Modulation of mucin secretion using combined polyethylene glycol–propylene glycol topical formulation in a hyperosmotic stress-based explant model

Purpose: Ocular surface discomfort and dry eye disease are caused by a dysfunctional tear film. The efficacy of lubricating eye drops on the human eye is known, but the compositions may show differential effects on rescuing the tear film. Mucins form a critical layer of the tear film, a reduction of which may be causative for ocular surface conditions. Therefore, it is essential to develop relevant human?derived models to test mucin production. Methods: Human corneoscleral rims were obtained from a healthy donor (n = 8) post?corneal keratoplasty and cultured in DMEM/F12 media. Hyperosmolar stress mimicking dry eye disease was induced by exposing the corneoscleral rim tissues to +200 mOsml NaCl?containing media. The corneoscleral rims were treated with polyethylene glycol–propylene glycol (PEG–PG)?based topical formulation. Gene expression analysis was performed for NFAT5, MUC5AC, and MUC16. Secreted mucins were measured by enzyme?linked immunosorbent assay (ELISA) (Elabscience, Houston, TX, USA) for MUC5AC and MUC16. Results: The corneoscleral rims responded to hyperosmolar stress by upregulating NFAT5, a marker for increased osmolarity, as observed in the case of dry eye disease. The expression of MUC5AC and MUC16 was reduced upon an increase in hyperosmotic stress. The corneoscleral rim tissues showed induction of MUC5AC and MUC16 expression upon treatment with PEG–PG topical formulation but did not show significant changes in the presence of hyperosmolar treatments. Conclusion: Our findings showed that PEG–PG?based topical formulation slightly alleviated hyperosmolar stress?induced decrease in MUC5AC and MUC16 gene expression that is encountered in DED

Multidisciplinary treatment of Class I Angle Malocclusion with severe crowding and peg lateral incisor: A case report

@#Class I malocclusions with severe crowding and tooth size discrepancies may be successfully treated orthodontically with extraction therapy, and co-management with other specialists. Correction of the discrepancies will optimize occlusal result (overjet, overbite, midline shift, and smile esthetics). This is a case of a 19-year-old male with severe crowding in upper and lower teeth and peg lateral incisor. The patient had malocclusion Class I. This case was treated comprehensively and successfully using fixed orthodontic appliances with extraction of four premolars, and veneer composite for peg lateral incisor with the help of a conservative dentist at the end of orthodontic treatment.

Clinical application value of pegylated recombinant human granulocyte-colony stimulating factor in neutropenia after chemotherapy / 中国生物制品学杂志

@#During chemotherapy of malignant tumors,neutropenia is the most important adverse event caused by myelosuppressive chemotherapeutics,of which the degree and duration are closely related to the risk of infection and even death.Granulocyte-colony stimulating factor(G-CSF) is an endogenous hematopoietic growth factor that can stimulate the proliferation and differentiation of neutrophil precursors,and increase the survival rate and activity of mature neutrophils.Recombinant human granulocyte-colony stimulating factor(rhG-CSF) is an artificially synthesized cytokine with G-CSF biological activity.It is used clinically for the prevention and treatment of neutropenia after treatment with cytotoxic chemotherapeutics,requiring multiple medications and repeated injections during application for its short half-life.Pegylated recombinant human granulocyte-colony stimulating factor(PEG-rhG-CSF) is its long-acting dosage form,and patients only need to be administered once per cycle of chemotherapy,which has been widely used in clinical practice because of its stability and convenience.This paper systematically described the clinical application value of PEG-rhG-CSF in neutropenia after chemotherapy,aiming to provide a reference for its further clinical application.

A case report of macro-AST with isolated elevated aspartate aminotransferase in a child / 中华检验医学杂志

We need to consider the macro-AST when the elevated AST activity cannot be explained. A 3-year-old child was found to have an increase in serum AST activity, but no obvious abnormality be found ofter examination. The PEG precipitation assay showed that the activity was 98.7%, which was diagnosed as macro-AST.

