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OBJECTIVE@#The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.@*METHODS@#We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg∙day) and 50 μg/(kg∙day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing.@*RESULTS@#Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.@*CONCLUSION@#Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.
Subject(s)
Male , Animals , Mice , Gastrointestinal Microbiome , Mice, Inbred C57BL , RNA, Ribosomal, 16S/genetics , Benzhydryl Compounds/toxicity , Bacteria/genetics , PhenolsABSTRACT
Gliomas are the most common primary intracranial tumors in adults, among which high-grade glioma patients are characterized by short survival and poor prognosis. The diagnosis, treatment, evaluation of effective treatments, and prognosis prediction of high-grade gliomas are of great significance for improving patient survival. Conventional enhanced magnetic resonance imaging has deficiencies in delineating tumor extent, identifying tumor progression and treatment-related changes. Therefore, there is a broad consensus to incorporate amino acid PET, and 18F-FET PET inparticular, into the diagnostic and therapeutic process of high-grade gliomas. In this article, we review the new research progress of 18F-FET PET in the diagnosis and treatment of adult high-grade glioma in recent years.
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AIM: To compare the outcome of C3F8 versus silicone oil tamponade after pars plana vitrectomy(PPV)and inverted internal limiting membrane(ILM)for the treatment of highly myopic macular hole retinal detachment(MHRD).METHODS: Retrospective clinical study. Totally 45 patients(45 eyes)with highly myopic MHRD who visited our hospital between January 2019 and August 2022 were selected as the research subjects. The patients were divided into two groups according to different intraocular tamponade agents: C3F8(22 eyes)and silicone oil(23 eyes)groups. All patients underwent conventional three-incision PPV, ILM was tamped, a venous blood clot was placed on the tamped ILM, and 15% C3F8 and silicone oil were used as tamponade, respectively. The best corrected visual acuity(BCVA), multifocal electroretinogram(mfERG), the closure of the macular hole, retinal reattachment and the complications were observed.RESULTS: The macular hole closure rate was 77% in the C3F8 group and 83% in the silicone oil group, respectively(P>0.05), and retinal reattachment rates were 95% and 96%, respectively(P>0.05). The visual acuity of the two groups significantly improved, which was 0.99±0.34 and 1.22±0.37, respectively, and the C3F8 group was better than that of the silicone oil group(t=-2.156, P=0.037). After operation, the response density of the first ring of P1 wave in the first order kernel in mfERG was 114.27±26.37 nV/deg2 for the C3F8 group and 98.08±24.36 nV/deg2 for the silicone oil group, and the response density of the second ring of P1 wave was 80.45±14.94 nV/deg2 for the C3F8 group and 67.73±15.33 nV/deg2 for the silicone oil group, all of which were significantly higher compared to pre-operation [the response density of the first ring of P1 wave: 58.13±13.96 nV/deg2 for the C3F8 group and 55.30±10.48 nV/deg2 for the silicone oil group, the response density of the second ring of P1 wave: 51.18±8.19 nV/deg2 for the C3F8 group and 47.43±11.97 nV/deg2 for the silicone oil group](all P<0.05). It was found that the response density of the first ring of P1 wave was lower in the silicone oil group than in the C3F8 group(P<0.05). There was no statistically significant difference in the incidence of complications between the two groups(P>0.05).CONCLUSION: Silicone oil tamponade or C3F8 tamponade after PPV combined with ILM can both promote retinal reattachment and macular hole closure in patients with MHRD, and the C3F8 tamponade was superior to silicone oil in visual function recovery.
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ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.
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Hepatic echinococcosis is a chronic parasitic disease, which is caused by the larvae of Echinococcus multilocularis. It has a high risk of disability and mortality, which is also known as "parasite cancer". In clinical practice, hepatic echinococcosis can be divided into hepatic alveolar echinococcosis and hepatic cystic echinococcosis. Hepatic echinococcosis is widely prevalent worldwide. It mainly occurs in the populations residing agricultural and pastoral areas in western China, posing significant threats to the quality of life of local residents. At present, surgery is the main treatment for hepatic echinococcosis in clinical settings. With rapid development of surgical diagnosis and treatment technology and deepening understanding of hepatic echinococcosis, diagnosis and treatment regimens have also been constantly improved. In this article, research progresses on the diagnosis and treatment of hepatic alveolar echinococcosis were reviewed, aiming to provide reference for clinicians, deliver early diagnosis and treatment, mitigate adverse effects of this disease upon patients and improve clinical prognosis.
