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Study design:This is a case report of a patient with hypertrophy of the posterior longitudinal ligament (HPLL) in the thoracic spine. This patient was followed for 10 years after surgery.Objectives:The purpose of this study was to report the long-term outcome of HPLL in the thoracic spine.Setting:Department of orthopedic surgery, Hiroshima Red Cross and Atomic-bomb Survivors Hospital, Hiroshima, Japan.Methods:A 58-year-old-woman with thoracic HPLL was reported. Magnetic resonance image (MRI) and computed tomography (CT) showed the expanded spinal cord compression from Th4 to Th12 due to HPLL. Anterior decompression and fusion (Th10–12) was performed. Histological findings of the surgical specimens showed thickening of the posterior longitudinal ligament with proliferation of chondroid tissue. The clinical outcome and the radiological findings (CT and MRI) were evaluated 10 years after surgery.Results:The patient was asymptomatic postoperatively. However, the subsequent CT examination revealed ossification of the previously hypertrophied posterior longitudinal ligament.Conclusions:HPLL in the thoracic spine is a rare pathological condition causing myelopathy. The results of this study support the hypothesis that HPLL is one of the prodromal conditions of HPLL.Spinal Cord (2006) 44, 200–202. doi:10.1038/sj.sc.3101812; published online 2 August 2005 [ABSTRACT FROM AUTHOR]

Background: Chemotherapy including cisplatin is recommended for the treatment of advanced bladder cancer, but its effectiveness is limited due to the acquisition of drug resistance. Although several mechanisms of cisplatin resistance have been reported, there are still many unknowns, and treatment of cisplatin-resistant bladder cancer remains difficult. Accordingly, in this study, we aimed to identify and characterize microRNAs involved in cisplatin resistance., Methods: Small RNA sequencing analysis was performed to search for microRNAs related to cisplatin resistance. The identified microRNAs were then characterized using gain-of-function studies, sensitivity analysis, target gene analysis, and cellular assays., Results: We identified miR-424-5p as a candidate microRNA that was downregulated in cisplatin-resistant strains compared with parental strains. Notably, in gain-of-function studies, miR-424-5p suppressed the proliferative ability of cisplatin-resistant bladder cancer (CDDP-R BC). Furthermore, miR-424-5p restored sensitivity to cisplatin. RNA sequence analysis revealed seven candidate genes targeted by this microRNA. Among them, cyclin E1 (CCNE1) was chosen for subsequent analyses because its expression was upregulated in cisplatin-resistant cells compared with parental cells and because recent studies have shown that CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. Therefore, we performed functional analysis using the PKMYT1 inhibitor RP-6306 and demonstrated that RP-6306 inhibited cell growth through suppression of mitotic entry and restored cisplatin sensitivity in CDDP-R BC., Conclusions: Overall, our findings provided insights into the development of novel therapeutic strategies for CDDP-R BC., (© 2024. The Author(s).)

Gemcitabine plus cisplatin (GC) combination chemotherapy is the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, most cases develop resistance to this therapy. We investigated whether drug resistance could be targeted through metabolic reprogramming therapies. Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells. Isocitrate dehydrogenase 2 (IDH2) gain of function stabilized hypoxia-inducible factor1α (HIF1α) expression, stimulating aerobic glycolysis. In gemcitabine-resistant cells, elevated fumaric acid suppressed prolyl hydroxylase domain-containing protein 2/Egl nine homolog 1 (PHD2) and stabilized HIF1α expression. PHGDH downregulation or inhibition in gemcitabine-resistant BC cells inhibited their proliferation, migration, and invasion. Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1α expression. Combination treatment with NCT503 and erdafitinib synergistically suppressed tumor cell proliferation and induced apoptosis in vitro and in vivo. Understanding these mechanisms could enable innovative BC therapeutic strategies to be developed., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the digestive tract. Its growth is primarily influenced by mutations in KIT or PDGFRA. Surgery is the primary treatment option for GIST; however, KIT inhibitors, such as imatinib, are used for inoperable cases. Resistance to imatinib is an upcoming challenge, especially because the effectiveness of alternative drugs is limited. Enhancement of the glycolysis pathway in cancer cells has been identified as a key feature in cancer. This unique metabolic activity has implications on tumor growth, prognosis, and resistance to therapy, even in GIST. Members of the glucose transporter (GLUT) family (particularly GLUT-1) play a significant role in GIST progression and response to treatment. Diagnostic imaging using 18F-fluorodeoxyglucose positron emission tomography/computed tomography, which enables visualization of glucose metabolism, can aid in GIST diagnosis and risk assessment. The interplay between glycolysis and GIST can lead to the development of various therapeutic strategies, especially those involving glycolysis-related molecules, such as hexokinase and lactate dehydrogenase. However, further research is required to understand the full spectrum of glycolysis in GIST and its therapeutic potential. Herein, we present an exhaustive overview and analysis of the role of glycolysis in GIST, especially as a therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is not an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for Neoplasia and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: none, (Copyright © 2024. Published by Elsevier Inc.)

