Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA ...replication. Thymidylate synthase enhancer region (TSER) and TS1494del6, two functionally important and ethnically diverse polymorphisms mapping to its gene region, are the most extensively studied. Considering the potential influence of altering TS activity, it is plausible that TS polymorphisms might play a role in the development of cancer. Although the effects of TS polymorphisms on susceptibility to human cancer have been investigated in many studies, the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and cancer risk, including 63 studies (19,707 cases and 27,398 controls) for TSER polymorphism and 39 studies (13,489 cases and 16,297 controls) for TS1494del6 polymorphism. Our meta‐analysis suggested that these two polymorphisms are not associated with cancer risk when all studies were pooled together. In the stratified analyses, we found that individuals with 2R/2R genotype had a significantly higher cancer risks among Asians (2R/2R vs. 3R/3R: odds ratio OR = 1.24, 95% confidence interval (95% CI) = 1.05–1.45; recessive model: OR = 1.23, 95% CI = 1.05–1.44). Further analyses revealed that 2R/2R genotype was significantly associated with an increased risk of gastroesophageal cancer among Asians, whereas it might provide protecting effects against colorectal cancer risk in a dominant genetic model for Caucasians. Additionally, TS1494del6 polymorphism may contribute to genetic susceptibility of breast cancer among Asians.
► A cowpea mosaic virus vector was used to express human serum albumin in plant cells. ► Recombinant human serum albumin (rHSA) was highly produced in tobacco BY-2 cells. ► Cultivation of BY-2 cells ...in pH 8.0 medium improved the yield of rHSA two-fold. ► A simple purification scheme was developed to purify the rHSA from culture medium. ► Detailed characterization showed pant cell-derived rHSA was identical to natural HSA.
Most human serum albumin (HSA) for medical applications is derived from human plasma due to the lack of suitable heterologous expression systems for recombinant HSA (rHSA). To determine whether plant cell cultures could provide an alternative source, we employed the hyper-translatable cowpea mosaic virus protein expression system (CPMV-
HT) to stably express rHSA in tobacco Bright Yellow-2 (BY-2) cells. rHSA was stably produced with yield up to 11.88
μg/ml in the culture medium, accounting for 0.7% of total soluble protein, in a 25-ml flask. Cultivation of transgenic cells in modified Murashige and Skoog medium with a pH of 8.0 improved the yield of rHSA two-fold, which may be the result of reduced proteolytic activity in the modified medium. A simple purification scheme was developed to purify the rHSA from culture medium, resulting in a recovery of 48.41% of the secreted rHSA. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and N-terminal sequence analysis of the purified rHSA revealed that plant cell-derived rHSA is identical to that of the plasma-derived HSA. Our results show that the CPMV-
HT system, which was originally developed as a transient expression system for use in whole plants, can also be used for high-level expression of rHSA, a protein highly susceptible to proteolysis, in transgenic tobacco cells.
Iron oxide nanoparticles (IONPs) as magnetic resonance imaging (MRI) contrast agents have received considerable interest due to their superior magnetic properties. To increase the biocompatibility ...and blood circulation time, polyethylene glycol (PEG) is usually chosen to decorate IONPs. Although the surface effect induced by the PEGylation has an impact on the relaxometric properties of IONPs and can subsequently affect the imaging results, the occurrence of particle aggregation has troubled researchers to deeply explore this correlation. To shed light on this relationship, three diphosphonate PEGs with molecular weights of 1000, 2000, and 5000 Da were used to replace the hydrophobic oleate ligands of 3.6 nm and 10.9 nm IONPs. Then, the contrast enhancement properties of the resultant “aggregation-free” nanoparticles were carefully evaluated. Moreover, related theories were adopted to predict certain properties of IONPs and to compare with the experimental data, as well as obtain profound knowledge about the impacts of the PEG chain length on transverse relaxivity (r2) and longitudinal relaxivity (r1). It was found that r2 and the saturated magnetization of the IONPs, independent of particle size, was closely related to the chain length of PEG. The results unveiled the correlation between the chain length of the coated PEG and the relaxometric properties of IONPs, providing valuable information which might hold great promise in designing optimized, high-performance IONPs for MRI-related applications.
