Phytochemical profile and biological activities of Bromelia antiacantha extracts / Perfil fitoquímico e atividades biológicas de extratos de Bromelia antiacantha

Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Temporal-spatial Generation of Astrocytes in the Developing Diencephalon / 神经科学通报·英文版

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.

Phytochemical profile and biological activities of Bromelia antiacantha extracts

Abstract Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Resumo Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype / Miosina 1g como un marcador de alto riesgo en una paciente pediátrica con cambio de linaje de leucemia linfoblástica aguda a fenotipo mieloide

Abstract Background: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). Case report: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. Conclusions: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

Resumen Introducción: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. Caso clínico: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. Conclusiones: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.

Lineage switch of acute myeloid leukemia to T-Cell acute lymphoblastic leukemia – A unique case report

“Lineage switch” is term described when leukemic cells on relapse exhibit a new phenotype, where losses of one lineage defining markers with simultaneous gain of another lineage defining markers occur. Relapse of acute leukemia is although a very common event, lineage switch occurs and reported very rarely in such cases. The pathogenesis involved in this phenomenon remains unclear; however plasticity of hematopoietic progenitor affected by intrinsic and extrinsic environmental cues can be a possible explanation. In most of the cases at the time of relapse conversion of B-acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML) occurs. Here, we presented an unusual case of 10 year old boy with AML switched to T-ALL upon relapse, which is very rare and not well documented till date in literature. The diagnosis was further supported by morphologic, cytochemistry and flowcytometric immunophenotyping (FCM-IPT). Prognosis and survival of such cases remains poor even by the use of standard chemotherapy.

Genetic inhibition of MLKL exerts protective effects against cognitive impairment and neuroinflammation in a cerebral small vessel disease model / 中国药理学与毒理学杂志

OBJECTIVE To identify the role of mixed lineage kinase domain like protein(MLKL)in cerebral small vessel disease(CSVD)and explore the underlying mechanism.METHODS Transient bilateral common carotid artery occlusion(tBCCAO)was used to establish a mouse model of CSVD.Immunofluorescence staining and Western blotting were used to observe the expres-sions of RIPK3/MLKL signaling molecules in brain tissues at 7,14 and 28 d after tBCCAO.Open field test,rotarod test,Y-maze and novel object recognition test were used to observe the effect of MLKL knockout on cognitive func-tion after tBCCAO.Blood-brain barrier(BBB)disruption was observed by sodium fluorescein permeability test and the expressions of tight junction proteins.Immunoflu-orescence staining and Western blotting were used to detect the expression of microglia marker Iba-1,astro-cyte marker GFAP,and NLRP3/Caspase-1 signaling mol-ecules in the hippocampus of CSVD mice.ELISA was used to detect the level of inflammatory factors(TNF-α,IL-1β,IL-18)in hippocampus.RESULTS The expres-sions of RIPK3/MLKL signaling molecules increased in cortex and hippocampus after tBCCAO,especially on day 14.The expression of pMLKL mainly increased in neurons,glia cells and endothelial cells in CSVD mice.MLKL knockout improved the cognitive functions such as motor learning,spatial learning and working memory,and object recognition ability in CSVD mice.MLKL knock-out alleviated the leakage of sodium fluorescein and attenuated the down-regulation of tight junction proteins at 1 d and 14 d after tBCCAO.At 14 d after tBCCAO,MLKL knock out inhibited the activations of microglia and astrocytes,attenuated the expressions of NLRP3/cas-pase-1 molecules,and decreased the levels of inflamma-tory factors in the hippocampus of mice.CONCLUSION Genetic inhibition of MLKL exerts protective effects against cognitive impairment by ameliorating BBB dam-age and neuroinflammation in a mouse cerebral small vessel disease model.

