Chlorogenic acid attenuates idiopathic pulmonary fibrosis: An integrated analysis of network pharmacology, molecular docking, and experimental validation.

AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition, the cause of which remains unknown and for which no effective therapeutic treatment is currently available. Chlorogenic acid (CGA), a natural polyphenolic compound found in different plants and foods, has emerged as a promising agent due to its anti-inflammatory, antioxidant, and antifibrotic properties. However, the molecular mechanisms underlying the therapeutic effect of CGA in IPF remain unclear. The purpose of this study was to analyze the pharmacological impact and underlying mechanisms of CGA in IPF. MAIN METHODS: Using network pharmacology analysis, genes associated with IPF and potential molecular targets of CGA were identified through specialized databases, and a protein-protein interaction (PPI) network was constructed. Molecular docking was performed to accurately select potential therapeutic targets. To investigate the effects of CGA on lung histology and key gene expression, a murine model of bleomycin-induced lung fibrosis was used. KEY FINDINGS: Network pharmacology analysis identified 384 were overlapped between CGA and IPF. Key targets including AKT1, TP53, JUN, CASP3, BCL2, MMP9, NFKB1, EGFR, HIF1A, and IL1B were identified. Pathway analysis suggested the involvement of cancer, atherosclerosis, and inflammatory processes. Molecular docking confirmed the stable binding between CGA and targets. CGA regulated the expression mRNA of EGFR, MMP9, AKT1, BCL2 and IL1B and attenuated pulmonary fibrosis in the mouse model. SIGNIFICANCE: CGA is a promising multi-target therapeutic agent for IPF, which is supported by its efficacy in reducing fibrosis through the modulation of key pathways. This evidence provides a basis to further investigate CGA as an IPF potential treatment.

Association between O-GlcNAc levels and platelet function in obese insulin-resistant subjects.

Obesity is an epidemic associated with platelet and vascular disorders. Platelet O-GlcNAcylation has been poorly studied in obese subjects. We aimed to evaluate O-linked N-acetyl-glucosamine (O-GlcNAc) levels and platelet activity in obese insulin-resistant (ObIR) subjects. Six healthy and six insulin-resistant obese subjects with a body mass index of 22.6 kg/m2 (SD ± 2.2) and 35.6 kg/m2 (SD ± 3.8), respectively, were included. Flow cytometry was used to measure markers of platelet activity, expression of P-selectin (CD62P antibody), glycoprotein IIb/IIIa (integrins αIIbß3 binding to PAC-1 antibody), and thrombin stimulation. O-GlcNAc was determined in the platelets of all test subjects by cytofluometry, intracellular calcium, percentage of platelet aggregation, and immunofluorescence microscopy and Western blot were used to assess O-GlcNAc and OGT (O-GlcNAc transferase) in platelets. Platelets from ObIR subjects had on average 221.4 nM intracellular calcium, 81.89% PAC-1, 22.85% CD62P, 57.48% OGT, and 66.62% O-GlcNAc, while platelets from healthy subjects had on average 719.2 nM intracellular calcium, 4.99% PAC-1, 3.17% CD62P, 18.38% OGT, and 23.41% O-GlcNAc. ObIR subjects showed lower platelet aggregation than healthy subjects, 13.83% and 54%, respectively. The results show that ObIR subjects have increased O-GlcNAc, and increased intraplatelet calcium associated with platelet hyperactivity and compared to healthy subjects, suggesting that changes in platelet protein O-GlcNAcylation and platelet activity might serve as a possible prognostic tool for insulin resistance, prediabetes and its progression to type 2 diabetes mellitus.

O-GlcNAcylation: Crosstalk between Hemostasis, Inflammation, and Cancer.

O-linked ß-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients' healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network.

LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Attention to health care in the context of instability. In health care for women international.

In Mexico, the first attack dates back to 1988, but it was not identified until 2022. This violence remained invisible and minimized, but since then 42 acid attacks against women have been recorded, of which 5 victims died as a result of the attack and its medical complications. We think that families should be educated to eliminate misogyny in families and ensure that women are valued equally as men. We also think that education from childhood, questioning one's own beliefs, challenging stereotypes and gender roles, deconstructing prejudices, reporting, and acting with empathy and compassion are fundamental in a society with gender equity.

Re. Re.: "Immunothrombotic dysregulation in Chagas disease and COVID19: a comparative study of anticoagulation".

Re. Re.: "Immunothrombotic dysregulation in Chagas disease (CD) and COVID-19: a comparative study of anticoagulation": In the commentary on our paper, Hasslocher-Moreno made the point that indeterminate and digestive forms are not related to thromboembolic events, only thrombogenic alterations occur in CD with cardiopathy, however there is indirect evidence related to thombotic alterations, such as cerebral thrombosis. Our assertion is based on previous data discussed in this letter.

The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus.

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand-receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.

Associations of Dynapenic Obesity and Sarcopenic Obesity with the Risk of Complications in COVID-19.

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.

