model, the butyrate-dosed therapeutic regimen reduced the number of lung metastases.

Lippia alba essential oil: A powerful and valuable antinociceptive and anti-inflammatory medicinal plant from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.

MIG1, TUP1 and NRG1 mediated yeast to hyphal morphogenesis inhibition in Candida albicans by ganciclovir.

Candida albicans is a polymorphic human fungal pathogen and the prime etiological agent responsible for candidiasis. The main two aspects of C. albicans virulence that have been suggested are yeast-to-hyphal (Y-H) morphological transitions and biofilm development. Anti-fungal agents targeting these virulence attributes enhances the antifungal drug development process. Repositioning with other non-fungal drugs offered a one of the new strategies and a potential alternative option to counter the urgent need for antifungal drug development. In the current study, an antiviral drug ganciclovir was screened as an antifungal agent against ATCC 90028, 10231 and clinical isolate (C1). Ganciclovir at 0.5 mg/ml concentration reduced 50% hyphal development on a silicon-based urinary catheter and was visualized using scanning electron microscopy. Ganciclovir reduced ergosterol biosynthesis in both strains and C1 isolate of C. albicans in a concentration-dependent manner. Additionally, a gene expression profile study showed that ganciclovir treatment resulted in upregulation of hyphal-specific repressors MIG1, TUP1, and NRG1 in C. albicans. Additionally, an in vivo study on the Bombyx mori silkworm model further evidenced the virulence inhibitory ability of ganciclovir (0.5 mg/ml) against C. albicans. This is the first report that explore the novel anti-morphogenic activities of ganciclovir against the pathogenic C. albicans strains, along with clinical isolates. Further, ganciclovir may be considered for therapeutic purpose after combinations with standard antifungal agents.