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Abstract Background Wheat seeds display different colors due to the types and contents of anthocyanins, which is closely related to anthocyanin metabolism. In this study, a transcriptomic and metabolomic analysis between white and purple color wheat pericarp aimed to explore some key genes and metabolites involved in anthocyanin metabolism. Results Two wheat cultivars, a white seed cultivar Shiluan02-1 and purple seed cultivar Hengzi151 were used to identify the variations in differentially expressed genes (DEGs) and differentially accumulated flavonoids (DAFs). Based on metabolomic data, 314 metabolites and 191 DAFs were identified. Chalcone, flavonol, pro-anthocyanidin and anthocyanidin were the most differentially accumulated flavonoid compounds in Hengzi151. 2610 up-regulated and 2668 down-regulated DEGs were identified according to transcriptomic data. The results showed that some structural genes in anthocyanin synthesis pathway were prominently activated in Hengzi151, such as PAL, CAD, CHS and so on. Transcription factors (TFs) of MYB, bHLH, WD40 and some other TFs probably involved in regulating anthocyanin biosynthesis were identified. Some genes from hormone synthetic and signaling pathways that may participate in regulating anthocyanin biosynthesis also have been identified. Conclusions Our results provide valuable information on the candidate genes and metabolites involved in the anthocyanin metabolism in wheat pericarp.

Acute Liver Injury (ALI), a highly prevalent liver disease in the last two decades, but there is still no effective treatment for it. As a member of Tibetan medicine, Swertia chirayita is commonly used for treating liver-related diseases, while the behavior of S. chirayita in CCl4-induced ALI is deficient. In this work, the chemical constituents of S. chirayita were identified using a UPLC-Q-Exactive Orbitrap MS method. And the potential targets of the active compound of S. chirayita in CCl4-induced ALI have been explored on the basis of bioinformatics analysis and ALI model. The findings revealed that a total of 49 compounds have been identified in S. chirayita, and 10 have been absorbed into blood as prototypes. Network pharmacology and molecular docking studies have shown that S. chirayita has a multi-component, multi-target profile for the treatment of CCl4-induced ALI. Biochemical indicators testing demonstrated that Swertiamarine (STW) improved the levels of AST, ALT, MDA, SOD, TNF-α and IL-6 in CCl4-induced ALI mouse model. Additionally, H&E staining indicated that STW significantly improved cellular necrosis, inflammatory infiltration, and other forms of pathological liver damage in mice. Meanwhile, quantitative reverse transcription PCR (qRT-PCR) showed that STW could ameliorate CCl4-induced ALI by regulate the expression of EGFR, CASP3, STAT3 and other targets. In conclusion, as one of the active compounds of S. chirayita, STW could alleviate ALI by modulating the expression of biochemical indicators, liver pathological indicators and critical targets. This will provide a theoretical basis for the further research and development of the S. chirayita.

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in‐depth exploration within this scientific domain.

Aconitum pendulum, a member of the Aconitum genus within the Ranunculaceae family, is known for its remarkable anti-inflammatory, anti-tumor, and analgesic properties. However, the application of Aconitum pendulum in traditional medicine is often restricted by its inherent toxicity, necessitating specific processing methods to ensure safe usage. Tibetan medicine utilizes distinctive processing techniques such as the barley wine, Hezitang, and zanba frying systems to render the herb safe for medicinal use. Despite the known pharmacological importance, scant research exists on how these processing methods affect the phytochemical profile of Aconitum pendulum, indicating a necessity for comparative analysis of the resulting concoctions. In this study, we employed 1H nuclear magnetic resonance (1H NMR) spectroscopy and ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) to explore the metabolomic variations among different processed products of Aconitum pendulum. Multivariate data analysis techniques, including pattern recognition, allowed us to investigate the intricacies of the compound profiles. To discover signature chemical markers that can differentiate the various processed products, we conducted paired t-tests and generated heat maps highlighting the detected differences. Our integrated analysis of the 1H NMR and UPLC-Q-TOF-MS data revealed distinct chemical signatures unique to each method of Aconitum pendulum processing. By employing chemometric analysis with variable importance in projection (VIP) scores greater than 1.0, and coupled with the statistical rigor of paired t-tests (P