Effect of preventive application of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) during concurrent chemoradiotherapy in patients with lung cancer / 中华放射医学与防护杂志

Objective:To evaluate the effect of preventive application of PEG-rhG-CSF on the prevention of neutropenia during concurrent chemoradiotherapy in patients with lung cancer.Methods:A total of 149 patients with lung cancer who received concurrent chemoradiotherapy at Peking University Cancer Hospital from April 2020 to April 2021 were retrospectively analyzed. There were 79 cases in the prevention group, including 48 cases of primary prevention group (preventive application of PEG-rhG-CSF in all concurrent chemoradiotherapy cycles) and 31 cases of secondary prevention group (preventive application of PEG-rhG-CSF in the concurrent chemoradiotherapy cycles after neutropenia occurred). There were 70 cases in non-prevention group. The incidence of grade 3-4 neutropenia, the completion rate of concurrent chemoradiotherapy, the rate of chemoradiotherapy dose reduction and treatment delay, and the rate of hematological toxicities related hospitalization were compared between the prevention group and the non-prevention group.Results:The incidence of grade 3-4 neutropenia in the whole group was 32.2% (48/149), including 6.3% (3/48) in the primary prevention group, 9.7% (3/31) in the secondary prevention group, and 35.7% (25/70) in the non-prevention group. The difference was statistically significant ( χ2=17.81, P<0.001) in the incidence of grade 3-4 neutropenia. The incidence of febrile neutropenia was 3.4% (5/149) in the whole group, but none of them occurred in the primary prevention group. The full completion rate of concurrent chemotherapy was 96.2% (76/79) in the prevention group, which was significantly higher than 82.9% (58/70) in the non-prevention group ( χ2=7.30, P=0.007). The incidence of treatment delayed and dose reduction of chemoradiotherapy was 19.0% (15/79) in the prevention group and 40.0% (28/70) in the non-prevention group, and the difference was statistically significant ( χ2=7.98, P=0.005). Conclusions:The preventive application of PEG-rhG-CSF can effectively reduce the incidence of neutropenia and better ensure the concurrent chemoradiotherapy in lung cancer patients on schedule.

Effect of PEG-rhG-CSF in Preventing Chemotherapy-induced Neutropenia in Locally Advanced Non-small Cell Lung Cancer Patients at Nutritional Risk / 肿瘤防治研究

Objective To explore the efficacy and safety of polyethylene glycol recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in locally advanced non small cell lung cancer (NSCLC) patients at nutritional risk. Methods A total of 337 locally advanced NSCLC patients at nutritional risk were selected. They were randomly divided into three groups: 112 cases in the non-prophylactic drug group (control group), 112 cases in the prophylactic use of rhG-CSF treatment group (rhG-CSF group), and 113 cases in the prophylactic use of PEG-rhG-CSF treatment group (PEG-rhG-CSF group). The incidence and duration of neutropenia after chemotherapy and the ratio of CD4+/CD8+T cells in peripheral blood were observed. Results The incidences of neutropenia in the control group, rhG-CSF group, and PEG-rhG-CSF group were 67.97%, 41.57%, and 38.98% (P < 0.05), respectively. The incidences of grade Ⅲ-Ⅳ neutropenia in the three groups were 22.39%, 14.25%, and 11.14% (P < 0.05); moreover, the incidence of febrile neutropenia in the three groups was 3.55%, 1.84%, and 1.21% (P < 0.05); in addition, the ratios of CD4+/CD8+T cells in peripheral blood were 1.27±0.44, 1.41±0.52, and 1.49±0.42 (P < 0.05). The duration of grade Ⅲ-Ⅳ neutropenia and the time required for the neutrophil value to reach 2.0×109/L from the lowest value in the PEG-rhG-CSF group were lower than those in the control and rhG-CSF groups (P < 0.05). Conclusion The PEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy in locally advanced NSCLC patients at nutritional risk can reduce the incidence of neutropenia and improve immunologic function. PEG-rhG-CSF preventive treatment is worthy of clinical recommendation.

Liposome-based multifunctional nanoplatform as effective therapeutics for the treatment of retinoblastoma

Photothermal therapy has the characteristics of minimal invasiveness, controllability, high efficiency, and strong specificity, which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. However, due to the limited tissue penetration of infrared light, it is difficult to promote and apply in clinical practice. The eye is the only transparent tissue in human, and infrared light can easily penetrate the eye tissue, so it is expected that photothermal therapy can be used to treat fundus diseases. Here in, a new nano-platform assembled by liposome and indocyanine green (ICG) was used to treat retinoblastoma. ICG was assembled in liposomes to overcome some problems of ICG itself. For example, ICG is easily quenched, self-aggregating and instability. Moreover, liposomes can prevent free ICG from being cleared through the systemic circulation. The construction of the nano-platform not only ensured the stability of ICG in vivo, but also realized imaging-guide photothermal therapy, which created a new strategy for the treatment of retinoblastoma.