Interleukin 37 (IL‐37), a member of the IL‐1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism ...and role of IL‐37 in skin cancer remain unclear. Here, we report that IL‐37b‐transgenic mice (IL‐37tg) treated with the carcinogenic 7,12‐dimethylbenzoanthracene (DMBA)/12‐o‐tetradecylphorbol‐13‐acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL‐37 induced rapid phosphorylation of adenosine 5‘‐monophosphate (AMP)‐activated protein kinase (AMPK), and via single immunoglobulin IL‐1‐related receptor (SIGIRR), inhibited the long‐term Akt activation. Specifically, by affecting the SIGIRR‐AMPK‐Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL‐37 inhibited their anti‐tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS‐like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C‐X‐C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA‐induced skin cancer. In a word, our results highlight that IL‐37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.
In the 7,12‐dimethylbenzoanthracene/tetradecylphorbol‐13‐acetate two‐stage skin cancer induction model, interleukin weakened the expression of CD40/CCR7 and the secretion of C‐X‐C motif chemokine ligand 9/CXCL10 in CD103+DCs through single immunoglobulin interleukin‐1‐related receptor‐activated protein kinase‐Akt signal axis, which leads to the suppression the function of CD8+T cells and accelerating the growth of tumor.
Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been ...elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8
T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8
T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8
T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC.
To the Editor： A 23-year-old otherwise healthy male presented with diffuse, erythematous, nonpruritic papules on the trunk and extremities, which gradually developed over 1 month Figure 1a and 1b. ...The patient was afebrile and had no other systemic symptoms. His personal and family histories were unremarkable. He denied any drug intake or episode of infection before the onset. Head, hands, feet, and mucosa were spared. No lymphadenopathies were detected. Histopathological examination revealed full-thickness epidermal necrosis, parakeratosis, vacuolization of the basal layer, and superficial perivascular infiltration of lymphocytes and histiocytes in the dermis. Exocytosis was prominent, and intraepidermal red blood cells could be seen Figure 1c. A diagnosis ofpityriasis licbenoides et varioliformis acuta （PLEVA） was established. He was prescribed with oral prednisolone （30mg/d） for 2 weeks, and complete remission was obtained. A follow-up visit at 3 years later showed no evidence of recurrence of PLEVA.
Chromogenic assays (color detection) result in colored reaction products. By detecting the color change before and after the reaction, substance concentration can be determined by the naked eye, ...light microscopes, or spectrophotometers. Color detection exhibits great potential in the field of quality monitoring, chemical technology, nanophysics, and clinical medicine, because of its rapid, direct, specific, convenient, and sensitive features. The intention of this book is to provide readers with a comprehensive overview of the principles, features, and applications of color detection.
Metabolic disturbances are well-known risk factors for atherosclerosis, but it remains unclear which cardiometabolic components are the predominant determinants. This study aimed to compare and ...identify the key determinants of carotid atherosclerosis in asymptomatic middle-aged and elderly Chinese.
A community-based cross-sectional study including 3,162 apparently healthy residents aged 37-75 years was performed from July 2008 to June 2010 in Guangzhou, China. Carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasound, and increased IMT was defined as IMT>1.00 mm. Obesity indices, blood pressure, fasting blood lipids, glucose and uric acid levels were determined. Principal components factor analysis was used to extract common factors underlying 11 metabolic factors.
Four common factors, defined as "adiposity," "blood lipids," "triglycerides/uric acid (TG/UA)" (in men) or "triglycerides/uric acid/glucose (TG/UA/Glu)" (in women), and "blood pressure," were retained for both sexes. After adjustment for potential covariates, the "adiposity" factor showed the strongest positive association with increased IMT in men. Comparing the extreme quartiles, ORs (95% CI) of increased IMT were 4.64 (2.04-10.59) at the CCA and 2.37 (1.54-3.64) at the BIF), followed by "blood pressure", the corresponding OR (95% CI) was 2.85 (1.37-5.90) at the CCA. Whereas, the four common factors showed comparable and weak relationship with increased IMTs, the ORs for quartile 4 vs. quartile 1 varied from 0.89 to 3.59 in women.
