Aceptación y reticencia a las vacunas contra COVID-19 en ingresantes a una universidad pública peruana durante la tercera ola pandémica

Introducción. Los estudiantes universitarios influyen en las decisiones de su familia y comunidad a favor de la vacunación. Objetivo. Identificar las principales razones para la aceptación o reticencia vacunal contra COVID-19 en ingresantes a una universidad pública. Métodos. Estudio transversal en una muestra de 408 estudiantes. Se preguntó si había completado las tres dosis de vacuna contra COVID-19 y la principal razón para la aceptación o reticencia vacunal. Se realizó un análisis descriptivo, se aplicó la prueba chi cuadrado y exacta de Fisher. Resultados. El 85,5% aceptó la vacuna principalmente por no querer contagiar a familiares (38,1%) y no querer enfermarse (27,8%). El 14,5% fue reticente, especialmente por prolongados tiempos de espera en vacunatorios (37,3%) y lejanía de los centros de vacunación (13,6%). Conclusiones. En los universitarios estudiados, el temor a la enfermedad impulsó la aceptación de la vacuna contra COVID-19 y la inaccesibilidad a los servicios de salud generó la reticencia.

Introduction. University students influence their family and community decisions in favor of vaccination. Objective. To identify the main reasons for COVID-19 vaccine acceptance or hesitancy among university entrants. Methods. A cross-sectional study in a sample of 408 students. We asked whether the student had completed the three doses the COVID-19 vaccine and the main reason for vaccine acceptance or hesitancy. A descriptive analysis was performed, the chi-square test and Fisher's exact were applied. Results. 85.5% accepted vaccination mainly because they did not want to infect family members (38.1%) and did not want to get sick (27.8%). 14.5% were hesitancy especially due to long waiting times in vaccination centers (37.3%) and distance from vaccination centers (13.6%). Conclusions. In the university students studied, the fear of disease drove COVID-19 vaccine acceptance and inaccessibility to health services generated vaccine hesitancy among university entrants.

Inhibition of C5AR1 impairs osteoclast mobilization and prevents bone loss.

Age-related and chemotherapy-induced bone loss depends on cellular senescence and the cell secretory phenotype. However, the factors secreted in the senescent microenvironment that contribute to bone loss remain elusive. Here, we report a central role for the inflammatory alternative complement system in skeletal bone loss. Through transcriptomic analysis of bone samples, we identified complement factor D, a rate-limiting factor of the alternative pathway of complement, which is among the most responsive factors to chemotherapy or estrogen deficiency. We show that osteoblasts and osteocytes are major inducers of complement activation, while monocytes and osteoclasts are their primary targets. Genetic deletion of C5ar1, the receptor of the anaphylatoxin C5a, or treatment with a C5AR1 inhibitor reduced monocyte chemotaxis and osteoclast differentiation. Moreover, genetic deficiency or inhibition of C5AR1 partially prevented bone loss and osteoclastogenesis upon chemotherapy or ovariectomy. Altogether, these lines of evidence support the idea that inhibition of alternative complement pathways may have some therapeutic benefit in osteopenic disorders.

Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.

Protein ubiquitylation acts as a complex cell signaling mechanism since the formation of different mono- and polyubiquitin chains determines the substrate's fate in the cell. E3 ligases define the specificity of this reaction by catalyzing the attachment of ubiquitin to the substrate protein. Thus, they represent an important regulatory component of this process. Large HERC ubiquitin ligases belong to the HECT E3 protein family and comprise HERC1 and HERC2 proteins. The physiological relevance of the Large HERCs is illustrated by their involvement in different pathologies, with a notable implication in cancer and neurological diseases. Understanding how cell signaling is altered in these different pathologies is important for uncovering novel therapeutic targets. To this end, this review summarizes the recent advances in how the Large HERCs regulate the MAPK signaling pathways. In addition, we emphasize the potential therapeutic strategies that could be followed to ameliorate the alterations in MAPK signaling caused by Large HERC deficiencies, focusing on the use of specific inhibitors and proteolysis-targeting chimeras.

HERC1 deficiency causes osteopenia through transcriptional program dysregulation during bone remodeling.

