Secondary Skin Cancer in a Case with Long-term Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.     

Associations of circulating xanthine oxidoreductase activity with cardiometabolic risk markers in overweight and obese Japanese men: a cross-sectional pilot study

Circulating xanthine oxidoreductase (XOR) activity may contribute to the pathogenesis of obesity-related adverse cardiometabolic profiles. This pilot study aimed to examine the cross-sectional associations between plasma XOR activity and cardiometabolic risk (CMR) markers in overweight and obese men. In 64 overweight and obese Japanese men (aged 31–63 years), plasma XOR activity and several CMR markers, such as homeostasis model assessment of insulin resistance (HOMA-IR), and clustered CMR score were measured in each participant. Clustered CMR score was constructed based on waist circumference, triglyceride, blood pressure, fasting plasma glucose, and high-density lipoprotein cholesterol. Plasma XOR activity in overweight and obese men was positively associated with the body mass index, waist circumference, visceral fat area, body fat mass, hemoglobin A1c, serum 8-hydroxy-2''-deoxyguanosine, HOMA-IR, and clustered CMR score and was inversely associated with handgrip strength and high-density lipoprotein cholesterol. Multiple linear regression analysis further demonstrated that the associations of plasma XOR activity with HOMA-IR and the clustered CMR score remained significant after adjustment for covariates including uric acid. Our data demonstrate that circulating XOR activity was independently associated, albeit modestly, with HOMA-IR and the clustered CMR score. These preliminary findings suggest that circulating XOR activity can potentially be one of the preventive targets and biomarkers of cardiometabolic disorders in over­weight and obese men.     

Effect of carbon on the co-presence of metallic tungsten as a nucleation agent and Eu2+ in glass: crystallization of CaO–Al2O3–SiO2 glass probed with Eu2+ luminescence

This study demonstrated simple redox control in glasses by improving the method used to added glass raw materials. Specifically, the effect of carbon on the co-presence of metallic tungsten (W) particles as nucleation agents and Eu²⁺ ions in CaO–Al₂O₃–SiO₂ (CAS) glass was investigated via their crystallization to form CAS glass-ceramics (GCs). In this study, the glass specimens were prepared by mixing glass cullet containing metallic W particles and Eu²⁺ ions, respectively, with a glass batch containing carbon. Whereas the glass specimen was yellowish because of the presence of Eu²⁺ when carbon was not added during the remelting process, the glass specimen prepared with carbon was black because of the presence of metallic W particles. In addition, this specimen displayed the 470 nm emission band in its fluorescence spectrum recorded under 393 nm excitation, which was attributed to the presence of Eu²⁺. According to the fluorescence and transmission spectra, the glass specimen showed a darker coloration and more intense 470 nm emission band compared with the specimen prepared by the conventional melting method that included a remelting process. These results indicated that metallic W and Eu²⁺ were reduced with greater efficiency by the melting method that involved mixing the glass cullet and batch. In addition, the heat-treated glass specimen prepared by the aforementioned mixing method contained a greater amount of metastable CaAl₂Si₂O₈ with increasing heat treatment time as revealed by X-ray diffraction analysis and scanning electron microscopy observation. The intensity of the 470 nm emission band decreased with increasing intensity of the band at 420 nm because of the incorporation of Eu²⁺ into the crystalline phase, and the increase in intensity of the 420 nm band was lineally proportional to the volume fraction of the crystallized glass specimens. The results therefore indicated that the co-presence of metallic W particles as nucleation agents and Eu²⁺ as a probe for tracking the crystallization process was achieved by the addition of carbon during the remelting process of mixed cullet containing W and Eu²⁺ through crystallization of the CAS glass. The results thus demonstrate the importance of improving the method used to added glass raw materials.

Effect of carbon on the co-presence of metallic tungsten (W) as nucleation agents and Eu²⁺ ions as a probe for tracking crystallization in CaO–Al₂O₃–SiO₂ (CAS) glass was demonstrated by efficient reduction method of Eu²⁺ and metallic W.     

