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Cannabis-based products have gained attention in recent years for their perceived therapeutic benefits (with cannabinoids such as THC and CBD) and widespread availability. However, these products often lack accurate labelling regarding their cannabinoid content. Our study, conducted with products available in Portugal, revealed significant discrepancies between label claims and actual cannabinoid compositions. A fully validated method was developed for the characterisation of different products acquired from pharmacies and street shops (beverages, herbal samples, oils, and cosmetic products) using high-performance liquid chromatography coupled with a diode array detector. Linearity ranged from 0.4 to 100 µg/mL (0.04-10 µg/mg) (THC, 8-THC, CBD, CBG, CBDA, CBGA), 0.1-100 µg/mL (0.01-10 µg/mg) (CBN), 0.4-250 µg/mL (0.04-25 µg/mg) (THCA-A), and 0.8-100 µg/mL (0.08-10 µg/mg) (CBCA). Among sampled beverages, none contained detectable cannabinoids, despite suggestive packaging. Similarly, oils often differed from the declared cannabinoid compositions, with some containing significantly higher CBD concentrations than labelled. These inconsistencies raise serious concerns regarding consumer safety and informed decision-making. Moreover, our findings underscore the need for stringent regulation and standardised testing protocols to ensure the accuracy and safety of cannabis-based products.
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Canabinoides , Cannabis , Portugal , Canabinoides/análise , Canabinoides/química , Cannabis/química , Cromatografia Líquida de Alta Pressão , Humanos , Cosméticos/análise , Cosméticos/química , Bebidas/análise , Maconha Medicinal/análise , Maconha Medicinal/químicaRESUMO
COVID-19 is a complex disease manifesting in a broad severity spectrum and involving distinct organs and systems. Hyperinflammation, including complement over-activation, has a pivotal role in severe COVID-19 pathobiology, stimulating the inflammatory response, causing microangiopathy, platelet-neutrophil activation, and hypercoagulability. SARS-CoV-2 can directly activate the complement system by the classic, alternative, and lectin pathways, and infected cells can produce intracellular complement (the complesome). COVID-19 severity appears to be associated with the degree of complement activation, and it has been hypothesized that patients with COVID-19 may benefit from therapeutic complement inhibition. Different complement cascade molecules may be targeted with potential advantages and disadvantages. Which target(s) is the most effective and when is the best timing for intervention remain open questions. Early phase I and phase II clinical trials have shown promising but conflicting results, warranting phase III controlled randomized trials. Upstream complement inhibition appears to better and more effectively block hyperinflammation with potential clinical significance. Understanding how SARS-CoV-2 exploits the complement system can add precious information about the pathogenesis of other infections, inflammatory, and autoimmune diseases beyond COVID-19.
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COVID-19 , Humanos , COVID-19/complicações , SARS-CoV-2 , Inflamação/metabolismo , Ativação do Complemento , Neutrófilos , Proteínas do Sistema Complemento/metabolismo , Proteínas do Sistema Complemento/farmacologiaRESUMO
The activation of the nuclear factor-κB (NF-κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well-known inhibitor of the NF-κB pathway, has emerged as an alternative treatment. However, whether PTL activity is tumor cell-specific and dependent on the mutational background has not been defined. This study investigated the antitumor role of PTL after tumor necrosis factor-α (TNF-α) stimulation in various CRC cell lines with different mutational statuses of TP53. We observed that CRC cells displayed different patterns of basal p-IκBα levels; PTL reduced cell viability according to p-IκBα levels and p-IκBα levels varied among the cell lines according to the time of TNF-α stimulation. High concentrations of PTL reduced more effectively p-IκBα levels than low doses of PTL. However, PTL increased total IκBα levels in Caco-2 and HT-29 cells. In addition, PTL treatment downregulated p-p65 levels in HT-29 and HCT-116 cells stimulated by TNF-α in a dose-dependent manner. Moreover, PTL induced cell death via apoptosis and reduced the proliferation rate of TNF-α-treated HT-29 cells. Finally, PTL downregulated the messenger RNA levels of interleukin-1ß, a downstream cytokine of NF-κB, reverted the E-cadherin-mediated disorganization of cell-cell contacts, and decreased the invasion of HT-29 cells. Together, these results suggest a differential antitumoral activity of PTL on CRC cells with different mutational statuses of TP53, modulating cell death, survival, and proliferation underlying the NF-κB pathway TNF-α-induced. Therefore, PTL has emerged as a potential treatment for CRC in an inflammatory NF-κB-dependent manner.