Amidst a global rise in lung cancer occurrences, conventional therapies continue to pose substantial side effects and possess notable toxicities while lacking specificity. Counteracting this, the incorporation of nanomedicines can notably enhance drug delivery at tumor sites, extend a drug’s half-life and mitigate inadvertent toxic and adverse impacts on healthy tissues, substantially influencing lung cancer’s early detection and targeted therapy. Numerous studies signal that while the nano-characteristics of lung cancer nanomedicines play a pivotal role, further interplay with immune, photothermal, and genetic factors exist. This review posits that the progression towards multimodal combination therapies could potentially establish an efficacious platform for multimodal targeted lung cancer treatments. Current nanomedicines split into active and passive targeting. Active therapies focus on a single target, often with unsatisfactory results. Yet, developing combination systems targeting multiple sites could chart new paths in lung cancer therapy. Conversely, low drug delivery rates limit passive therapies. Utilizing the EPR effect to bind specific ligands on nanoparticles to tumor cell receptors might create a new regime combining active-passive targeting, potentially elevating the nanomedicines’ concentration at target sites. This review collates recent advancements through the lens of nanomedicine’s attributes for lung cancer therapeutics, the novel carrier classifications, targeted therapeutic modalities and their mechanisms, proposing that the emergence of multi-target nanocomposite therapeutics, combined active-passive targeting therapies and multimodal combined treatments will pioneer novel approaches and tools for future lung cancer clinical therapies.

Introduction: Hepatocellular carcinoma (HCC) is responsible for approximately 90% of liver malignancies and is the third most common cause of cancer-related mortality worldwide. However, the role of anoikis, a programmed cell death mechanism crucial for maintaining tissue equilibrium, is not yet fully understood in the context of HCC.Methods: Our study aimed to investigate the expression of 10 anoikis-related genes (ARGs) in HCC, including BIRC5, SFN, UBE2C, SPP1, E2F1, etc., and their significance in the disease.Results: Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we discovered that these ARGs are involved in important processes such as tissue homeostasis, ion transport, cell cycle regulation, and viral infection pathways. Furthermore, we found a significant correlation between the prognostic value of five ARGs and immune cell infiltrates. Analysis of clinical datasets revealed a strong association between BIRC5 expression and HCC pathological progression, including pathological stage, T stage, overall survival (OS), and race. By constructing a competing endogenous RNA (ceRNA) network and using molecular docking, we identified ten bioactive compounds from traditional Chinese medicine (TCM) that could potentially modulate BIRC5. Subsequent in vitro experiments confirmed the influence of platycodin D, one of the identified compounds, on key elements within the ceRNA network.Discussion: In conclusion, our study presents a novel framework for an anoikis-centered prognostic model and an immune-involved ceRNA network in HCC, revealing potential regulatory targets. These insights contribute to our understanding of HCC pathology and may lead to improved therapeutic interventions.

Background: Adipose fibrosis is a major factor of adipose dysfunction, which causes metabolic dysfunction during obesity, but its molecular mechanisms are poorly understood. This study investigated the role and potential mechanisms of mTORC1 in obesity-induced adipose fibrosis. Methods: ob/ob mice were injected with rapamycin or the same volume of normal saline. The level of fibrosis in epididymal adipose tissue (EAT) was detected by observing aberrant deposition of extracellular matrix. Expression of fibrotic related genes was analysed using RNA-seq. 3T3-L1 preadipocytes were treated with cobalt chloride (CoCl2) and TGF-β1 to induce preadipocyte fibrosis. The fibrosis-related gene expression and protein levels were determined by RT-PCR, WB, and immunofluorescence in two types of fibrotic preadipocytes with or without rapamycin. Results: Compared with vehicle treatment, EAT fibrosis-related aberrant deposition of extracellular matrix proteins and fibrotic gene expression were reduced in ob/ob mice treated with rapamycin. Both CoCl2-induced hypoxia and TGF-β1 successfully promoted adipocyte fibrosis, and the upregulated fibrosis-related genes expression was inhibited after the mTORC1 pathway was inhibited by rapamycin. Conclusion: Inhibition of the mTORC1 pathway ameliorates adipose fibrosis by suppressing fibrosis-related genes in hypoxia- and TGF-β-induced fibrotic preadipocytes.