Pancreatitis aguda: una complicación infrecuente de las gastrostomías por migración del balón interno. Reporte de un caso y revisión de literatura / Acute pancreatitis: A rare complication of gastrostomy due to intragastric balloon migration. Case report and literature review

Resumen La pancreatitis aguda secundaria a la obstrucción de la papila mayor causada por la migración del balón interno es uno de los efectos secundarios poco frecuentes, pero potencialmente graves relacionados con el uso de gastrostomías endoscópicas percutáneas (PEG). Hasta ahora solo existen 15 casos reportados en el mundo, presentamos el que para nuestro conocimiento sería el caso número 16 en la literatura internacional.

Abstract Acute pancreatitis secondary to major papilla obstruction caused by intragastric balloon migration is one of the rare but potentially severe side effects associated with the use of percutaneous endoscopic gastrostomy (PEG). To date, there are only 15 cases reported worldwide. This article presents a case that, to the best of our knowledge, is the sixteenth case reported in the international literature.

Enamel Deproteinization: Will It Save The Shear Bond Strength For The Sake Of Preventing White Spot Lesions? / Desproteinização do esmalte: salvará a resistência ao cisalhamento para prevenir lesões de manchas brancas?

Objective: This study attempted to investigate the effect of enamel deproteinization using citric acid, PEG 400 and NaOCL on the shear bond strength of orthodontic brackets to enamel using nano-silver modified resin for the prevention of white spot lesions. Material and Methods: 68 premolars were used in the study; nano-silver modified adhesive resin was used to bond orthodontic brackets to the enamel. Specimens were divided into 4 groups according to the applied surface treatment before bonding. Group I (control): acid etching with 37% phosphoric acid. Group II: deproteinization using 5.25% sodium hypochlorite (NaOCl) before acid etching. Group III:deproteinization using 10% citric acid before acid etching. Group IV:deproteinization using 5% polyethylene glycol (PEG 400) before acid etching. The specimens were then thermo- cycled for 6000 cycles. They were examined for surface roughness, shear bond strength and using electron microscope. Results: In both surface roughness and shear bond strength tests, Group III (citric acid) showed the highest values, followed by Group II (sodium hypochlorite); (p < 0.001). The least values were shown for Groups I (control) and IV (PEG 400), with no statistically significant difference between them (p = 0.948). SEM revealed etching pattern type 1 and 2 in the citric acid group while PEG 400 showed shallower micro- porosities. Conclusions: Deproteinization of enamel using either NaOCl or citric acid increased the bond strength of nano-sliver modified resin to enamel, with citric acid showing greater increase in bond strength. Deproteinization using PEG 400 did not increase the bond strength. (AU)

Objetivo: Este estudo buscou investigar o efeito da desproteinização do esmalte utilizando ácido cítrico, PEG 400 e NaOCl na resistência ao cisalhamento de braquetes ortodônticos ao esmalte usando resina modificada com nanoprata para a prevenção de lesões de manchas brancas. Material e Métodos: 68 pré-molares foram usados no estudo; resina adesiva modificada com nanoprata foi usada para colar os braquetes ortodônticos ao esmalte. Os corpos-de-prova foram divididos em 4 grupos de acordo com o tratamento de superfície aplicado antes da colagem. Grupo I (controle): condicionamento ácido com ácido fosfórico a 37%. Grupo II: desproteinização com hipoclorito de sódio a 5,25% (NaOCl) antes do condicionamento ácido. Grupo III: desproteinização com ácido cítrico a 10% antes do condicionamento ácido. Grupo IV: desproteinização com polietilenoglicol 5% (PEG 400) antes do condicionamento ácido. As amostras foram então termocicladas por 6.000 ciclos. Eles foram examinados quanto à rugosidade da superfície, resistência ao cisalhamento e usando microscópio eletrônico. Resultados: Nos testes de rugosidade superficial e resistência ao cisalhamento, o Grupo III (ácido cítrico) apresentou os maiores valores, seguido do Grupo II (hipoclorito de sódio); (p <0,001). Os menores valores foram apresentados para os Grupos I (controle) e IV (PEG 400), sem diferença estatisticamente significativa entre eles (p = 0,948). A microscopia eletrônica revelou padrão de ataque tipo 1 e 2 no grupo de ácido cítrico, enquanto PEG 400 mostrou microporosidades mais rasas. Conclusões: A desproteinização do esmalte com NaOCl ou ácido cítrico aumentou a força de união da resina modificada com nanoprata ao esmalte, com o ácido cítrico apresentando maior aumento na força de união. A desproteinização usando PEG 400 não aumentou a resistência de união. (AU)

Cetoacidose diabética e pancreatite secundárias à peg-asparaginase / Diabetic ketoacidosis and pancreatitis secondary to peg-asparaginase

