Identificación del alelo HLA B*57: 01 en una población militar, de Lima-Perú / Identification of the allele HLA B*57: 01 in a military population, from Lima-Peru

El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.

The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Relationship between self-reported occupational noise exposure and expression levels of plasma inflammatory cytokines in adult asthmatic patients / 公共卫生与预防医学

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Mechanism of Danshenyin in Inhibiting Platelet Activation in Rat Model of Hyperlipidemia Based on Proteomics / 中国实验方剂学杂志

ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.

Latest research and prospect of CD47 in kidney transplantation / 器官移植

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

METTL3-mediated HPV vaccine enhances the effect of anti PD-1 immunotherapy to alleviate the development of cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

Prevalencia de endometritis crónica en mujeres infértiles establecida mediante histeroscopia y biopsia endometrial con CD138 / Prevalence of chronic endometritis in infertile women by hysteroscopy and endometrial biopsy with CD138

Resumen OBJETIVO: Determinar, mediante histeroscopia de evaluación y biopsia de endometrio, con análisis histológico endometrial e identificación de células plasmáticas con inmunohisdtoquímica con CD138 positiva, la prevalencia de endometritis crónica en pacientes infértiles. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, efectuado de marzo de 2016 a noviembre del 2021 en el Centro de Reproducción Asistida de Saltillo (CREAS), Coahuila, México, en pacientes que consultaron por infertilidad. El diagnóstico de endometritis crónica se estableció mediante histeroscopia y biopsia de endometrio con inmunohistoquímica CD138. Se analizaron la prevalencia y precisión diagnóstica de la histeroscopia y la biopsia de endometrio. Además, la relación entre las características histeroscópicas específicas y la endometritis crónica confirmada por biopsia con CD138 positiva. RESULTADOS: La prevalencia de endometritis crónica por biopsia de endometrio CD138 positiva en las 170 pacientes estudiadas fue de 36% (n = 62) y por histeroscopia del 48.8% (n = 83), esta última con una sensibilidad del 48.3%, especificidad del 50.9%, valor predictivo positivo y negativo del 36.1 y 63.2%, respectivamente. En relación con las características histeroscópicas, la hiperemia endometrial tuvo una relación estadísticamente significativa con la prevalencia de endometritis crónica (p-value = 0.008; RM = 0.357; IC95%: 0.14-0.81) y con ≥ 2 características sugerentes de endometritis crónica (p-value = 0.015; RM = 3.63; IC95%: 1.15-12.69). CONCLUSIONES: En el procedimiento diagnóstico de la paciente infértil es importante descartar la endometritis crónica. Para ello es decisivo recurrir a herramientas diagnósticas, como la histeroscopia y confirmar el diagnóstico con una biopsia de endometrio con inmunohistoquímica CD138 positiva para que de esta manera pueda dirigirse el tratamiento.

Abstract OBJECTIVE: To determine the prevalence of chronic endometritis in infertile patients by evaluating hysteroscopy and endometrial biopsy with endometrial histologic analysis and identification of plasma cells by CD138-positive immunohistochemistry. MATERIALS AND METHODS: Observational, retrospective study performed from March 2016 to November 2021 at the Center for Assisted Reproduction of Saltillo (CREAS), Coahuila, Mexico, in patients who consulted for infertility. Chronic endometritis was diagnosed by hysteroscopy and endometrial biopsy with CD138 immunohistochemistry. The prevalence and diagnostic accuracy of hysteroscopy and endometrial biopsy were analysed. The association between specific hysteroscopic features and chronic endometritis confirmed by CD138-positive endometrial biopsy was also investigated. RESULTS: The prevalence of chronic endometritis by CD138-positive endometrial biopsy in the 170 patients studied was 36% (n = 62) and by hysteroscopy 48.8% (n = 83), the latter with a sensitivity of 48.3%, specificity of 50.9%, positive and negative predictive values of 36.1 and 63.2%, respectively. In relation to hysteroscopic features, endometrial hyperemia had a statistically significant relationship with the prevalence of chronic endometritis (p-value = 0.008; RM = 0.357; 95%CI: 0.14-0.81) and with ≥ 2 features suggestive of chronic endometritis (p-value = 0.015; RM = 3.63; 95%CI: 1.15-12.69). CONCLUSIONS: In the diagnostic process of infertile patients, it is important to exclude chronic endometritis. It is crucial to use diagnostic tools such as hysteroscopy and to confirm the diagnosis by endometrial biopsy with positive CD138 immunohistochemistry in order to guide treatment.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Effect of intensive training on immune system cells in elite female weightlifters