Abstract Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.

Coriolopsis trogii and Cerrena unicolor were investigated for laccase production in submerged fermentation with different nutrient medium containing metal ions and lignocellulosic materials. The maximum laccase activity of C. trogii Han751 was 8584.44 ± 98.45 U/L and was obtained from nutrient medium 7. However, the maximum laccase activity of C. unicolor Han 849 was 16144.26 ± 635.30 U/L from nutrient medium 9. Thus, the capacity of secreting laccase of C. unicolor Han 849 was superior to that of C. trogii Han751. Different fungal species have different medium components suitable for laccase production. The content of CuSO4·5H2O and MnSO4 in nutrient medium with the concentration of 0.25 g/L and 0.151 g/L, respectively, was more beneficial to C. trogii Han751 secreting laccase. However, the vital components of nutrient medium that contribute to the laccase activity of C. unicolor Han 849 were corncob, glucose, and CuSO4·5H2O, with the corresponding concentrations of 1 g/flask, 5 g/L, and 0.25 g/L, respectively. The results will contribute to the development of new methods to produce low-cost laccase.

A theoretical approach for the intramolecular energy transfer process involving the ligand-to-metal charge transfer (LMCT) state in lanthanide compounds is developed. Considering a two-electron interaction, both the direct Coulomb and exchange interactions are taken into account, leading to expressions from which selection rules may be derived and transfer rates may be calculated. These selection rules show that the direct Coulomb and exchange mechanisms are complementary, in the same way as obtained in previous works for the case of ligand-lanthanide ion energy transfer processes. An important result from numerical estimates is that the channel ligand–LMCT state is by far the dominant case, leading to transfer rates higher than for the channel lanthanide ion–LMCT state by several orders of magnitude. The analysis of the emission quantum yield as a function of the relative energy position of the LMCT state in a typical Eu3+ compound allows the identification of two quenching regions, the most pronounced one occurring close to the lower ligand triplet level. © 2005 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Laccase activity secreted by Pleurotus eryngii Han 1787 and Lentinus edodes Han 1788 grown on six types of agroindustrial wastes was investigated. Maximum laccase activity of P. eryngii Han 1787 on Ulmus pumila, Juniperus formosana, Pinus tabuliformis, cottonseed shell, corncob, and leaf of corncob was nearly 5.77-fold, 2.37-fold, 2.78-fold, 2.81-fold, 11.53-fold, and 6.73-fold higher than that of L. edodes Han1788 on corresponding agroindustrial wastes. In general, the capacity of secreting laccase of P. eryngii Han 1787 was superior to that of L. edodes Han 1788. Furthermore, laccase activity of P. eryngii Han 1787 on the leaf of corncob, the corncob, Ulmus pumila, and Juniperus formosana was relatively stable during the whole fermentation process. Different fungi showed different preferences in different agroindustrial wastes to secret laccase on whole fermentation stage. The presence of leaf of corncob was useful for improving laccase activity of P. eryngii Han 1787, while L. edodes Han 1788 was more preferred to produce laccase along with the presence of Juniperus formosana. These results were preliminary conducive in laying the foundation for increasing industrial laccase-producing strains and producing low-cost laccase.

