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1.
Curr Issues Mol Biol ; 46(9): 9298-9311, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39329902

RESUMEN

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, which has not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA's antiproliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent indole-3-carbinol (I3C) was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migration and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA's lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C.

2.
Molecules ; 29(18)2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39339471

RESUMEN

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Cloruro de Litio , Neoplasias del Cuello Uterino , Humanos , Cloruro de Litio/farmacología , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Movimiento Celular/efectos de los fármacos , Femenino , Células HeLa , Línea Celular Tumoral , Antineoplásicos/farmacología , Carbonato de Litio/farmacología , Ciclo Celular/efectos de los fármacos , Reposicionamiento de Medicamentos
3.
PLoS One ; 19(9): e0310399, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39264906

RESUMEN

Antioxidant supplementation in critical periods may be useful for improvement of piglet early viability and development. We have evaluated the effects of maternal perinatal diet inclusion of a high vitamin E level (VE, 100 mg all-rac-α-tocopheryl acetate /kg), hydroxytyrosol (HT, 1.5 mg/kg), or their combination (VEHT), in comparison to a control diet (C, 30 mg all-rac-α-tocopheryl acetate /kg), on the offspring homeostasis and metabolism, analysing the weaned piglets' adipose tissue transcriptome and adipocyte morphology. Diets were provided to pregnant Iberian sows (n = 48, 12 per treatment) from gestation day 85 to weaning (28 days postpartum) and 48 piglets (n = 12 per treatment) were sampled 5 days postweaning for dorsal subcutaneous adipose tissue analyses. RNA obtained from 6 animals for each diet was used for paired-end RNA sequencing. Results show that supplementation of sows' diet with either vitamin E or hydroxytyrosol had substantial effects on weaned piglet adipose transcriptome, with 664 and 587 genes being differentially expressed, in comparison to C, respectively (q-value<0.10, Fold Change>1.5). Genes upregulated in C were mainly involved in inflammatory and immune response, as well as oxidative stress, and relevant canonical pathways and upstream regulators involved in these processes were predicted as activated, such as TNF, IFNB or NFKB. Vitamin E, when supplemented alone at high dose, activated lipid biosynthesis functions, pathways and regulators, this finding being accompanied by increased adipocyte size. Results suggest an improved metabolic and antioxidant status of adipose tissue in animals born from sows supplemented with individual antioxidants, while the combined supplementation barely affected gene expression, with VEHT showing a prooxidant/proinflamatory functional profile similar to C animals. Different hypothesis are proposed to explain this unexpected result. Findings allow a deeper understanding of the processes taking place in adipose tissue of genetically fat animals and the role of antioxidants in the regulation of fat cells function.


Asunto(s)
Tejido Adiposo , Antioxidantes , Suplementos Dietéticos , Alcohol Feniletílico , Transcriptoma , Destete , Animales , Antioxidantes/metabolismo , Femenino , Transcriptoma/efectos de los fármacos , Porcinos , Embarazo , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/administración & dosificación , Vitamina E/farmacología , Vitamina E/administración & dosificación , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Alimentación Animal/análisis
4.
Exp Parasitol ; 266: 108830, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260814

RESUMEN

Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days -8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7-100%) and adult parasites (98.9-100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes.

