Modulation of Electronic Availability in g-C3N4 Using Nickel (II), Manganese (II), and Copper (II) to Enhance the Disinfection and Photocatalytic Properties.

Carbon nitrides can form coordination compounds or metallic oxides in the presence of transition metals, depending on the reaction conditions. By adjusting the pH to basic levels for mild synthesis with metals, composites like g-C3N4-M(OH)x (where M represents metals) were obtained for nickel (II) and manganese (II), while copper (II) yielded coordination compounds such as Cu-g-C3N4. These materials underwent spectroscopic and electrochemical characterization, revealing their photocatalytic potential to generate superoxide anion radicals-a feature consistent across all metals. Notably, the copper coordination compound also produced significant hydroxyl radicals. Leveraging this catalytic advantage, with band gap energy in the visible region, all compounds were activated to disinfect E. coli bacteria, achieving total disinfection with Cu-g-C3N4. The textural properties influence the catalytic performance, with copper's stabilization as a coordination compound enabling more efficient activity compared to the other metals. Additionally, the determination of radicals generated under light in the presence of dicloxacillin supported the proposed mechanism and highlighted the potential for degrading organic molecules with this new material, alongside its disinfectant properties.

Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.

Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.

Carcinogenic effect of human tumor-derived cell-free filtrates in nude mice.

Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-Myc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice.

Enantioselective Biomimetic Structures Inspired by Oxi-Dase-Type Metalloenzymes, Utilizing Polynuclear Compounds Containing Copper (II) and Manganese (II) Ions as Building Blocks.

This study focuses on developing and evaluating two novel enantioselective biomimetic models for the active centers of oxidases (ascorbate oxidase and catalase). These models aim to serve as alternatives to enzymes, which often have limited action and a delicate nature. For the ascorbate oxidase (AO) model (compound 1), two enantiomers, S,S(+)cpse and R,R(-)cpse, were combined in a crystalline structure, resulting in a racemic compound. The analysis of their magnetic properties and electrochemical behavior revealed electronic transfer between six metal centers. Compound 1 effectively catalyzed the oxidation of ascorbic to dehydroascorbic acid, showing a 45.5% yield for the racemic form. This was notably higher than the enantiopure compounds synthesized previously and tested in the current report, which exhibited yields of 32% and 28% for the S,S(+)cpse and R,R(-)cpse enantiomers, respectively. This outcome highlights the influence of electronic interactions between metal ions in the racemic compound compared to pure enantiomers. On the other hand, for the catalase model (compound 2), both the compound and its enantiomer displayed polymeric properties and dimeric behavior in the solid and solution states, respectively. Compound 2 proved to be effective in catalyzing the oxidation of hydrogen peroxide to oxygen with a yield of 64.7%. In contrast, its enantiomer (with R,R(-)cpse) achieved only a 27% yield. This further validates the functional nature of the prepared biomimetic models for oxidases. This research underscores the importance of understanding and designing biomimetic models of metalloenzyme active centers for both biological and industrial applications. These models show promising potential as viable alternatives to natural enzymes in various processes.

Modelo predictivo del riesgo de amputación en pacientes con pie diabético / Predictive Model of Amputation Risk in Patients with Diabetic Foot

Introducción: El pie diabético es una complicación de la diabetes mellitus y cada 20 segundos se realiza una amputación ocasionada por esta causa. La estratificación adecuada del paciente con pie diabético permite realizar acciones oportunas para evitar, en un porcentaje elevado de casos, las amputaciones. Objetivo: Validar un modelo predictivo para el riesgo de amputación en pacientes con pie diabético. Métodos: Estudio longitudinal prospectivo. La muestra estuvo conformada por 280 pacientes divididos en dos grupos. Las variables utilizadas para la confección del modelo fueron: edad, hematocrito, leucocitos, linfocitos, neutrófilos, albumina, índice neutrófilo/linfocito, plaquetas, creatinina, tamaño de la lesión y grado de la lesión. Se aplicó un modelo predictivo cuya puntuación permitió estratificar de forma individual a cada paciente. Resultados: Se realizó una validación interna con el 60 por ciento de la muestra, que mostró buena capacidad discriminatoria para el 96,0 por ciento con una sensibilidad de 57,69 por ciento, un valor predictivo positivo del 95,4 por ciento y un Alpha de Cronbach de 0,71. En la prueba final y depuración del modelo se trabajó con el 40 por ciento de la muestra y se realizó la validación externa mediante el estadígrafo Alpha de Cronbach = 0,85. El grupo de prueba tuvo una especificidad de 97,40 por ciento y un valor predictivo positivo del 96,65, lo que fue superior al grupo de entrenamiento. Conclusiones: El modelo predictivo mostró ser una herramienta útil para la estratificación del paciente con pie diabético y permitió aplicar una conducta adecuada en cada paciente(AU)