Bone remodeling is a continuous process between bone-forming osteoblasts and bone-resorbing osteoclasts, with any imbalance resulting in metabolic bone disease, including osteopenia. The HERC1 gene encodes an E3 ubiquitin ligase that affects cellular processes by regulating the ubiquitination of target proteins, such as C-RAF. Of interest, an association exists between biallelic pathogenic sequence variants in the HERC1 gene and the neurodevelopmental disorder MDFPMR syndrome (macrocephaly, dysmorphic facies, and psychomotor retardation). Most pathogenic variants cause loss of HERC1 function, and the affected individuals present with features related to altered bone homeostasis. Herc1-knockout mice offer an excellent model in which to study the role of HERC1 in bone remodeling and to understand its role in disease. In this study, we show that HERC1 regulates osteoblastogenesis and osteoclastogenesis, proving that its depletion increases gene expression of osteoblastic makers during the osteogenic differentiation of mesenchymal stem cells. During this process, HERC1 deficiency increases the levels of C-RAF and of phosphorylated ERK and p38. The Herc1-knockout adult mice developed imbalanced bone homeostasis that presented as osteopenia in both sexes of the adult mice. By contrast, only young female knockout mice had osteopenia and increased number of osteoclasts, with the changes associated with reductions in testosterone and dihydrotestosterone levels. Finally, osteocytes isolated from knockout mice showed a higher expression of osteocytic genes and an increase in the Rankl/Opg ratio, indicating a relevant cell-autonomous role of HERC1 when regulating the transcriptional program of bone formation. Overall, these findings present HERC1 as a modulator of bone homeostasis and highlight potential therapeutic targets for individuals affected by pathological HERC1 variants.

Apendicitis aguda y el riesgo de tumor maligno oculto. Presentación de un caso y revisión sistemática de la literatura / Acute appendicitis and the risk of hidden malignant tumor. Presentation of a case and systematic review of literature

Introducción: Los tumores apendiculares representan aproximadamente 1% de los tumores malignos del intestino grueso. Más del 50% de las neoplasias primarias del apéndice se manifiestan inicialmente como apendicitis aguda. Métodos: Se reporta caso de paciente masculino que presentó adenocarcinoma invasor en biopsia de pieza quirúrgica de apéndice cecal tras apendicectomía, tomando la decisión de realizar hemicolectomía derecha laparoscópica diferida. Discusión: En este caso y como en la mayoría de los reportes de la bibliografía mundial, el adenocarcinoma simula un cuadro de AA. En un metaanálisis y una revisión sistemática de 2.771 pacientes diagnosticados de masa apendicular inflamatoria (flemón o absceso), Andersson et al. encontró 31 con tumores malignos. Estas lesiones se detectan en el 0,9% al 1,4% de las apendicectomías realizadas para tratar la AA. Conclusión: Este subtipo histológico presenta mayor incidencia de metástasis en los ganglios linfáticos y la supervivencia global era del 47,5%. Es por ello por lo que abogamos por la resección colónica como tratamiento definitivo del adenocarcinoma de apéndice cecal.

INTRODUCTION: Appendulular tumors represent approximately 1% of malignant tumors of the large intestine. More than 50% of the primary neoplasms of the appendix initially manifest as acute appendicitis. Methods: Men's patient who presented invading adenocarcinoma in Cecal Appendix Surgical Party Biopsy after appendectomy, making the decision to perform deferred laparoscopic right hemicolectomy, is reported. Discussion: In this case and as in most world literature reports, adenocarcinoma simulates an AA picture. In a meta -analysis and a systematic review of 2,771 diagnosed patients of inflammatory appendicular mass (phlegmon or abscess), Andersson et al. He found 31 with malignant tumors. These lesions are detected at 0.9% to 1.4% of appendectomies made to treat the AA. Conclusion: This histological subtype has a greater incidence of metastasis in lymph nodes and global survival was 47.5%. That is why we advocate colonic resection as a definitive treatment of cecal appendix adenocarcinoma.