RESUMO: Objetivos: Apresentar um caso raro de cetoacidose diabética (CAD) e pancreatite secundários ao uso de PEG-asparaginase em paciente pediátrico em tratamento para leucemia linfoblástica aguda (LLA) e alertar quanto aos sinais que remetem a esses diagnósticos. Descrição do caso: Adolescente do sexo feminino, 10 anos e 11 meses, em tratamento para LLA e uso prévio de PEG-asparaginase há seis dias da internação, admitida com choque hipotensivo grave e encaminhada à Unidade de Terapia Intensiva. Inicialmente o quadro foi interpretado como choque séptico. Em seguida a anamnese detalhada e os exames laboratoriais direcionaram para os diagnósticos de CAD e pancreatite, iniciando-se as intervenções específicas. Recebe alta hospitalar após 30 dias, sem necessidade de insulinoterapia, mas com reposição de enzimas pancreáticas. Comentários: Geralmente, às crianças com LLA gravemente enfermos e leucopênicos, atribui-se apenas o diagnóstico de sepse, que é um diagnóstico prioritário. Entretanto, no grupo em uso de PEG-asparaginase, o pediatra emergencista deve estar alerta ao raciocínio diferencial envolvendo CAD e pancreatite, o que pode ser bem difícil inicialmente. O alerta dos diagnósticos diferenciais do choque séptico, mesmo que raros, na assistência a pacientes oncológicos pediátricos, além da correta e pronta identificação do quadro e seu manejo apropriado, correlacionam-se diretamente ao sucesso terapêutico e, em algumas situações, à sobrevivência do paciente. (AU)

ABSTRACT: Objectives: We present a rare case of diabetic ketoacidosis (DKA) and pancreatitis secondary to the use of PEG-asparaginase in a pediatric patient being treated for acute lymphoblastic leukemia (ALL) and draw attention to the signs that refer to these diagnoses. Case description: A female adolescent, aged 10 years and 11 months, undergoing treatment for ALL, used PEG-asparaginase for 6 days prior to admission. She was hospitalized due to severe hypotensive shock and was then referred to the intensive care unit. Initially, the clinical condition was interpreted as septic shock. However, detailed anamnesis and results of laboratory tests led to the diagnoses of DKA and pancreatitis; hence, appropriate interventions were initiated. She was discharged after 30 days without the need for insulin therapy but received pancreatic enzyme replacement therapy. Comments: Generally, diagnosing severely ill and leukopenic children with ALL is only attributed to sepsis, which is a priority diagnosis. However, in the group treated with PEG-asparaginase, the pediatric emergency specialist should consider differential reasoning in patients with DKA and pancreatitis, which can be quite difficult to assess initially. Alertness towards the differential diagnoses of septic shock, although rare, in the care of pediatric oncology patients, in addition to the correct and prompt identification of the condition and provision of appropriate management, directly correlates with treatment success and, in some situations, the improvement in patient's survival. (AU)

Effects of polyethylene glycol length on oral absorption of coumarin 6-loaded nanostructured lipid carrier / 中国药科大学学报

@#Polyethylene glycol (PEG) of different lengths were prepared to investigate their effects on oral absorption of nanostructured lipid carrier (NLCs).Three kinds of PEG-modified NLCs with different chain lengths, including polyethylene glycol (100) monostearate (S100), polyethylene glycol (55) monostearate (S55), polyethylene glycol (40) monostearate (S40), were prepared by film dispersion method.Coumarin 6 was chosen as a fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile, the stability of NLCs in simulate buffer, the release behavior, cytotoxicity of NLCs, the uptake kinetics and cellular uptake mechanisms were evaluated. This work demonstrated that the thickness of the hydrated layer increased with the increase of PEG length. Of note, S100-modified NLCs (pNLC-EG100) exhibited higher cellular uptake efficiency compared with other formulations. Thus, S100 was optimized as the best molecular weight for PEG-modified NLCs on oral drug delivery system.

Innate and adaptive immune responses toward nanomedicines

Since the commercialization of the first liposomes used for drug delivery, Doxil/Caelyx® and Myocet®, tremendous progress has been made in understanding interactions between nanomedicines and biological systems. Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more efficiently. While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics, the clinical successes of gene silencing approaches like patisiran lipid complexes (Onpattro®) have paved the way for a variety of therapies beyond cancer. In parallel, the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential of mRNA vaccines to develop immunization strategies at unprecedented speed. To rationally design therapeutic and vaccines, chemists, materials scientists, and drug delivery experts need to better understand how nanotechnologies interact with the immune system. This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.