6.
Ann Bot ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136192

RESUMEN

BACKGROUND AND AIMS: Pollination failure occurs from insufficient pollen quantity or quality. However, the relative contributions of pollen quantity vs quality to overall pollen limitation, and how this is affected by the co-flowering context, remain unknown for most plant populations. Here, we studied patterns of pollen deposition and pollen tube formation across populations of four predominately outcrossing species in the genus Clarkia to evaluate how richness of co-flowering congeners affects the contribution of pollen quantity and quality to pollen limitation. METHODS: We partition variation in pollen deposition and pollen tube production across individuals, populations and species to identify the main sources of variation in components of reproductive success. We further quantify the relative contribution of pollen quantity and quality limitation to the reproductive success of the four Clarkia species using piecewise regression analyses. Finally, we evaluate how variation in the number of co-flowering Clarkia species in the community affects the strength of pollen quality and quality limitation. RESULTS: Across all contexts, pollen deposition and the proportion of pollen tubes produced varied greatly among individuals, populations, and species, and these were not always correlated. For instance, C. xantiana received the smallest pollen loads yet produced the highest proportion of pollen tubes, while C. speciosa exhibited the opposite pattern. Yet, co-flowering richness had variable effects on the strength of pollen quantity and quality limitation among populations. Specifically, breakpoint values, which are an indicator of overall pollen limitation, were two times larger in the four-species community compared with one and two-species communities for two Clarkia species, suggesting that pollen limitation can increase with increasing richness of co-flowering congeners. CONCLUSIONS: Our results reveal a complex interplay between quantity and quality of pollen limitation and co-flowering context that may have different evolutionary outcomes across species and populations.

7.
Pharmaceutics ; 16(8)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39204356

RESUMEN

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.

8.
Food Sci Nutr ; 12(7): 4513-4533, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39055196

RESUMEN

Cancer is a major global health challenge that affects every nation and accounts for a large portion of the worldwide disease burden. Furthermore, cancer cases will rise significantly in the next few decades. The Food and Drug Administration has approved more than 600 drugs for treating diverse types of cancer. However, many conventional anticancer medications cause side effects, and drug resistance develops as the treatment proceeds with a concomitant impact on patients' quality of life. Thus, exploring natural products with antitumor properties and nontoxic action mechanisms is essential. Ginger (Zingiber officinale Roscoe) rhizome has a long history of use in traditional medicine, and it contains biologically active compounds, gingerols and shogaols. The main ginger shogaol is 6-shogaol, whose concentration dramatically increases during the processing of ginger, primarily due to the heat-induced conversion of 6-gingerol. Some studies have demonstrated that 6-shogaol possesses biological and pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. The mechanism of action of 6-shogaol as an anticancer drug includes induction of paraptosis, induction of apoptosis, increase in the production of reactive oxygen species, induction of autophagy, and the inhibition of AKT/mTOR signaling. Despite this knowledge, the mechanism of action of 6-shogaol is not fully understood, and the scientific data on its therapeutic dose, safety, and toxicity are not entirely described. This review article examines the potential of 6-shogaol as an anticancer drug, addressing the limitations of current medications; it covers 6-shogaol's attributes, mechanism of action in cancer cells, and opportunities for future research.

9.
Surg Oncol ; 55: 102098, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38991627

RESUMEN

BACKGROUND: Minimally invasive techniques have demonstrated several advantages over the open approach. In the field of prostate cancer, the LAP-01 trial demonstrated the superiority of robotic-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) when comparing continence at 3-month after surgery, with no statistically significant differences at 6 and 12 months of follow-up. OBJECTIVES: Externally validate the LAP-01 study and compare functional outcomes between the two minimally invasive approaches. MATERIAL AND METHODS: This retrospective study, conducted by a single surgeon (MRB), utilized data from a prospectively collected database, which included patients who underwent both RARP or LRP. Data regarding baseline characteristics, continence (assessed through the 24-h Pad test and ICIQ questionnaire) and potency were collected at multiple time points: 1 and 6 weeks after catheter removal, 3-, 6-, and 12-months post-surgery. RESULTS: The study encompasses 601 patients, 455 who underwent LRP and 146 RARP. The median age at diagnosis was 64 for LRP and 62 for RARP, while the median PSA levels at diagnosis were 6.7 ng/mL for LRP and 6.5 ng/mL for RARP. Bilateral nerve-sparing procedures were performed in 34.07 % of LRP cases and 51.37 % of RARP cases. RARP exhibited a significant advantage over LRP both in continence and potency. Continence rates at 3-, 6- and 9-month after radical prostatectomy (RP) were 36.43 %, 61.86 % and 79.87 % for LRP, compared to 50.98 %, 69.87 % and 91.69 % for RARP. Potency rates at the same intervals were 0.90 %, 3.16 % and 6.39 % for LRP, and 6.19 %, 9.16 % and 18.96 % for RARP. These rates were more pronounced in patients with bilateral nerve-sparing. CONCLUSION: Our study demonstrates that RARP results in significantly better continence recovery and superior potency outcomes throughout the entire follow-up period compared to LRP, even at the beginning of the robotic approach learning curve.


