Search Results (42)

Breast cancer (BC) is the most common type of cancer in women worldwide. Hexokinase II (HKII) overexpression is associated with the proliferation and survival of tumor cells, as it inhibits apoptosis. Incomptine A (IA) is cytotoxic to breast cancer cells, likely due to a decrease in the expression of HKII. This study evaluated the antitumor activity of IA in an in vivo mouse model of BC. A model was generated from 4T1 cells and grouped tumor-bearing animals according to treatment: in IA or doxorubicin (DOXO), or untreated (UT). Comparing the body weight and tumor size between groups, tumors were analyzed using histopathological, Western blot, flow cytometry, and mitochondrial activity assays. Tumors IA-treated showed a reduction in size, weight, and number of tumor cells; the expression of HKII and Bcl-2 decreased, while that of Caspase-3 increased. IA treatment increased apoptosis and reduced mitochondrial activity in tumor cells. This data showed that IA has an impact on tumor cells by reducing tumor volume and size, increasing cell apoptosis, and decreasing mitochondrial activity, all of which could be attributed to reduced HKII expression. Therefore, IA may be a promising compound that requires further studies to elucidate its mechanism of action and analyze its possible future use in BC. Full article

Kalanchoe pinnata is used in traditional medicine to treat cancer, as it contains flavonoids and phenols known to regulate key cellular processes associated with cancer. Breast cancer, the most common cancer among women globally, presents ongoing challenges in treatment. The discovery of m⁶A methylation and its regulation by methylosome proteins offers novel therapeutic avenues for cancer management. This study aimed to investigate the cytotoxic and epitranscriptomic effects of an aqueous extract from K. pinnata on MCF-7 (luminal A) and HCC1937 (triple-negative) breast cancer cells. Cell lines were treated with the aqueous K. pinnata extract, characterized by HPLC, for 72 h, followed by an assessment of cytotoxicity and migration. The expression of methylosome components METTL3 and FTO was measured using RT-PCR. m⁶A global methylation was assessed via colorimetry, and molecular docking studies were conducted. The results indicated that only HCC1937 cells exhibited altered migration capacity. This change was correlated in silico with the inhibition of METTL3 by luteolin and quercetin, constituents of the aqueous extract. METTL3, a methyltransferase, was overexpressed by scratch stimuli but was downregulated following K. pinnata treatment in both MCF-7 and HCC1937 cells. The FTO demethylase was overexpressed in both cell lines. In silico analysis suggested an interaction between FTO and compounds such as gallic acid and myricetin. Additionally, m⁶A global methylation decreased in MCF-7 cells but increased in HCC1937 cells, potentially affecting cell migration. Our findings indicate that K. pinnata influences both METTL3 and FTO, altering m⁶A methylation in a cell-type-dependent manner, with HCC1937 cells being particularly sensitive. Further research is required to elucidate the complete molecular mechanism of K. pinnata’s aqueous extract in breast cancer treatment. Full article

Terpenoids are a large group of molecules present in several plant species and in many essential oils reported with cytotoxic and anticancer properties. The aim of this study was to evaluate the anticancer activity of eleven acyclic terpenes; seven monoterpenoids: geranyl acetate (C1), geranic acid (C2), citral (C3, mixture of neral and geranial), geraniol (C4), methyl geranate (C5), nerol (C6) and citronellic acid (C7); two sesquiterpenes: farnesal (C8) and farnesol (C9); and one triterpene: squalene (C10), using in vivo, in vitro, and in silico models. Anti-lymphoma activity was evaluated using male Balb/c mice inoculated with U-937 cells. Cytotoxic activity was evaluated using the WST-1 method. Computer tools were used to obtain a molecular docking study, measuring pharmacokinetic and toxicological properties of the acyclic terpenoids with greater antitumor activity. The results showed that the terpenoids with the highest cytotoxic and nodal growth inhibitory activity were C3, C4, C6, and C9, and their effects were better compared to MTX. The data obtained suggest that the anti-lymphoma activity could be due to the presence of the aldehyde, hydroxyl, and acetate groups in the C1 of the monoterpenes and sesquiterpenes evaluated. The theoretical results obtained from molecular docking showed that geranial (C3A), neral (C3B), C9, and C6 terpenoids obtained a higher affinity for the HMG-CoA reductase enzyme and suggest that it could be a target to induce anti-lymphoma activity of bioactive terpenoids. Our study provides evidence that C3, C6, and C9 could be potential anticancer agents for the treatment of histiocytic lymphoma. Full article