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@#Objective To express glycoprotein H(gH)of pseudorabies virus(PRV)in mammalian cells and detect its immunogenicity.Methods The gH gene fragment of PRV-XiangA strain was amplified by PCR and inserted into mammalian cell expression vector pIRES-neo3 to construct recombinant expression plasmid pIRES-gH,which was transfected to HEK-293F cells and cultured in suspension for 5 d. The cell culture supernatant was identified by Western blot and purified by nickel ion chromatography column. The purified gH was emulsified with ISA 201 VG adjuvant to immunize 8 female ICR mice,and 8 mice in control group were immunized with the same amount of adjuvant,which was strengthened at 5 and 8weeks after the first dose respectively. The blood samples were collected at 4,7 and 10 weeks after the first dose and detected for the titer of specific antibody and neutralizing antibody in serum of mice;The mice were challenged with PRVXiangA strain(1. 5 × 104TCID50)by nasal drops 2 d after the third blood collection,and observed for the morbidity and mortality daily.Results The recombinant expression plasmid pIRES-gH was constructed correctly as identified by sequencing. The gH protein was successfully expressed and modified by glycosylation in mammalian cells with good reactivity,and about 625 μg purified protein was obtained under 100 mL culture volume. After three times of immunization,mice produced high level of specific antibody and showed the effect of neutralizing PRV,and the titer of neutralizing antibody reached 1∶256. In the challenge test,all the mice in control group became ill and died,while half of the mice in gH immunized group did not get sick with a survival rate of 50%.Conclusion PRV gH was successfully expressed in mammalian cells,and its immune protection was confirmed for the first time,which provided experimental basis for the further research and application of gH,and also provided a new idea for the development of PRV subunit vaccine.
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OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.
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OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.
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ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.
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Resumen Antecedentes: Chlamydia trachomatis es la bacteria que se detecta con mayor frecuencia en las infecciones de transmisión sexual. Se han identificado 20 genotipos de C. trachomatis mediante el gen ompA y varias genovariantes mediante el análisis de polimorfismo de un solo nucleótido (SNP). En México, el genotipo F es el más frecuente. Objetivo: Identificar la existencia de subtipos del genotipo F. Método: Se analizaron siete cepas del genotipo F de C. trachomatis aisladas en 2011, mediante secuenciación de nucleótidos y mapeo con enzimas de restricción. Resultados: El análisis de SNP mostró dos cepas con el mismo SNP en el nucleótido 288 (C288T), mientras que con enzimas de restricción se identificó una variante con diferente RFLP (polimorfismo de la longitud de fragmentos de restricción) cuando se tratan con la mezcla de enzimas HinfI y TaqI. Conclusión: En México se encuentran dos subtipos del genotipo F y solo las enzimas de restricción HinfI y TaqI pueden identificar la existencia de uno de estos genotipos F.
Abstract Background: Chlamydia trachomatis is the most frequently identified bacterium in sexually transmitted infections. Twenty C. trachomatis genotypes have been determined using the ompA gene and several genovariants by single nucleotide polymorphism (SNP) analysis. In Mexico, the F genotype is the most frequent. Objective: To identify subtypes of the F genotype. Method: Seven C. trachomatis genotype F strains isolated in 2011 were analyzed by nucleotide sequencing and restriction enzyme mapping. Results: SNP analysis showed two strains with the same SNP at nucleotide 288 (C288T), while with res-triction enzymes, a variant with different RFLP (restriction fragment length polymorphism) was identified when treated with the mixture of HinfI and TaqI enzymes. Conclusion: In Mexico, there are two subtypes of F, and only with restriction enzymes HinfI and TaqI can identify one of the genovariants of the F genotype.