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Neoplasias Colorretais , NF-kappa B , Humanos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Baixo , Adesão Celular , Células CACO-2 , Apoptose , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Research concerning leptospirosis in donkeys and mules has been neglected around the world. Therefore, the aim of this study was to investigate the epidemiological situation of the prevalence of anti-Leptospira spp. antibodies in donkeys and mules from the state of Minas Gerais, Brazil. Blood serum samples were collected from 180 animals (109 donkeys and 71 mules) in two rural properties from the state of Minas Gerais, Brazil, and then submitted to a microscopic agglutination test (MAT). Urea and creatinine values were also quantified. Epidemiological variables such as age, breeding system, contact with other animal species, source of water and food, vaccination against leptospirosis, presence of reproductive alterations, and rodent control were also investigated. From 180 samples collected, 39 (21.67%) showed positive results in the MAT, at a dilution ≥ 1:100. Some animals were reactive for more than one serovar. The serovar Tarassovi was the most frequent (14.07%), followed by Hardjo (11.85%) and Wolffi (11.11%). There was a statistically significant difference between animals from 0 to 3 years of age reactive in the MAT in comparison to the other age groups. Most of the animals had urea and creatinine concentrations within the acceptable reference limit; however, there was a significant increase in creatinine levels in some of the test animals. The studied properties showed differences in some epidemiological aspects such as vaccination of the animals, presence of reproductive problems in the herd, and rodent control. Such aspects pointed as risk factors that may influence the frequency of positive serological results in property 1. The present study demonstrated that the prevalence of leptospirosis in donkeys and mules is high and several serovars are being maintained by these animals, representing a potential public health risk.
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Leptospira , Leptospirose , Animais , Brasil/epidemiologia , Equidae , Creatinina , Leptospirose/epidemiologia , Leptospirose/veterinária , Testes de Aglutinação/veterinária , Anticorpos AntibacterianosRESUMO
OBJECTIVE: The aim of this study was to assess the clinicopathological features of florid cemento-osseous dysplasia (FCOD)-related osteonecrosis highlighting their histopathological aspects and bone structure. METHODS: Twenty-two FCOD-related osteonecrosis cases were evaluated retrospectively. Osteonecrosis, osteomyelitis, bacterial colonization, bone resorption, reactive bone, osteon-like structure, lamellar bone, and basophilic lines were analyzed. Specific staining and fluorescence and polarized light microscopy analyses were also performed. RESULTS: The mandible was more affected by FCOD-related osteonecrosis. There was a predominance of African-Brazilian women in the fifth and seventh decades of life. Osteomyelitis was present in 82 % of cases whereas bone resorption and bacterial colonization were present in 100 % of FCOD-related osteonecrosis cases. Thick basophilic lines were seen in all cases (100 %). Actinomycosis and osteoclasts were not often. CONCLUSIONS: This study showed female adult preference, mandibular location, and some findings such as osteomyelitis, bone resorption, and bacterial colonization were histopathological features more frequent in FCOD-related osteonecrosis. In the absence of a close clinical and radiographic correlation, the morphology of the necrotized bone similar to cementum could help to recognize FCOD.
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Reabsorção Óssea , Osteomielite , Osteonecrose , Adulto , Feminino , Displasia Fibrosa Óssea , Humanos , Osteomielite/patologia , Estudos RetrospectivosRESUMO
Breast cancer (BC) is a heterogeneous disease composed of multiple subtypes with different molecular characteristics and clinical outcomes. The metastatic process in BC depends on the transcription factors (TFs) related to epithelial-mesenchymal transition (EMT), including the master regulator Twist1. However, its role beyond EMT in BC subtypes remains unclear. Our study aimed to investigate the role of Twist1, beyond EMT, in the molecular subtypes of BC. In patients, we observed the overexpression of TWIST1 in the HER2+ group. The silencing of TWIST1 in HER2+ BC cells resulted in the upregulation of 138 genes and the downregulation of 174 genes compared to control cells in a microarray assay. In silico analysis revealed correlations between Twist1 and important biological processes such as the Th17-mediated immune response, suggesting that Twist1 could be relevant for IL-17 signaling in HER2+ BC. IL-17 signaling was then examined, and it was shown that TWIST1 knockdown caused the downregulation of leading members of IL-17 signaling pathway. Taken together, our findings suggest that Twist1 plays a role on IL-17 signaling in HER2+ BC.