Construction and in vivo evaluation of a thermosensitive hydrogel system loading with Pseudomonas aeruginosa DNA vaccine / 中国药科大学学报

@#A thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine was constructed and the immune efficacy of the system was evaluated. The PLGA-PEG-PLGA thermosensitive hydrogel containing Pseudomonas aeruginosa DNA vaccine was prepared by a simple physical mixing method. The gelation temperature, cytotoxicity, and release curve in vitro were tested.The degradability of hydrogel in vivo was evaluated. The mice were divided into control group (PBS), hydrogel group (Hydrogel), in vivo-jetPEI/plasmid DNA group (in vivo-jetPEI/pDNA), and hydrogel + in vivo-jetPEI/plasmid group (Gel+in vivo-jetPEI/pDNA). Mice were immunized three times with a ten-day interval. Two weeks after the last immunization, the mice were sacrificed. The proliferation of splenic lymphocytes, serum specific IgG antibodies and IFN-γ in supernatant of splenic lymphocytes were detected. The gelation temperature of PLGA-PEG-PLGA hydrogel was (32 ± 0.5) ℃. There was no obvious toxicity to cells in vitro, and about 80% of plasmid DNA was released after 7 days in vitro. PLGA-PEG-PLGA hydrogel was biodegradable, and degraded almost completely after 15 days in vivo. The spleen lymphocytes proliferated; the levels of specific IgG antibodies and IFN-γ of in vivo-jetPEI/pDNA and Gel+in vivo-jetPEI/pDNA groups increased. The hydrogel could enhance the immune response induced by DNA vaccine.Results suggest that the thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine is a promising new strategy for the development of PA vaccine.

Synthesis of two folate conjugates and their targeting effect in vitro / 中国药科大学学报

@#The aim of this study was to study the synthesis of two folate conjugates and their application in the preparation of folate targeted liposome, and to investigate their targeting effect in hepatocellular carcinoma HepG2 cell line in vitro. In this study, Folate-PEG-Cholesteryl hemisuccinate(Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS)were synthesized by linking folate and cholesterol succinate with two kinds of PEG materials. Structures of Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS were characterized by 1H NMR and ultra-high resolution mass spectrometry. Calcein was selected as the model drug, and calcein liposomes FA-PEG2000-L and FA-PEG4000-L were prepared by film dispersion method using Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS, respectively. The particle size and Zeta potential of FA-PEG2000-L and FA-PEG4000-L were measured by laser particle size analyzer. The drug delivery effect of FA-PEG2000-L and FA-PEG4000-L was evaluated by cellular uptake experiment in HepG2 cell line in vitro. Flow cytometry and laser confocal scanning microscope were used to determine fluorescence in HepG2 cells in vitro. The results showed that the average particle size of calcein liposome was (205.8 ± 10.2) nm, and the Zeta potential of calcein liposome was -(1.19 ± 0.31) mV.There was no significant difference in particle size and Zeta potential between FA-PEG2000-L and FA-PEG4000-L. The fluorescence intensity of FA-PEG4000-L liposome group was about 3.6 and 3.1 times higher than that of non-targeted liposome group and FA-PEG2000-L liposome group, with statistically significant difference (P < 0.01). The drug delivery efficiency of FA-PEG4000-L group in HepG2 cells was higher than that in FA-PEG2000-L and non-targeted groups, and the results indicated that Folate-PEG4000-CHEMS can promote the uptake of liposome by HepG2 cells in vitro. All in all, Folate-PEG4000-CHEMS could be applied in the preparation of folate targeted liposome, which could promote the uptake of liposome by HepG2 cells.

Effect of EBR on Seed Germination， Seedling Growth and Key Enzyme Activities for Flavonoid Biosynthesis in Astragalus membranaceus var. mongholicus Under PEG-induced Drought Stress / 中国实验方剂学杂志