Introdução e objetivo: A telangiectasia hemorrágica hereditária (THH) ou síndrome de Rendu-Osler-Weber é uma doença rara de herança autossômica dominante, que afeta a formação dos vasos sanguíneos, levando a sangramentos no sistema nervoso central, gastrointestinal e respiratório. Neste relato, descrevemos o caso de uma mulher com anemia ferropriva refratária ao tratamento convencional e os desafios no diagnóstico dessa doença hematológica em uma cidade de pequeno porte. Materiais e métodos: Foram coletadas informações por meio de entrevista, registros de prontuário médico, exames laboratoriais e fotografias de características clínicas. Os dados foram interpretados com base na literatura científica por meio de revisão narrativa. O trabalho foi realizado respeitando os princípios éticos de pesquisa. Resultados: Mulher, 59 anos, moradora de cidade de pequeno porte do leste de Minas Gerais, com anemia ferropriva crônica foi encaminhada pela atenção básica para avaliação com hematologista no ambulatório da faculdade de Medicina em cidade vizinha. Encontrava-se desesperançada com seu quadro clínico com histórico de internações hospitalares frequentes para melhora de epistaxes não traumáticas de repetição e estabilização da hemoglobina, com recebimento de transfusões sanguíneas e suplementação de ferro. Informa que há 20 anos iniciaram as telangiectasias em mãos, pés, lábios e língua. No histórico familiar há casos semelhantes. Foram apresentados exames laboratoriais recentes solicitados pela atenção primária com investigação inconclusiva que indicaram anemia e deficiências de ferro e vitamina B12. Não refere outros sangramentos externos. Paciente foi orientada por critérios clínicos sobre o diagnóstico de THH. Iniciou-se reposição de vitamina B12 e de ferro venoso conforme cálculo de déficit de ferro, foi encaminhada para avaliação da otorrinolaringologia no mesmo ambulatório da faculdade. Solicitou-se endoscopia digestiva alta para investigação de sangramento e teste genético. Discussão: A paciente apresentava os sintomas comuns da THH, como a epistaxe recorrente e telangiectasias mucocutâneas, além de parentes de primeiro grau possivelmente acometidos pela doença. Dessa forma, foi classificada conforme os critérios de Curaçao como THH possível ou suspeita. Em situações em que familiares apresentam a doença, mas não preenchem os critérios clínicos, os testes genéticos são indicados para especificar a mutação pertencente àquela família portadora da síndrome. Por conta de sua expressão fenotípica mais aflorada com o avançar da idade, a THH apresenta o risco de causar sangramentos graves, como no caso do pai da paciente, que faleceu por hemorragia gastrointestinal. O tratamento dos sangramentos pode envolver abordagens endoscópicas, hormonais, imunomoduladoras e antiangiogênicas. A anemia ferropriva crônica requer reposição de ferro e, em alguns casos, hemotransfusões. Conclusão: A THH é uma doença rara, subdiagnosticada, que apresenta riscos de hemorragias graves. O diagnóstico precoce é essencial para evitar complicações secundárias.A parceria entre instituições de ensino superior e o poder público pode aprimorar o acesso a cuidados especializados e avançar no tratamento da THH, beneficiando populações em regiões com recursos limitados. A troca de conhecimentos e ações integradas podem contribuir para o avanço da hematologia clínica e a prevenção de complicações em pacientes com THH.