Introduction: The diabetic foot is a complication of diabetes mellitus and every 20 seconds an amputation by this cause is performed. The adequate stratification of the patient with diabetic foot allows timely actions to avoid, in a high percentage of cases, amputations. Objective: To validate a predictive model for amputation risk in patients with diabetic foot. Methods: Prospective longitudinal study. The sample consisted of 280 patients divided into two groups. The variables used to prepare the model were: age, hematocrit, leukocytes, lymphocytes, neutrophils, albumin, neutrophil/lymphocyte index, platelets, creatinine, lesion size and lesion grade. A predictive model was applied whose score allowed each patient to be individually stratified. Results: An internal validation was performed with 60 percent of the sample, which showed good discriminatory capacity for 96.0 percent with a sensitivity of 57.69 percent, a positive predictive value of 95.4 percent and a Cronbach's Alpha of 0.71. In the final test and debugging of the model, 40 percent of the sample was worked with and external validation was carried out using Cronbach's Alpha statistic = 0.85. The test group had a specificity of 97.40 percent and a positive predictive value of 96.65, which was higher than the training group. Conclusions: The predictive model proved to be a useful tool for the stratification of patients with diabetic foot and allowed to apply an appropriate behavior in each patient(AU)

Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections.

An impaired healing response underlies diabetic foot wound chronicity, frequently translating to amputation, disability, and mortality. Diabetics suffer from underappreciated episodes of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high, so the ulcer is considered in "remission" and not healed from the time it remains epithelialized. Recurrence may result from the combined effects of behavioral and endogenous biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, it still remains elusive in the identification of endogenous biological culprits that may prime the residual scar tissue for recurrence. Furthermore, the event of ulcer recurrence still waits for the identification of a molecular predictor. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblast-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers induce the onset of "at-risk phenotypes" such as premature skin cell aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cell demise. Post-epithelialization recurrence rate data are missing in clinical studies of reputed ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis.

There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis. We identified the SARS-CoV-2 nucleocapsid (NC) in a variety of cells, colocalizing with mitochondrial proteins, lipid droplets (LDs), and key host proteins that have been implicated in inflammation, tissue repair, and the SARS-CoV-2 life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, and PPARγ), pointing to vimentin and LDs as platforms involved not only in the viral life cycle but also in inflammation and pathogenesis. SARS-CoV-2 isolated from a patient´s nasal swab was grown in cell culture and used to infect hamsters. Target cells identified in human tissue samples included lung epithelial and endothelial cells; lipogenic fibroblast-like cells (FLCs) showing features of lipofibroblasts such as activated PPARγ signaling and LDs; lung FLCs expressing fibronectin and vimentin and macrophages, both with evidence of NLRP3- and IL1ß-induced responses; regulatory cells expressing immune-checkpoint proteins involved in lung repair responses and contributing to inflammatory responses in the lung; CD34+ liver endothelial cells and hepatocytes expressing vimentin; renal interstitial cells; and the juxtaglomerular apparatus. This suggests that SARS-CoV-2 may directly interfere with critical lung, renal, and liver functions involved in COVID-19-pathogenesis.

Factores de riesgo cardiometabólico y tratamiento antitrombótico en población mexicana con fibrilación auricular e insuficiencia cardiaca con fracción de expulsión reducida / Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction

Resumen Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Abstract Introduction: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. Objective: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. Methods: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. Results: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. Conclusions: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

Evidence of sea level rise at the Peruvian coast (1942-2019).