Background/Objectives: Mucormycosis is a rare but life-threatening fungal infection, particularly in neonates, due to their undeveloped immune system. This systematic review aims to analyze the risk factors, clinical presentations, treatments, and outcomes of neonatal mucormycosis reported between 2004 and 2024. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science following PRISMA guidelines. Only studies reporting cases of mucormycosis in neonates (≤28 days old) were included. Data on risk factors, clinical features, diagnostic methods, antifungal therapies, surgical interventions, and outcomes were extracted and analyzed. Results: A total of 44 studies met the inclusion criteria, comprising 61 neonatal cases. The most common clinical presentations were gastrointestinal (n = 39), cutaneous (n = 19), rhino-orbito-cerebral (n = 2), and disseminated mucormycosis (n = 1). Diagnosis was primarily based on histopathology (93.4%) and fungal culture (26.2%). The main antifungal treatment was liposomal amphotericin B (63.9%), often combined with surgical debridement (60.6%). Mortality rates remained high (47.5%), particularly in cases of prematurely extreme neonates with angioinvasive disease or delayed diagnosis. Conclusions: Neonatal mucormycosis remains a severe condition with high morbidity and mortality. Early diagnosis through a combination of clinical suspicion and laboratory confirmation, along with prompt antifungal therapy and surgical management, apparently is crucial for improving outcomes. Further studies are needed to optimize treatment strategies and improve neonatal survival. Full article

Pleopeltis crassinervata has demonstrated antimicrobial effects, including anti-Toxoplasma activity, which has been attributed to the presence of compounds such as terpenes and fatty acid methyl esters. In this study, the effects of P. crassinervata hexane subfraction one (Hsf1) on the Toxoplasma gondii tachyzoite ultrastructure were evaluated using TEM and SEM, and lytic cycle processes such as adhesion, invasion, and proliferation were evaluated using phase-contrast microscopy. Additionally, the antioxidant capacity of the subfraction and its main compounds (phytol and hexadecenoic acid methyl ester) were determined as well as their effects on parasite viability. Hsf1 exhibited a dose-dependent inhibitory effect on the lytic process at a concentration of 47.2 µg/mL. Among the eighteen compounds identified in this subfraction, six were evaluated, of which two (phytol and hexadecanoic acid methyl ester) significantly reduced the viability of T. gondii to 0.11% and 16.6%, respectively, at a concentration of 100 µg/mL. Additionally, Hsf1 demonstrated an antioxidant capacity of 30% as assessed using the ORAC method. The two active compounds also exhibited antioxidant properties, with antioxidant capacities of 13.33% and 33% for hexadecanoic acid methyl ester and phytol, respectively, at concentrations up to 15.4 mg/mL. Hsf1 showed membrane damage and conoid extrusion in T. gondii tachyzoites, suggesting direct interference with the lytic cycle of the parasite. These findings underscore the therapeutic potential of Hsf1 as a promising tool for controlling infections caused by T. gondii, thereby providing an alternative in the search for new antiparasitic agents. However, further research is required to determine the in vivo pharmacological effects and properties of these compounds with potential anti-Toxoplasma activity. Full article