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Neoplasias da Mama/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Interleucina-17/imunologia , Proteínas Nucleares/imunologia , Receptor ErbB-2/imunologia , Transdução de Sinais/imunologia , Proteína 1 Relacionada a Twist/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Interleucina-17/genética , Proteínas Nucleares/genética , Receptor ErbB-2/genética , Transdução de Sinais/genética , Proteína 1 Relacionada a Twist/genéticaRESUMO
A metal- and photocatalyst-free photoinduced radical cascade hydroalkylation of 1,7-enynes has been disclosed. The process is triggered by a single electron transfer (SET) event involving a photoexcited electron-donor-acceptor complex between an NHPI ester and a Hantzsch ester, which decomposes to afford a tertiary radical that is readily trapped by the enyne. The method provides an operationally simple, robust, and step-economical approach toward the construction of diversely functionalized dihydroquinolinones bearing quaternary centers. A sequential one-pot hydroalkylation-isomerization approach is also offered, giving access to a family of quinolinones. A wide substrate scope and high functional group tolerance were observed in both approaches.
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Raman spectroelectrochemistry is a powerful technique for characterizing structural changes of materials during electrochemical reactions and investigating the mechanism of film deposition and adsorption processes on the surfaces of electrodes. Moreover, in situ measurements enable identification of catalytic sites and reaction intermediates, which facilitates the comprehension of reaction mechanisms. The limitations of this technique include the high-cost and the complexity of the experimental arrangement required by commercial spectroelectrochemical cells (SEC). Thus, 3D-printing technology emerges as an excellent alternative for the production of SEC, with desirable shape, low-cost, and robustness in a short period of time. In this work, an SEC and a 3D-printed working electrode were fabricated from acrylonitrile-butadiene-styrene (ABS) and conductive graphene polylactic acid (PLA) filaments, respectively. The proposed SEC and the 3D-printed electrode were printed within 3.5 h with an estimated cost of materials of less than US $2. Then, the 3D-printed SEC and the electrode were used in a study of structural changes of Prussian blue according to different voltage bias.
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Reproductive tract is an important site of infection for chronic leptospirosis and cooperate in pathogenesis of reproductive failure, leading to economic losses. Since serology techniques cannot detect chronic carriers, the molecular analysis of clinical samples is an alternative to detect these animals on livestock. The aim of the present study was to perform a retrospective study in order to detect leptospiral uterine carriers in slaughtered cows. Tissue samples were collected from 50 post-pubertal, nonpregnant cows. These samples were fixed in 10% buffered formalin, paraffin-embedded and stored. PCR targeting lipL32 gene and molecular characterization by secY sequence was performed. Leptospiral DNA was identified in 18% (9/50) examined blocks. Two sequences were characterized as L. interrogans. These findings suggest that the presence of infectious leptospires in uterus is associated with the physiopathogenesis of the reproductive failure.
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Doenças dos Bovinos/microbiologia , Leptospira interrogans/isolamento & purificação , Leptospirose/veterinária , Útero/microbiologia , Matadouros , Animais , Bovinos , Feminino , Leptospira interrogans/classificação , Leptospira interrogans/genética , Leptospirose/microbiologia , Estudos RetrospectivosRESUMO
This study aimed to develop a Geographic Information System (GIS), for storage of information and geographic location of apiaries in eight counties in western Paraná; study the local flora; the land used; and the honey productivity in the harvest of 2010 in two of these areas: Marechal Cândido Rondon and Santa Helena. In order to do so we used the software SPRING, delimiting a radius of action of bees of three kilometers around the apiaries. We interviewed and registered 126 beekeepers with 383 apiaries. By using the images we selected areas with greater and lower overlap of hives in Marechal Cândido Rondon (144 and 44 hives, respectively) and Santa Helena (165 and 40 hives, respectively), in a three kilometers radius, selecting 15 colonies in each area, for the study of the parameters cited. In the multivariate analysis of the grouping, five groups were formed, by their similarity of management, indicating the higher average production in the hives of the most populated area of Santa Helena and lower average production in the most populated of Marechal Cândido Rondon. The grouping of hives, the differences in the production of honey and floristic survey indicated that these differences could be associated with management, floristic and climatic differences recorded in the period of production, in the areas studied.
