Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor.

TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of , a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign.

Comparison of bacterial community profiles from large intestine specimens, rectal swabs, and stool samples.

The human gastrointestinal tract contains a complex and dynamic population of microorganisms, known as the gut microbiota. Although interest in the role of the gut microbiota in human health has increased in recent years, there remains no standard sampling protocol for analyzing these organisms. Here, we aimed to characterize the microbial composition of distinct segments of the large intestine and to determine whether rectal swabs are suitable for identifying colon microbiota.

Unique binding mode of Evogliptin with human dipeptidyl peptidase IV.

Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin.

Ankle Fusion Combined With Calcaneal Sliding Osteotomy for Severe Arthritic Ball and Socket Ankle Deformity.

Background: Although a ball and socket ankle deformity is usually congenital and asymptomatic, abnormal inversion and eversion mobility can result in recurrent ankle sprain and osteoarthritis. This retrospective study was performed to evaluate the clinical and radiologic outcomes of ankle fusion combined with calcaneal sliding osteotomy for severe arthritic ball and socket ankle deformity.

Methods: Fourteen patients with severe arthritic ball and socket ankle deformity were followed for more than 3 years after operation.

Negatively-charged amino acids at the peptide-binding pocket of HLA-DPB1 alleles are associated with susceptibility to anti-topoisomerase I-positive systemic sclerosis.

We investigated shared characteristics of amino acid sequences in the at risk HLA-DPB1 alleles in systemic sclerosis (SSc). Amino acid sequences and their structural features of HLA-DP molecules in 127 Korean SSc patients and 548 healthy Korean controls were analyzed with a focus on known HLA-DP binding motifs. The binding grooves containing more negatively-charged triplets (NCT) had higher odds ratios of anti-topoisomerase I antibody (ATA)-positive SSc.

Comparison of a novel bedside portable endoscopy device with nasogastric aspiration for identifying upper gastrointestinal bleeding.

Aim: To compare outcomes using the novel portable endoscopy with that of nasogastric (NG) aspiration in patients with gastrointestinal bleeding.

Methods: Patients who underwent NG aspiration for the evaluation of upper gastrointestinal (UGI) bleeding were eligible for the study. After NG aspiration, we performed the portable endoscopy to identify bleeding evidence in the UGI tract.

Gastrostomy in a patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare condition in which there is complete right to left reversal of the abdominal and thoracic organs. SIT generally does not bear any pathophysiological significance, and the survival rate of patients with SIT does not differ from that of healthy individuals. However, patients with SIT require a thorough radiological examination to identify the presence of associated anatomic variations before undergoing invasive procedures such as surgery or hemostasis of gastrointestinal hemorrhage because they may have accompanying abnormalities in anatomical structures along with reversed organs.

Naturally occurring hepatitis B virus X deletions and insertions among Korean chronic patients.

Deletions and insertions in the hepatitis B virus (HBV) X region have been associated with severe forms of liver disease, including hepatocellular carcinoma (HCC). However, the molecular epidemiologic features of this virus have been described rarely. Deletions and insertions in the X region were determined by direct sequencing in a Korean cohort of 267 patients with different clinical statuses.

First case of disseminated Mycobacterium bolletii infection in a young adult patient.

Mycobacterium bolletii is a rapidly growing nontuberculous mycobacterium first characterized in 2006. Here, we report a case of disseminated infection caused by M. bolletii in a young adult patient.

Mycobacterium paraseoulense sp. nov., a slowly growing, scotochromogenic species related genetically to Mycobacterium seoulense.

A previously unidentified, slowly growing, scotochromogenic Mycobacterium species, represented by strain 31118(T), was discovered during hsp65 sequence-based reidentification of Korean clinical isolates that had been previously identified as Mycobacterium scrofulaceum by conventional biochemical tests. Although the 16S rRNA gene sequence of strain 31118(T) was identical to that of the recently described Mycobacterium seoulense, phylogenetic analyses based on three independent alternative targets (rpoB, hsp65 and the 16S-23S internal transcribed spacer) showed that it was closely related to M. seoulense but was a distinct phylogenetic entity.

Crystallization and preliminary X-ray crystallographic analysis of human RGS10 complexed with Galphai3.

G-protein-coupled receptors, which are major targets for drug discovery, play a major role in diverse physiological processes by relating changes in the extracellular environment to intracellular functions via activation of heterotrimeric G-proteins. However, G-protein activity is also modulated by a family of proteins called regulators of G-protein signalling (RGS), which are classified into six subfamilies. RGS10 belongs to the subgroup D/R12 and is known to act specifically on activated forms of three Galpha proteins (Galphai3, Galphaz and Galphao but not Galphas).