Background/Objectives: Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph nodes of an in vivo mouse model. Methods: We induced an in vivo model with Balb/c mice with U-937 cells and treated it with IA or methotrexate, as well as healthy mice. We determined expressed proteins by TMT based on the LC-MS/MS method (Data are available via ProteomeXchange with identifier PXD060392) and a molecular docking study targeting 15 deregulated proteins. We developed analyses through the KEGG, Reactome, and Gene Ontology databases. Results: A total of 2717 proteins from the axillary and inguinal lymph nodes were analyzed and compared with healthy mice. Of 412 differentially expressed proteins, 132 were overexpressed (FC ≥ 1.5) and 117 were underexpressed (FC ≤ 0.67). This altered expression was associated with 20 significantly enriched processes, including chromatin remodeling, transcription, translation, metabolic and energetic processes, oxidative phosphorylation, glycolysis/gluconeogenesis, cell proliferation, cytoskeletal organization, and with cell death with necroptosis. Conclusions: We confirmed the previously observed dose-dependent effect of IA as a secondary metabolite with important potential as an anticancer agent for the treatment of NHL, showing that the type of drug or the anatomical location influences the response to treatment. The IA promises to be a likely safer and more effective treatment to improve outcomes, reduce toxicities, and improve survival in patients with NHL, initially targeting histones and transcription factors that will affect cell death proteins. Full article

Background: Incomptine A (IA) has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolytic enzymes. Also, IA has cytotoxic activity in the triple-negative subtypes, HER2+, and luminal A of breast cancer cells, with its properties being associated with an effect on the antiapoptotic function of Hexokinase II (HKII). Objectives: In this research, we reviewed the altered levels of proteins present in the lymph nodes of male Balb/c mice inoculated with U-937 cells and treated with IA or methotrexate, as well as mice only inoculated with cancer cells. Methods: Five approaches, including Tandem Mass Tag (TMT), Gene ontology (GO), Reactome, KEGG pathway analysis, and molecular docking, were used. Results: TMT showed that 74 proteins were differentially expressed, out of which 12 presented overexpression (FC ≥ 1.5) and 62 were under expressed (FC ≤ 0.67). In general, the TMT approach showed that IA had a better effect on proteins than methotrexate. Gene ontology, Reactome, and KEGG pathway analysis showed that proteins with altered levels may be implicated in several processes, including gene silencing by RNA, oxidative phosphorylation, glycolysis/gluconeogenesis, cytoskeleton organization, and ATP metabolic and energetic processes. The molecular docking analysis, which used 23 altered proteins as targets, revealed that IA interacted with all the proteins used. Conclusions: The results obtained using the five bioinformatic approaches provide information and show that IA could be used to treat non-Hodgkin lymphoma induced with the U-937 cell line. Also, it could provide a basis for future research and the development of clinical trials. Full article

The Annona genus contains some species used in Mexican traditional medicine for the treatment cancer, including Annona macroprophyllata (A. macroprophyllata). The present study aimed to investigate the anticancer activity of caryophyllene oxide (CO) isolated from A. macroprophyllata using in vivo, in vitro, and in silico approaches. The identification of CO was performed using gas chromatography-mass spectroscopy and NMR methods. Antilymphoma activity was evaluated in male and female Balb/c mice inoculated with U-937 cells. Cytotoxic activity was evaluated using the WST method and flow cytometry was used to determine the type of cell death. Acute oral toxicity was determined, and a molecular docking study was performed using target proteins associated with cancer, including, HMG-CoA, Bcl-2, Mcl-1, and VEGFR-2. Results showed that CO exhibited significant antilymphoma and cytotoxic activities, and its effects were comparable to MTX. In addition, flow cytometry showed that the anticancer activity of CO could be mediated by the induction of late apoptosis and necrosis. The result for the acute oral toxicity of CO was classified in category 4, suggesting it is low risk. Finally, molecular coupling studies showed that CO had more affinity for the enzymes HMG-CoA reductase and Bcl-2. Our study provides evidences that CO is a potential anticancer agent for the treatment of histiocytic lymphoma. Full article