The present work aims to analyze the variability of the sea level of the Peruvian coast with time series over a long observation period (Seventy-eight years, from 1942 to 2019). Data came from the Talara, Callao and Matarani tide gauge stations located at the north, center and south of the coast. Variations of sea level as well as air and seawater surface temperature were analyzed. Among the different scenarios studied, a sea level rise of 6.79, 4.21 and 5.16 mm/year for Talara, Callao and Matarani, respectively was found during the 1979-1997 nodal cycle. However, these results decreased significantly during the next cycle (1998-2016) until values of 1.53, 2.16 and 1.0 mm/year for Talara, Callao and Matarani, respectively. Thus, it has been demonstrated that sea level rise are highly dependent on the time interval chosen. Moreover, large interannual changes of up to 200 mm/year are observed, due to recurring phenomena, such as "El Niño". On the other hand, the trends obtained are slightly lower than those shown by the IPCC up until 2006 but significantly higher values have been observed. Finally, the results presented herein show the necessity of a local study of the sea level variability at the coastal areas.

¡El tamaño sí importa! Incidencia del tamaño del cebo en la captura de escarabajos coprófagos en el bosque seco tropical / Size does matter! Incidence of bait size on the capture of dung beetles in the tropical dry forest

Resumen Introducción: Tradicionalmente, los estudios de escarabajos coprófagos en los bosques secos tropicales (BST) del Caribe colombiano han aplicado metodologías diseñadas para zonas húmedas y andinas del país, lo cual podría estar incidiendo en el rendimiento y la eficiencia del muestreo. Objetivo: Con el fin de aportar a esta discusión, se analizó cómo la cantidad de cebo y el tiempo de operación de la trampa de caída inciden en la efectividad de captura de escarabajos coprófagos en un fragmento de BST en La Reserva Campesina la Flecha, San Jacinto, Colombia. Métodos: Para la captura de los escarabajos, se utilizó trampas de caída, cebadas con tres cantidades diferentes de atrayente: pequeño (34.6 g), mediano (53.8 g) y grande (114.9 g), las cuales permanecieron activas en campo durante 48 h. Cuatro muestreos fueron realizados entre marzo y septiembre de 2015, abarcando por igual la época seca y de lluvia. Resultados: Se registró un total de 4 563 individuos, agrupados en 10 géneros y 27 especies de escarabajos coprófagos. Los mayores valores de riqueza, abundancia y biomasa se presentaron en el cebo grande, a las 48 h, durante la época de lluvias. Sin embargo, el tiempo de operación de la trampa no tuvo efecto en la estimación de la riqueza, abundancia y biomasa de escarabajos independientemente de los tamaños de cebo. Los tres órdenes de la diversidad ( 0 D, 1 D y 2 D), presentaron valores similares entre las cantidades de cebo durante la época de lluvia, pero en la época seca, los cebos de mayor tamaño presentaron los valores de diversidad más altos. Por su parte con el cebo de mayor tamaño se capturó significativamente más riqueza, abundancia y biomasa de escarabajos de cuerpo pequeño y grande siendo esta situación más notaria durante la época seca. Conclusiones: Los resultados de este trabajo evidencian que para el estudio de los ensamblajes de escarabajos en el BST la utilización de un cebo de mayor tamaño contribuye a una mejor estimación de riqueza, abundancia, diversidad y biomasa, sobre todo durante la época seca, cuando las condiciones ambientales propician que los cebos pierdan su atractividad con mayor rapidez.

Abstract Introduction: Typically, research on dung beetles in the Tropical Dry Forests (TDF) of Colombian Caribbean region, have applied methodologies designed for wet or Andean areas of the country, which could be influencing the performance and efficiency of sampling. Objective: In order to contribute to this discussion, we analyzed how the bait amount and pitfall trap operating time influence the collection effectiveness of dung beetles in a TDF fragment at Reserva Campesina La Flecha, San Jacinto, Colombia. Methods: For the collection of beetles, we utilized pitfall traps baited with three different amounts of attractants: small (34.6 g), medium (53.8 g), and large (114.9 g), which remained active in the field for 48 h., 4 samplings between March and September 2015 were carried out, covering both, dry and rainy seasons. Results: A total of 4 563 individuals were recorded, grouped into 10 genera and 27 species of dung beetles. The highest values of richness, abundance and biomass were registered in the large bait, at 48 h, during the rainy season. However, the trap operating time had no effect on the estimation of beetles' richness, abundance, and biomass, regardless of bait sizes. The three diversity orders ( 0 D, 1 D y 2 D) showed similar values between the bait amounts during rainy season, but in the dry season, the largest baits displayed the highest diversity values. On the other hand, with the largest bait, significantly more richness, abundance, and biomass of small and large body beetles were registered, especially during the dry season. Conclusions: The results of this research show that, for the study of beetles' assemblages in the BST, the use of a larger bait contributes to a better estimate of richness, abundance, diversity and biomass, especially during the dry season, when environmental conditions promote a more rapidly loss of baits attractiveness.