Revisión Anatómica de Sistema Venoso Intrahepático. Hematoma Intrahepático Subcapsular en Colecistectomia Laparoscópica / Anatomical Review of Intrahepatic Venous System. Subcapsular Intrahepatic Hematoma In Laparoscopic Cholecystectomy

La aparición del hematoma intrahepático subcapsular (SHI) después de la colecistectomía laparoscópica es una complicación poco frecuente. El estudio anatómico de las venas suprahepáticas nos permitió observar que existen numerosos patrones de ramificación de estos. Presentamos el caso de una mujer de 37 años que, durante la intervención de colecistectomía laparoscópica, se observa en el acto quirúrgico, la formación espontánea de hematomas subcapsulares, secundario a la tracción forzada del fondo del órgano

The appearance of subcapsular intrahepatic hematoma (SHI) after laparoscopic cholecystectomy is an infrequent complication.The anatomical study of the suprahepatic veins allowed us to observe that there are numerous branching patterns of these. We present the case of a 37-year-old female who, during the laparoscopic cholecystectomy intervention, is observed in the surgical act, the spontaneous formation of subcapsular hematomas, secondary to forced traction of the fundus of the organ

HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.

HERC2 gene encodes an E3 ubiquitin ligase involved in several cellular processes by regulating the ubiquitylation of different protein substrates. Biallelic pathogenic sequence variants in the HERC2 gene are associated with HERC2 Angelman-like syndrome. In pathogenic HERC2 variants, complete absence or marked reduction in HERC2 protein levels are observed. The most common pathological variant, c.1781C > T (p.Pro594Leu), encodes an unstable HERC2 protein. A better understanding of how pathologic HERC2 variants affect intracellular signalling may aid definition of potential new therapies for these disorders. For this purpose, we studied patient-derived cells with the HERC2 Pro594Leu variant. We observed alteration of mitogen-activated protein kinase signalling pathways, reflected by increased levels of C-RAF protein and p38 phosphorylation. HERC2 knockdown experiments reproduced the same effects in other human and mouse cells. Moreover, we demonstrated that HERC2 and RAF proteins form molecular complexes, pull-down and proteomic experiments showed that HERC2 regulates C-RAF ubiquitylation and we found out that the p38 activation due to HERC2 depletion occurs in a RAF/MKK3-dependent manner. The displayed cellular response was that patient-derived and other human cells with HERC2 deficiency showed higher resistance to oxidative stress with an increase in the master regulator of the antioxidant response NRF2 and its target genes. This resistance was independent of p53 and abolished by RAF or p38 inhibitors. Altogether, these findings identify the activation of C-RAF/MKK3/p38 signalling pathway in HERC2 Angelman-like syndrome and highlight the inhibition of RAF activity as a potential therapeutic option for individuals affected with these rare diseases.

Bezoar. A propósito de un caso / Bezoar. A case report

Introducción: la obstrucción del intestino delgado (SBO) es una presentación común en cualquier unidad de cirugía general. Sin embargo, su diagnóstico y manejo preoperatorio a menudo pueden ser difíciles debido a sus múltiples causas. La obstrucción intestinal pequeña secundaria a la impactación de bezoar es considerablemente infrecuente, con una frecuencia reportada de aproximadamente 0.4% a 4%. La incidencia de bezoar como causa de obstrucción intestinal es baja. El método complementario con la mayor sensibilidad y especificidad continúa siendo CT del abdomen y la pelvis con contraste oral e intravenoso. El tratamiento debe ser quirúrgico. Modificar la dieta junto con el manejo de los trastornos es la mejor forma de prevención.

Introduction: Small Bowel Obstruction (SBO) is a common presentation in any general surgery unit. However, its diagnosis and preoperative management can often be difficult due to its multiple causes. Small bowel obstruction secondary to bezoar impaction is considerably uncommon, with a reported frequency of about 0.4% to 4%. The incidence of bezoar as a cause of intestinal obstruction is low. The complementary method with the highest sensitivity and specificity continues to be CT of the abdomen and pelvis with oral and intravenous contrast. Treatment must be surgical. Modifying the diet along with managing the disorders is the best form of prevention

[Usefulness of the Difficult Cholecystectomy Score according to laparoscopic conversion]. / Utilidad del Score de la Colecistectomía Dificultosa según conversión laparoscópica.