SUMMARY OBJECTIVE: This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. METHODS: A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). RESULTS: Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). CONCLUSION: This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

Platelet transfusion in patients with liver cirrhosis crosstalk with neutrophil: Prospective study

ABSTRACT Introduction: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. Methods: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. Results: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CDllb among cirrhotic patients. Conclusions: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CDllb on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

Telocytes in Human Embryonic Development: A Preliminary Microscopic Anatomy Study / Telocitos en el Desarrollo Embrionario Humano: Un Estudio Preliminar de Anatomía Microscópica

SUMMARY: Telocytes are a cell population described in 2011 with a multitude of functions such as tissue support, regulation of stem cell niches or intercellular signal transmission. However, there are no studies about their embryonic origin, their function in development, or their moment of appearance. The objective of this work is to try to answer these questions through histological and immunofluorescence studies with samples from the embryological collection of the Department of Anatomy of the University of Granada. In the results obtained, as demonstrated by immunofluorescence for CD34, the presence of these cells can be seen in the fourth week of embryonic development in the perinotochordal region. Its presence is evident from the sixth week of development in a multitude of organs such as the heart, skeletal muscle tissue and supporting tissue of various organs such as the kidney, brain or pericardium. Its function seems to be when the embryonic histological images are analyzed in an evolutionary way, to act as a scaffold or scaffold for the subsequent population by mature tissue elements. In conclusion, telocytes appear at a very early stage of embryonic development and would have a fundamental role in it as scaffolding and directors of organ and tissue growth.

Los telocitos son una población celular descrita en 2011 con multitud de funciones como el sostén tisular, la regulación de los nichos de células madre o la transmisión de señales intercelulares. Sin embargo, no existen estudios acerca del origen embrionario de los mismos, su función en el desarrollo ni su momento de aparición. El objetivo de este trabajo es tratar de responder a estos interrogantes mediante estudios histológicos y por inmunofluorescencia con muestras de la colección embriológica del Departamento de Anatomía de la Universidad de Granada. En los resultados se puede observar como se demuestra mediante inmunofluorescencia para CD34, la presencia de estas células en la cuarta semana del desarrollo embrionario en la región perinotocordal. Su presencia se evidencia a partir de la sexta semana del desarrollo en multitud de órganos como corazón, tejidos músculo esqueléticos y tejidos de sostén de diversos órganos como riñón, encéfalo o pericardio. Su función parece ser al ser analizadas las imágenes histológicas embrionarias de forma evolutiva, la de actuar como un andamiaje o scafold para el posterior poblamiento por elementos tisulares maduros. Como conclusión, los telocitos aparecen en un momento muy precoz del desarrollo embrionario y presentarían una función fundamental en el mismo como andamiajes y directores del crecimiento de los órganos y tejidos.

Hemangioendotelioma Retiforme en Tórax. Reporte de un caso

Introducción: El hemangioendotelioma retiforme es una neoplasia de grado intermedio o potencialmente maligna, su incidencia es entre la segunda y cuarta década de la vida, más frecuente 2:1 en mujeres, la etiología es incierta, se manifiesta generalmente como lesión nodular o en forma de placa en tronco o extremidades. El diagnóstico es por histopatología e inmunohistoquímica, su tratamiento es resección de la lesión, con una recurrencia del 60% posterior al manejo quirúrgico. Caso clínico: Se describe un caso atípico de hemangioendotelioma retiforme en tórax, en una paciente de sexo femenino de 43 años, su padecimiento inicia con aumento de volumen de 6 meses en axila derecha, acompañándose de dolor y limitación de la movilidad. Se realiza tomografía de tórax con reporte de tumoración del musculo pectoral de 83 mm. Se realiza exéresis de tumoración con reporte histopatológico de: hemangioendotelioma retiforme e inmunohistoquímica positiva a CD34.

Background: Retiform hemangioendothelioma is an intermediate grade or potentially malignant neoplasm, its incidence is between the second and fourth decade of life, more frequent 2:1 in women. Etiology is uncertain, it generally manifests as a nodular or plaque-shaped lesion on the trunk or extremities, the diagnosis is made by histopathology and immunohistochemistry, the treatment is resection of the lesion, presenting a recurrence of 60%. Clinical case: A case of retiform hemangioendothelioma is describes, a 43-year-old female began her condition with a 6-month increase in volume in the right armpit, with pain and limited mobility. A chest tomography was performed with a report of 83 mm pectoral muscle tumor, a tumor excision was performed with a histopathological report of: retiform hemangioendothelioma and CD34 positive immunohistochemistry.

