-
Pharmaceuticals (Basel, Switzerland) Jun 2024Peru is one of the most biodiverse countries in the world, which is reflected in its wealth of knowledge about medicinal plants. However, there is a lack of information...
BACKGROUND
Peru is one of the most biodiverse countries in the world, which is reflected in its wealth of knowledge about medicinal plants. However, there is a lack of information regarding intestinal absorption and the permeability of natural products. The human colon adenocarcinoma cell line (Caco-2) is an in vitro assay used to measure apparent permeability. This study aims to develop a quantitative structure-property relationship (QSPR) model using machine learning algorithms to predict the apparent permeability of the Caco-2 cell in natural products from Peru.
METHODS
A dataset of 1817 compounds, including experimental log Papp values and molecular descriptors, was utilized. Six QSPR models were constructed: a multiple linear regression (MLR) model, a partial least squares regression (PLS) model, a support vector machine regression (SVM) model, a random forest (RF) model, a gradient boosting machine (GBM) model, and an SVM-RF-GBM model.
RESULTS
An evaluation of the testing set revealed that the MLR and PLS models exhibited an RMSE = 0.47 and R = 0.63. In contrast, the SVM, RF, and GBM models showcased an RMSE = 0.39-0.40 and R = 0.73-0.74. Notably, the SVM-RF-GBM model demonstrated superior performance, with an RMSE = 0.38 and R = 0.76. The model predicted log Papp values for 502 natural products falling within the applicability domain, with 68.9% ( = 346) showing high permeability, suggesting the potential for intestinal absorption. Additionally, we categorized the natural products into six metabolic pathways and assessed their drug-likeness.
CONCLUSIONS
Our results provide insights into the potential intestinal absorption of natural products in Peru, thus facilitating drug development and pharmaceutical discovery efforts.
PubMed: 38931417
DOI: 10.3390/ph17060750 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The psychedelic beverage ayahuasca is originally obtained by () (BC) and () (PV). However, sometimes these plant species are replaced by others that mimic the original...
The psychedelic beverage ayahuasca is originally obtained by () (BC) and () (PV). However, sometimes these plant species are replaced by others that mimic the original effects, such as () (MH) and () (PH). Its worldwide consumption and the number of studies on its potential therapeutic effects has increased. This study aimed to evaluate the anticancer properties of ayahuasca in human colorectal adenocarcinoma cells. Thus, the maximum inhibitory concentration (IC) of decoctions of MH, PH, and a mixture of these (MHPH) was determined. The activities of caspases 3 and 9 were evaluated, and the cell proliferation index was determined through immunocytochemical analysis (Ki-67). Two fluorescent probes were used to evaluate the production of oxidative stress and the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was also evaluated. It was demonstrated that exposure to the extracts significantly induced apoptosis in Caco-2 cells, while decreasing cell proliferation. MH and MHPH samples significantly reduced oxidative stress and significantly increased glutathione peroxidase activity. No significant differences were found in SOD activity. Overall, it was demonstrated that the decoctions have a potential anticancer activity in Caco-2 cells.
PubMed: 38931386
DOI: 10.3390/ph17060719 -
Nutrients Jun 2024Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular... (Review)
Review
Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.
Topics: Humans; Amino Acids, Branched-Chain; Liver Diseases; Dietary Supplements; Liver; Liver Cirrhosis; Liver Neoplasms; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Hepatic Encephalopathy
PubMed: 38931228
DOI: 10.3390/nu16121875 -
Molecules (Basel, Switzerland) Jun 2024L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP)...
L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.
Topics: Humans; Fruit; Cell Line, Tumor; Furocoumarins; Plant Extracts; Ammi; Cell Proliferation; Antineoplastic Agents, Phytogenic; Apoptosis; Chromatography, High Pressure Liquid; Cell Survival
PubMed: 38930940
DOI: 10.3390/molecules29122874 -
Molecules (Basel, Switzerland) Jun 2024(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present...
(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. (2) Methods: The cell viability, migration, invasion, apoptosis, and cell cycle of A549 and PC-9 cells were tested after GHaK treatment. miRNA sequencing, RT-PCR, Western blotting, and luciferase reporter gene assay were further performed to reveal the potential mechanism. (3) Results: GHaK significantly suppressed cell viability, migration, and invasion; induced apoptosis; and caused cell cycle arrest in the G2/M and S phase in PC-9 and A549 cells, respectively. The miRNA sequencing results show a total of 161 up-regulated and 115 down-regulated miRNAs. Furthermore, the study identified six up-regulated miRNAs (miR-4516, miR-4284, miR-204-5p, miR-12136, miR-4463, and miR-1296-3p) and their inhibitory effects on the expressions of target genes (Wnt 8B, FZD2, DVL3, and FOSL1) caused by miR-4516 directly interacting with Wnt 8B. Western blotting revealed the down-regulation of p-GSK-3β, along with a decreased expressions of cyclin A1 and CDK2 in A549 cells and cyclin B1 and CDK1 in PC-9 cells. (4) Conclusions: Temporin-GHaK exhibits antineoplastic activity against human lung adenocarcinoma by inhibiting the Wnt signaling pathway through miRNA-4516.