Strain Lactiplantibacillus plantarum D1 with bacteriocin producing ability was found in the intestine of Gambusia affinis. The bacteriocin was found to have high inhibitory activity against multiple Streptococcus species and several other Gram-positive and Gram-negative bacteria. Bacteriocin was purified from culture supernatant by ion-exchange chromatography, Sep-Pak C 18 cartridge, and reverse-phase high-performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectral analysis determined that purified bacteriocin has a molecular mass of 2,731 Da. A partial N-terminal sequence KRKKHKXQIYNNGM was obtained from the Edman analysis. The N-terminal sequence was employed to search against a translation of the draft genome of strain D1. The translated full amino acid sequence of the mature peptide is as follows: NH 2 - KRKKHKCQIYNNGMPTGQYRWC, which has a molecular weight of 2738 Da. A BLAST search revealed that this bacteriocin was most similar to bactofencin A but differed from it with three amino acid residues. No identical peptide or protein has been previously reported, and this peptide, termed bactofencin YH, was therefore considered to be a new bacteriocin produced by Lactiplantibacillus plantarum D1., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 ( BCYRN1 ) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G 2 /M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC ( n = 31) was significantly higher than that in healthy donors ( n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased ( n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

Background: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods., Methods: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19., Results: Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081-2.441)., Conclusion: These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs., (© 2024. The Author(s).)

Metazoans use silicon traces but rarely develop extensive silica skeletons, except for the early-diverging lineage of sponges. The mechanisms underlying metazoan silicification remain incompletely understood, despite significant biotechnological and evolutionary implications. Here, the characterization of two proteins identified from hexactinellid sponge silica, hexaxilin and perisilin, supports that the three classes of siliceous sponges (Hexactinellida, Demospongiae, and Homoscleromorpha) use independent protein machineries to build their skeletons, which become non-homologous structures. Hexaxilin forms the axial filament to intracellularly pattern the main symmetry of the skeletal parts, while perisilin appears to operate in their thickening, guiding extracellular deposition of peripheral silica, as does glassin, a previously characterized hexactinellid silicifying protein. Distant hexaxilin homologs occur in some bilaterians with siliceous parts, suggesting putative conserved silicifying activity along metazoan evolution. The findings also support that ancestral Porifera were non-skeletonized, acquiring silica skeletons only after diverging into major classes, what reconciles molecular-clock dating and the fossil record., (© 2024. The Author(s).)