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Objetives: to evaluate the benefit of implementing 18F-FDG PET/TC in the staging and treatment adjustment of patients with sarcoidosis, compared with the signs and symptoms and complementary test results usually employed. Materials and methods: an observational, analytical electronic chart review of a retrospective cohort of patients seen for sarcoidosis in the internal medicine department of a Spanish university hospital. Results: a total of 31 patients (18 males) were evaluated, with an average age of 54.6±14.71 years and 11±5.75 years since their sarcoidosis diagnosis. In the 84.6% of the reviews, positive uptake was objectified on the 18F-FDG PET/TC. In the 42.3% of the occasions, the objectified find ing allowed restaging of the patient. The 18F-FDG PET/TC result justified the choice of treatment in the 71% of the reviews. Conclusions: 18F-FDG PET/TC provided additional advantages in the staging and therapeutic management of patients with sarcoidosis, compared with the evaluation of signs and symptoms and other clinical tests usually employed in follow up, due to its greater accuracy in determining the activity and extension of the disease. (Acta Med Colomb 2022; 48. DOI: https://doi.org/10.36104/amc.2023.2778).
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Se presenta en este artículo una reseña del libro Diccionario histórico geográfico de Costa Rica (1904-1923), del autor Félix F. Noriega, elaborada por Saray Córdoba González, Catedrática jubilada de la Universidad de Costa Rica. El documento rescata las principales apreciaciones de parte de la comentarista sobre el aporte del diccionario como una obra de construcción colectiva, que contribuyó -y podría continuar haciéndolo- a la educación costarricense. Sin duda, la misma es parte de la memoria que debemos guardar y fortalecer, porque solo repasándola podremos comprender el presente y no reiterar los errores cometidos en otras épocas.
This article presents a review of the book Diccionario histórico geográfico de Costa Rica (1904-1923), by Félix F. Noriega, written by Saray Córdoba González, retired professor of the University of Costa Rica. The document rescues the main appreciations of the commentator on the contribution of the dictionary as a work of collective construction, which contributed -and could continue to do so- to Costa Rican education. Undoubtedly, it is part of the memory that we must keep and strengthen, because only by reviewing it we will be able to understand the present and not repeat the mistakes made in other times.
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Background: The aim of this study is to evaluate the role of preoperative 18F?fluorodeoxyglucose (FDG) positron emission tomography朿omputed tomography (PET/CT) parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), hematologic prognostic indicators in patients with colorectal cancer (CRC) in terms of predicting prognosis. Methods: One hundred and one patients who had undergone 18F?FDG PET/CT for initial staging were evaluated retrospectively. Patient data including pathologic stage at presentation, histology, tumor location, and overall survival (OS) were analyzed. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), serum carcinoembryonic antigen (CEA) (ng/mL), CA?125 (cancer antigen 125) (U/mL), and CA19?9 (U/mL) levels, which were obtained within 2 weeks of the PET/CT examination, were used for hematological data. Results: The TNM Classification of Malignant Tumors stage and PET/CT parameters, including SUVmax, MTV, and TLG, were found to be correlated with survival rate in univariate analysis (P < 0.05). All hematological markers excluding PLR were also significantly associated with survival time. Receiver operating characteristics (ROC) analysis revealed that the optimal SUVmax cutoff value for predicting survival time in patients with CRC was >17.9 (Area under curve (AUC) = 0.625; P < 0.05). The calculated sensitivity and specificity values for this cutoff were 60% and 65.7%, respectively. To predict the survival time in these patients, the optimal MTV cutoff value was >34.29 (AUC = 0.775; P < 0.001; sensitivity = 85%; specificity = 62.3%). The optimal TLG cutoff value for predicting survival time was >270.4 (AUC = 0.790; P < 0.001; sensitivity = 77.5%; specificity = 68.9%). Conclusions: FDG PET/CT metabolical parameters are useful for predicting the prognosis in patients with CRC. High preoperative NLR and high tumor markers were also shown to be negative independent prognostic factors in these patients
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RESUMEN La captación de 18 FDG en PET-TC por un adenoma hepatocelular (HCA) es poco frecuente. Esta situación genera dudas en cuanto a los diagnósticos diferenciales y tratamiento. El objetivo de este artículo fue realizar una mini revisión de los últimos 37 años de HCA con avidez por el 18FDG y presentar un nuevo caso. Sobre la base de un estudio realizado por otros autores entre 1984 y 2014, se amplía la búsqueda utilizando las mismas palabras clave hasta el año 2021. Se analizan los datos relevantes. Entre 1984 y 2021 detectamos 38 casos en 37 años. Fue más frecuente en mujeres en edad reproductiva. Los subtipos H-HCA e I-HCA fueron los más frecuentes. El tratamiento quirúrgico fue el más empleado. La diferenciación celular y los trastornos metabólicos de la glucosa y de los lípidos favorecerían la captación de 18FDG. La resección hepática ofrecería mayores garantías permitiendo el estudio completo de la lesión.