Introdução e objetivo: A leucemia linfocítica crônica (LLC) é uma doença linfoproliferativa que acomete principalmente idosos. Sua etiologia não está esclarecida, não havendo fatores ambientais com forte associação ao surgimento da doença. A LLC familiar, é definida quando mais de um membro da família possui a doença e o diagnóstico nesses membros costuma ocorrer em idade mais precoce O presente relato descreve o caso de uma paciente que por conhecer a LLC ao acompanhar a mãe e o irmão com a doença percebeu alterações nos próprios exames. Materiais e métodos: Foram coletadas informações por meio de registros de prontuário médico e exames laboratoriais fornecidos pela paciente. O trabalho foi realizado respeitando os princípios éticos de pesquisa. Relato de caso: Mulher, 45 anos, realiza consulta médica, assintomática, por apresentar mãe e irmão com histórico de LLC, ambos falecidos. Relata que a mãe conviveu com a doença por muitos anos e que faleceu de infecção quando iniciou a quimioterapia em 2004 e o irmão cursou com doença mais agressiva, teve dificuldade em tolerar o tratamento e faleceu em 2006. Relata que após quadro de COVID-19 em 2020 notou alterações no hemograma procurando hematologista para avaliação. Exame do dia 01/10/21: hm 4,8 milhões/mm3; hgb 13,9 g/dL; vcm 89,3 fL l g 13.660 cel/mm3; neut 5160/mm3; linf 7.790/mm3; pl 152.000/mm3. 19/10/21: imunofenotipagem: marcadores positivos CD5, CD11c+, CD19, CD20+/++, CD23, CD38 (96%), CD79b, CD200, Kappa. Marcadores negativos: CD10, CD22, CD103, IgM e Lambda. Os achados imunofenotípicos em associação aos citomorfológicos são compatíveis com leucemia linfocítica crônica, classificação OMS – 2016. FISH: resultados: nuc (D6Z1, MYB)x2 [200], (D11Z1, ATM) x2 [200], (CCND1, IGH)x2 [200], (D12Z3x3) [87/200], (D13S319-D13S25, D13S1825)x2[200], (IGHx2)[200], (IGH, BCL2)x2 [200], (D17Z1, TP53)x2 [220]. Conclusão: trissomia do cromossomo 12 em 43,5% das intérfases analisadas. As demais pesquisas apresentam-se normais. Tomografia de pescoço, tórax, abdome e pelve: sem linfonodomegalias ou visceromegalias. Atualmente paciente em acompanhamento hematológico trimestral, mantem-se assintomática e sem tratamento. Discussão: Ainda não foi identificado uma mutação gênica específica para a LLC familiar, o irmão e mãe da paciente em questão não realizaram FISH na época do diagnóstico, há quase 20 anos. Não há associação na literatura da LLC familiar com maior agressividade da doença, porém é descrito que o diagnóstico pode ser feito em idades mais precoces, conforme caso relatado. Apesar do acompanhamento e tratamento dos pacientes com LLC familiar ser o mesmo que os outros pacientes, na LLC familiar os pacientes possuem maior conhecimento sobre a doença e podem apresentar maior ansiedade e preocupação com a evolução da doença, por terem presenciado nos familiares. Conclusão: A LLC é uma doença comum de idosos e que possui componente familiar, a paciente em questão por acompanhar parentes com a patologia notou alterações nos próprios exames e procurou acompanhamento especializado precocemente.

Introdução e objetivo: Deficiência de ferro é a causa mais comum de anemia, principalmente em mulheres em idade fértil, porém, é necessário cogitar outros diagnósticos em pacientes que não apresentam boa resposta ao tratamento. Nesse relato, é descrito o caso de uma paciente em tratamento para anemia ferropriva mantendo hemoglobina baixa, inclusive após reposição venosa de ferro. Materiais e métodos: Foram coletadas informações por meio de registros de prontuário médico e exames laboratoriais. O trabalho foi realizado respeitando os princípios éticos de pesquisa. Relato de caso: Mulher, 47 anos, em atendimento na UBS, apresentava sintomas de climatério e metrorragia além de sintomas compatíveis com anemia. Refere histórico de anemia com diversos tratamentos ao longo da vida. Exame do dia 23/12/23: hm 5,8 milhões/mm3; Hgb 10,60 g/dL; vcm 61,1 fL l g 2.790 cel/mm3; neut 781/mm3; linf 1.590/mm3; pl 105.000/mm³; ferro 74 mcg/dL; ferritina 17,6 ng/mL; vitamina B12 443 pg/mL. Recebeu tratamento com 10 ampolas de ferro venoso. Retornou com o seguinte exame (01/03/23): hm 5,4 milhões/mm3; hgb 10 g/dL; vcm 61,7 fL l g 2.510 cel/mm3; neut 1.157/mm3; linf 1.097/mm3; pl 84.000/mm3. Foi prescrito mais 5 ampolas de ferro venoso e encaminhada para avaliação da hematologia no ambulatório da Afya- faculdade de Ciências Médicas de Ipatinga. Na consulta com especialista foi aventada possibilidade de talassemia com ferropenia secundária a metrorragia e deficiência de ácido fólico. Prescrito ácido fólico e solicitado exames para investigação. Retorna com exames em 12/04/23: ferritina 469,2 ng/mL, ferro 118 mcg/dL LDH 252 zinco 82 FAN não reagente, VHS 10 mm, CTLF 306 mcg/dL reticulócitos 0,6% eletroforese de hemoglobina A1 93,8% A2 5,2% F 1% não trouxe novo hemograma, plaqueta fônio e sorologias solicitadas. Mantido acido fólico e orientado paciente diagnóstico de Beta talassemia menor, manter acompanhamento e retornar com restante de exames solicitados. Discussão: Paciente apresentava anemia de longa data com diversos tratamentos sem resposta efetiva, ao ser avaliada pelo especialista foi aventada hipótese de talassemia, visto valor de hemácias elevadas e VCM com valor muito baixo, desproporcional ao valor da hemoglobina. Apresentava leucopenia com neutropenia leve/moderada e plaquetopenia leve, sem sintomas associados, aventada a possibilidade de deficiência de ácido fólico, ainda em investigação. Conclusão: A paciente em questão apresentava fator de risco para ferropenia, sendo corretamente tratada, porém, já apresentava sinais em hemograma que poderiam sugerir o diagnóstico de talassemia associado, é importante pensar em diagnósticos diferenciais ao avaliar os pacientes anêmicos.

