Clinical results of ultrasound-guided intra-arterial embolization targeting abnormal neovessels for plantar fasciitis: 66 cases with up to 4 years of follow-up.

BACKGROUND: Plantar fasciitis (PF) is the most common cause of chronic heel pain, affecting young and older patients. METHODS: This retrospective study included patients with PF refractory to conservative treatment who underwent intra-arterial embolization of abnormal neovessels. All patients received temporary embolic material through a needle percutaneously inserted into the posterior tibial artery. The numeric rating scale (NRS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and procedure-related adverse events were evaluated. RESULTS: Between January 2020 and February 2022, 66 patients with PF were treated with intra-arterial embolization without major adverse events. The NRS pain score improved significantly, and the AOFAS score increased from 65.8 pre-treatment to 92.8 at 1 year post-treatment. The treatment effect was maintained until the final follow-up (mean duration: 30.9 months). CONCLUSIONS: Ultrasound-guided intraarterial embolization using temporary embolic material may be effective for PF. LEVEL OF EVIDENCE: IV.

Biological evaluation for anti-inflammatory effect of africane-type sesquiterpenoids.

Africane-type sesquiterpenoids are a unique tricyclic carbon architecture sesquiterpenoid isolated as natural products. Δ9(15) -africanene has been reported to exhibit anti-inflammatory activity for carrageenan-induced rat foot edema. In this study, we reported structure-activity relationship study of africane-type sesquiterpenoids and found that some africane-type sesquiterpenoid analogs and their synthetic intermediate showed potent anti-inflammatory activity. To identify the mode of action of africane-type sesquiterpenoids and their synthetic intermediate, we evaluated the anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. Treatment with the africane-type compounds and their synthetic intermediate suppressed LPS-induced expressions of Cox-2 protein and mRNAs of the inflammatory cytokines IL-1ß and IL-6 at the concentrations that did not affect cell viability. Interestingly, although these africane-type compounds and their synthetic intermediate suppressed the pro-inflammatory cytokines' expressions, the compounds did not modulate NF-κB activation. These results suggest that the africane-type compounds and their synthetic intermediate are anti-inflammatory compounds that suppress the expression of LPS-induced inflammatory mediators independently of NF-κB activation.

Scalable Syntheses and Biological Evaluation of Africane-Type Sesquiterpenoids.

Practical total syntheses of africane-type sesquiterpenoids were realized by reexamination of a divergent strategy employing optimized three-component coupling followed by ring-closing metathesis and substrate-controlled cyclopropanation. This sequential eight-step conversion provided Δ9(15) -africanene, a common bicyclo[5.3.0]decane intermediate for the syntheses of africane derivatives, in more than twice the yield as in the previous approach. The scalability and robustness of this improved synthetic route were confirmed by gram-scale preparation of Δ9(15) -africanene. In vitro cell-based assays of the synthesized africane-type sesquiterpenoids disclosed that ester-incorporating derivatives showed cytotoxic activity against HeLa cells. The effect of relative and absolute configuration of africane-9,15-diol monoacetates on the cytotoxicity against HeLa cells was also investigated.

Particle swarm optimization of silicon photonic crystal waveguide transition.

Slow light generated through silicon (Si) photonic crystal waveguides (PCWs) is useful for improving the performance of Si photonic devices. However, the accumulation of coupling loss between a PCW and Si optical wiring waveguides is a problem when slow-light devices are connected in a series in a photonic integrated circuit. Previously, we reported a tapered transition structure between these waveguides and observed a coupling loss of 0.46 dB per transition. This Letter employed particle swarm optimization to engineer the arrangement of photonic crystal holes to reduce loss and succeeded in demonstrating theoretical loss value of 0.12 dB on average in the wavelength range of 1540-1560 nm and an experimental one of 0.21 dB. Crucially, this structure enhances the versatility of slow light.

Identification of a cyanidin-3-O-ß-galactoside in gall tissue induced by midges on Japanese beech (Fagus crenata Blume).

Insect gall structures have many characteristic forms and colors, which are distinguishable from host plants. In this study, we identified an anthocyanin from red color insect galls and revealed that the anthocyanin biosynthesis of plants was induced by the gall extracts. The galling insects presumably regulate the anthocyanin biosynthesis of host plants to protect their larvae from environmental stresses.

Convergent Total Synthesis of Paecilomycin B and 6'- epi-Paecilomycin B by a Barbier-Type Reaction Using 2,4,6-Triisopropylphenyllithium.

The convergent total synthesis of the natural product paecilomycin B and its 6'-epimer was investigated. The aryl- C-glycoside skeleton was constructed by an intramolecular Barbier-type reaction using 2,4,6-triisopropylphenyllithium and subsequent deoxygenation of the resulting anomeric hydroxy group. Starting from aryl iodide 24, the addition reaction afforded the thermodynamically stable C-ß macrocyclic adduct 41a in 29% yield and the C-α adduct 41b in 1% yield. Meanwhile, aryl iodide 43 (6'-epimer of 24) gave only the C-α adduct 44 in 76% yield. The stereoselectivities of these nucleophilic addition reactions are also discussed.