Analysis of SARS-CoV-2 mutations in Mexico, Belize, and isolated regions of Guatemala and its implication in the diagnosis.

The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The importance of study of mutations is related to the possible virulence and diagnosis of SARS-CoV-2. To identify circulating mutations present in SARS-CoV-2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS-CoV-2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID-19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS-CoV-2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation.

Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.

Aggregation and Molecular Properties of ß-Glucosidase Isoform II in Chayote (Sechium edule).

The presence of isoforms of ß-glucosidase has been reported in some grasses such as sorghum, rice and maize. This work aims to extract and characterize isoform II in ß-glucosidase from S. edule. A crude extract was prepared without buffer solution and adjusted to pH 4.6. Contaminating proteins were precipitated at 4 °C for 24 h. The supernatant was purified by chromatography on carboxymethyl cellulose (CMC) column, molecular exclusion on Sephacryl S-200HR, and exchange anionic on QFF column. Electrophoretic analyzes revealed a purified enzyme with aggregating molecular complex on SDS-PAGE, Native-PAGE, and AU-PAGE. Twelve peptides fragments were identified by nano liquid chromatography-tandem mass spectrometry (nano LC-ESI-MS/MS), which presented as 61% identical to Cucurbita moschata ß-glucosidase and 55.74% identical to ß-glucosidase from Cucumis sativus, another Cucurbitaceous member. The relative masses which contained 39% hydrophobic amino acids ranged from 982.49 to 2,781.26. The enzyme showed a specificity to ß-d-glucose with a Km of 4.59 mM, a Vmax value of 104.3 µM∙min-1 and a kcat of 10,087 µM∙min-1 using p-nitrophenyl-ß-D-glucopyranoside. The presence of molecular aggregates can be attributed to non-polar amino acids. This property is not mediated by a ß-glucosidase aggregating factor (BGAF) as in grasses (maize and sorghum). The role of these aggregates is discussed.

Reduced platelet aggregation in women after intercourse: a possible role for the cyclooxygenase pathway.

We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay. Platelets and prostanoids were evaluated in women, periodically, before and after intercourse. The platelets were tested with adenosine diphosphate (ADP) and arachidonic acid (AA). To block the interaction between the uterus and SF, some couples used condoms. We found that the 6-keto prostaglandin F1α in urine at 2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre-intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in platelet aggregation was observed in women whose partners did not use condoms. Averages for platelet aggregation were 20.16% with ADP, and more significantly, 37.79% with AA after 2 hours. In contrast, couples using condoms showed no changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were taking aspirin or indomethacin also showed no changes. SF from men taking aspirin or indomethacin led to no reduction in platelet aggregometry in their partners. These results indicate that in cases of exposure to SF, the transient change in women's platelet activity could be related to the cyclooxygenase pathway.

Reduction of Platelet Aggregation From Ingestion of Oleic and Linoleic Acids Found in Vitis vinifera and Arachis hypogaea Oils.

The purpose of this study was to evaluate the effect of the consumption of seed oils from Vitis vinifera and Arachis hypogaea in platelet aggregation. The initial hypothesis suggested that subjects who have consumed these seed oils undergo modified platelet aggregation. This study was performed using a pre-post test design, with a control group, and double blind. The effects of the consumption of grape seed and peanut oils were measured for platelet aggregation in clinical and laboratory tests in 30 healthy subjects. In addition to this group, a control group of 4 health subjects received no treatment with oils, just 500 mg oral administration acetylsalicylic acid for 7 days. Platelet aggregation was assessed by the Born turbidimetric method, using 3 different concentrations of adenosine diphosphate as agonists (2, 54; 1, 17; and 0, 58 µM). The study subjects had very similar results; both oils were shown to have a significant reduction in platelet aggregation. Grape seed oil showed a decrease of 8.4 ± 1% in aggregation, compared with peanut oil, which decreased aggregation by 10.4 ± 1%. The control group, taking 500 mg OD aspirin for 7 days, showed a significant decrease in platelet aggregation, similar to that of oil ingestion. Each of the oils was analyzed for fatty acids, to determine which particular acids were presents in greater levels, which could explain the reduction in platelet aggregation. The oil found to be most abundant in grape seeds was linoleic acid (omega-6), and in peanuts, it was oleic acid (omega-9). However, in fact, both acids reduced platelet aggregation. Consumption of plant oils from grape seeds and peanuts had a lowering effect on platelet aggregation, in addition to containing a high content of unsaturated fatty acids. However, omega-3, omega-6, and omega-9 fatty acids were not specifically responsible for the reductions mentioned above.

[Hyperinsulinemia and insulin resistance in children]. / Hiperinsulinemia y resistencia insulínica en niños de dos escuelas públicas de Oaxaca, México.