Flavonoid compounds improve hippocampal neuro-genesis and cognitive dysfunction in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the improve-ment functions of flavonoid compounds on temozolomide(TMZ)-,aging-or AD model-induced dysregulation of hip-pocampal NSC lineage progression,retardancy of den-dritic spine maturation in new-born neurons,as well as impairment of hippocampal-related learning and memory.METHODS We applied 30-week-old neural stem cell(NSC)specific promoter Nestin-GFP and NestinCreERT2:Rosa26-LSL-tdTomato transgenic mice and 16-week-old AD model 5XFAD transgenic mice,together with hippo-campal microinjection(ih),endogenous fluorescence trac-ing and immunofluorescent staining.RESULTS Both fla-vonoid compound A and its functional derivative flavo-noid compound B dose-dependently improved TMZ-,aging-or AD-induced defects of hippocampal NSC lin-eage progression and the maturation of dendritic spines of newborn neurons,thereby improving hippocampus related learning and memory.CONCLUSION This paper provides a new idea and treatment strategy for the devel-opment of new flavonoids that can promote neurogene-sis for neurodegenerative diseases and aging.

Optimized treatment of childhood B-lineage acute lymphoblastic leukemia / 中国当代儿科杂志

Childhood acute lymphoblastic leukemia (ALL) accounts for about 75% of childhood leukemia cases, and B-lineage acute lymphoblastic leukemia (B-ALL) accounts for more than 80% of childhood ALL cases. Over the past half century, new molecular biological targets discovered by new techniques have been used in precise stratification of disease prognosis, and there has been a gradual increase in the 5-year overall survival rate of childhood ALL. With the increasing attention to long-term quality of life, the treatment of childhood B-ALL has been constantly optimized from induction therapy to the intensity of maintenance therapy, including the treatment of extramedullary leukemia without radiotherapy, which has been tried with successful results. The realization of optimized treatment also benefits from the development of new techniques associated with immunology and molecular biology and the establishment of standardized clinical cohorts and corresponding biobanks. This article summarizes the relevant research on the implementation of precise stratification and the intensity reduction and optimization treatment of B-ALL in recent years, providing reference for clinicians.

Application of Familial Y-STR Haplotype Mismatch Tolerance in Genealogy Inference / 法医学杂志

OBJECTIVES@#To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage.@*METHODS@#Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed.@*RESULTS@#Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6.@*CONCLUSIONS@#Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.

Hematopoietic regulation of transcription factor GATA1 and mutations causing hereditary erythroid and megakaryocytic disorders / 中国输血杂志

GATA-binding protein 1 (GATA1), an important hematopoietic transcription factor, specifically regulates the proliferation and differentiation of erythroid and megakaryoid cells at the transcription level, which maintains the normal development and maturation of these two lineages. The functional structure of GATA1 is composed of one N-terminal transactivation domain (N-TAD) and two zinc fingers (NF and CF). GATA1 is highly conserved in different species. Alteration of GATA1 expression or function will lead to transcriptional disorder of erythrocyte and megakaryocyte related genes, resulting in various clinical phenotypes. This article reviews the molecular structure of GATA1, its transcriptional regulation in erythrocyte and megakaryocyte, and the hereditary hematopoietic regulatory disorders of these two lineages caused by GATA1 mutations.

Generation of Mlk3 KO mice by CRISPR/Cas9 and its effect on blood pressure / 生物工程学报

To explore the effect of Mlk3 (mixed lineage kinase 3) deficiency on blood pressure, Mlk3 gene knockout (Mlk3KO) mice were generated. Activities of sgRNAs targeted Mlk3 gene were evaluated by T7 endonuclease I (T7E1) assay. CRISPR/Cas9 mRNA and sgRNA were obtained by in vitro transcription, microinjected into zygote, followed by transferring into a foster mother. Genotyping and DNA sequencing confirmed the deletion of Mlk3 gene. Real- time PCR (RT-PCR), Western blotting or immunofluorescence analysis showed that Mlk3KO mice had an undetectable expression of Mlk3 mRNA or Mlk3 protein. Mlk3KO mice exhibited an elevated systolic blood pressure compared with wild-type mice as measured by tail-cuff system. Immunohistochemistry and Western blotting analysis showed that the phosphorylation of MLC (myosin light chain) was significantly increased in aorta isolated from Mlk3KO mice. Together, Mlk3KO mice was successfully generated by CRISPR/Cas9 system. MLK3 functions in maintaining blood pressure homeostasis by regulating MLC phosphorylation. This study provides an animal model for exploring the mechanism by which Mlk3 protects against the development of hypertension and hypertensive cardiovascular remodeling.

Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

Progress in study on the final executor of necroptosis MLKL and its inhibitors / 中南大学学报(医学版)

Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.

Dynamic Changes of ROS and Nrf2-Related Factors During Erythroid Development / 中国实验血液学杂志

OBJECTIVE@#To investigate the changes and roles of reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) related antioxidases during erythroid development.@*METHODS@#Flow cytometry was used to detect the sensibility of peripheral red blood cells of wild-type mice to a strong oxidant hydrogen peroxide (H2O2). Erythroid cells from different developmental stages in bone marrow (BM) were obtained using fluorescence-activated cell sorter and the ROS levels were detected by flow cytometry. RT-qPCR was used to detect the changes of expression levels of Nrf2 and related antioxidases in erythroid cells from different developmental stages in BM. The ROS levels of the peripheral blood and BM nucleated erythrocytes in Nrf2 knockout mice were further examined. The expression level of Nrf2 in erythroid precursors isolated from 14.5 d embryonic liver of wild-type mice during differentiation and culture in vitro was detected.@*RESULTS@#In the peripheral blood of wild-type mice, the ROS level of reticulocytes and mature erythrocytes treated with H2O2 increased about 4 times and 7 times, respectively (P<0.01). In BM erythrocytes, the ROS level gradually decreased as the cells matured (r=0.85), while the expression level of Nrf2 and its related anti-oxidative genes increased (r=0.99). The ROS levels in peripheral blood erythrocytes and BM nucleated erythrocytes of Nrf2 knockout mice were significantly increased compared with wild-type mice (P<0.01). The expression of Nrf2 increased during the early erythroid development after embryonic liver cell sorting (P<0.01).@*CONCLUSION@#The expression levels of Nrf2 and its related factors vary during erythropoiesis. Nrf2 at physiological level plays an important antioxidant role during the erythroid development.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region / Papillomavirus humano 16 da linhagem D associado a alto risco de câncer de colo do útero em região do nordeste brasileiro

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Research progress in lineage tracing to explore hepatic parenchymal cell regeneration and repair mechanisms / 中华肝脏病杂志

Hepatic parenchymal cells are a type of liver cells that performs important functions such as metabolism and detoxification. The contribution of hepatic parenchymal cells, bile duct cells, and hepatic stem/progenitor cells to new hepatic parenchymal cells in the process of liver injury repair has become a controversial issue due to their strong proliferation ability. Lineage tracing technology, which has emerged in the past decade as a new method for exploring the origin of cells, can trace specific type of cells and their daughter cells by labeling cells that express the specific gene and their progeny. The article reviews the current literature on the origin and contribution of hepatic parenchymal cells by this technique. About 98% of new hepatic parenchymal cells originate from the existing hepatic parenchymal cells during liver homeostasis and after acute injury. However, under conditions of severe liver injury, such as inhibition of hepatic parenchymal cell proliferation, bile duct cells (mainly liver stem/progenitor cells) become the predominant source of hepatic parenchymal cells, contributing a steady increased hepatocyte regeneration with the extension of time.

Frecuencia elevada de casos de dengue grave durante la epidemia por el linaje II del DENV-2 americano/asiático en el Perú / High frequency of severe dengue cases during the American/Asian DENV-2 lineage II epidemic in Peru

RESUMEN Introducción. El ingreso del linaje II del DENV-2 americano/asiático en la región Loreto de la Amazonia Peruana, coincidió con un incremento súbito de los casos de dengue con necesidad de hospitalización. Sin embargo, las estadísticas oficiales reportaron pocos casos graves. Se postula, que existió una subnotificación de los casos graves en los reportes oficiales del Ministerio de Salud. Objetivos. Conocer la frecuencia de pacientes con signos de gravedad entre los pacientes hospitalizados por dengue probable durante el brote del 2011 en el Hospital Iquitos, Perú. Métodos. Se realizó un estudio longitudinal, aplicando una lista de chequeo diaria, sobre la presencia de signos de gravedad durante la estancia hospitalaria, a un grupo de pacientes hospitalizados en la unidad de dengue del Hospital Iquitos. Resultados. De 178 pacientes evaluados 66 (37%, IC: 29,9 - 44,6%) presentaron algún signo de gravedad, la mayor parte por shock (75,7%). Este resultado contrasta con el número de pacientes con dengue grave reportado por el Ministerio de Salud durante el año 2011 en la región Loreto. Conclusión. Aproximadamente un tercio de los pacientes que fueron hospitalizados con el diagnostico de dengue, durante el brote por el linaje II del DENV-2 americano/asiático, desarrollaron signos de gravedad durante su hospitalización.