Asunto(s)
Laparoscopía , Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Incontinencia Urinaria , Humanos , Masculino , Prostatectomía/métodos , Prostatectomía/efectos adversos , Laparoscopía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Procedimientos Quirúrgicos Robotizados/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control , Estudios de Seguimiento , Complicaciones Posoperatorias , Anciano , Disfunción Eréctil/etiología , Disfunción Eréctil/prevención & control , Estudios Prospectivos , Pronóstico
10.
Biomed Pharmacother ; 177: 117047, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38959604

RESUMEN

Cancer remains a leading cause of death, with increasing incidence. Conventional treatments offer limited efficacy and cause significant side effects, hence novel drugs with improved pharmacological properties and safety are required. Silvestrol (SLV) is a flavagline derived from some plants of the Aglaia genus that has shown potent anticancer effects, warranting further study. Despite its efficacy in inhibiting the growth of several types of cancer cells, SLV is characterized by an unfavorable pharmacokinetics that hamper its use as a drug. A consistent research over the recent years has led to develop novel SLV derivatives with comparable pharmacodynamics and an ameliorated pharmacokinetic profile, demonstrating potential applications in the clinical management of cancer. This comprehensive review aims to highlight the most recent data available on SLV and its synthetic derivatives, addressing their pharmacological profile and therapeutic potential in cancer treatment. A systematic literature review of both in vitro and in vivo studies focusing on anticancer effects, pharmacodynamics, and pharmacokinetics of these compounds is presented. Overall, literature data highlight that rationale chemical modifications of SLV are critical for the development of novel drugs with high efficacy on a broad variety of cancers and improved bioavailability in vivo. Nevertheless, SLV analogues need to be further studied to better understand their mechanisms of action, which can be partially different to SLV. Furthermore, clinical research is still required to assess their efficacy in humans and their safety.


Asunto(s)
Antineoplásicos , Neoplasias , Triterpenos , Humanos , Animales , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Triterpenos/farmacocinética , Triterpenos/farmacología , Triterpenos/química , Desarrollo de Medicamentos/métodos , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Benzofuranos
11.
Med Oncol ; 41(8): 186, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918260

RESUMEN

This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies.


Asunto(s)
Iridoides , Neoplasias , Humanos , Iridoides/farmacología , Iridoides/química , Iridoides/uso terapéutico , Neoplasias/tratamiento farmacológico , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Fitoquímicos/química , Animales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Apoptosis/efectos de los fármacos
12.
Ecol Evol ; 14(6): e11494, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38855315

RESUMEN

Land-use change is one the greatest threats to biodiversity and is projected to increase in magnitude in the coming years, stressing the importance of better understanding how land-use change may affect vital ecosystem services, such as pollination. Past studies on the impact of land-use change have largely focused on only one aspect of the pollination process (e.g., pollinator composition, pollinator visitation, and pollen transfer), potentially misrepresenting the full complexity of land-use effects on pollination services. Evaluating the impacts across multiple components of the pollination process can also help pinpoint the underlying mechanisms driving land-use change effects. This study evaluates how land-use change affects multiple aspects of the pollination process in common milkweed populations, including pollinator community composition, pollinator visitation rate, pollen removal, and pollen deposition. Overall, land-use change altered floral visitor composition, with small bees having a larger presence in developed areas. Insect visitation rate and pollen removal were also higher in more developed areas, perhaps suggesting a positive impact of land-use change. However, pollen deposition did not differ between developed and undeveloped sites. Our findings highlight the complexity evaluating land-use change effects on pollination, as these likely depend on the specific aspect of pollination evaluated and on the of the intensity of disturbance. Our study stresses the importance of evaluating multiple components of the pollination process in order to fully understand overall effects and mechanisms underlying land-use change effects on this vital ecosystem service.