Replenishing tumor-suppressor miRNAs (TS-miRNAs) is a potential next-generation nucleic acid-based therapeutic approach. Establishing an effective miRNA delivery system is essential to successful TS-miRNA therapy. To overcome vulnerability to RNA nucleases, we previously developed a chemically modified miRNA143-3p (CM-miR-143). In clinical practice, colorectal cancer (CRC) pelvic recurrence is an occasional challenge following curative resection, requiring a novel therapy because reoperative surgery poses a significant burden to the patient. Hence, we considered the use of CM-miR-143 as an alternative treatment. In this study, we used a mouse model bearing pelvic CRC adjacent to the rectum and investigated the anticancer effects of CM-miR-143 lipoplexes formulated from miRNA and a cationic liposome. Compared with commercial synthetic miR-143, CM-miR-143 lipoplexes accumulated heavily in regions of the pelvic CRC tumor where the blood flow was high. As a result, systemic administration of CM-miR-143 lipoplexes improved animal survival by significantly suppressing pelvic CRC tumors and relieving a lethal bowel obstruction caused by rectal compression. Detailed protein analysis revealed that the myristoylated alanine-rich C kinase is a novel target for CM-miR-143 lipoplexes. Our results suggest that CM-miR-143 is a potential next-generation drug candidate in the treatment of CRC pelvic recurrence., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which may affect prognosis after KT. At our institution, all patients' glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT. We analyzed the insulinogenic index (ISI) and homeostasis model assessment beta cell (HOMA-β) based on the immunoreactive insulin (IRI) levels to determine how glucose tolerance changed after KT in 214 patients who had not been diagnosed with DM before KT. In addition, we analyzed the body mass index (BMI) which may also influence glucose tolerance after KT. The concentration of tacrolimus (TAC) in blood was also measured as the area under the curve (AUC) to examine its effects at each sampling point. The preoperative-OGTTs showed that DM was newly diagnosed in 22 of 214 patients (10.3%) who had not been given a diagnosis of DM by the pre-KT fasting blood sugar (FBS) tests. The glucose tolerance was improved in 15 of 22 DM patients at 12 mo. after KT. ISI and IRI deteriorated only at 3 mo. after KT but improved over time. There was a trend of an inverse correlation between HOMA-β and TAC-AUC. We also found inverse correlations between IRI and an increase in BMI from 3 to 12 mo. after KT. Early corticosteroid withdrawal or the steroid minimization protocol with tacrolimus to maintain a low level of diabetogenic tacrolimus and BMI decrease after KT used by our hospital individualizes lifestyle interventions for each patient might contribute to an improvement in post-KT glucose tolerance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mitsuke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib-resistant RCC (SUR-Caki1, SUR-ACHN, and SUR-A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR-RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high-expression group was significantly lower than that of the RCC low-expression group. Thus, we investigated the involvement of SCG2 in sunitinib-resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia-inducible factor 1α (HIF1α). Expression levels of VEGF-A and VEGF-C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib-resistant RCC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Vitamin B 12 is an essential vitamin that is absent in plant-derived foods such as fruits and vegetables. This can result in an increased risk of developing vitamin B 12 deficiency in strict vegetarians (vegans). There are several studies that have aimed to enhance nutrients in food crops. The purpose of the present study was to fortify tomato fruits with vitamin B 12 (or cyanocobalamin)., Results: Tomato plants were grown for 70 days in hydroponic culture pots and treated with 5 μm of cyanocobalamin on days 1-24 after the fruiting, and then harvested for tomato fruits. The ripened tomato fruits contained 4.0 × 10 -7  g of cyanocobalamin per 100 g of dry weight and showed a significant increase in glucose and lycopene levels., Conclusion: The present study highlights the use of a cyanocobalamin-supplementation system for the production of B 12 fortified tomato fruits that can help prevent B 12 deficiency in vegetarians. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Acetylcholinesterase (AChE) from Pseudomonas aeruginosa PAO1 has a catalytic Ser residue in its active site. In this study, we examined the aminolysis and alcoholysis reactions of AChE that occurred alongside its hydrolysis reaction. The recombinant AChE recognized ethyl acetate as a substrate. Therefore, we evaluated acetylation of the amine and hydroxyl group by AChE, using acetylcholine and ethyl acetate as the acetyl donor. AChE recognized diaminoalkanes with 4- to 12-carbon chains and aminoalcohols with 4- to 8-carbon chains as acetyl acceptors, resulting in their acetylated products. In the acetylation of 1,6-diaminohexane, AChE preferentially used ethyl acetate as the acetyl donor above pH 8.0 and the efficiency increased with increasing pH. In contrast, the acetylation