ABSTRACT Introduction. The entry of American/Asian DENV-2 lineage II in the Loreto region of the Peruvian Amazon coincided with a sudden increase in dengue cases requiring hospitalization. However, official statistics reported few severe cases. It is postulated that there was an underreporting of severe cases in the official reports of the Ministry of Health. Objectives. To determine the frequency of patients with signs of severity among patients hospitalized for probable dengue fever during the 2011 outbreak at the Iquitos Hospital, Peru. Methods. A longitudinal study was carried out applying a daily checklist on the presence of signs of severity during hospital stay to a group of patients hospitalized in the dengue unit of the Iquitos hospital. Results. Of 178 patients evaluated, 66 (37%, CI: 29.9-44.6%) presented some sign of severity, mostly due to shock (75,7%). This result contrasts with the number of patients with severe dengue reported by the Ministry of Health during 2011 in the Loreto region. Conclusion. Approximately one third of the patients who were hospitalized with a diagnosis of dengue during the outbreak of American/Asian DENV-2 lineage II developed signs of severity during their hospitalization.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

Aberrant Expression of CD19 in Early T-cell Precursor Lymphoblastic Leukemia-A Diagnostic Challenge

A systematic approach is required to diagnose acute leukemia. Most of the cases are satisfactorily diagnosed and categorized into subtypes. However, a few cases pose diagnostic dilemma secondary to immunophenotypic aberrancies which are defined as antigens that are normally restricted to a different lineage and expressed by a neoplastic population while absent from its normal non neoplastic counterpart. We report a rare case of Early T-cell PrecursorLymphoblastic Leukemia with aberrant expression of CD19. A 7-year-old boy referred to our hospital with his cervical lymph node biopsy reported as lymphoproliferative disorder. The patient was COVID-19 positive. Chest X-ray showed mild right sided pleuraleffusion with huge mediastinal mass. Flow cytometry on peripheral blood used to establish the diagnosis. The case is reported to improve knowledge regarding aberrant expression of markers. Hematopathology teams should be aware of this phenomenon so that appropriate workup can be done to reach correct diagnosis.

Prevalence of influenza A(H1N1) viruses in Hangzhou after 2009 pandemic and characteristics in lineage changes / 中华微生物学和免疫学杂志

Objective:To study the epidemiological features of local influenza A(H1N1)pdm09 epidemic strains through analyzing the changes in lineages and to analyze how well the vaccine strains were matched to the circulating strains in Hangzhou.Methods:Of 1 112 clinical specimens from laboratory-confirmed A(H1N1)pdm09 infections in Hangzhou in consecutive seasons from 2009 to 2020, 208 (18.7%) with high viral load (Ct value <30) were randomly selected from 10 influenza epidemics for full-length hemagglutinin gene ( HA) gene sequencing. Genetic variation, evolution and lineage changes of these representative local strains were analyzed by comparison with vaccine strains and reference strains. Results:Since the 2009 pandemic, A(H1N1)pdm09 had become one of the predominant viruses causing seasonal influenza and been reported to co-circulate with influenza A(H3N2) and influenza B viruses in Hangzhou in the past decade. It caused 10 local influenza epidemics in the 12 consecutive seasons from 2009 to 2020. HA gene sequencing revealed complex sources and rapid variation of the local A(H1N1)pdm09 strains. The main epidemic strains often genetically drifted from the recommended northern hemisphere vaccine strains due to lineage changes. Conclusions:This study suggested that it was essential to update the recommended vaccine strains year by year. Besides, enhanced periodic monitoring of influenza A(H1N1)pdm09 strains circulating in the region was important for the prevention and control of influenza A(H1N1)pdm09 infection in the next epidemic season.