A large negative magnetoresistance effect in semiconducting crystals composed of an octahedrally ligated phthalocyanine complex with high-spin manganese(iii)

A design for an octahedrally ligated phthalocyanine complex with high-spin manganese(iii) (S = 2) and Mn^III(Pc)Cl₂ (Pc = phthalocyanine) is presented. The presence of high-spin state Mn^III in the fabricated Ph₄P[Mn^III(Pc)Cl₂]₂ (Ph₄P = tetraphenylphosphonium) semiconducting molecular crystal is indicated by the Mn–Cl distance, which suggests an electronic configuration of (d_yz, d_zx)²(d_xy)¹(d_z²)¹. This was confirmed by the Curie constant (C = 5.69 emu K mol⁻¹), which was found to be significantly larger than that of the isostructural Ph₄P[Mn^III(Pc)(CN)₂]₂, where Mn^III adopts a low-spin state (S = 1). The magnetoresistance (MR) effects of Ph₄P[Mn^III(Pc)Cl₂]₂ at 26.5 K under 9 T static magnetic fields perpendicular and parallel to the c-axis were determined to be −30% and −20%, respectively, which are significantly larger values than those of Ph₄P[Mn^III(Pc)(CN)₂]₂. Furthermore, the negative MR effect is comparable to that of Ph₄P[Fe^III(Pc)(CN)₂]₂ (S = 1/2), which exhibits the largest negative MR effect reported for [M^III(Mc)L₂]-based systems (Mc = macrocyclic ligand, L = axial ligand). This suggests that the spin state of the metal ion is the key to tuning the MR effect.

A Ph4P[Mn^III(Pc)Cl2]2 molecular crystal where Mn^III adopts a high-spin state (S = 2) was designed. The large magnetoresistance effect of fabricated Ph4P[Mn^III(Pc)Cl2]2 suggests that the spin state of the metal ion is the key to tuning the MR effect.     

Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease

Objective

To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice models with Alzheimer disease (AD), and to explore the possible protective mechanism of acupuncture on mitochondria.

Methods

Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group, an acupuncture at non-acupoint group and a model group, 20 mice in each group. The 20 male senescence-accelerated mouse/resistance 1 (SAMR1) mice of the same age were used as a normal control group. Shenshu (BL 23), Baihui (GV 20), Xuehai (SP 10) and Geshu (BL 17) were selected for acupuncture intervention in acupuncture at acupoint group. After an 8-week intervention, mitochondrial tissues were extracted from the hippocampus. Differentially expressed proteins were identified by subcellular organelle proteomics. Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.

Results

Compared with the model group, there were 13 differentially expressed protein spots in the acupuncture at acupoint group, of which, 9 were up-regulated, including neurofilament light polypeptide (NFL), actin (cytoplasmic 1, database ID: ACTB), tubulin beta-2A chain (TBB2A), tropomodulin-2 (TMOD2), pyruvate dehydrogenase E1 component subunit beta (PDHE1-β), NADH-ubiquinone oxidoreductase 75 kDa subunit (database ID: NDUS1), heat shock cognate 71 kDa protein (HSC71), pyruvate dehydrogenase E1 component subunit alpha (PDHE1-α) and ATP synthase beta subunit (ATP-β); 4 were down-regulated, including glial fibrillary acidic protein (GFAP), pyruvate dehydrogenase phosphatase 1 (PDP1), mitochondrial-processing peptidase subunit alpha (MMP-α) and adenosine kinase (ADK). According to the information provided in the protein database, most of the differentially expressed proteins involve the regulation of mitochondrial function and structure. The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group (P<0.05). ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group (P<0.05); there was no significant difference between the acupuncture at non-acupoint group and the model group (P>0.05).

Conclusion

Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.

     

Treatment of Infantile Muscular Torticollis with Tuina： A Report of 22 Cases

以推、揉、拿、扳、拉等手法,治疗22例肌性斜颈患儿,治愈18例,显效3例,无效1例.总有效率95.4%.     