Manganese Dioxide Nanoparticles Prepared by Laser Ablation as Materials with Interesting Electronic, Electrochemical, and Disinfecting Properties in Both Colloidal Suspensions and Deposited on Fluorine-Doped Tin Oxide.

Nanoparticles (NPs) of α-MnO2 have high applicability in photoelectrochemical, heterogeneous photocatalysis, optical switching, and disinfection processes. To widen this panorama about MnO2 NPs, the formation of this material by laser ablation and deposition by dip-coating on fluorine-doped tin oxide (FTO), were considered in this study. The optical, spectroscopic, electrochemical characterization, and the evaluation of the antimicrobial activity, plus the photocatalytic response, were measured herein in colloidal media and deposited. For the deposition of NPs on FTO sheet, an anode is produced with a pseudocapacitive behavior, and 2.82 eV of band gap (GAP) in comparison with colloidal NPs for a value of 3.84 eV. Both colloidal suspension and deposited NPs have intrinsic antibacterial activity against two representative microorganisms (E. coli and S. aureus), and this biological activity was significantly enhanced in the presence of UVA light, indicating photocatalytic activity of the material. Thus, both the colloidal suspension and deposited NPs can act as disinfecting agents themselves or via light activation. However, an antibacterial behavior different for E. coli and S. aureus was observed, in function of the aggregation state, obtaining total E. coli disinfection at 30 min for deposited samples on FTO.

Cell-Free Filtrates (CFF) as Vectors of a Transmissible Pathologic Tissue Memory Code: A Hypothetical and Narrative Review.

Cellular memory is a controversial concept representing the ability of cells to "write and memorize" stressful experiences via epigenetic operators. The progressive course of chronic, non-communicable diseases such as type 2 diabetes mellitus, cancer, and arteriosclerosis, is likely driven through an abnormal epigenetic reprogramming, fostering the hypothesis of a cellular pathologic memory. Accordingly, cultured diabetic and cancer patient-derived cells recall behavioral traits as when in the donor's organism irrespective to culture time and conditions. Here, we analyze the data of studies conducted by our group and led by a cascade of hypothesis, in which we aimed to validate the hypothetical existence and transmissibility of a cellular pathologic memory in diabetes, arteriosclerotic peripheral arterial disease, and cancer. These experiments were based on the administration to otherwise healthy animals of cell-free filtrates prepared from human pathologic tissue samples representative of each disease condition. The administration of each pathologic tissue homogenate consistently induced the faithful recapitulation of: (1) Diabetic archetypical changes in cutaneous arterioles and nerves. (2) Non-thrombotic arteriosclerotic thickening, collagenous arterial encroachment, aberrant angiogenesis, and vascular remodeling. (3) Pre-malignant and malignant epithelial and mesenchymal tumors in different organs; all evocative of the donor's tissue histopathology and with no barriers for interspecies transmission. We hypothesize that homogenates contain pathologic tissue memory codes represented in soluble drivers that "infiltrate" host's animal cells, and ultimately impose their phenotypic signatures. The identification and validation of the actors in behind may pave the way for future therapies.

Business analytics approach to artificial intelligence.

Artificial Intelligence has become an essential element for strengthening the business fabric. The advances obtained in recent years as a result of the incorporation of technology for the improvement of productive activities and the positioning of companies in the markets are remarkable. Hence, the purpose of this paper is to analyze the origin, evolution and development of business analytics (BA) and its relationship with Artificial Intelligence (AI); from the conceptualization, evolution and identification of the main characteristics and research areas of AI and BA, as well as research conducted and published in journals indexed in Scopus between 2002 and 2022. The aim is to define the incidence of BA in business activities and analyze scientific activity and advances of BA to define new research horizons in this field. For this purpose, a bibliometric and documentary analysis is applied, allowing to highlight the findings that provide recognition and comparison of the results. This will facilitate the understanding of the current dynamics, its importance for organizations, and its impact in the face of the new challenges generated by the requirements of world trade.

Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats.

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats' full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor's vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these "vascular disease drivers" may pave novel research avenues for atherosclerosis pathobiology.

Epidermal growth factor effect on lipopolysaccharide-induced inflammation in fibroblasts derived from diabetic foot ulcer.

BACKGROUND: Diabetic foot ulcers (DFU) are characterised by high levels of inflammatory mediators, resulting from sustained hyperglycaemic insult and the local microbial biofilm. The intralesional administration of epidermal growth factor (EGF) has emerged as an effective treatment that stimulates granulation and closure of DFU, reducing the risk of amputation. Within the wound, fibroblasts play key roles during the healing process, promoting granulation and contraction. The aim of the present study was to examine the anti-inflammatory effect of EGF in DFU-derived fibroblasts, challenged with lipopolysaccharide (LPS), under hyperglycaemic conditions, recreating in vitro what happens in a clinical scenario. METHODS: Healthy skin (HS) and DFU granulation tissue biopsies were used to isolate primary fibroblasts. The effect of LPS on cell proliferation was analysed. Transcriptional expression of toll-like receptor (TLR) pathway mediators (TLR4, TLR2, CD14, MYD88 and NFKB) and pro-inflammatory cytokines (TNF, IL-6 and IL-1B) were measured by semi-quantitative polymerase chain reaction (qPCR), in cells treated with appropriate concentrations of LPS, EGF and their combination. IL-6 protein concentration was quantified by ELISA. RESULTS: LPS stimulated proliferation of HS-derived fibroblasts, while inhibiting the proliferation of cells derived from DFU at the highest assayed concentration of 1 µg/mL. Regarding the TLR signalling pathway, LPS increased messenger RNA levels of mediators and pro-inflammatory genes, while EGF, alone or in the presence of LPS, downregulated them, except for IL-1B. CONCLUSION: The results suggest that EGF might elicit an anti-inflammatory response in LPS-challenged fibroblasts, even in a hyperglycaemic milieu. Collectively, our findings contribute to explain newly observed effects of EGF in the clinical arena. LAY SUMMARY: In this research article, we analyse the putative anti-inflammatory effect of epidermal growth factor (EGF) on fibroblast isolated from diabetic foot ulcer (DFU) granulation tissue. To induce the inflammatory response, the cells were treated with lipopolysaccharide (LPS), simulating the gram-negative bacterial infection that takes place in the wounds of diabetic patients. We studied the expression of genes involved in bacterial recognition receptors signalling pathway and those that code for different pro-inflammatory cytokines.We obtained primary fibroblasts from biopsies of a neuropathic diabetic ulcer and from healthy skin, the former was used as the control. Cells were isolated and grown in high glucose Dulbecco's Modified Eagle Medium (DMEM) culture medium, to simulate the hyperglycaemic insult. The effect of increasing concentrations of LPS on cell proliferation was analysed. Relative transcriptional expression of genes in the study was quantified by quantitative polymerase chain reaction (qPCR) in cells treated with LPS, EGF or a combination. Untreated cells served to normalise the expression.In the present study, we demonstrated that EGF modulated the primary immune response by reducing the activation of pathogen-recognition receptors and common genes involved in these signalling pathways, even in hyperglycaemic conditions. This effect translated in a decreased expression of pro-inflammatory cytokines. These results contribute to explain our previous observations about the reduction of circulating levels of inflammatory cytokines after local administration of human recombinant EGF in DFU. Further molecular studies should be carried out to fully understand the biological mechanisms elicited by EGF in this clinical scenario.

Wound Chronicity, Impaired Immunity and Infection in Diabetic Patients.

