A Case of Disseminated and Fulminant Plasmacytomas That Developed during Bortezomib Treatment

Multiple myeloma is an incurable and slow growing plasma cell neoplasm. The introduction of new drugs has increased the number of treatment options. Bortezomib, the first-in-class proteasome inhibitor, has been shown to have a significant antitumor activity in the treatment of relapse/refractory patients with multiple myeloma. Additionally, plasmacytomas have shown significant response to bortezomib. In this case report, we describe a patient who developed disseminated and fulminant extramedullary plasmacytomas during combination chemotherapy treatment with bortezomib within a short period, after having shown clinical improvement

Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

Whole-genome sequencing and analysis of Streptomyces strains producing multiple antinematode drugs

Background : Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain. Results : The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC–MS) analysis. Conclusions : Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers.This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through“Crop Viruses and Pests Response Industry Technology Development” Program (No.321110–4) funded by Ministry of Agriculture, Food and Rural Afairs (MAFRA), National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No.2022R1A2C3004621) and the Ministry of Education (2022R1I1A1A01068507), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2020M3H1A1073304)

Rate of Isolation and Trends of Antimicrobial Resistance of Multidrug Resistant Pseudomonas Aeruginosa from Otorrhea in Chronic Suppurative Otitis Media

ObjectivesTo assess the rate of isolation of Pseudomonas aeruginosa (PA) and multidrug-resistant PA (MDR-PA) from patients with chronic suppurative otitis media (CSOM) otorrhea and the annual trend of antibiotic-resistance.MethodsOtorrhea samples were collected aseptically from 1,598 CSOM patients. The rate of bacterial isolation and the results of antibiotic susceptibility testing were evaluated retrospectively.ResultsThe PA isolation rate from CSOM otorrhea was 24.4%. Of the 398 isolated strains tested for their susceptibilities to 10 antibiotics, 395 strains showed definitive results. Of these, 183 (46.3%) were susceptible to whole antibiotics and 212 (53.7%) was resistant to more than 1 antibiotics, with the frequency of antibiotics-resistance increasing significantly over time. Although strains susceptible to all antibiotics decreased over time, the rate of isolation of MDR-PA did not change significantly. Resistance to aminoglycosides and quinolones was higher than to other antibiotics and significantly increased over time, whereas resistance to other antibiotics showed no trend.ConclusionMDR-PA, assessed using five individual antibiotics and six antibiotic-classes, showed no tendency to increase or decrease over time. This may have been due to increased concern about antibiotic-resistant bacterial strains, leading to improved infection control within hospitals and healthcare centers

Bi-weekly Chemotherapy of Paclitaxel and Cisplatin in Patients with Metastatic or Recurrent Esophageal Cancer

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m2) followed by cisplatin (50 mg/m2). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer

Nuclear Factor I-C Regulates Stemness Genes and Proliferation of Stem Cells in Various Mineralized Tissue through Epithelial-Mesenchymal Interactions in Dental Epithelial Stem Cells

© 2022 Dong-Seol Lee et al.Tooth development includes numerous cell divisions and cell-cell interactions generating the stem cell niche. After an indefinite number of divisions, pluripotent cells differentiate into various types of cells. Nuclear factor I (NFI) transcription factors are known as crucial regulators in various organ development and stem cell biology. Among its members, nuclear factor I-C (NFI-C) has been reported to play an essential role in odontogenesis. Nfic knockout mice show malformation in all mineralized tissues, but it remains unclear which stage of development Nfic is involved in. We previously reported that Nfic induces the differentiation of ameloblast, odontoblast, and osteoblast. However, the question remains whether Nfic participates in the late stage of development, perpetuating the proliferation of stem cells. This study aimed to elucidate the underlying mechanism of NFI-C function in stem cells capable of forming hard tissues. Here, we demonstrate that Nfic regulates Sox2 and cell proliferation in diverse mineralized tissue stem cells such as dental epithelial stem cells (DESCs), dental pulp stem cells, and bone marrow stem cells, but not in fibroblasts. It was also involved in the expression of pluripotency genes Lin28 and NANOG. Especially in DESCs, Nfic regulates the proliferation of epithelial cells via epithelial-mesenchymal interactions, which are the Fgf8-Nfic-Sox2 pathway in epithelium and Nfic-Fgf10 in the mesenchyme. Moreover, Nfic slightly increased reprogramming efficiency in induced pluripotent stem cells of mineralized tissues, but not in soft tissues. In conclusion, these results suggest that Nfic is a crucial factor for maintaining the stem cell niche of mineralized tissues and provides a possibility for Nfic as an additional factor in improving reprogramming efficiency.N

Supplementing in the diet of lactating Holstein cows may naturally produce coenzyme Q10-enriched milk

Objective To examine the effects of Rhodobacter sphaeroides (R. sphaeroides) supplementation as a direct-fed microbial (DFM) on rumen fermentation in dairy cows and on coenzyme Q10 (CoQ10) transition into milk, an in vitro rumen simulation batch culture and an in vivo dairy cow experiment were conducted. Methods The characteristics of in vitro ruminal fermentation were investigated using rumen fluids from six cannulated Holstein dairy cows at 2 h post-afternoon feeding. A control treatment was included in the experiments based on a typified total mixed ration (TMR) for lactating dairy cows, which was identical to the one used in the in vivo study, plus R. sphaeroides at 0.1%, 0.3%, and 0.5% TMR dry matter. The in vivo study employed six ruminally cannulated lactating Holstein cows randomly allotted to either the control TMR (C-TMR) treatment or to a diet supplemented with a 0.5% R. sphaeroides culture (S-TMR, dry matter basis) ad libitum. The presence of R. sphaeroides was verified using denaturing gradient gel electrophoresis (DGGE) applied to the bacterial samples obtained from the in vivo study. The concentration of CoQ10 in milk and in the supernatant from the in vitro study was determined using high performance liquid chromatography. Results The results of the in vitro batch culture and DGGE showed that the concentration of CoQ10 significantly increased after 2 h of R. sphaeroides supplementation above 0.1%. When supplemented to the diet of lactating cows at the level of 0.5%, R. sphaeroides did not present any adverse effect on dry matter intake and milk yield. However, the concentration of CoQ10 in milk dramatically increased, with treated cows producing 70.9% more CoQ10 than control cows. Conclusion The CoQ10 concentration in milk increased via the use of a novel DFM, and R. sphaeroides might be used for producing value-added milk and dairy products in the future