The prognostic effect of immunohistochemical staining rates in patients with non–muscle-invasive bladder cancer

Context: Despite the follow-up protocols developed in non–muscle-invasive bladder cancer patients, progression and recurrence could not be prevented. Aims: We aimed to investigate whether proteins such as OCT-4, CD47, p53, Ki-67, and Survivin, which increase in bladder cancer cells, can be used as prognostic markers for patients with non–muscle-invasive bladder cancer. Settings and Design: The study included a total of 89 patients with newly diagnosed non–muscle-invasive bladder cancer between January 2015 and December 2020. Materials and Methods: Levels of OCT-4, CD47, p53, K?-67, and Survivin proteins in cancer cells were determined with a semi-quantitative immunohistochemical experiment. Pathological data and survival rates were compared according to the staining rates. Statistical Analysis Used: Data obtained in the study were analyzed statistically with SPSS 22.0 (SPSS, Chicago, IL, USA). Results: The mean age of the patients was 64.25 ± 9.91 years, and the median follow-up period was 55 months. Recurrence rate was determined to be 36% (n = 32), and the rate of progression at 40.4% (n = 36). The staining rates were stronger for each marker in the progression group and advanced-stage tumors (p < 0.001). The findings of the multivariate analysis carried out as part of the study showed that older age and higher tumor stage were independent risk factors for recurrence-free survival (HR = 1.048 and 7.074, respectively; P = 0.02). Also, higher tumor stages, diameters, and grades were associated with reduced progression-free survival (HR = 0.105, 0.395, 0.225, respectively; P < 0.05). Conclusions: Although immunohistochemical staining rates are promising, it is more appropriate to use tumor characteristics when assessing survival rate in patients with non–muscle-invasive bladder cancer.

Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study

Introduction: Minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) are the two common causes of nephrotic syndrome (NS) in both children and adults with overlapping clinical features, but with distinct prognostic and therapeutic implications. The distinction between these relies entirely on histopathology, which can sometimes be difficult. CD44 is expressed by activated parietal epithelial cells, plays a role in matrix deposition and thus in the pathogenesis of FSGS. Aims: To assess the expression of CD44 in MCNS and FSGS and to evaluate its association with the known clinical and histopathological prognostic factors. Materials and Methods: Thirty cases each of MCNS and FSGS were studied. The clinical, laboratory, histopathological, and CD 44 immunohistochemical data were recorded. The findings were analyzed and correlated. A P value of < 0.05 was considered statistically significant. Results: Statistical association was noted between CD44 positivity and serum creatinine (p = 0.031), estimated glomerular filtration rate (p = 0.040), segmental sclerosis (p < 0.001), tubular atrophy (p = 0.027), interstitial fibrosis (p = 0.027), and histological diagnosis (p < 0.001). The sensitivity, specificity, positive predictive, and negative predictive values were 90%, 76.67%, 79.41% and 88.46%, respectively. Conclusions: CD44 immunostain can effectively distinguish MCNS from FSGS. The congruent results of CD44 positivity with known prognostic factors support the possibility of using the CD44 marker as a predictive tool in selecting high-risk patients and offering appropriate therapeutic measures.

Metformin Inhibits ROS/TNF-alpha Axis-Mediated Chronic Kidney Disease Induced by TAA Independent of Leukocyte Infiltration in Association with the Inhibition of Kidney Injury Biomarkers / La Metformina Inhibe la Enfermedad Renal Crónica Mediada por el Eje ROS/TNF-alfa Inducida por TAA Independientemente de la Infiltración de Leucocitos en Asociación con la Inhibición de Biomarcadores de Lesión Renal

SUMMARY: The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.

Son bien conocidosos los efectos tóxicos de la tioacetamida (TAA) y el tetracloruro de carbono en el cuerpo humano. En este estudio, examinamos si la intoxicación por TAA puede inducir la infiltración de leucocitos renales (medida como antígeno leucocitario común CD45) asociada con el aumento de las especies reactivas de oxígeno (ROS)/factor de necrosis tumoral-alfa (TNF-α), así como biomarcadores de daño renal con y sin tratamiento con metformina. A las ratas se les inyectó TAA (200 mg/kg; dos veces por semana durante 8 semanas) antes de sacrificarlas a las 10 semanas (grupo experimental) o se les pretrató con metformina (200 mg/kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuaron recibiendo ambos agentes hasta el final del experimento, en la semana 10 (grupo protector). Usando tinción histológica básica, métodos de inmunohistoquímica y análisis químico de la sangre, observamos una lesión profunda del tejido renal, como daño glomerular y tubular en el grupo experimental, que mejoraron sustancialmente con la metformina. La metformina también inhibió significativamente (p0,05) en la expresión renal de células de inmunotinción positivas para CD45. En conclusión, encontramos que el TAA induce la lesión renal en asociación con el aumento del eje ROS/TNF-α, independientemente de la infiltración de leucocitos, que está protegida por metformina.