Objective:To study the effects of 24-epibrassinolide （EBR） at different concentrations on seed germination， seedling growth and key enzyme activities for flavonoid biosynthesis in <italic>Astragalus membranaceus </italic>var.<italic> mongholicus</italic> under polyethylene glycol （PEG）-induced drought stress， in order to provide theoretical reference for standardizing the drought-resistant cultivation techniques of <italic>A. membranaceus </italic>var.<italic> mongholicus</italic>. Method:The seeds of <italic>A. membranaceus </italic>var.<italic> mongholicus </italic>were soaked in EBR solution at different concentrations（0.001， 0.01， 0.1， 1， 10 μmol·L^-1） followed by foliar spraying to explore their effects on seed germination， seedling growth， photosynthesis， chlorophyll and malondialdehyde （MDA） contents， and key enzyme activities for flavonoid biosynthesis under drought stress induced by 20% polyethylene glycol （PEG）-6000. Result:Compared with the control（CK）group， PEG-induced drought stress led to an obvious decrease in germination potential， germination rate， germination index， vigor index， relative germination rate， plant height， root length， aboveground and root dry weight， net photosynthetic rate （<italic>Pn</italic>）， stomata conductance （<italic>Gs</italic>）<italic>， </italic>transpiration rate （<italic>Tr</italic>）， chlorophyll contents and chlorophyll a/b ratio， while a significant increase in intercellular carbon dioxide concentration （<italic>Gi</italic>）， MDA， flavonoids contents， and key enzyme activities for flavonoid biosynthesis such as phenylalanine ammonia lyase （PAL）. The treatment with exogenous EBR solution at the suitable concentration significantly enhanced the adaptation of <italic>A. membranaceus </italic>var.<italic> mongholicus </italic>seeds and seedlings to PEG-induced drought stress， manifested as significantly elevated germination potential， germination rate， germination index， vigor index， relative germination rate， plant height， root length， aboveground and root dry weight， <italic>Pn</italic>， <italic>Gs， Tr</italic>， chlorophyll a/b ratio， chlorophyll and flavonoids contents and key enzyme activities for flavonoid biosynthesis like PAL while lowered <italic>Ci</italic> and MDA contents. The optimal concentration of EBR solution was 0.1 μmol·L^-1. Conclusion:Exogenous EBR solution at the suitable concentration ameliorates the inhibitory effect of 20% PEG stress against seed germination and seedling growth of <italic>A. membranaceus </italic>var.<italic> mongholicus</italic>， reduces the oxidative damage in leaves， and improves the stress resistance to a certain extent by up-regulating the key enzyme activities and promoting flavonoid synthesis.

Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques / 中国实验方剂学杂志

Objective:To investigate the effects of polyethylene glycol 400 （PEG400） on the pharmacokinetics and anti-inflammatory effect of baicalin， and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucuronide （B6G） by molecular docking. Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix， and rats were administrated the equal dose of baicalin aqueous solution （baicalin+water group） and baicalin PEG400 solution （baicalin+PEG400 group）. After the plasma samples were processed at different time periods， the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group （normal saline， 20 mL·kg^-1）， aspirin group （dose of 0.2 g·kg^-1）， baicalin/baicalin+PEG400 high and low dose （3.0， 1.5 g·kg^-1） groups， after continuous administration for 7 days， the mouse ear swelling and foot swelling models were established， and the swelling degree and swelling inhibition rate were calculated. Result:The pharmacokinetic study showed that compared with baicalin+water group， the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution， and the area under the curve （AUC_0-<italic>_t</italic>） increased by 2.36， 1.97 times， and the peak concentration （<italic>C</italic>_max） increased by 2.12， 1.65 times， respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition， molecular docking results showed that baicalin and B6G could site bind to multiple target proteins ［tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-6， IL-1<italic>β</italic>， prostaglandin E₂ （PGE₂） and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）］ with higher affinity， which was superior to the positive drug aspirin. Conclusion:PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G， and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors， it is speculated that baicalin and B6G jointly play an anti-inflammatory role.

Cross pollination of different peony cultivars with 'Feng dan' / Polinização cruzada de diferentes cultivares de peônia com 'Fengdan'

ABSTRACT: Paeonia ostii 'Feng dan' is recommended as a new promising oil crop because of the nutrient elements in its seed; however, the development of this new oil crop is now limited due to its low seed setting rate. This study identified ways to improve the cross pollination of Feng dan as the maternal parent, which has been proved to be a suitable oil crop, so as to improve the seed setting rate of 'Feng dan', and to predict the functional relationship between pollen vigor and seed setting rate. improving the efficiency of cross pollination. Three major steps were conducted, first, to screen the appropriate method of measuring pollen vigor of the paternal parent, which could have a strong relationship with seed setting rate. Second, to obtain the corresponding seed setting rate by cross pollination. Third, the functional relationship between two indexes was founded which could be used in cross pollination practice. Results indicated that the best paternal parents of 'Feng dan' were 'Feng dan' cultivars from other different cultivation populations; The most suitable medium concentration for pollen germination was 100~150 g/L sucrose, 0.06~0.08 g/L boric acid, and 50~200 g/L PEG-6000. Both the seed setting rate and the number of seed grains were positively correlated with the pollen activity, and the seed setting rate was negatively correlated with the local precipitation.