Among the metabolic factors, "adiposity" and "blood pressure" play predominant roles in the presence of carotid atherosclerosis in men, but no key factor is identified in women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to assess the diagnostic value of prenatal echocardiography for identifying transposition of the great arteries (TGA) during pregnancy and evaluating the associated outcomes.
We ...conducted a retrospective analysis of 121 prenatally diagnosed patients with TGA at our hospital between January 2012 and September 2022. This analysis included prenatal ultrasound, prenatal screening, clinical management and follow-up procedures.
Among the 103 fetuses considered in the study, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), while 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses were distributed across the trimester, with 8 D-TGA and 2 CC-TGA patients identified in the first trimester, 68 D-TGA patients and 9 CC-TGA patients in the second trimester, and 14 D-TGA and 2 CC-TGA patients referred for diagnosis in the third trimester. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), and 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients, 9 fetuses (10.0%) underwent surgery, two of which were inadvertent fatality, while the remaining seven experienced positive outcomes. Additionally, seven TGA patients received palliative care, leading to four fatalities among D-TGA patients (5.2%), whereas 1 D-TGA patients and 2 CC-TGA patients survived.
This study underscores the feasibility of achieving an accurate prenatal diagnosis of TGA during early pregnancy. The utility of prenatal ultrasound in the development of personalized perinatal plans and the application of multidisciplinary treatment during delivery are conducive.
AIM:To investigate the clinical role of contrast-enhanced ultrasound(CEUS) combined with contrast-enhanced computed tomography(CE-CT) or magnetic resonance imaging to improve the preoperative staging ...of hepatocellular carcinoma(HCC) and guide surgical decisionmaking.METHODS:Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study.CEUS and CE-CT/MRI were performed before surgery.Intraoperative ultrasound(IOUS)wascarried out after liver mobilization.Lesions depicted by each imaging modality were counted and mapped.To investigate the impact of tumor size on the study,we divided the patients into two groups,the"Smaller group"(S-group,≤5 cm in diameter)and the"Largergroup"(L-group,>5 cm in diameter).The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CE-CT/MRI,CEUS,IOUS,CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared.Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.RESULTS:One hundred and twenty-seven nodules,comprising 94 HCCs confirmed by histopathology and33 benign lesions confirmed by histopathology and follow-up,were identified in 69 patients.The overall diagnostic sensitivity rates of CE-CT/MRI,CEUS,IOUS and CEUS+CE-CT/MRI were 78.7%,89.4%,89.4%and 89.4%,respectively.There was a significant difference between CEUS+CE-CT/MRI and CE-CT/MRI(P=0.046).Combining CEUS with CT or MRI increased,the diagnostic specificity compared with CT/MRI,CEUS and IOUS,and this difference was statistically significant(100%,72.7%,97.0%,and 69.7%,P=0.004,P=0.002,P=0.002,respectively).The diagnostic accuracy was significantly higher for CEUS+CT/MRI compared with CT/MRI(92.1%vs 77.2%,P=0.001).The TNM staging of tumors based on CEUS+CE-CT/MRI approximated to the final pathological TNM staging(P=0.977).There was a significant difference in the accuracy of TNM staging when comparing CEUS+CECT/MRI with CE-CT/MRI(P=0.002).Before surgery,strategies were changed in 15.9%(11/69)of patients as a result of CEUS.Finally,only 5.7%(4/69)of surgical strategies were changed because of IOUS findings.In the S-group,CEUS revealed 12 false positive lesions,including seven false positive lesions that were diagnosedby preoperative imaging examinations and five by IOUS.In contrast,in the L-group,IUOS revealed eight new malignant lesions;six of these lesions were true HCCs that were also identified by preoperative CEUS.CONCLUSION:CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC.CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.
PDF