ABSTRACT Hepatocellular adenoma (HCA) uptake of 18FDG uptake on PET-CT is rare. This situation poses doubts about the differential diagnoses and treatment. The aim of this article is to perform a mini review of 18FDG avid HCA over the past 37 years and to describe a new case presentation. Based on a study conducted by other authors between 1984 and 2014, we extended the search until 2021 using the same keywords. The relevant data were analyzed. Between 1984 and 2021 we detected 38 cases in 37 years. HCAs were more common in women of childbearing age. The most common types were H-HCA an I-HCA. Surgical resection was the treatment most used. Cell differentiation and glucose and lipid metabolic diseases would favor 18FDG uptake. Liver resection provides better outcomes, allowing for a complete examination of the lesion.
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Objective: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Methods: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Results: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Conclusion: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.
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Background: We aimed to evaluate the role of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography朿omputed tomography (PET-CT) in determining the correct stage and predicting the pathological response. Methods: Seventy one patients with pathologic proven rectal adenocarcinoma, clinical stage IIA-IVA, and neoadjuvant chemoradiotherapy (CRT) were evaluated retrospectively. Radiotherapy was delivered 45� Gy in 25 fractions with concomitant oral capecitabine. Pelvic MRI, colonoscopy, and 18F-FDG PET-CT were performed before the neoadjuvant treatment (NAT). After NAT, MRI and PET-CT were performed for re-evaluation. Results: The median follow-up time was 25 months (range: 3� months). Of the 71 patients who underwent NAT, 57 patients underwent surgery. Downstaging was recorded in 48 (84.2%) of 57 patients who underwent surgery. There was no statistically significant difference between both MRI and PET-CT with pathology results in terms of response evaluation. As a result of the comparison of MRI and PET-CT with pathological results; sensitivity and specificity were 91.6% (44/48) and 22.2% (2/9) for MRI, and 100% (47/47) and 12.5% (1/8) for PET-CT, respectively. Conclusion: PET-CT and MRI are effective in predicting response to NAT and predictive for the pathological response. A more accurate response can be judged when both PET-CT and MRI are executed together in restaging after NAT
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Background: BCR?ABL mutation on the Philadelphia chromosome is the key driver of chronic myeloid leukemia (CML) pathogenesis. However, there are certain cases of myeloproliferative neoplasms (MPN) wherein no inherent driver mutation is detected resulting in clinical phenotype. It is important to identify key genes and pathways in driving the disease. The aim of the study was to use a gene-based omics approach to molecularly characterize these mutation-positive and negative cases to further strengthen diagnostics and precision medicine. Methods: A microarray profiling was done on CD34 positive cells isolated from two BCR?ABL positive and five BCR?ABL negative samples. JAK2V617F mutation testing was also done to rule out the presence of any other mutation in the latter group. The fold change cut-off was taken as �5 with p?0.5 for significant genes. The gene network and pathway analysis were done using DAVID and STRING software. Results: The genes upregulated in BCR?ABL negative samples were shown to be involved in immune regulation, signal transduction and T- and B-cell signalling. The protein-protein interaction network of upregulated genes in these samples were enriched for various immunomodulatory genes such as HLADP, HLADQ , IL7R, CCR7, CD3 subtypes. These genes further formed a network with signal transduction genes such as LCK, FYN, RAG1, DOCK1, AKT3, SMAD3, LEF1. Conclusion: The results suggested a modulation of immune response genes and its subsequent effect on oncogenic signalling in BCR?ABL negative samples as compared to BCR?ABL positive samples. The protein network analysis was enriched for genes involved in Src, TGF-beta and PI3K-AKT pathway contributing to the proliferation of neoplastic clone.