RESUMO: Peonia, Feng dan' (Paeonia ostia) do género Paeonia (o grupo lenhoso) é recomendado como uma nova cultura promissora na produção de óleos, devido aos elementos nutritivos na semente, no entanto, o desenvolvimento desta nova cultura está agora limitado devido às baixas taxas de fixação de sementes. Este estudo tem por objetivo identificar meios de melhorar a polinização cruzada de 'Feng dan' como o parental paterno, por ser uma cultura de óleo adequada, de modo a melhorar as taxas de fixação de sementes de 'Feng dan', e para prever a relação funcional entre o vigor do pólen e as taxas de fixação de sementes para melhorar a eficiência da experiência de polinização. Em primeiro lugar, foram realizados três passos para analisar o método de medição do vigor do pólen do pai paternal, que poderia ter uma relação forte com as taxas de fixação das sementes. Em segundo lugar, obter as taxas de fixação de sementes correspondentes por polinização cruzada. Em terceiro lugar, foi estabelecida a relação funcional entre dois índices que poderiam ser utilizados na prática da polinização cruzada. Os resultados indicaram que os melhores parentais paternos de 'Feng dan' eram cultivares de 'Feng dan' de outras populações de cultivo diferentes. A concentração de meio mais adequada para a germinação do pólen foi 100~150 g/L de sacarose, 0,06~0,08 g/L ácido bórico, e 50~200 g/L PEG-6000. Tanto a taxa de estabelecimento das sementes como o número de sementes foram positivamente correlacionados com a atividade do pólen, e a taxa de estabelecimento das sementes foi negativamente correlacionada com a precipitação local.

Clinical characteristics of children with acute lymphoblastic leukemia presenting with secondary acute pancreatitis / 中国肿瘤临床

Objective: To analyze the clinical characteristics of children with acute lymphoblastic leukemia (ALL) diagnosed with secondary acute pancreatitis(AP). Methods: We collected data from a total of 11 patients with ALL and secondary acute pancreatitis who were treated in Tianjin Children's Hospital from February 2013 to February 2020. All patients followed the China Children's Leukemia Collaborative Group-Acute Lymphocytic Leukemia-2008 (CCLG- ALL 2008) combined regimen. We summarized the patient's risk stratification, primary clinical manifestations, treatment stage, cause of pancreatitis, and cumulative dosage of polyethylene glycol conjugated asparaginase (PEG-ASP). The results from examinations such as pancreatic enzyme index, imaging, blood routine, liver and kidney function, blood lipid and blood glucose, and coagulation function were also compared. Finally, the therapeutic effects and outcomes of the patients were compared; and subsequently their clinical characteristics were analyzed. Results: Among the 11 patients 7 were male, and 4 were female; aged between 1-14 years old, with a median age of 6 years. Ten patients had type B acute lymphoblastic leukemia (B-ALL) and 1 had type T acute lymphoblastic leukemia (T-ALL). Pancreatitis was observed in 8 cases within 45 days after start of therapy, in one high-risk case after the second cycle of HR3' chemotherapy and in 2 cases after intensive chemotherapy. It was observed in 10 cases after PEG-ASP treatment, and in one T-ALL case concomitant with tumor lysis syndrome following cyclophosphamide-dexamethasone cytoduction treatment. It manifested primarily as abdominal pain, nausea and vomiting in 11 patients; 8 patients had hypocalcemia; 9 patients had low albumin levels; and 8 patients had abnormal coagulation function. No hypersensitivity was observed. Conclusions: Secondary AP occurs in children with ALL during the early stages of combined chemotherapy. Most of the complications are related to the asparaginase treatment. The severity of the disease is not significantly correlated with the risk stratification of the disease and the cumulative dose of asparaginase. Serum pancreatic enzyme (PE) testing and imaging tests can help assess the clinical status and guide the later prognosis and medication.

A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving

@#Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

Funcionalização do polietilenoglicol metil éter via reação de bromoacetilação: ativação, caracterização por MALDI-TOF e mecanismo de reação / Poly(ethylene glycol) methyl ether functionalization by bromoacetylation reaction: Activation, characterization by MALDI-TOF and reaction mechanism / Funcionalización de polietilenglicol metil éter mediante reacción de bromoacetilación: activación, caracterización por MALDI-TOF y mecanismo de reacción