13.
Naunyn Schmiedebergs Arch Pharmacol ; 397(10): 7337-7351, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-38739152

RESUMEN

As peptide-based therapies gain recognition for their potential anti-cancer activity, cyclic peptides like Sansalvamide A, a marine-derived cyclic depsipeptide, have emerged as a potential anti-cancer agent due to their potent activity against various cancer types in preclinical studies. This review offers a comprehensive overview of Sansalvamide A, including its sources, structure-activity relationship, and semi-synthetic derivatives. The review also aims to outline the mechanisms through which Sansalvamide A and its analogs exert their anti-proliferative effects and to discuss the need for enhancements in pharmacokinetic profiles for better clinical utility. An extensive literature search was conducted, focusing on studies that detailed the anti-cancer activity of Sansalvamide A, its pharmacokinetics, and mechanistic pathways. Data from both in vitro and in vivo studies were collated and analyzed. Sansalvamide A and its analogs demonstrated significant anti-cancer activity across various cancer models, mediated through Hsp 90 inhibition, Topoisomerase inhibition, and G0/G1 cell cycle arrest. However, their pharmacokinetic properties were identified as a significant limitation, requiring improvement for effective clinical translation. Despite its notable anti-cancer effects, the utility of Sansalvamide A is currently limited by its pharmacokinetic characteristics. Therefore, while Sansalvamide A exhibits promise as an anti-cancer agent, there is a compelling need for further clinical and toxicological studies and optimization of its pharmacokinetic profile to fully exploit its therapeutic potential alongside modern cancer therapies.


Asunto(s)
Antineoplásicos , Depsipéptidos , Neoplasias , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacocinética , Antineoplásicos/química , Depsipéptidos/farmacología , Depsipéptidos/uso terapéutico , Depsipéptidos/farmacocinética , Depsipéptidos/química , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Relación Estructura-Actividad
14.
Naunyn Schmiedebergs Arch Pharmacol ; 397(9): 6317-6336, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38652277

RESUMEN

Arnicolide D, a potent sesquiterpene lactone from Centipeda minima, has emerged as a promising anticancer candidate, demonstrating significant efficacy in inhibiting cancer cell proliferation, inducing apoptosis, and suppressing metastasis across various cancer models. This comprehensive study delves into the molecular underpinnings of Arnicolide D's anticancer actions, emphasizing its impact on key signaling pathways such as PI3K/AKT/mTOR and STAT3, and its role in modulating cell cycle and survival mechanisms. Quantitative data from preclinical studies reveal Arnicolide D's dose-dependent cytotoxicity against cancer cell lines, including nasopharyngeal carcinoma, triple-negative breast cancer, and human colon carcinoma, showcasing its broad-spectrum anticancer potential. Given its multifaceted mechanisms and preclinical efficacy, Arnicolide D warrants further investigation in clinical settings to validate its therapeutic utility against cancer. The evidence presented underscores the need for rigorous pharmacokinetic and toxicological studies to establish safe dosing parameters for future clinical trials.