Diseases caused by intestinal parasites such as protozoa represent a worldwide problem mainly for developing countries. From morbidity in different groups of people to cases of mortality in children and/or immunocompromised patients. In addition to the above, there is growing resistance to the drugs used in the treatment of these diseases, as well as undesirable side effects in patients. Therefore, there is an interest in the search for new alternatives for the base and/or development of new drugs with antiparasitic activities without harmful effects. In this sense, natural products offer to be a diverse source of compounds with biological activities. In this work, we describe the isolation and elucidation by 1D and 2D NMR spectroscopy of three cyclopeptides obtained from seeds of A. diversifolia Saff.: cherimolacyclopeptide D (1), squamin D (2), and squamin C (3). The fractions enriched in cyclopeptides, as well as a pure compound (1), showed antiprotozoal activity against E. hystolitica Schaudinn and Giardia lamblia Kunstler in vitro assays, with values of IC₅₀ = 3.49 and 5.39 μg mL⁻¹, respectively. The molecular docking study revealed that 1 has a strong interaction with targets used, including aldose reductase and PFOR enzymes. The antiprotozoal activity of cherimolacyclopeptide D is reported for the first time in this study. Full article

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in Mesocricetus auratus. An ALA was induced in male hamsters with 1.5 × 10⁵Entamoeba histolytica (E. histolytica) trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) (p ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; p ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by E. histolytica. However, additional clinical studies in different contexts are required to reaffirm this assertion. Full article

Pleopeltis crassinervata is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting biological and pharmacological assays is crucial to validate the therapeutic efficacy of this plant within the context of traditional medicine. In the present study, we investigated the biological activity of extracts and fractions obtained from P. crassinervata organs against bacteria (Salmonella typhimurium, Salmonella typhi, Staphylococcus aureus, Proteus mirabilis, Shigella flexneri, Bacillus subtilis, Escherichia coli) and Trichomonas vaginalis using in vitro models. The precipitate fraction obtained from the frond methanolic extract showed significant antibacterial activity (minimal inhibitory concentration [MIC] 120 µg/mL) against the Staphylococcus aureus strain and was effective against both Gram-positive and Gram-negative bacteria. The hexane fraction also obtained from frond methanolic extract, showed a trichomonacidal effect with an IC₅₀ of 82.8 μg/mL and a low cytotoxic effect. Hsf6 exhibited the highest activity against T. vaginalis, and the GC-MS analysis revealed that the predominant compound was 16-pregnenolone. The remaining identified compounds were primarily terpene-type compounds. Full article

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin’s lymphoma. Full article

This study explores the perception of a “sense of place” among tourists visiting Hegra, an archaeological site in northern Saudi Arabia, through reviews on TripAdvisor. The 267 reviews on TripAdvisor between 2020 and 2023 were analyzed using the VADER sentiment polarity analysis tool and object modeling using the NMF machine learning algorithm. The results highlight positive factors linked to the history and uniqueness of the place while showing some critical issues related to isolation, cost, privatization, and competitiveness. The originality of the research lies in the type of case study chosen, an archaeological site of a country that has recently opened its doors to tourism, and in the pragmatic nature of the investigation, oriented towards the search for possible solutions to be adopted in terms of heritage management based on the feedback received for the development of the tourist destination. Full article

Despite ongoing efforts for elimination, malaria continues to be a major public health problem in the Republic of Panama. For effective elimination, it is key that malaria foci and areas of high transmission are identified in a timely manner. Here, we study malaria transmission records for the 2015–2022 period, a time when cases have increased by a factor of ten. Using several methods to study spatial and spatiotemporal malaria confirmed case clusters at the level of localities, including LISA and scan, we found that cases are clustered across indigenous villages located within the autonomous indigenous regions of Ngäbe–Buglé, Guna Yala, and Embera, with the latter on the eastern border of Panama (with Colombia). We discuss the different factors that might be shaping the marked increase in malaria transmission associated with these clusters, which include an inflow of malaria-exposed migrating populations hoping to reach the USA, insufficient health services, and the lack of culturally sensitive actionable tools to reduce malaria exposure among the ethnically diverse and impoverished indigenous populations of Panama. Full article

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through in vitro assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its in silico comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells. Full article