Introduction: Biliary lithiasis (LB) is a very frequent problem in the daily consultation of a general surgeon, so currently, 10 to 15% of the adult population in the experienced countries has LB. Methodology: A descriptive, observational and cross-sectional study was carried out with patients sometimes having a laparoscopic cholecystectomy in a period between January 1, 2018 and December 31, 2018. The main objective of this study is to determine the differences in the risk scoring means of difficult cholecystectomy according to the conversion to open surgery in patients diagnosed with symptomatic biliary lithiasis. Results: Through the registered data, it can be said that being a man, with a leukocyte count> 12,000 mm3, with a BMI> 30, the presence of choledocholithiasis and a greater gallbladder cut with 3 mm are factors that increase the risk of conversion to open surgery in this series of patients. It is feasible and safe to use this score to determine the patients with the highest risk of conversion since all the independent factors identified are not modifiable. Conclusion: In short, being a man, with a leukocyte count> 10,000 mm3, with a BMI> 30, the presence of choledocholithiasis and a gallbladder wall greater than 3 mm are factors that increase the risk of conversion to open surgery in a series of patients undergoing video laparoscopy. in a university hospital and it is feasible and safe to use this score to identify those patients with the highest risk of conversion.

Introducción: La litiasis biliar (LB) es un problema muy frecuente en la consulta diaria de un cirujano general, por lo que actualmente, del 10 al 15% de la población adulta en los países desarrollados presenta LB. Metodología: Se realizó un estudio descriptivo, observacional y transversal con los pacientes sometidos a colecistectomía laparoscópica en un período comprendido entre el 1 de enero del 2018 y el 31 de diciembre del 2018. El objetivo principal de este estudio es determinar diferencias de media del score de riesgo de colecistectomía dificultosa según conversión a cirugía abierta en pacientes con diagnóstico de litiasis biliar sintomática. Resultados: A través de los datos registrados se puede decir que ser hombre, con recuento de leucocitos >12.000 mm3, con IMC >30, presencia de coledocolitiasis y pared vesicular mayor a 3 mm son factores que incrementan el riesgo de conversión a cirugía abierta en esta serie de pacientes. Es factible y seguro utilizar este score para determinar aquellos pacientes con mayor riesgo de conversión dado que todos los factores independientes identificados no son modificables. Conclusión: En definitiva, ser hombre, con recuento de leucocitos >10.000 mm3, con IMC >30, presencia de coledocolitiasis y pared vesicular mayor a 3 mm son factores que incrementan el riesgo de conversión a cirugía abierta en una serie de pacientes sometidos a video laparoscopía en un Hospital universitario y es factible y seguro utilizar este score para identificar esos pacientes con mayor riesgo de conversión.

HERC Ubiquitin Ligases in Cancer.

HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3-HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies.

Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions.

We report the in vivo regulation of Inosine-5´-monophosphate dehydrogenase 1 (IMPDH1) in the retina. IMPDH1 catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides, impacting the cellular pools of GMP, GDP and GTP. Guanine nucleotide homeostasis is central to photoreceptor cells, where cGMP is the signal transducing molecule in the light response. Mutations in IMPDH1 lead to inherited blindness. We unveil a light-dependent phosphorylation of retinal IMPDH1 at Thr159/Ser160 in the Bateman domain that desensitizes the enzyme to allosteric inhibition by GDP/GTP. When exposed to bright light, living mice increase the rate of GTP and ATP synthesis in their retinas; concomitant with IMPDH1 aggregate formation at the outer segment layer. Inhibiting IMPDH activity in living mice delays rod mass recovery. We unveil a novel mechanism of regulation of IMPDH1 in vivo, important for understanding GTP homeostasis in the retina and the pathogenesis of adRP10 IMPDH1 mutations.

The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling.