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Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
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Background : Convalescent Plasma-therapy, a classic adaptive immunotherapy used in the treatment of SARS, MERS and 2009 H1N1 pandemic with acceptable efficacy and safety in the past. Convalescent Plasma-therapy was taken into consideration in management of COVID-19 disease during the initial days of pandemic but was withdrawn later due to its doubtful beneficial role. This study aims to explore the beneficial role of Convalescent plasma and to determine whether Convalescent Plasma-therapy holds a second chance in treating SARS-CoV-2. Methods : This cross-sectional observational study includes 82 cases of moderate to severely ill COVID-19 patients who received Convalescent Plasma-therapy and 41 controls who didn抰. regular monitoring of Total Leukocyte Count (TLC), PaO2/FiO2 (PaO2 is partial pressure of Oxygen in arterial blood, fractional inspired oxygen (P/F ratio), Neutrophil to Lymphocyte Ratio (N/L ratio) inflammatory markers, respiratory rate, oxygen saturation, ABG and Radiological Imaging was done for comparative analysis. Results : In case group 39 patients (47.56%) were on oxygen mask, 17 patients (20.73%) on Non-invasive Ventilation (NIV), 9 Patients on Non-rebrether Mask (NRM) (10.97%), 16 patients (19.51%) on room air, 1(1.21%) on High Flow Nasal Cannula (HFNC) initially. After 7th day of Convalescent Plasma-therapy 49 patients (59.75%) were on room air which suggests significant improvement in mode of ventilation in case group as compared to Control Group. Mean respiratory rate in case group was 30.46 Cycles Per Minute (CPM) initially and 24.7 CPM on day 7th of Plasma-therapy which is statically significant. Conclusion : Plasma-therapy is effective if given in early stage of disease and Convalescent Plasma donors having adequate antibody titre.
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@#Objective To express recombinant human interferon λ1(rhIFNλ1)by transient transfection in HEK-293F cells and identify it. Methods Two signal peptides[T cell receptor(TCR)and nature signal peptide(NSP)],three vectors[pcDNA3.4,ubiquitous chromatin opening element(UCOE)and PFR]and the target gene rhIFNλ1 were used to construct recombinant plasmids of six signal peptide-vector combinations. Using HEK-293F as host cells,the recombinant plasmids were transfected transiently to express rhIFNλ1 on a shake flask scale. The recombinant plasmid UCOE-Q46-λ with low glycosylation rhIFNλ1 was constructed by using NSP and vector UCOE,and transfected transiently into HEK-293F cells. The expressed product was purified by cation exchange chromatography(HiTrap SP FF),blue gel chromatography(HiTrap Blue HP)and gel filtration chromatography(Sephacryl S-100 HR),which was then analyzed by Western blot and reversed-phase HPLC,and determined for its molecular mass and N-terminal amino acid sequence by mass spectrometry. Results Six recombinant plasmids were constructed correctly as identified by double enzyme digestion and sequencing. With the extension of transfection time,the expression levels of the six expressed products increased gradually,and reached the highest level of10 ～ 20 mg/L at the 6th day of transfection. Double enzyme digestion and sequencing identification proved that the recombinant plasmid UCOE-Q46-λ with low glycosylation rhIFNλ1 was constructed correctly. The recombinant plasmid UCOE-Q46-λwas transfected into HEK-293F cells for 6 d. The purified product of cell culture supernatant showed a relative molecular mass of about 27 800 and a purity of 97. 372%,which showed specific binding to mouse anti-human IL-29/IFNλ1 monoclonal antibody;Two peaks were detected by reversed-phase HPLC,and the peak was showed at 15. 6 min and 20. 0 min respectively;The mass spectrometry molecular mass was about 24 000;The N-terminal five amino acids were G-P-V-P-T.Conclusion The rhIFNλ1 expressed by HEK-293F cells has high purity,which lays a foundation of further study of the protein.