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Several protocols for the analysis of amphetamine-type stimulants (ATS) in hair have been developed over the years, with microextraction by packed sorbent (MEPS) being used for drugs like opiates, cocaine and ketamine. However, concerning ATS determination in hair samples, this approach has only been applied so far to amphetamine (AMP) and methamphetamine (MAMP). This study aimed at developing and validating a MEPS-based procedure for the determination in hair of not only AMP and MAMP but also of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 1-(1,3-benzodioxol-5-yl)propan-2-yl (ethyl)amine (MDE) and N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (MBDB) as well. Hair, 50 mg, was incubated with 1 M sodium hydroxide (NaOH) at 45°C overnight, neutralization with 10 M hydrochloric acid (HCl) and centrifugation followed. The design of experiments approach was used for MEPS optimization, with the final optimized conditions including conditioning (250 µL methanol and deionized water), loading (18 × 100 µL) and elution (7 × 100 µL 2% NH4OH in acetonitrile). The eluted extract was evaporated to dryness and underwent microwave-assisted derivatization with N-methyl-bis(trifluoroacetamide) (MBTFA), and it was afterwards injected onto the gas chromatography-mass spectrometer (GC-MS). The obtained recoveries ranged between 8% and 14% for AMP, 14% and 20% for MAMP, 10% and 15% for MDA, 18% and 28% for MDMA, 25% and 43% for MDE and 34% and 52% for MBDB, and the method was linear from 0.2 to 5.0 ng/mg. Precision and accuracy were in accordance with international method validation guidelines. This novel method involving MEPS coupled to GC-MS offers a swift, eco-friendly and cost-effective alternative to traditional procedures for detecting these AMPs in hair samples.
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Unbalanced redox status and constitutive STAT3 activation are related to several aspects of tumor biology and poor prognosis, including metastasis and drug resistance. The triple-negative breast cancer (TNBC) is listed as the most aggressive and exhibits the worst prognosis among the breast cancer subtypes. Although the mechanism of reactive oxygen species (ROS) generation led to STAT3 activation is described, there is no data concerning the STAT3 influence on redox homeostasis in TNBC. To address the role of STAT3 signaling in redox balance, we inhibited STAT3 in TNBC cells and investigated its impact on total ROS levels, contents of hydroperoxides, nitric oxide (NO), and total glutathione (GSH), as well as the expression levels of 3-nitrotyrosine (3NT), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nuclear factor kappa B (NF-κB)/p65. Our results indicate that ROS levels depend on the STAT3 activation, while the hydroperoxide level remained unchanged, and NO and 3NT expression increased. Furthermore, GSH levels, Nrf2, and NF-κB/p65 protein levels are decreased in the STAT3-inhibited cells. Accordingly, TNBC patients' data from TCGA demonstrated that both STAT3 mRNA levels and STAT3 signature are correlated to NF-κB/p65 and Nrf2 signatures. Our findings implicate STAT3 in controlling redox balance and regulating redox-related genes' expression in triple-negative breast cancer.
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Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activating immune cells via Toll-like receptors 7/8 when formulated in carriers, like nanogels, for topical use. An effective alternative to conventional therapies is the nanoparticle drug delivery system. We studied lipidic nanoparticles with IQ (Lipo IQ) and functionalized them with a DNA aptamer, AT11 (Lipo IQ AT11), to improve the selectivity for cervical cancer cells combined with the efficacy of essential oils. The formulations showed that the physicochemical properties are adequate for vaginal drug delivery and have antimicrobial activity at higher concentrations (with MIC50 starting from 0.625%). The final formulations exhibited cytotoxicity in cancer cells, enhanced by essential oils without affecting healthy cells, resulting in less than 10% cell viability in HeLa cells and over 60% in NHDF cells. Essential oils potentiate Lipo IQ's effectiveness, while AT11 increases the selectivity for cervical cancer cells. As suggested by the results of the permeation assay, the formulations were internalized by the cancer cells. Overall, the obtained results suggested that the synergistic effect of the essential oils and the nanosystem potentiate the cytotoxic effect of Lipo IQ and that Lipo IQ AT11 promotes selectivity towards cancer cells.
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Mitochondrial dysfunction is one of the leading causes of disease development. Dysfunctional mitochondria limit energy production, increase reactive oxygen species generation, and trigger apoptotic signals. Photobiomodulation is a noninvasive, nonthermal technique involving the application of monochromatic light with low energy density, inducing non-thermal photochemical effects at the cellular level, and it has been used due to its therapeutic potential. This review focuses on the mitochondrial dynamic's role in various diseases, evaluating the possible therapeutic role of low-power lasers (LPL) and light-emitting diodes (LED). Studies increasingly support that mitochondrial dysfunction is correlated with severe neurodegenerative diseases such as Parkinson's, Huntington's, Alzheimer's, and Charcot-Marie-Tooth diseases. Furthermore, a disturbance in mitofusin activity is also associated with metabolic disorders, including obesity and type 2 diabetes. The effects of PBM on mitochondrial dynamics have been observed in cells using a human fibroblast cell line and in vivo models of brain injury, diabetes, spinal cord injury, Alzheimer's disease, and skin injury. Thus, new therapies aiming to improve mitochondrial dynamics are clinically relevant. Several studies have demonstrated that LPL and LED can be important therapies to improve health conditions when there is dysfunction in mitochondrial dynamics.