Resumo A PEGuilação, reação química de conjugação com a molécula de polietilenoglicol (PEG) ou polietilenoglicol metil éter (mPEG), tem sido amplamente aplicada pelas indústrias farmacêuticas como estratégia de melhoria das propriedades farmaco-cinéticas de compostos bioativos. O PEG é um polímero que possui um esqueleto de poliéter quimicamente inerte e que apresenta grupos hidroxilas (-OH) em suas extremidades. Assim, o PEG para tornar-se apto como reagente de conjugação deve ser ativado com um grupo funcional que seja reativo. Nesse sentido, a bromoaceti-lação apresenta-se como uma alternativa para a funcionalização do PEG. Portanto, nesse trabalho objetivamos descrever em detalhes os procedimentos e o mecanismo de reação envolvida na funcionalização do mPEG, através da reação de bromoacetilação. Além do mais, estudamos a aplicação do MALDI-ToF para a caracterização do produto ativado. Após a bromoacetilação, por um procedimento adaptado, obteve-se o bromoacetil-mPEG-éster, com rendimento bruto de 56,78%. Análises posteriores, por espectrometria de massas por MALDI-ToF, possibilitaram identificar e caracterizar o produto bromoacetilado. Entre as condições de reação, o controle de temperatura (-10 °C a 0 °C) mostrou-se eficaz favorecendo a adição nucleofílica essencial à bromoacetilação. Assim, concluímos que o controle da baixa temperatura reacional é um fator chave para o favorecimento da adição nucleofílica à carbonila e, portanto, essencial na obtenção do mPEG funcionalizado via bromoacetilação. Estudos posteriores serão necessários, no entanto, para confirmar se o mPEG esterificado, nessas condições, poderá ser utilizado na conjugação com moléculas de natureza proteica ou peptídica, por meio de substituição nucleofílica bimolecular.

SUMMARY PEGylation, a chemical reaction of conjugation with the polyethylene glycol molecule (PEG), has been widely applied by the pharmaceutical industries as a strategy to improve the pharmacokinetic properties of bioactive compounds. PEG is a polymer that has a chemically inert polyether backbone and hydroxyl groups (-OH) at its ends. Thus, PEG to become fit as a reagent for conjugation must be activated with a functional group that is reactive. In this sense, bromoacetylation presents itself as an alternative for the functionalization of PEG. Therefore, in this study we aim to describe in detail the procedures and reaction mechanism involved in the functionalization of mPEG through the bromoacetylation reaction. In addition, we used the spectrometric technique, by MALDI-ToF, for the characterization of the activated product. After applying an adapted bromoacetylation procedure, bromoacetyl-mPEG-ester was obtained with a yield of 56.78%. Subsequent analyzes of MALDI-ToF mass spectrometry were able to correctly identify and characterize the bromoacety-lated product. Among the reaction conditions, temperature control (from -10 °C to 0 °C) was effective in favoring the essential nucleophilic addition to bromoacetylation. Thus, we conclude that the control of the low reaction temperature is a key factor in favoring the nucleophilic addition to carbonyl and, therefore, obtaining a favorable conversion to functionalized PEG via bromoacetylation. Further studies, however, will be necessary to confirm whether PEG esterified with these conditions can be used in conjunction with molecules of a protein or peptide nature by means of bimolecular nucleophilic substitution.

RESUMEN La PEGilación, una reacción química de conjugación con la molécula de polietilenglicol (PEG), ha sido ampliamente aplicada por las industrias farmacéuticas como una estrategia para mejorar las propiedades farmacocinéticas de los compuestos bioactivos. El PEG es un polímero formado por un esqueleto de poliéter químicamente inerte con grupos hidroxilo (-OH) en sus extremos. Por lo tanto, para usar el PEG como reactivo de conjugación debe activarse con un grupo funcional que sea reactivo. En este sentido, la bromoacetilación es una alternativa para la funcionalización de PEG. De esta manera, en este trabajo nuestro objetivo es describir en detalle los procedimientos y el mecanismo de reacción involucrados en la funcionalización de PEG a través de la reacción de bromoacetilación. Además, estudiamos la aplicación de MALDI-ToF para la caracterización del producto activado. Después de aplicar un procedimiento de bromoacetilación adaptado, se obtuvo bromoacetil-mPEG-éster con un rendimiento bruto de 56,78%. Los análisis posteriores de espectrometría de masas por MALDI-ToF pudieron identificar y caracterizar correctamente el producto bromoacetilado. Entre las condiciones de reacción, el control de la temperatura (desde -10 °C hasta 0 °C) fue eficaz para favorecer la adición nucleofílica esencial a la bromoacetilación. Así, concluimos que el control de la baja temperatura de reacción es un factor clave para favorecer la adición nucleofílica al carbonilo y, por lo tanto, esencial para obtener el mPEG funcionalizado mediante la bromoacetilación. Sin embargo, serán necesarios más estudios para confirmar si el mPEG esterificado en estas condiciones puede usarse junto con moléculas de naturaleza proteica o peptídica por medio de la sustitución nucleófila bimolecular.