BACKGROUND: Diabetic foot ulcers are a common diabetic complication leading to alarming figures of amputation, disability, and early mortality. The diabetic glucooxidative environment impairs the healing response, promoting the onset of a 'wound chronicity phenotype'. In 50% of ulcers, these non-healing wounds act as an open door for developing infections, a process facilitated by diabetic patients' dysimmunity. Infection can elicit biofilm formation that worsens wound prognosis. How this microorganism community is able to take advantage of underlying diabetic conditions and thrive both within the wound and the diabetic host is an expanding research field. OBJECTIVES: 1) Offer an overview of the major cellular and molecular derangements of the diabetic healing process versus physiological cascades in a non-diabetic host. 2) Describe the main immunopathological aspects of diabetics' immune response and explore how these contribute to wound infection susceptibility. 3) Conceptualize infection and biofilim in diabetic foot ulcers and analyze their dynamic interactions with wound bed cells and matrices, and their systemic effects at the organism level. 4) Offer an integrative conceptual framework of wound-dysimmunity-infection-organism damage. EVIDENCE AQUISITION: We retrieved 683 articles indexed in Medline/PubMed, SciELO, Bioline International and Google Scholar. 280 articles were selected for discussion under four major subheadings: 1) normal healing processes, 2) impaired healing processes in the diabetic population, 3) diabetic dysimmunity and 4) diabetic foot infection and its interaction with the host. DEVELOPMENT: The diabetic healing response is heterogeneous, torpid and asynchronous, leading to wound chronicity. The accumulation of senescent cells and a protracted inflammatory profile with a pro-catabolic balance hinder the proliferative response and delay re-epithelialization. Diabetes reduces the immune system's abilities to orchestrate an appropriate antimicrobial response and offers ideal conditions for microbiota establishment and biofilm formation. Biofilm-microbial entrenchment hinders antimicrobial therapy effectiveness, amplifies the host's pre-existing immunodepression, arrests the wound's proliferative phase, increases localized catabolism, prolongs pathogenic inflammation and perpetuates wound chronicity. In such circumstances the infected wound may act as a proinflammatory and pro-oxidant organ superimposed onto the host, which eventually intensifies peripheral insulin resistance and disrupts homeostasis. CONCLUSIONS: The number of lower-limb amputations remains high worldwide despite continued research efforts on diabetic foot ulcers. Identifying and manipulating the molecular drivers underlying diabetic wound healing failure, and dysimmunity-driven susceptibility to infection will offer more effective therapeutic tools for the diabetic population.

Registro sanitario de Heberprot-P®, medicamento biotecnológico innovador para el tratamiento de las úlceras del pie diabético / Sanitary registration of Heberprot-P®, an innovative biotechnological drug for the treatment of diabetic foot ulcers

Introducción: Heberprot-P® obtuvo su primer registro sanitario en Cuba en el año 2006, actualmente está aprobado en otros 26 países. Objetivo: Describir el proceso de registro sanitario en México, del medicamento biotecnológico Heberprot-P® para el tratamiento de las úlceras del pie diabético. Métodos: El proceso de registro sanitario de Heberprot-P® siguió las pautas de la reglamentación sanitaria de México sobre la base de la Ley general de salud y el Reglamento de insumos para la salud. Se revisaron además la Farmacopea de los Estados Unidos Mexicanos y las normas oficiales mexicanas en función de cumplir las exigencias para la comercialización de medicamentos en este territorio. Resultados: El proceso de registro se inició en junio de 2017 en México con acciones en función de completar los documentos e informaciones exigidas en el expediente de registro sanitario a presentarse. Entre ellos resaltan las consideraciones del Subcomité de Evaluación de Productos Biotecnológicos y el Comité de Moléculas Nuevas, la evaluación del expediente por un Tercero Autorizado y documentos emitidos por el Centro Nacional de Farmacovigilancia e Instituto Mexicano de la Propiedad Industrial. Se presentó la solicitud del registro sanitario ante Cofepris y esta se aprobó en mayo de 2018. Conclusiones: El trabajo con grupos de expertos permitió a la autoridad mexicana hacer un trabajo más expedito basado en las evidencias de las evaluaciones realizadas que son parte de la información del registro sanitario. Como resultado de este proceso, se otorgó el Registro Sanitario a Heberprot-P® en mayo de 2018 y Cofepris lo reconoció como un medicamento biotecnológico innovador(AU)