of 6-amino-1-hexanol was efficient with acetylcholine as the acetyl donor in the pH range of 4-10. In addition, acetylated 6-amino-1-hexanol was decomposed by AChE. The kinetic study indicated that the acetyl donor and acceptor are competitively recognized by AChE as substrates., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Glassin is a water-soluble protein from the siliceous skeleton of a marine sponge that adsorbs tightly to silica at pH 7.0-9.0 and accelerates silica particle formation from silicic acid. Glassin comprises three distinct domains: a His and Asp-rich (HD) domain, a Pro-rich (P) domain, and a His and Thr-rich (HT) domain. Here, we investigated the roles of these three domains in silica adsorption by using glutathione S-transferase (GST) fused with glassin or with each domain. GST fused with the HD domain exhibited tight adsorption, equivalent to that of GST fused with the full-length glassin sequence at values above 7.0. The apparent K d values for the binding of full-length glassin and HD to fumed silica at pH 7.0 were 20.8 and 22.7 nM, respectively, indicating that this domain greatly contributes to the silica adsorption ability of glassin. In addition, no internal cleavage was observed in the HD domain, whereas GST fused with the full-length glassin sequence exhibited internal cleavage. The HD domain adsorbed on silica did not dissociate even at pH 6.0. Given these findings, we concluded that the HD domain has potential as a tag for the immobilization of soluble proteins., (Copyright © 2022 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Exosomes are 40-100 nm nano-sized extracellular vesicles and are receiving increasing attention as novel structures that participate in intracellular communication. We previously found that miRNA-1 (miR-1) functions as a tumor suppressor in renal cell carcinoma (RCC). In this study, we investigated the function of exosomal miR-1 and the possibility that the exosome constitutes a tumor maker in RCC. First, we established the method to collect exosomes from cell lysates and human serum by a spin column-based method. Next, we assessed exosomes using Nanosight nanoparticle tracking analysis and Western blot analysis with exosome marker CD63. We confirmed that exosomes labeled with PKH26 fused with recipient cells. Moreover, miR-1 expression was elevated in RCC cells treated with exosomes derived from miR-1-transfected cells. Functional analyses showed that exosomal miR-1 significantly inhibited cell proliferation, migration and invasion compared to control treatment. Our analyses with TCGA database of RCCs showed that miR-1 expression was significantly downregulated in clinical RCC samples compared to that in normal kidney samples, and patients with low miR-1 expression had poorer overall survival in comparison to patients with high expression. Furthermore, RNA sequence analyses showed that expression levels of several genes were altered by exposure to exosomal miR-1. The analyses with TCGA database indicated that high expression of MYO15A was associated with a poorer outcome in RCC. In addition, RT-qPCR analysis of exosomes from clinical patients' sera showed that MYO15A was significantly upregulated in RCC patients compared to that in healthy controls. This study showed that treatment with exosomal miR-1 might be an effective approach to treating RCCs. In addition, exosomal MYO15A could be a diagnostic tumor marker in RCCs., Competing Interests: Declaration of competing interest None of the authors has any direct or indirect commercial financial incentives associated with the publication of this article entitled “Exosomal microRNA-1 and MY6O15A as a target for therapy and diagnosis in renal cell carcinoma”., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Both fish-oil lipid injectable emulsion (FO-ILE) and mixed-oil lipid injectable emulsion (MO-ILE) are key components of parenteral nutrition and require importation into Japan, and they are easily oxidized after opening. Given the small daily volumes of these lipids dispensed in infants and children with intestinal failure (IF), the purpose of the study was to identify the optimal storage method., Methods: Lipids were prepared in polypropylene syringes in the following manner: air-sealing and photoprotection, air-sealing only, photoprotection only, and uncovered. Samples were stored for 14 days at 4°C or 26°C. The degree of oxidative degradation was evaluated by measuring malondialdehyde (MDA) concentration and pH and comparing them to the values measured immediately after opening., Results: For FO-ILE, the increase in MDA concentration for 14 days was insignificant in air-sealed samples, regardless of photoprotection (+0.45 μM, P = 1.0) or no photoprotection (+0.52 μM, P = 1.0). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.08 at 4°C. MO-ILE exhibited an insignificant increase in MDA concentration for 14 days with air-sealed samples, regardless of photoprotection (+0.36 μM, P = 0.11) or no photoprotection (+0.33 μM, P = 0.76). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.12 at 4°C. For soybean-oil lipid injectable emulsion, the trend was similar with no considerable deterioration., Conclusion: Syringe-dispensed FO-ILE and MO-ILE stored under airtight refrigeration remained undeteriorated for 14 days. Our results are considered clinically valuable when supplying these expensive resources for infants with IF., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Local recurrence of colorectal cancer (CRC) can occur in patients after curative resection, and additional surgical resection may therefore be required; however, this is a significant burden for patients, because additional surgical resection may necessitate the resection of other organs such as the bladder, prostate, uterus, or sacral bone. Therefore, there is a need for alternative therapeutic strategies. We focused on boron neutron capture therapy (BNCT) as a treatment modality that can selectively target tumor cells without excessive damage to normal tissues. The usefulness of BNCT to pelvic CRC remains unknown. This study investigated the anti-cancer effect of boronophenylalanine (BPA)-mediated BNCT in a previously established mouse model of pelvic recurrence of CRC. Uptake of BPA in CRC was observed both in vitro and in vivo, and the concentrations were sufficient for BNCT. Our results are the first to show that BPA-mediated BNCT prolonged the survival of experimental mice with pelvic tumors; moreover, it did not cause any obvious severe side effects in the treated animals. In conclusion, BPA-mediated BNCT could contribute to treating local recurrence of pelvic CRC., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masashi Yamamoto reports financial support was provided by Japan society for the promotion of science., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Strombidae is one of the major molluscan families in Sudan and due to their opercula, has tremendous economic value. In traditional Sudanese homemade perfumes and body care cosmetics, Strombidae family operculum is one of the main ingredients. Their fumigation generates a charming odor preferred by Sudanese people, used for body smoke baths by married women. Moreover, these fumes are believed to treat several gynecological disorders. In this study, we attempted to confirm the presence of volatiles with pleasant odors and compounds with pharmaceutical importance in the Strombidae opercula. Volatiles from the smoke and soak extracts of the burned opercula were analyzed using gas chromatography-mass spectrometry (GC-MS). Furthermore, polar components from the methanol extract of opercula powder were isolated using high-performance liquid chromatography (HPLC) and identified by nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), and UV spectra. The elemental and metal contents were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). GC-MS analysis revealed several phenols, aldehydes, ketones, and other functional fragrant and volatile constituents. Further, two compounds were purified from the methanol extract of Strombidae opercula, and named compounds B and D, which were identified as cyclo-(Tyr-Gly) and 4-hydroxybenzaldehyde, respectively. ICP-MS analysis revealed the presence of various elements and metals at different levels. These findings support the historical and traditional practices and usage of the Strombidae opercula in therapeutic and esthetic products. The opercula contains many biologically active compounds and produces smoke containing volatile scent compounds, which might provide alternative pharmaceuticals and cosmetic ingredients that can cooperate to improve the manufacturing of numerous medical products., (Copyright © 2022 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Rationale: Postoperative recurrence of congenital diaphragmatic hernia (CDH) in adults is very rare. There is currently no precedent and no established treatment. We encountered a case of CDH which recurred 57 years, postoperatively., Patient Concerns: A 57-year-old man with dyspnea on exertion was referred to our hospital. He had undergone surgery at the same hospital for CDH when he was 46 days old., Diagnosis and Interventions: Laboratory studies, except diagnostic imaging and spirometry, were otherwise within normal limits. He was diagnosed with recurrent CDH based on computed tomography and underwent laparoscopic surgery., Outcomes: His postoperative course was uneventful, and there was no recurrence on follow-up., Lessons: We reported our encounter with a case of recurrent CDH, more than 50 years after the initial surgery. When managing diaphragmatic hernias, prompt surgical treatment, with consideration to prior surgical history for CDH, leads to satisfactory results., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Imatinib mesylate (imatinib) is the primary agent of choice used to treat gastrointestinal stromal tumors (GIST). However, drug resistance to imatinib poses a major obstacle to treatment efficacy. In addition, the relationship between imatinib resistance and glycolysis is poorly understood. Glucose transporter (GLUT)‑1 is a key component of glycolysis. The present study aimed to assess the potential relationship between components in the glycolytic pathway and the acquisition of imatinib resistance by GIST cells, with particular focus on GLUT‑1. An imatinib‑resistant GIST cell line was established through the gradual and continuous imatinib treatment of the parental human GIST cell line GIST‑T1. The expression of glycolysis‑related molecules (GLUT‑1, hexokinase 2, pyruvate kinase M2 and lactate