A potential inhibitor of rat aortic vascular smooth muscle cell proliferation from the pollen of <Emphasis Type="Italic">Typha angustata</Emphasis>

By various chromatographic methods, three flavonoids, (2S)-naringenin (1), isorhamnetin 3-O-(2-O-α-l-rhamnopyranosyl) β-d-glucopyranoside (2), typhaneoside (3), and two sterol glycosides, β-sitosterol-3-O-(6-octadecanoyl) β-d-glucopyranoside (4) and β-sitosterol-3-O-(6-octadeca-9Z,12Z-dienoyl) β-d-glucopyranoside (5), were isolated from the pollen of Typha angustata. Their structures were determined on the basis of spectroscopic analyses. The flavonoids (1–3) were evaluated for their effects on the viability and proliferation of rat aortic smooth muscle cells. (2S)-naringenin (1) significantly inhibited cell proliferation in a dose-dependent manner without cytotoxic at concentrations of 30, and 50 μM; it reduced the number of cells following PDGF-BB treatment to 1.83 ± 0.30 × 10⁴ and 2.20 ± 0.60 × 10⁴ cells/well, respectively. These findings suggest that (2S)-naringenin has antiproliferative effects on aortic smooth muscle cells.     

Improved intestinal membrane permeability of hexose-quinoline derivatives via the hexose transporter, SGLT1

Intestinal membrane permeability is an important factor affecting the bioavailability of drugs. As a strategy to improve membrane permeability, membrane transporters are useful targets since essential nutrients are absorbed efficiently via specific transporters. For example, there are reports that intestinal hexose transporters could be used as a tool to improve permeability; however, there has been no direct evidence that the transporter protein, sodium/glucose cotransporter 1 (SGLT1), is involved in the transport of hexose analogs. Accordingly, we examined directly whether the intestinal membrane permeability of hexose analogs can be improved by utilizing SGLT1. Three hexose-quinoline derivatives were synthesized and their interactions with SGLT1 were evaluated. Among the three derivatives, the glucose-quinoline molecule exhibited an inhibitory effect on D-glucose uptake by both rat intestinal brush-border membrane vesicles (BBMVs) and Xenopus oocytes expressing SGLT1. In addition, significant uptake of the glucose-quinoline derivative by Xenopus oocytes expressing SGLT1 was observed by both an electrophysiological assay and direct measurement of the uptake of the compound, while the galactose-quinoline derivative did not show significant uptake via SGLT1. Thus, it was directly demonstrated that SGLT1 could be used as a tool for the improvement of intestinal membrane permeability of drugs by modification to the glucose analogs.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Simple and rapid analysis of aristolochic acid contained in crude drugs and Kampo formulations with solid-phase extraction and HPLC photodiode-array detection

Simple and rapid analysis of aristolochic acid (AA) in crude drugs and Kampo extracts using a solid-phase extraction method and HPLC-PDA analysis was investigated. Extraction of AA from samples was accomplished by adding methanol containing 1% ammonia. The addition of ammonia ionized the AA of acidic substances so that they adhered to an acrylamide copolymer of a strong anion exchange resin (Sep-Pak QMA) coupled to diol silica easily. Furthermore, a mixture of acetonitrile–water–phosphoric acid (75:25:2, v/v) was effective in isolating AA from its carrier. Since almost all interfering peaks originating from contaminants in crude drugs and Kampo extract formulations could be removed, a satisfactory HPLC chromatogram of AA was obtained. A good result was also obtained when Aristolochiaceae and crude drugs containing AA were tested. Particularly in the case of the medicinal parts of Asarum, several interfering peaks and a ghost peak detected near the AA peak were eliminated. The AA contents of two Kampo extract formulations, tokishigyakukagoshuyushokyoto and ryutanshakanto, were calculated by HPLC analysis. The AA content (the sum of AA-I and AA-II) was 1.25–6.13 mg per daily dose. From an additional recovery experiment for Kampo formulations, high recovery rates of AA were obtained. Neither LC/MS nor special instrumentation was necessary. Our results suggest that this simple, quick, and sensitive analytical method to detect AA in crude drugs and Kampo extract formulations would be valuable in safety inspections of AA in crude drugs and their products.