Introduction: Heberprot-P® obtained its first Sanitary Registration in Cuba in 2006, and it is currently approved in 26 other countries. Objective: Describe the sanitary registration process in Mexico of the biotechnological drug Heberprot-P® for the treatment of diabetic foot ulcers. Methods: The sanitary registration process of Heberprot-P® followed the guidelines of the sanitary regulations of Mexico on the basis of the General Health Law and the Regulation of Supplies for Health. The Pharmacopoeia of the United Mexican States and the official Mexican standards were also revised in order to comply with the requirements for the marketing of medicines in this territory. Results: The registration process began in June 2017 in Mexico with actions to complete the documents and information required in the sanitary registration file to be submitted. Among them are the considerations of the Sub-committee on the Evaluation of Biotechnological Products and the Committee on New Molecules, the evaluation of the file by an Authorized Third Party and documents issued by the National Center for Pharmacovigilance and the Mexican Institute of Industrial Property. The application for sanitary registration was submitted to Cofepris and this was approved in May 2018. Conclusions: The work with groups of experts allowed the Mexican authority to do a more expeditious work based on the evidence of the evaluations carried out that are part of the information of the sanitary registry. As a result of this process, Heberprot-P® was granted the Sanitary Registry in May 2018 and COFEPRIS recognized it as an innovative biotechnological medicine(AU)

Revisiting Pleiotropic Effects of Type I Interferons: Rationale for Its Prophylactic and Therapeutic Use Against SARS-CoV-2.

The pandemic distribution of SARS-CoV-2 together with its particular feature of inactivating the interferon-based endogenous response and accordingly, impairing the innate immunity, has become a challenge for the international scientific and medical community. Fortunately, recombinant interferons as therapeutic products have accumulated a long history of beneficial therapeutic results in the treatment of chronic and acute viral diseases and also in the therapy of some types of cancer. One of the first antiviral treatments during the onset of COVID-19 in China was based on the use of recombinant interferon alfa 2b, so many clinicians began to use it, not only as therapy but also as a prophylactic approach, mainly in medical personnel. At the same time, basic research on interferons provided new insights that have contributed to a much better understanding of how treatment with interferons, initially considered as antivirals, actually has a much broader pharmacological scope. In this review, we briefly describe interferons, how they are induced in the event of a viral infection, and how they elicit signaling after contact with their specific receptor on target cells. Additionally, some of the genes stimulated by type I interferons are described, as well as the way interferon-mediated signaling is torpedoed by coronaviruses and in particular by SARS-CoV-2. Angiotensin converting enzyme 2 (ACE2) gene is one of the interferon response genes. Although for many scientists this fact could result in an adverse effect of interferon treatment in COVID-19 patients, ACE2 expression contributes to the balance of the renin-angiotensin system, which is greatly affected by SARS-CoV-2 in its internalization into the cell. This manuscript also includes the relationship between type I interferons and neutrophils, NETosis, and interleukin 17. Finally, under the subtitle of "take-home messages", we discuss the rationale behind a timely treatment with interferons in the context of COVID-19 is emphasized.

Intralesional Infiltrations of Cell-Free Filtrates Derived from Human Diabetic Tissues Delay the Healing Process and Recreate Diabetes Histopathological Changes in Healthy Rats.

Lower limb ulcers in type-2 diabetic patients are a frequent complication that tributes to amputation and reduces survival. We hypothesized that diabetic healing impairment and other histopathologic hallmarks are mediated by a T2DM-induced tissue priming/metabolic memory that can be transferred from humans to healthy recipient animals and consequently reproduce diabetic donor's phenotypes. We examined the effect of human T2DM tissue homogenates injected into non-diabetic rat excisional wounds. Fresh granulation tissue, popliteal artery, and peroneal nerve of patients with T2DM were obtained following amputation. Post-mammoplasty granulation and post-traumatic amputation-tissue of normal subjects acted as controls. The homogenates were intralesionally injected for 6-7 days into rats' excisional thickness wounds. Infiltration with the different homogenates caused impaired wound closure, inflammation, nerve degeneration, and arterial thickening (all P < 0.01 vs relevant control) resembling histopathology of diabetic donor tissues. Control materials caused marginal inflammation only. Infiltration with glycated bovine albumin provoked inflammation and wound healing delay but did not induce arterial thickening. The reproduction of human diabetic traits in healthy recipient animals through a tissue homogenate support the notion on the existence of tissue metabolic memory-associated and transmissible factors, involved in the pathogenesis of diabetic complications. These may have futuristic clinical implications for medical interventions.