In this study, we constructed a series of recombinant Fc variants of immunoglobulin G4 (IgG4), screened the fragment crystallizable (Fc) variants with significantly prolonged serum half-lives, and analyzed the relationship between mutation site and half-life, aiming to provide a theoretical basis for the development of IgG4 antibodies and Fc fusion protein-based drugs. Nine gene sites were selected for mutation, and different mutation sites were combined. The variant expression plasmids pET24b-Fc were constructed by molecular cloning and point mutation. The plasmids were transformed into Escherichia coli BL21(DE3) for the expression of different recombinant proteins of Fc. Fc2 and Fc3 variants had slightly lower recombinant protein yields, and the expression of other variants was not affected. The toxicity of different Fc variants was determined by cell counting kit-8 (CCK-8) and calcein acetoxymethyl ester/ propidium iodide (calcein AM/PI) in vitro and enzyme-linked immuno sorbent assay (ELISA) in vivo. The results showed that the recombinant Fc variants had good biocompatibility and safety. Finally, the Fc variants were labeled with fluorescent markers, and the effects of different mutations on their serum half-lives were investigated by in vivo experiments. The Fc5 variant with prolonged serum half-life was successfully screened out, which provided a theoretical and practical basis for the optimal design of IgG4 subtype antibody and Fc fusion protein drugs.
Immunoglobulin G/blood* ; Immunoglobulin Fc Fragments/biosynthesis* ; Half-Life ; Animals ; Escherichia coli/metabolism* ; Humans ; Recombinant Fusion Proteins/biosynthesis* ; Recombinant Proteins/biosynthesis* ; Mice

With the widespread application of genomics and transcriptomics in the genetics and cell biology of different species, synonymous codon usage bias has been gradually accepted and used to study the deep connection between biological evolution and biological phenotypes. It is an important part of the life activities that mRNA is expressed into proteins with normal biological activities. The synonymous codon usage patterns, which were named as 'the second genetic codon', can express genetic information carried by themselves at the levels of transcriptional regulations, translational regulations and metabolic activities through molecular mechanisms such as fine-tune translation selection. Some studies have shown that the length of mRNA half-life has significant impacts on mRNA activity and the process of transcription and translation. This review summarized the roles of synonymous codon usage patterns in transcription, translational regulation and post-translational modification, with the aim to better understand how organisms skillfully utilize the genetic effects caused by codon usage patterns to accurately synthesize different types of proteins, so as to ensure the growth or differentiation of the specific gene expression procedures to carry out smoothly and maintain the normal life cycle.
Codon/genetics* ; Codon Usage ; Half-Life ; Protein Processing, Post-Translational ; RNA, Messenger/genetics*

Foam stability affects the efficacy and incidence of side effects of foam sclerotherapy. Exploring the relationship between foam pressure difference and foam stability can provide ideas and basis for obtaining more stable foam. In the experiment, sodium cod liver oleate foam was selected, and poloxamer 188 (concentration of 0%, 4%, 8%, 12%) was added to realize the change of foam pressure. By using the self-written program to process the foam pictures, the foam pressure difference and the relationship between the foam stability indicators (water separation rate curve, half-life) and the foam pressure difference were obtained. The results showed that at first the foam pressure increased with the increase of the concentration, and then it decreased with the increase of the concentration and reached a peak at the concentration of 4%. The foam pressure difference decreases continuously with the increase of decay time. When the additive concentration is low, the foam average pressure difference increases. And if the additive concentration is too high, the foam average pressure difference decreases. The smaller the foam pressure difference is, the better the foam stability is. This paper lays a foundation for the research on the stability of foam hardener.
Half-Life ; Humans ; Poloxamer ; Sclerosing Solutions/adverse effects* ; Sclerotherapy ; Varicose Veins

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the template for HBV replication. Currently, there is a lack of therapeutic drugs that directly target cccDNA. Therefore, blocking cccDNA supplements as fast as possible and reducing the existing cccDNA is the key to achieving a complete cure of chronic hepatitis B. Previous studies have suggested that cccDNA had a long half-life, but a recent study showed that it only took a few months to update cycle of cccDNA pool, and its number was much less than previously predicted. In the future, with the advent of new antiviral drugs that can completely inhibit HBV replication, it is expected that the cccDNA pool will be completely cleared due to its supplement complete blockade, so as to achieve virological cure of chronic hepatitis B.
Antiviral Agents/therapeutic use* ; DNA, Circular/genetics* ; DNA, Viral ; Half-Life ; Hepatitis B/drug therapy* ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Virus Replication