Topics: Humans; MicroRNAs; Wnt Signaling Pathway; Adenocarcinoma of Lung; Antineoplastic Agents; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Apoptosis; Cell Line, Tumor; Cell Movement; A549 Cells; Cell Proliferation; Cell Survival; Antimicrobial Cationic Peptides
PubMed: 38930863
DOI: 10.3390/molecules29122797 -
Microorganisms May 2024Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic,... (Review)
Review
Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.
Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.
PubMed: 38930460
DOI: 10.3390/microorganisms12061078 -
Journal of Clinical Medicine Jun 2024: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct....
: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct. Reconstruction is mainly based on the use of alloplastic joint prosthesis, costochondral grafting, distraction osteogenesis of the dorsal part of the mandibular ramus, or osseous microvascular flaps of various origin. With the objective of developing a method that overcomes the restrictions of these methods, we recently introduced a sequential chimeric flap consisting of a lateral femoral condyle flap (LFC) and deep circumflex iliac artery flap (DCIA) for reconstruction of up to half of the mandible and the condylar head and neck. : The chimeric flap was used in four patients with the following diagnoses: therapy-refractory osteomyelitis, extended recurrent odontogenic keratozyst, Goldenhar syndrome, and adenocarcinoma of the parotid gland. After a diagnostic workup, LFC and DCIA flaps were harvested in all patients and used in a sequential chimeric design for the reconstruction of the mandibular body and condylar head and neck. : Follow-up from at least 24 months up to 70 month after surgery showed a successful reconstruction in all four patients. The LFC provided a cartilaginous joint surface, allowing for a satisfactory masticatory function with a stable occlusion and unrestricted mouth opening and preserved or regained lateral and medial excursions in all patients. The DCIA allowed for a bony reconstruction anatomically resembling a non-atrophied mandibular body. No flap-related complications were observed. : The sequential chimeric LFC and DCIA flap is an appropriate method for reconstructing up to half of the mandible and the condylar head and neck. It is suitable in cases where alloplastic joint replacement cannot be used or where other methods have failed. Due to the necessity of harvesting two flaps, the burden of care is increased, and a careful indication is required. The technique is reserved for maxillofacial surgeons who have already gained significant experience in the field of microsurgery.
PubMed: 38930140
DOI: 10.3390/jcm13123613 -
Journal of Personalized Medicine Jun 2024An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders,...
An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum β2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting β2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based β2M removal column, in reducing the β2M level and suppressing cancer cell-induced EMT and metastasis. We assessed the effects of Filtor on the changes in metastasis based on the number of circulating tumor cells (CTCs), which reflects the post-EMT cancer cell population. We performed therapeutic apheresis using Filtor on a male patient with sinonasal neuroendocrine carcinoma, a female patient with a history of colorectal cancer, and another female patient with a history of pancreatic ductal adenocarcinoma. Significantly low serum β2M levels and CTC counts were observed immediately and 4 weeks after treatment compared with those in the pretreatment phase. Moreover, the CTC count immediately after therapeutic intervention was markedly reduced, likely because Filtor had trapped CTCs directly. These findings suggest that therapeutic apheresis with Filtor can prevent cancer metastasis and recurrence by directly removing CTCs.
PubMed: 38929860
DOI: 10.3390/jpm14060640 -
Journal of Personalized Medicine May 2024, , , and are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this...
BACKGROUND/OBJECTIVES
, , , and are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes.
METHODS
PVs were identified using NGS DNA sequencing and were confirmed by Sanger.
RESULTS
Families 1, 2, and 3 presented PVs in and , family 4 in and , and family 5 in and . PVs were identified using NGS DNA sequencing and were confirmed by Sanger. The first family included patients with kidney, prostate, and breast cancer, in addition to pancreatic adenocarcinomas. In the second family, a female had breast cancer, while a male from the third family had prostate, gastric, and pancreatic cancer. The fourth family included a male with pancreatic cancer, and the fifth family a female with breast cancer.
CONCLUSIONS
The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double-heterozygous patients associated with PVs in HR-related CPGs. Therefore, in families with patients who differ from other family members in terms of phenotype, age of diagnosis, or type of cancer, the cascade testing needs to include the study of other CPGs.
PubMed: 38929805
DOI: 10.3390/jpm14060584 -
Life (Basel, Switzerland) May 2024Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although... (Review)
Review
Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.
PubMed: 38929687
DOI: 10.3390/life14060704