Introduction and Objective: High-grade monomorphic B-cell jejunal lymphoma in a post-liver transplant patient: the post-transplant lymphoproliferative disease (PTLD) hepatic has an incidence of 3%, 85% for B cells and 15% for T cells. The incidence increases in rich organs with B cells, like the small intestine. The Epstein-Barr virus (EBV) is crucial in the pathogenesis. Up next is the case of a patient post-liver transplant (PLT) with proximal jejunal stenosis for lymphoma. This study aimed to report a case of jejunal lymphoma in a patient with PLTD. Material and Methods: Male of 71 years, in 2007 PLT for cirrhosis related to alcohol consumption, in treatment with cyclosporine and mycophenolic acid. It started in 2002 with 10 kg weight loss, nausea and vomit for three months of evolution; the abdominal tomography was performed and founded jejunal stenosis, enteroscopy found ulcerated tumor in the proximal jejunum of 60%, and the biopsy reported lymphoma diffuse of large cells CD 20+bcl-6/Ki-67 90%, PCR for EBV (-). Started treatment with R-CHOP-21. Discussion: PTLD in adults frequently occurs late in presentation, up to 20% intestinal. What is relevant in our case is the 15 years between transplant and presentation, EBV (-) and intestinal presentation. Conclusions: The PTLD occurs in a period between the transplant and the diagnosis of 5.5 years, our patient, it occurs after 15 years. The negative serology is related to late PTLD, it does not respond to immunosuppression and it is treated with chemotherapy like in our patient. Funding: The resources used in this study were from the hospital without any additional financing Declaration of interest: The authors declare no potential conflicts of interest.

Dengue during pregnancy carries a higher risk of maternal and foetal complications, either through haemodynamic instability from disruption of the placental perfusion or through vertical transmission to the foetus.A previously healthy 29-year-old primigravidae with a POA of 34 weeks presented with one day fever to a tertiary hospital. NS 1 antigen for dengue was positive. She entered the critical phase the following day and her platelet count dropped to 3000/ml by day 3. Intra uterine death was diagnosed on day 4. She continuously deteriorated and died on day 7. At autopsy, gross bleeding manifestations were noted in the mother, along with bilateral pleural effusions, massive sub endocardial haemorrhages and an enlarged liver with sub capsular haemorrhages. The placenta was devoid of any haemorrhages or infarcts. Sub-aponeurotic and subarachnoid haemorrhages and 50ml of blood within the thoracic and peritoneal cavities were found in a mature female foetus with minimal signs of maceration. Laboratory confirmation of foetal dengue virus infection was not possible.This is a rare case where fatal haemorrhagic manifestations were seen in both the mother and the foetus suggesting vertical transmission. The autopsy findings highlight the unpredictable haemodynamic changes in the uterine circulation which severely hinder dengue management during pregnancy. Dengue infection, especially in late pregnancy, can lead to unpredictable fatal outcomes. The potential benefit of performing an emergency caesarean in such cases should be further explored.

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL.