half-life and lower liposolubility. These are commonly found in plastics, medical equipment, detergents, and cosmetics. Recently, role of npEDCs on the changes of ovary and/or uterus development and alterations in hormonal signaling has been emphasized. However, many controversial results exist on the effects of npEDCs and reproductive health of women. Thus, we have focused to review the scientific evidence of a causal relationship between exposure to npEDCs and representative female reproductive issues such as menstrual cycle, endometriosis, uterine fibroids, polycystic ovarian syndrome and infertility/subfertility. Though not all studies indicated a positive correlation of npEDCs with female reproductive issues, the reviewed data illustrated that the majority of the available data strengthen the evidence of reproductive health-related actions of npEDCs. In future, recommendations should be made in order to reduce human exposure to npEDCs and to protect from steadily increasing reproductive health risks.]]>
Detergents ; Endocrine Disruptors ; Endometriosis ; Female ; Half-Life ; Humans ; Infertility ; Leiomyoma ; Menstrual Cycle ; Ovary ; Plastics ; Polycystic Ovary Syndrome ; Reproductive Health ; Uterus

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction, which causes most CF morbidity and mortality. This article reviews the pathophysiology of CF, recent animal models, and current treatment of CF.
Airway Obstruction ; Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator ; Cystic Fibrosis ; Epithelial Cells ; Epithelial Sodium Channels ; Half-Life ; Inflammation ; Intestines ; Lung Diseases ; Lung ; Membranes ; Models, Animal ; Mortality ; Pancreas

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Antiviral Agents ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Follow-Up Studies ; Half-Life ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoglobulins ; Korea ; Liver Transplantation ; Liver ; Organ Transplantation ; Polymerase Chain Reaction ; Recurrence ; Transplants

Suppressor of Variegation 3–9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G1 cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120–172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.
Amino Acids ; Apoptosis ; Carrier Proteins ; Cell Cycle ; Cell Death ; Cell Proliferation ; Embryonic Development ; Female ; Fluorescent Antibody Technique ; G1 Phase Cell Cycle Checkpoints ; Half-Life ; Heterochromatin ; Histones ; Humans ; Immunoprecipitation ; Lung Neoplasms ; Lysine ; Mass Screening ; Pregnancy ; Repression, Psychology ; RNA Interference ; Up-Regulation ; Yeasts

The effects of CYP1A enzyme on the pharmacokinetics of p-acetaminophen were studied in Bactrian camel. Twelve Bactrian camels were divided into 2 groups, then given a single dose of p-acetaminophen only or with the enzyme inhibitor lomefloxacin. Blood samples were collected after different intervals, and p-acetaminophen concentration was determined by high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by Phoenix WinNonLin v.7.0. The results show that lomefloxacin can significantly inhibit Bactrian camel CYP1A enzyme, as evidenced by the prolonged elimination half-life, increased maximum plasma concentration and area under the curve values and the shortened time to peak concentration for p-acetaminophenol in the substrate with inhibitor group. The results lay a foundation for revealing the particular characteristics of the CYP1A enzyme in Bactrian camels.
Camels ; Chromatography, Liquid ; Half-Life ; Pharmacokinetics ; Plasma

BACKGROUND: Physiological changes during pregnancy, such as dilutional anemia and a reduced half-life of red blood cells, have prevented the use of glycated Hb (HbA1c) as a biomarker for gestational diabetes mellitus (GDM). Nevertheless, increasing evidence supports the use of HbA1c in GDM diagnostic strategies.We studied HbA1c as a biomarker of GDM and its possible use as a screening test to avoid the use of the glucose challenge test (GCT). METHODS: This case-control study involved 607 pregnant women between the 24th and 28th week of gestation. HbA1c level was determined, and GDM was diagnosed according to the National Diabetes Data Group criteria. The area under the ROC curve (AUC) was determined; two low and two high cut-off points were established to rule out GDM and classify high-risk pregnant women, respectively. For each cut-off, sensitivity (S), specificity (SP), and total number and percentage of GCTs avoided were determined. RESULTS: The AUC for HbA1c diagnostic performance was 0.68 (95% confidence interval 0.57–0.79). Using 4.6% HbA1c (27 mmol/mol) as the lower cut-off (S=100%), 14% of participants could avoid the GCT. Using 5.5% HbA1c (36 mmol/mol) as the upper cut-off (SP =94.5%), 6% of participants would be considered at high risk. CONCLUSIONS: HbA1c can be used as a screening test prior to the GCT, thereby reducing the need for the GCT among pregnant women at a low risk of GDM.
Anemia ; Area Under Curve ; Case-Control Studies ; Diabetes, Gestational ; Erythrocytes ; Female ; Glucose ; Half-Life ; Hemoglobin A, Glycosylated ; Humans ; Mass Screening ; Pregnancy ; Pregnant Women ; ROC Curve ; Sensitivity and Specificity