Protein modifications by phosphorylation or ubiquitylation have been selected throughout evolution as efficient regulatory mechanisms of cellular processes. Cell migration is a complex, highly coordinated process where these mechanisms must participate in an integrated manner to transmit signaling during migration. In this study, we show that the ubiquitin ligase HERC1 regulates the p38 signaling pathway, and that this regulation is mediated by the MAPK kinase MKK3. Moreover, we demonstrate a crosstalk between RAF and MKK3/p38 pathways where RAF acts upstream of MKK3. Mechanistically, HERC1 regulates the protein levels of C-RAF and MKK3. Thus, HERC1 ubiquitylates C-RAF, targeting it for proteasomal degradation, and RAF proteins regulate MKK3 mRNA levels. Accordingly, HERC1 knockdown induces C-RAF stabilization and activation of RAF proteins; in turn, this activation increases MKK3, which phosphorylates and activates p38. The importance of these observations is demonstrated by HERC1 regulation of cell migration through regulation of p38 signaling via a RAF-dependent mechanism. Thus, HERC1 plays an essential role as a regulator of crosstalk between RAF/MKK3/p38 signaling pathways during cell migration.

Regulation of the MDM2-p53 pathway by the ubiquitin ligase HERC2.

The p53 tumor suppressor protein is a transcription factor that plays a prominent role in protecting cells from malignant transformation. Protein levels of p53 and its transcriptional activity are tightly regulated by the ubiquitin E3 ligase MDM2, the gene expression of which is transcriptionally regulated by p53 in a negative feedback loop. The p53 protein is transcriptionally active as a tetramer, and this oligomerization state is modulated by a complex formed by NEURL4 and the ubiquitin E3 ligase HERC2. Here, we report that MDM2 forms a complex with oligomeric p53, HERC2, and NEURL4. HERC2 knockdown results in a decline in MDM2 protein levels without affecting its protein stability, as it reduces its mRNA expression by inhibition of its promoter activation. DNA damage induced by bleomycin dissociates MDM2 from the p53/HERC2/NEURL4 complex and increases the phosphorylation and acetylation of oligomeric p53 bound to HERC2 and NEURL4. Moreover, the MDM2 promoter, which contains p53-response elements, competes with HERC2 for binding of oligomeric, phosphorylated and acetylated p53. We integrate these findings in a model showing the pivotal role of HERC2 in p53-MDM2 loop regulation. Altogether, these new insights in p53 pathway regulation are of great interest in cancer and may provide new therapeutic targets.

ACVR1 Function in Health and Disease.

Activin A receptor type I (ACVR1) encodes for a bone morphogenetic protein type I receptor of the TGFß receptor superfamily. It is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. Moreover, ACVR1 has been extensively studied for its causal role in fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterised by progressive heterotopic ossification. ACVR1 is linked to different pathologies, including cardiac malformations and alterations in the reproductive system. More recently, ACVR1 has been experimentally validated as a cancer driver gene in diffuse intrinsic pontine glioma (DIPG), a malignant childhood brainstem glioma, and its function is being studied in other cancer types. Here, we review ACVR1 receptor function and signalling in physiological and pathological processes and its regulation according to cell type and mutational status. Learning from different functions and alterations linked to ACVR1 is a key step in the development of interdisciplinary research towards the identification of novel treatments for these pathologies.

HERCing: Structural and Functional Relevance of the Large HERC Ubiquitin Ligases.

Homologous to the E6AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing proteins (HERCs) belong to the superfamily of ubiquitin ligases. HERC proteins are divided into two subfamilies, Large and Small HERCs. Despite their similarities in terms of both structure and domains, these subfamilies are evolutionarily very distant and result from a convergence phenomenon rather than from a common origin. Large HERC genes, HERC1 and HERC2, are present in most metazoan taxa. They encode very large proteins (approximately 5,000 amino acid residues in a single polypeptide chain) that contain more than one RCC1-like domain as a structural characteristic. Accumulating evidences show that these unusually large proteins play key roles in a wide range of cellular functions which include neurodevelopment, DNA damage repair, and cell proliferation. To better understand the origin, evolution, and function of the Large HERC family, this minireview provides with an integrated overview of their structure and function and details their physiological implications. This study also highlights and discusses how dysregulation of these proteins is associated with severe human diseases such as neurological disorders and cancer.

The E3 ubiquitin ligase HERC1 controls the ERK signaling pathway targeting C-RAF for degradation.