dehydrogenase) was assessed in parental and imatinib‑resistant cells by western blotting, reverse transcription‑quantitative PCR and glucose and lactate measurement kits. In addition, clinical information and transcriptomic data obtained from the gene expression omnibus database (GSE15966) were used to confirm the in vitro results. The potential effects of GLUT‑1 inhibition on the expression of proteins in the glycolysis (GLUT‑1, hexokinase 2, pyruvate kinase M2 and lactate dehydrogenase) and apoptosis pathways (Bcl‑2, cleaved PARP, caspase-3 and caspase-9) in imatinib‑resistant cells were then investigated following gene silencing and treatment using the GLUT‑1 inhibitor WZB117 by western blotting. For gene silencing, the mature siRNAs for SLC2A1 were used for cell transfection. Annexin V‑FITC/PI double‑staining followed by flow cytometry was used to measure apoptosis whereas three‑dimensional culture experiments were used to create three‑dimensional spheroid cells where cell viability and spheroid diameter were measured. Although imatinib treatment downregulated GLUT‑1 expression and other glycolysis pathway components hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase in parental GIST‑T1 cells even at low concentrations. By contrast, expression of these glycolysis pathway components in imatinib‑resistant cells were increased by imatinib treatment. WZB117 administration significantly downregulated AKT phosphorylation and Bcl‑2 expression in imatinib‑resistant cells, whereas the combined administration of imatinib and WZB117 conferred synergistic growth inhibition effects in apoptosis assay. WZB117 was found to exert additional inhibitory effects by inducing apoptosis in imatinib‑resistant cells. Therefore, the present study suggests that GLUT‑1 is involved in the acquisition of imatinib resistance by GIST cells, which can be overcome by combined treatment with WZB117 and imatinib.

Most osteoporotic vertebral fractures (OVFs) are treated conservatively, but surgery is often indicated for residual pain, neuropathy, or severe deformity. OVFs tend to develop in elderly patients, so less invasive surgery is desirable. Surgery is mainly performed to stabilize the fractured vertebral body. Percutaneous cement augmentation, such as via balloon kyphoplasty (BKP), has produced satisfactory results as a surgical method for managing OVFs. Posterior fixation with implants is often performed with or without cement augmentation when stronger fixation is considered necessary for OVFs with local kyphosis and angular instability. Pedicle screws (PSs) are widely used as an implant for posterior fixation, but given the risk of backing out in bones with severe osteoporosis, several measures have been taken to increase the strength such as by adding hooks. In cases of osteoporosis, hooks that can use cortical bone as an anchor are considered more useful than PS but are rarely used in minimally invasive surgery. We developed a minimally invasive posterior hook stabilization approach to directly stabilize the posterior spinal components as a new augmentation method for BKP and applied it to four cases of thoracolumbar OVF with neurological symptoms. The operation time was about 60 minutes, including BKP, and the estimated blood loss was about 10 ml. No postoperative implant problems occurred, and in all cases, neurological symptoms, such as buttocks and leg pain, were alleviated at an early stage after surgery. One patient had a postoperative adjacent vertebral body fracture that was conservatively treatable. Minimally invasive posterior hook stabilization, which we developed as a way of augmenting BKP, was considered useful for managing vertebral body fractures of the thoracolumbar spine with local kyphosis and angular instability., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Doi et al.)

The effects of psychotropic agents such as fluvoxamine, fluoxetine, paroxetine, milnacipran, and fluphenazine on dopamine formation from p -tyramine catalysed by cytochrome P450 (CYP) 2D6.2 (Arg296Cys;Ser486Thr), CYP2D6.10 (Pro34Ser;Ser486Thr), and CYP2D6.39 (Ser486Thr) were compared with the effects on dopamine formation from p -tyramine by CYP2D6.1. Michaelis constants ( K m ) and maximal velocity ( k cat ) values for dopamine formation and inhibition constants ( K i ) of the psychotropic agents were determined.For CYP2D6.39, the k cat values for fluvoxamine, fluoxetine, and milnacipran, but not for paroxetine and fluphenazine, gradually increased with increasing concentrations, indicating activation of the catalysed reaction.Fluphenazine competitively inhibited dopamine formation catalysed by all variants, with a higher K i value for CYP2D6.10. Among the three compounds that have a trifluoromethyl group in their chemical structure, only fluvoxamine and fluoxetine, as well as milnacipran that does not have this group, decreased K m values and/or increased k cat values for dopamine formation, suggesting that the group may not be essential for the activation.These findings indicate that substitution of amino acids at positions 34 and 486 can affect the affinity ( K m ) and enzymatic activity ( k cat ), respectively, for milnacipran and that the effect of substitution of arginine to cysteine at the 296 th position on the activation would be effector dependent.