Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Background: The preventative effect of melatonin on the development of obesity and the progression of fatty liver under a high-fat diet (HFD) has been well elucidated through previous studies. We investigated the mechanism behind this effect regarding cholesterol biosynthesis and regulation of cholesterol levels. Methods: Mice were divided into three groups: normal chow diet (NCD); HFD; and HFD and melatonin administration group (HFD+M). We assessed the serum lipid profile, mRNA expression levels of proteins involved in cholesterol synthesis and reabsorption in the liver and nutrient transporters in the intestines, and cytokine levels. Additionally, an in vitro experiment using HepG2 cells was performed. Results: Expression of hepatic sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) demonstrated that melatonin administration significantly reduces hepatic cholesterol synthesis in mice fed an HFD. Expression of intestinal sodium-glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), GLUT5, and Niemann-pick C1-like 1 (NPC1L1) demonstrated that melatonin administration significantly reduces intestinal carbohydrate and lipid absorption in mice fed an HFD. There were no differences in local and circulatory inflammatory cytokine levels among the NCD, HFD, and HFD+M group. HepG2 cells stimulated with palmitate showed reduced levels of SREBP, LDLR, and HMGCR indicating these results are due to the direct mechanistic effect of melatonin on hepatocytes. Conclusion Collectively, these data indicate the mechanism behind the protective effects of melatonin from weight gain and liver steatosis under HFD is through a reduction in intestinal caloric absorption and hepatic cholesterol synthesis highlighting its potential in the treatment of obesity and fatty liver disease.

Background and Objectives: The newly introduced upright head roll test (UHRT), which exploits head rotations in the roll plane with the patient in the upright sitting position, is a diagnostic maneuver for horizontal canal-benign paroxysmal positional vertigo (HC-BPPV). This study is designed to determine whether UHRT, compared to supine head roll test (SHRT), can more accurately diagnose HC-BPPV and determine the subtype of HC-BPPV.Subjects and Method A total of 455 video nystagmus tests performed between April 2019 to June 2021 were retrospectively reviewed, and 63 patients with direction-changing positional nystagmus at UHRT or SHRT were enrolled in this study. UHRT result was classified as negative (if no nystagmus was observed), positive incomplete (if nystagmus was detected in one side), and positive complete (if nystagmus was evoked in both side). The frequency of nystagmus is also included in our assessment. In addition, the results of 4 patients with bow and lean test (BLT) records on videonystagmography were also analysed. Results: The concordance rate between UHRT and SHRT was 97.8%, and the positive concordance rate was 91.38%. UHRT and SHRT provided identical subtype diagnosis in 98.1% (52 of 53 cases). In one case, UHRT and SHRT showed opposite results. Evaluating the affected side with bow and lean records, the SHRT, UHRT and BLT showed consistent results. The mean frequency of nystagmus was faster in SHRT than in UHRT. Conclusion UHRT showed equivalent results to SHRT in distinguishing subtype of HC-BPPV. UHRT is a useful method in diagnosing HC-BPPV simply in a sitting position.

No abstract available.
Capecitabine ; Constriction, Pathologic ; Nasolacrimal Duct

The microbial community is known to have a key role during the rearing period of broilers. In this study, gut microbial composition and diversity were examined to evaluate the relationships between these factors and broiler growth performance. By applying 454-pyrosequencing of the V1–V3 regions of bacterial 16S rRNA genes, six fecal samples from four- and 28-day-old chickens from three broiler farms and 24 intestinal samples of broilers with heavy and light body weights were analyzed. Microbial composition assessment revealed Firmicutes to be the most prevalent phylum at farm A, while Proteobacteria were predominant at farms B and C. Fecal microbial richness and diversity indices gradually increased from four to 28 days at all three farms. Microbial diversity assessment revealed that small intestine microbial diversity was lower in heavy birds than in light birds. In light birds, the Firmicutes proportion was lower than that in heavy birds. In conclusion, each broiler farm revealed a specific microbial profile which varied with the age of the birds. The microbial communities appeared to affect growth performance; therefore, gut microbial profiles can be utilized to monitor growth performance at broiler farms.
Agriculture ; Birds ; Body Weight ; Chickens ; Firmicutes ; Genes, rRNA ; Intestine, Small ; Proteobacteria

BACKGROUND: Pregnancy considerably alters cardiovascular dynamics, and thereby affects the transition of blood pressure after delivery in women. We aimed to analyze the association between parity and blood pressure in Korean adult women. METHODS: We included 8,890 women who participated in Korean National Health and Nutrition Examination Survey between 2010 and 2012. We divided the population according to the menopause status and analyzed the association between parity and blood pressure by using multiple regression analysis, and on hypertension, by using logistic regression analysis. RESULTS: Systolic and diastolic blood pressures were significantly associated with parity in premenopausal women (beta=-0.091 [P<0.001] and beta=-0.069 [P<0.001], respectively). In the analysis that excluded women receiving antihypertensive medication, the systolic and diastolic blood pressure of postmenopausal women were significantly associated with parity (beta=-0.059 [P=0.022] and beta=-0.054 [P=0.044], respectively). Parity was found to prevent hypertension after adjustment for confounders in postmenopausal women (odds ratio, 0.55; 95% confidence interval, 0.310-0.985). CONCLUSION: We found that parity prevented hypertension in Korean women.
Adult ; Blood Pressure* ; Female ; Humans ; Hypertension ; Logistic Models ; Menopause ; Nutrition Surveys* ; Parity* ; Pregnancy