TPMD: a database and resources of microsatellite marker genotyped in Taiwanese populations

Taiwan Polymorphic Marker Database (TPMD) (http://tpmd.nhri.org.tw/) is a marker database designed to provide experimental details and useful marker information allelotyped in Taiwanese populations accompanied by resources and technical supports. The current version deposited more than 372 000 allelotyping data from 1425 frequently used and fluorescent-labeled microsatellite markers with variation types of dinucleotide, trinucleotide and tetranucleotide. TPMD contains text and map displays with searchable and retrievable options for marker names, chromosomal location in various human genome maps and marker heterozygosity in populations of Taiwanese, Japanese and Caucasian. The integration of marker information in map display is useful for the selection of high heterozygosity and commonly used microsatellite markers to refine mapping of diseases locus followed by identification of disease gene by positional candidate cloning. In addition, our results indicated that the number of markers with heterozygosity over 0.7 in Asian populations is lower than that in Caucasian. To increase accuracy and facilitate genetic studies using microsatellite markers, we also list markers with genotyping difficulty due to ambiguity of allele calling and recommend an optimal set of microsatellite markers for genotyping in Taiwanese, and possible extension of genotyping in other Mongoloid populations

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS

Dioscorea Phytocompounds Enhance Murine Splenocyte Proliferation Ex Vivo and Improve Regeneration of Bone Marrow Cells In Vivo

Specific cytokines have been tested clinically for immunotherapy of cancers; however, cytotoxicity has often impaired their usefulness. Consequently, alternative approaches are increasingly desirable. Dioscorea spp. tuber is a widely used traditional Chinese medicinal herb claimed to confer immunostimulatory activity. In this study, we evaluated Dioscorea as an adjuvant therapy for use alongside chemotherapy for cancer. Phytocompounds from Dioscorea tubers were ethanol fractioned and used for ex vivo splenocyte proliferation assay or in vivo force-feeding of mice pre-treated with the chemotherapy agent 5-fluorouracil. Co-treatment with a 50–75% ethanol-partitioned fraction of the tuber extract of D. batatas (DsCE-II) and interleukin (IL)-2 resulted in a significantly higher rate of murine splenocyte cell proliferation ex vivo than treatment with DsCE-II or IL-2 alone. This DsCE-II fraction, which contains a polysaccharide with a high proportion of β-1,4-linkage mannose (≥64%), also promoted the regeneration of specific progenitor cell populations in damaged bone marrow tissues of 5-fluorouracil-treated mice. Colony-forming unit (CFU) analyses demonstrated that the population of CFU-GM cells, but not CFU-GEMM or BFU-E cells, preferentially recovered to ~67% in the bone marrow of immune-suppressed mice fed with DsCE-II. DsCE-II efficacy level was ~85% of that obtained by subcutaneous administration of recombinant G-CSF proteins (5 μg kg−1) in mice tested in parallel. This study suggests that the DsCE-II fraction of D. batatas extract may be considered for further development as a dietary supplement for use alongside chemotherapy during cancer treatment

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension

Enhancement of TKI Sensitivity in Lung Adenocarcinoma through m6A-dependent Translational Repression of Wnt Signaling by circ-FBXW7

BACKGROUND: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. METHODS: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing TKI resistance may involve targeting the renewal and repopulation of stem-like cells. To investigate the underlying mechanisms, we conducted RNA Microarray and m6A Epi-Transcriptomic Microarray analyses, followed by assessment of transcription factors. Additionally, we specifically designed a tag to detect the polypeptide circRNA-AA, and its expression was confirmed through m6A regulations. RESULTS: We initially identified unique molecular signatures present in cancer stem cells that contributed to poor therapeutic responses. Activation of the alternative Wnt pathway was found to sustain the renewal and resistant status of these cells. Through bioinformatics analysis and array studies, we observed a significant decrease in the expression of circFBXW7 in Osimertinib-resistant cell lines. Notably, the abnormal expression pattern of circFBXW7 determined the cellular response to Osimertinib. Functional investigations revealed that circFBXW7 inhibits the renewal of cancer stem cells and resensitizes both resistant LUAD cells and stem cells to Osimertinib. In terms of the underlying mechanism, we discovered that circFBXW7 can be translated into short polypeptides known as circFBXW7-185AA. These polypeptides interact with β-catenin in an m6A-dependent manner. This interaction leads to reduced stability of β-catenin by inducing subsequent ubiquitination, thereby suppressing the activation of canonical Wnt signaling. Additionally, we predicted that the m6A reader, YTHDF3, shares common binding sites with hsa-Let-7d-5p. Enforced expression of Let-7d post-transcriptionally decreases the levels of YTHDF3. The repression of Let-7d by Wnt signaling releases the stimulation of m6A modification by YTHDF3, promoting the translation of circFBXW7-185AA. This creates a positive feedback loop contributing to the cascade of cancer initiation and promotion. CONCLUSIONS: Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on β-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments

Genetic and Mechanistic Evaluation for the Mixed-Field Agglutination in B3 Blood Type with IVS3+5G>A ABO Gene Mutation

Background: The ABO blood type B3 is the most common B subtype in the Chinese population with a frequency of 1/900. Although IVS3+5G.A (rs55852701) mutation of B gene has been shown to associate with the development of B3 blood type, genetic and mechanistic evaluation for the unique mixed-field agglutination phenotype has not yet been completely addressed. Methodology/Principal Findings: In this study, we analyzed 16 cases of confirmed B3 individuals and found that IVS3+5G.A attributes to all cases of B3. RT-PCR analyses revealed the presence of at least 7 types of aberrant B3 splicing transcripts with most of the transcripts causing early termination and producing non-functional protein during translation. The splicing transcript without exon 3 that was predicted to generate functional B3 glycosyltransferase lacking 19 amino acids at the N-terminal segment constituted only 0.9 % of the splicing transcripts. Expression of the B3 cDNA with exon 3 deletion in the K562 erythroleukemia cells revealed that the B3 glycosyltransferase had only 40 % of B1 activity in converting H antigen to B antigen. Notably, the typical mixed-field agglutination of B3-RBCs can be mimicked by adding anti-B antibody to the K562-B3 cells. Conclusions/Significance: This study thereby demonstrates that both aberrant splicing of B transcripts and the reduced B3 glycosyltransferase activity contribute to weak B expression and the mixed-field agglutination of B3, adding to th