BACKGROUND: Obesity during childhood is a risk factor for developing cardiovascular diseases during adulthood. AIM: To measure insulin and glucose levels and parameters of insulin resistance in obese, overweight and normal weight Mexican children. MATERIAL AND METHODS: Comparative study of 21 obese children with a body mass index (BMI) over percentile 95, aged 10 ± 1 years (10 males), 14 children aged 10 ± 2 (7 males) with a BMI between percentiles 85 and 94 and 16 children aged 9 ± 2 years (3 males) with a body mass index between percentiles 10 and 84. Body weight, blood pressure and waist circumference were measured and a blood sample was obtained to measure fasting glucose and insulin levels. Homeostasis model of insulin resistance (HOMA) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Among obese, overweight and normal weight children, insulin levels were 14.9 (95% CI 10.90-18.99), 7.20 (CI 5.12-9.28) and 4.73 (CI 95% 1.92-7.53) uU/ml, respectively. The figures for HOMA were 3.16 (95% CI 2.20-4.12), 1.49 (95% CI 1.03-1.94) and 0.97 (95% CI 0.35-1.60), respectively. The figures for QUICKI were 0.331 (95% CI 0.319-0.343), 0.371 (95% CI 0.349-0.393) and 0.419 (95% CI 0.391-0.446), respectively. Compared to their normal weight counterparts, the risk of obese children and those with a waist circumference over percentile 90 of having a HOMA over 3.16 was 17 and 10 times higher, respectively. BMI correlated better than waist circumference with insulin levels. CONCLUSIONS: Obese children have higher levels of insulin resistance than their normal weight counterparts.

[Asymptomatic human infection from contact with dogs: a case of human ehrlichiosis]. / Infección humana asintomática por contacto con perros. Un caso de ehrlichiosis humana.

INTRODUCTION: Living with dogs leads one to consider the necessity of identifying canine infections found in the people with whom the dogs live. OBJECTIVE: Dogs which were clinically and serologically positive with the infections Ehirlichia canis, Anaplasma phagocytophilum, Borrelia burgdorferi, and Dirofilaria Immitis were sought. People with the same infections were also identified. MATERIAL AND METHODS: From a population of 80 dogs identified in the villages of San Bartolo Coyotepec and San Agustín Etla (suburbs peripheral to the city of Oaxaca, Mexico), 27 dogs were selected for study, all of which had adenomegaly, hepatomegaly, splenomegaly, and fevers of at least 43° C. Using enzyme immunoassay in this population of dogs and their closest human contacts, antibodies for Ehirlichia canis, Anaplasma phagocytophilum, Borrelia burgdorferi, and the antigen for Dirofilaria immitis were sought. Positive results in humans were confirmed by polymerase chain reaction (PCR). RESULTS: Ten dogs with the clinical signs mentioned above tested positive for antibodies to Ehrlichia canis; two cases tested positive for Anaplasma phagocytophilum; one case tested positive for Dirofilaria Immitis. From human contact, one person tested positive for Ehirlichia canis; this case was confirmed by DNA amplification by means of PCR. CONCLUSION: It is necessary to identify the population of sick dogs in order to reduce related infections in people.

Relevance of a Customized Version of ChatGPT Explaining Laboratory Test Results in Patient Education.

ChatGPT is an artificial intelligence (AI) chatbot application. In this study, we explore the creation and use of a customized version of ChatGPT designed specifically for patient education, called "Lab Explainer." Lab Explainer aims to simplify and clarify the results of complex laboratory tests for patients, using the sophisticated capabilities of AI in natural language processing; it analyses various laboratory test data and provides clear explanations and contextual information. The approach involved adapting OpenAI's ChatGPT model specifically to analyze laboratory test data. The results suggest that Lab Explainer has the potential to improve understanding by providing an interpretation of laboratory tests to the patient. In conclusion, the Lab Explainer can assist patient education by providing intelligible interpretations of laboratory tests.

Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study.

Extracellular vesicles (EVs) represent an attractive source of biomarkers due to their biomolecular cargo. The aim of this study was to identify candidate protein biomarkers from plasma-derived EVs of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Plasma-derived EVs from healthy participants (HP), LC, and HCC patients (eight samples each) were subjected to label-free quantitative proteomic analysis using LC-MS/MS. A total of 248 proteins were identified, and differentially expressed proteins (DEPs) were obtained after pairwise comparison. We found that DEPs mainly involve complement cascade activation, coagulation pathways, cholesterol metabolism, and extracellular matrix components. By choosing a panel of up- and down-regulated proteins involved in cirrhotic and carcinogenesis processes, TGFBI, LGALS3BP, C7, SERPIND1, and APOC3 were found to be relevant for LC patients, while LRG1, TUBA1C, TUBB2B, ACTG1, C9, HP, FGA, FGG, FN1, PLG, APOB and ITIH2 were associated with HCC patients, which could discriminate both diseases. In addition, we identified the top shared proteins in both diseases, which included LCAT, SERPINF2, A2M, CRP, and VWF. Thus, our exploratory proteomic study revealed that these proteins might play an important role in the disease progression and represent a panel of candidate biomarkers for the prognosis and diagnosis of LC and HCC.

Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.

Modulatory role of prolactin in type 1 diabetes.

OBJECTIVES: Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus. CONTENT: Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus. SUMMARY: Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control. OUTLOOK: Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.