Asunto(s)
Antineoplásicos Fitogénicos , Lactonas , Sesquiterpenos , Humanos , Sesquiterpenos/farmacología , Sesquiterpenos/farmacocinética , Sesquiterpenos/uso terapéutico , Animales , Lactonas/farmacología , Lactonas/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Proliferación Celular/efectos de los fármacos
15.
Drug Dev Res ; 85(2): e22175, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38567708

RESUMEN

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Línea Celular Tumoral , Microambiente Tumoral
16.
Carbohydr Polym ; 336: 122121, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38670753

RESUMEN

This study aimed to modify chitosan (CS) by gamma irradiation and use it as a surface coating of nanoparticles (NPs) fabricated of poly lactic-co-glycolic acid (PLGA) to create mostly biocompatible nanosystems that can transport drugs to neurons. Gamma irradiation produced irradiated CS (CSγ) with a very low molecular weight (15.2-19.2 kDa). Coating NPs-PLGA with CSγ caused significant changes in their Z potential, making it slightly positive (from -21.7 ± 2.8 mV to +7.1 ± 2.3 mV) and in their particle size (184.4 0.4 ± 7.9 nm to 211.9 ± 14.04 nm). However, these changes were more pronounced in NPs coated with non-irradiated CS (Z potential = +54.0 ± 1.43 mV, size = 348.1 ± 16.44 nm). NPs coated with CSγ presented lower cytotoxicity and similar internalization levels in SH-SY5Y neuronal cells than NPs coated with non-irradiated CS, suggesting higher biocompatibility. Highly biocompatible NPs are desirable as nanocarriers to deliver drugs to the brain, as they help maintain the structure and function of the blood-brain barrier. Therefore, the NPs developed in this study could be evaluated as drug-delivery systems for treating brain diseases.


Asunto(s)
Quitosano , Nanopartículas , Neuronas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Quitosano/química , Humanos , Nanopartículas/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Portadores de Fármacos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Tamaño de la Partícula , Rayos gamma
17.
Mol Nutr Food Res ; 68(8): e2400063, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38600885

RESUMEN

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.


Asunto(s)
Isotiocianatos , Neoplasias , Isotiocianatos/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , FN-kappa B/metabolismo , Antineoplásicos Fitogénicos/farmacología
18.
Phytother Res ; 38(6): 3169-3189, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38616356

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti-neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Antiinflamatorios , Curcumina , Fármacos Neuroprotectores , Curcumina/farmacología , Curcumina/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Fármacos Neuroprotectores/farmacología , Antiinflamatorios/farmacología , Animales , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Antioxidantes/farmacología , Curcuma/química , Disponibilidad Biológica
19.
Antioxidants (Basel) ; 13(3)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38539912

RESUMEN

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet's plasma and tissues' fatty acid profiles and lipid stability according to the sow's parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows' PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows' supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets' tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows' antioxidant supplementation, with positive effects on quality by both compounds.

20.
J Mater Sci Mater Med ; 35(1): 20, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526669

RESUMEN

Xyloglucan is a rigid polysaccharide that belongs to the carbohydrate family. This hemicellulose compound has been widely used in biomedical research because of its pseudoplastic, mucoadhesive, mucomimetic, and biocompatibility properties. Xyloglucan is a polyose with no amino groups in its structure, which also limits its range of applications. It is still unknown whether grafting hydrophilic monomers onto xyloglucan can produce derivatives that overcome these shortcomings. This work aimed to prepare the first copolymers in which N-hydroxyethyl acrylamide is grafted onto tamarind xyloglucan by free-radical polymerization. The biocompatibility of these structures in vitro was evaluated using human dermal fibroblasts. Gamma radiation-induced graft polymerization was employed as an initiator by varying the radiation dose from 5-25 kGy. The structure of the graft copolymer, Xy-g-poly(N-hydroxyethyl acrylamide), was verified by thermal analysis, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The findings indicate that the degree of grafting and the cytotoxicity/viability of the xyloglucan-based copolymer were independent of dose. Notably, the grafted galactoxyloglucan exhibited efficient support for human dermal fibroblasts, showing heightened proliferative capacity and superior migration capabilities compared to the unmodified polymer. This copolymer might have the potential to be used in skin tissue engineering.


Asunto(s)
Acrilamida , Glucanos , Polímeros , Humanos , Acrilamida/química , Polimerizacion , Polímeros/química , Xilanos/química , Espectroscopía Infrarroja por Transformada de Fourier
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