The RAF/MEK/ERK cascade is a conserved intracellular signaling pathway that controls fundamental cellular processes including growth, proliferation, differentiation, survival and migration. Aberrant regulation of this signaling pathway has long been associated with human cancers. A major point of regulation of this pathway occurs at the level of the serine/threonine protein kinase C-RAF. Here, we show how the E3 ubiquitin ligase HERC1 regulates ERK signaling. HERC1 knockdown induced cellular proliferation, which is associated with an increase in ERK phosphorylation and in C-RAF protein levels. We demonstrate that overexpression of wild-type C-RAF is sufficient to increase ERK phosphorylation. Experiments with pharmacological inhibitors of RAF activity, or with interference RNA, show that the regulation of ERK phosphorylation by HERC1 is RAF-dependent. Immunoprecipitation, pull-down and confocal fluorescence microscopy experiments demonstrate an interaction between HERC1 and C-RAF proteins. Mechanistically, HERC1 controls C-RAF stability by regulating its polyubiquitylation in a lysine 48-linked chain. In vitro ubiquitylation assays indicate that C-RAF is a substrate of the E3 ubiquitin ligase HERC1. Altogether, we show how HERC1 can regulate cell proliferation through the activation of ERK signaling by a mechanism that affects C-RAF's stability.

HERC1 Ubiquitin Ligase Is Required for Normal Axonal Myelination in the Peripheral Nervous System.

A missense mutation in HERC1 provokes loss of cerebellar Purkinje cells, tremor, and unstable gait in tambaleante (tbl) mice. Recently, we have shown that before cerebellar degeneration takes place, the tbl mouse suffers from a reduction in the number of vesicles available for release at the neuromuscular junction (NMJ). The aim of the present work was to study to which extent the alteration in HERC1 may affect other cells in the nervous system and how this may influence the motor dysfunction observed in these mice. The functional analysis showed a consistent delay in the propagation of the action potential in mutant mice in comparison with control littermates. Morphological analyses of glial cells in motor axons revealed signs of compact myelin damage as tomacula and local hypermyelination foci. Moreover, we observed an alteration in non-myelinated terminal Schwann cells at the level of the NMJ. Additionally, we found a significant increment of phosphorylated Akt-2 in the sciatic nerve. Based on these findings, we propose a molecular model that could explain how mutated HERC1 in tbl mice affects the myelination process in the peripheral nervous system. Finally, since the myelin abnormalities found in tbl mice are histological hallmarks of neuropathic periphery diseases, tbl mutant mice could be considered as a new mouse model for this type of diseases.

Mesenchymal stem cells decrease lung inflammation during sepsis, acting through inhibition of the MAPK pathway.

BACKGROUND: Sepsis is a severe medical condition that ranks among the top 10 causes of death worldwide and which has permanently high incidence rates. Mesenchymal stem cells (MSCs) have been found to be potent modulators of immune responses. More importantly, there is evidence that MSCs have a beneficial effect on preclinical models of polymicrobial sepsis. However, the changes caused by the MSCs in the effector cells of the host immune system remain unclear. METHODS: A mouse model of sepsis (male C57BL/6 mice) with three experimental groups was used for experiments in vivo: a control group, an untreated septic group, and a septic group treated with MSCs. In vitro experiments were performed using a cell line of pulmonary macrophages (RAW 264.7) co-cultured with MSCs and stimulated with lipopolysaccharide (LPS). RESULTS: In vivo we demonstrated that treatment with MSCs was able to reduce the expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), and thereby decrease the production of inflammatory cytokines. In vitro experiments using a co-culture of macrophages with MSCs showed a decrease in COX-2 and NF-κB, and showed that this reduction was directly related to the ability of MSCs to inhibit phosphorylation of ERK, RSK, and p38, enzymes that belong to the family of mitogen-activated protein kinases (MAPKs). CONCLUSIONS: This study demonstrated that MSCs are able to inhibit the MAPK pathway activation, modulating the inflammatory response during sepsis. This understanding that MSCs can remodel the response of host cells and improve the course of sepsis is essential for developing new treatments for this pathology.