Tabaristan (current Mazandaran), in northern Iran and the south of the Caspian Sea, is considered as one of the scientific and medical centers in both scientific and Islamic worlds. The emergence of numerous scholars in this area indicates the centrality of science in this amazing geography. One of the greatest men of this land is Abolhassan Ahmad bin Mohammad Tabari Taranji. Information about him is very limited in historical sources but he is recognized for writing a scientific book on al-mu'alaja al-buqratiya. Moreover, he has also played a role in the political system of Buyid dynasty and Abbasid Caliphate. In this research, his life, his scientific experiences and his medical works are discussed.

Background and Objectives: The cause of death in children under one year can be an important tool for designing prevention strategies and reducing the mortality rate. The aim of this study was to estimate the number of deaths in children under one year using the Mr. Murray’s estimation index in Mazandaran Province, and to compare this estimation with reported cases of civil registration organization. Methods: All deaths of children under one year between 2011 to 2014 registered in hospitals across Mazandaran Province were included in this study. The cause of death as coded in the International Classification of Diseases (ICD-10) was converted to Murray classification. The coefficients in each of the Murray levels were used to estimate actual death cases. We compared this estimation with the number of deaths that is reported annually by civil registration organization. Results: Seven hundred and sixty four deaths occurred in this period. The leading causes of death in children under one year were conditions of the perinatal period, congenital anomalies and chromosomal disorders, respiratory diseases, and diseases of the cardiovascular system. The Murray method estimated 1711 deaths for the entire Province. Conclusion: the Murray method predicted that from 2011 to 2014, 390-445 children under one year died in Mazandaran Province annually. There is a controversy between the estimates obtained in this study and the number of deaths reported by the civil registration organization, which may indicate a defect in a complete registration of deaths by this organization.

Europium- and terbium-doped zinc aluminate oxide nanocrystals with a spinel structure were successfully prepared by a combustion method, using urea as fuel. The samples thus obtained were characterized by X-ray diffraction, scanning electron microscopy and luminescence spectroscopy. X-ray diffraction results confirmed the formation of ZnAl2O4 spinel phase and a minor amount of ZnO. Our SEM results revealed agglomerates in the shape of irregular plates composed of nanoparticles with dispersed points of second phase in the surface. Powders containing Eu3+ and Tb3+ ions displayed red and green photoluminescence, respectively. [ABSTRACT FROM AUTHOR]

Abir Kumar Panda, Dwaipayan Chakraborty, Irene Sarkar, Tila Khan, Gaurisankar Sa Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India Abstract: Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer. Keywords: apoptosis, cancer, cell signaling, combinatorial therapy, curcumin/nanocurcumin, drug resistance

Purpose The Shanghai Preconception Cohort (SPCC) was initially established to investigate the associations of parental periconceptional nutritional factors with congenital heart disease (CHD) but has further analysed child growth and development and paediatric diseases.Participants Preparing-for-pregnancy couples who presented at Shanghai preconception examination clinics and early-pregnancy women before 14 gestational weeks were enrolled to comprise the periconceptional baseline study population. General characteristics, routine clinical data and consumption of diet supplements, such as folic acid and multivitamins, were collected. Blood samples were obtained at preconception and early, middle and late gestations using standard procedures. Multiple nutritional factors, including folate, homocysteine, vitamin A, vitamin D, vitamin E and metals, in the blood samples of participants selected using a case–control design were examined. Genomic DNA was extracted.Findings to date The baseline population included 8045 preconception couples, 3054 single women and 15 615 early-pregnancy women. Data from 12 402 births were collected, and follow-up of the cohort for other outcomes is ongoing. Currently, 151 cases of CHD were identified after birth. The pilot analysis in a small subgroup showed that approximately 20.0% of preconception women and 44.9% of early-pregnancy women had red blood cell (RBC) folate levels that met the international recommendation for preventing neural tube defects.Future plans Once a sufficient number of CHD cases are achieved, we will investigate the quantitative association of preconception RBC folate levels with CHD using a nested case–control design. The SPCC will be followed up for 18 years to investigate extensive outcomes of growth, development, obesity, and common and rare diseases during childhood and adolescence according to our plan. Blood nutritional factors will be examined in participants selected for specific aims. The SPCC will also allow for prospective cohort studies on extensive research questions.Trial registration number NCT 02737644