Immunoexpression of ALDH1A1, FGFR2, CD44 and Caspase-3 in Oral Squamous Cell Carcinoma and Leukoplakia: A pilot study

Current research highlighted the importance to recognize feasible biomarkers for early diagnoses and treatment in oral cancer. Our study analyzed the expression and spatial distribution of ALDH1A1, FGFR2, caspase-3, and CD44 in Oral Squamous Cell Carcinoma (OSCC) and leukoplakia with and without oral mucosal dysplasia. Paraffin-embedded samples of OSCC (n=5), leukoplakia with (n=5) and without (n=5) dysplasia obtained by incisional biopsies were processed using conventional histochemical techniques. Immunohistochemistry was performed using antibodies against ALDH1A1, FGFR2, caspase-3, and CD44. Images of the immunohistochemically stained tissue sections were analyzed according to the intensity of the immunostaining of each marker and classified in Scores. The Kruskal- Wallis test was performed (p≤0.05). Our results demonstrated a statically difference in the expression of all immunomarkers between OSCC and leukoplakia without dysplasia, being more significant in FGFR2 and ALDH1A1. Within the limitations of this study, our data showed that all biomarkers were overexpressed in OSCC and leukoplakia with oral mucosa dysplasia, suggesting that the presence of dysplasia is a significant clinic-pathologic predictor for malignant transformation.

La actual evidencia científica enfatiza la importancia de reconocer biomarcadores viables para el diagnóstico y tratamiento temprano del cáncer oral. Nuestro estudio piloto analizó la expresión y distribución espacial de ALDH1A1, FGFR2, caspasa-3 y CD44 en carcinoma oral de células escamosas (COCE) y en leucoplasia con o sin displasia de la mucosa oral. Las muestras incluidas en parafina de COCE (n=5), con (n=5) y sin (n=5) displasia fueron obtenidas mediante biopsias incisionales, las cuales se procesaron utilizando técnicas histoquímicas convencionales. El análisis inmunohistoquímico se realizó utilizando anticuerpos contra ALDH1A1, FGFR2, caspasa-3 y CD44. Las imágenes de las secciones de cada muestra fueron analizadas según la intensidad de inmunoexpresión de cada marcador y se clasificaron en diferentes escalas (scores). Se realizó la prueba de Kruskal-Wallis (valores de p<0,05). Nuestros resultados demostraron una diferencia estadística en la expresión de todos los inmunomarcadores entre COCE y las muestras con leucoplasia sin displasia, siendo más significativa en FGFR2 y ALDH1A1. Considerando las limitaciones de este estudio, los datos sugieren que la presencia de displasia en la mucosa oral es un importante predictor clínico-patológico de transformación maligna.

Evaluación comparativa de medición de linfocitos CD4+ por dos técnicas: estándar nacional versus test rápido de ejecución local / Comparative evaluation of CD4+ lymphocyte measurement by two techniques: national standard versus point-of-care rapid test

ANTECEDENTES: El recuento de linfocitos CD4+ (LTCD4) es una herramienta fundamental para la evaluación y seguimiento de los pacientes que viven con VIH. En Chile, la medición de LTCD4 estandarizada es por citometría de flujo. En el sistema público se realiza en forma centralizada en tres centros. Actualmente existen tecnologías de medición rápida de recuento de LTCD4 en el lugar de atención, permitiendo optimizar la atención de pacientes con infección por VIH. OBJETIVO: Comparar la precisión de un test rápido de ejecución local versus la técnica estándar. METODOLOGÍA: Realización de ambas técnicas en un grupo de 102 pacientes durante su control regular de salud. RESULTADOS: El rango de variación promedio de los resultados entre las dos técnicas fue de 10%, con una concordancia en los recuentos de LTCD4 de 97% para el rango de CD4 < 200 cél/uL, de 88% para los pacientes con recuento de LTCD4 entre 200 y 349 cél/uL y de 67% en los rangos superiores. CONCLUSIÓN: La técnica por test rápido es un sistema fácil de aplicar, de bajo costo, con alta concordancia con la técnica estándar, lo que debería considerarse en la atención de los pacientes que viven con VIH.