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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.
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Doença Relacionada a Imunoglobulina G4 , Sialadenite , Humanos , Masculino , Sialadenite/patologia , Feminino , Pessoa de Meia-Idade , Adulto , Doença Relacionada a Imunoglobulina G4/patologia , Idoso , Esclerose/patologia , Doença Crônica , Glândula Submandibular/patologia , Imuno-HistoquímicaRESUMO
The Girolando breed is used in pasture-based dairy production systems in Brazil to associate the high production of Bos taurus to the rusticity and thermal adaptation of Bos indicus. This study was designed to evaluate the physiological response to a gonadotropin-releasing hormone (GnRH)-prostaglandin F2α (PGF2α)-GnRH protocol to synchronize the ovulation in 40 Girolando heifers of a pasture-based dairy production system and its relationships with the temperature and humidity index (THI) during the dry (DS) and rainy season (RS) in the tropical savannah-Brazil's cerrado biome. Responses were characterized by follicular and corpus luteum number and diameter, ovulation (D9), and pregnancy rates after first AI. Total follicle number (8.1 ± 0.3 × 8.8 ± 0.3), D9 ovulatory follicle diameter (11.9 ± 0.4 × 10.1 ± 0.4 mm), corpus luteum diameter (8.6 ± 1.3 × 3.9 ± 1.5 mm), corpus luteum score (3.7 ± 0.8 × 1.8 ± 1.0), corpus luteum diameter after AI (9.6 ± 1.6 × 3.9 ± 1.5 mm), and corpus luteum score after AI (3.2 ± 0.4 × 0.9 ± 0.6) in DS and RS differed (P < 0.01). D9 ovulation rate was 40 % (DS) and 20 % (RS), without differences (P > 0.05). Pregnancy rate was 45 % (DS) and 11 % (RS), with differences (P < 0.01). THI differed between DS and RS (P < 0.01). THI may interfere in the follicular and luteal dynamics and in the response of Girolando heifers to the GnRH-PGF2α protocol in the tropical savannah, thus reducing the chances of pregnancy at the first artificial insemination.
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Bovinos/fisiologia , Corpo Lúteo/fisiologia , Dinoprosta/farmacologia , Sincronização do Estro/métodos , Hormônio Liberador de Gonadotropina/farmacologia , Folículo Ovariano/fisiologia , Ovulação/efeitos dos fármacos , Criação de Animais Domésticos , Animais , Brasil , Bovinos/genética , Corpo Lúteo/diagnóstico por imagem , Feminino , Umidade , Folículo Ovariano/diagnóstico por imagem , Gravidez , Taxa de Gravidez , Progesterona/sangue , Radioimunoensaio/veterinária , Estações do Ano , Temperatura , Clima Tropical , Ultrassonografia/veterináriaRESUMO
This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations.
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Forensic toxicology plays a pivotal role in elucidating the presence of drugs of abuse in both biological and solid samples, thereby aiding criminal investigations and public health initiatives. This review article explores the significance of sensor technologies in this field, focusing on diverse applications and their impact on the determination of drug abuse markers. This manuscript intends to review the transformative role of portable sensor technologies in detecting drugs of abuse in various samples. They offer precise, efficient, and real-time detection capabilities in both biological samples and solid substances. These sensors have become indispensable tools, with particular applications in various scenarios, including traffic stops, crime scenes, and workplace drug testing. The integration of portable sensor technologies in forensic toxicology is a remarkable advancement in the field. It has not only improved the speed and accuracy of drug abuse detection but has also extended the reach of forensic toxicology, making it more accessible and versatile. These advancements continue to shape forensic toxicology, ensuring swift, precise, and reliable results in criminal investigations and public health endeavours.
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BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.
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The emergence of horizontal transmission of cancer between vertebrates is an issue that interests scientists and medical society. Transmission requires: (i) a mechanism by which cancer cells can transfer to another organism and (ii) a repressed immune response on the part of the recipient. Transmissible tumors are unique models to comprehend the responses and mechanisms mediated by the major histocompatibility complex (MHC), which can be transposed for transplant biology. Here, we discuss the mechanisms involved in immune-mediated tissue rejection, making a parallel with transmissible cancers. We also discuss cellular and molecular mechanisms involved in cancer immunotherapy and anti-rejection therapies.