BACKGROUND: The CD4+ lymphocyte cell count is an instrumental tool for the assessment and follow-up in the therapeutic management of patients living with HIV. In Chile, the standardized CD4+ lymphocyte count technique is by flow cytometry. In the public health system, it is performed centralized in 3 sites. Currently, there are technologies that allow measuring the CD4 lymphocyte count at the point of care, allowing to optimize the care of HIV-infected patients. AIM: To compare the accuracy of a point of care rapid test versus the standard technique in patients under regular care at a single HIV center. RESULTS: The average variation of the results between the two techniques was 10%, with a 97% concordance in CD4 range values for patients with CD4 below 200 cells/uL, 88% for CD4 counts between 200 and 349 cells/uL. and 67% above that range. CONCLUSION: This point of care test is an easy-to-operate, low-cost system with high correlation with the standard technique and should be considered in the care of patients living with HIV.

Relación entre ansiedad, depresión y linfocitos T CD4+ en pacientes con virus de inmunodeficiencia humana (VIH) en un hospital general de Lima* / Relationship between anxiety, depression and CD4+ T lymphocytes in patients with Human Immunodeficiency Virus (HIV) in a general hospital in Lima

RESUMEN Objetivo: Determinar la relación entre ansiedad, depresión y recuento de linfocitos T CD4+ en una muestra de personas portadoras del virus de inmunodeficiencia humana (VIH). Metodología: Estudio observacional y analítico. Se evaluó a 144 pacientes con VIH en un hospital general de Lima, Perú. Se utilizó la Escala de Ansiedad y Depresión Hospitalaria (HADS). Resultados: La edad media de los sujetos de estudio fue de 41 años. La mayoría estuvo constituida por varones (71,5 %), solteros (86,1 %) y con grado de instrucción secundaria (57,6 %). La duración promedio de la enfermedad fue 7,7 años; el 11,1 % presentó alguna comorbilidad; y el 95,1 % utilizó tenofovir como tratamiento. El 34 % y el 16,7 % presentaron algún nivel de ansiedad y depresión, respectivamente. Los pacientes que se encontraban en estadio de sida presentaron mayores niveles de ansiedad (p < 0,001) y depresión (p < 0,001). Los pacientes con VIH y comorbilidades médicas presentaron mayores niveles de depresión (p = 0,044). Los niveles de ansiedad (ρ = -0,516, p = 0,01) y depresión (ρ = -0,509; p = 0,01) estuvieron relacionados con el recuento de linfocitos T CD4+. Conclusión: Se encontraron mayores niveles de depresión en pacientes con comorbilidades y estadio de sida, así como mayores niveles de ansiedad en pacientes en estadio de sida. Se comprobó, además, una relación indirecta y significativa entre los niveles de ansiedad, depresión y el recuento de linfocitos T CD4+. Se recomienda capacitar a los profesionales de salud en el tamizaje de ansiedad y depresión, a fin de mejorar la salud mental de pacientes con VIH.

ABSTRACT Objective: To determine the relationship between anxiety, depression and CD4+ T lymphocyte count in a sample of people carrying the human immunodeficiency virus (HIV). Methodology: Observational and analytical study. A total of 144 HIV-positive patients were evaluated. The Hospital Anxiety and Depression Scale (HADS) was used. Results: The sample's mean age was 41 years. Most of the probands were male (71.5%), single (86.1%) and with secondary education (57.6%). The average length of the disease was 7.7 years, 11.1% presented some comorbidity, and 95.1% used tenofovir as treatment. Thirty-four and 16.7% presented some level of anxiety and depression, respectively. Patients at the AIDS stage presented higher levels of anxiety (p < 0.001) and depression (p < 0.001). Patients with HIV and medical comorbidities had higher levels of depression (p = 0.044). Anxiety (ρ = -0.516, p = 0.01) and depression (ρ = -0.509; p = 0.01) levels were related to CD4+ T lymphocyte count. Conclusion: Higher levels of depression were found in patients with comorbidities and AIDS stage, and higher levels of anxiety were found in patients at the AIDS stage. In addition, a significant indirect relationship was found between anxiety and depression levels and the CD4+ T cell count. Training healthcare professionals to screen for anxiety and depression in order to improve the mental health of HIV patients, is highly recommended.