Identification of Cyclopropylacetyl-(R)-carnitine, a Unique Chemical Marker of the Fatally Toxic Mushroom Russula subnigricans.

A toxic mushroom, Russula subnigricans, causes fatal poisoning by mistaken ingestion. In spite of the potent bioactivity, the responsible toxin had not been identified for about 50 years since its first documentation. Recently, we isolated an unstable toxin and determined the structure. The slow elucidation was partly due to the instability of the toxin and also due to misidentification of R. subnigricans for similar mushrooms. To discriminate genuine Russula subnigricans from similar unidentified Russula species, we searched for a unique chemical marker contained in the mushroom. Cyclopropylacetyl-(R)-carnitine specific to R. subnigricans was identified as a novel compound whose (1)H-NMR signals appearing in the upfield region were easily recognizable among the complicated signals of the crude extract.

Synthesis and biological evaluation of kendomycin and its analogues.

Ansa compounds are gifts from microbes with intriguing molecular structures and highly potent bioactivities. One of the ansa compounds, kendomycin, has an oxa-metacyclophane skeleton with a quinone methide core and a fully substituted tetrahydropyran ring. Beyond a common synthetic strategy for construction of the ansa skeleton (i.e., elongation of an alkyl chain from an aromatic core followed by macrocyclization), we challenged a new method for construction of the ansa skeleton via simultaneous macrocyclization and benzannulation (using an intramolecular Dötz benzannulation). Understanding the reactivity of various Fischer-type ω-alkynyloxy chromium carbene complexes with kendomycin analogue syntheses led to achievement of the total synthesis of kendomycin. Investigations of structure-activity relationships revealed the need for an ansa skeleton for antimicrobial activity. Therefore, we envisage that this intramolecular Dötz benzannulation will enable divergent syntheses of ansa compounds which have important bioactive potential.

Transcatheter Arterial Embolization for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Retrospective Study of 44 Patients.

PURPOSE: To investigate the preliminary treatment outcomes of transcatheter arterial embolization (TAE) for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: This retrospective study included patients with refractory CP/CPPS who underwent TAE between April 2022 and February 2023. All patients had persistent pelvic pain for at least 3 months, a total score of at least 15 on the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and lacked evidence of infection. All procedures were performed by injecting imipenem/cilastatin sodium (IPM/CS) from bilateral prostatic arteries ± internal pudendal arteries. NIH-CPSI, pain numeric rating scale (NRS), and complications were evaluated at 1, 3, and 6 months after the initial TAE and at the final follow-up. RESULTS: Out of 48 patients, 44 were included in this study, with four excluded because of loss of follow-up. No severe procedure-related complications were observed. Pretreatment and post-treatment evaluations at 1, 3, and 6 months after the initial TAE and at the final follow-up (mean 16.6 months) revealed a decrease in the mean NIH-CPSI scores from 27 ± 6 to 21 ± 8, 20 ± 9, 17 ± 9, and 18 ± 9, respectively (all P < 0.001). Pain NRS scores were also decreased from 7.0 ± 1.6 to 4.8 ± 2.5, 4.1 ± 2.6, 3.7 ± 2.4, and 3.4 ± 2.3, respectively (all P < 0.001). The proportions of clinical success, defined as a reduction of at least 6 points from baseline in the NIH-CPSI, at 6 months after TAE and at the final follow-up were 70 and 64%, respectively. CONCLUSIONS: This study provides evidence of the feasibility of TAE using IPM/CS for CP/CPPS, suggesting both symptomatic improvement and safety.

Intra-Arterial Injection of Temporary Embolic Material Through a Needle Inserted into the Radial or Ulnar Artery for Distal and Proximal Interphalangeal Joint Osteoarthritis: A Retrospective Study of 92 Patients.

PURPOSE: To assess the efficacy and safety of intra-arterial injection of imipenem/cilastatin sodium (IPM/CS) via a needle placed into the radial artery or ulnar artery (RA/UA) for distal interphalangeal and proximal interphalangeal joint osteoarthritis (DIP/PIP-OA). MATERIALS AND METHODS: This is a retrospective single-arm cohort study. Ninety-two patients [92% women, mean (SD) age 55(8.3) years] with a primary DIP/PIP-OA meet the American College of Rheumatology criteria for hand osteoarthritis with pain ≥ 4 on the 0-10 numeric rating scale (NRS) were enrolled. All procedures were performed by injecting IPM/CS through a 24-gauge needle percutaneously inserted into the RA/UA. Two procedures were planned; the second procedure was scheduled 1-2 months after the first. NRS, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, Patient Global Impression of Change (PGIC) scale, and procedure-related adverse events were evaluated. RESULTS: Technical success, defined as injection of IPM/CS into the RA/UA, was achieved in all patients. Clinical success, defined as a reduction of 2 points or more in the NRS at 12 months, was 77% (95% confidence interval 68-85%). The NRS improved from the baseline to 3, 6, and 12 months (7.8 ± 1.6 vs. 3.8 ± 2.6, 3.9 ± 2.7, and 4.0 ± 2.8, respectively, all p < 0.001). The QuickDASH score improved from the baseline to 12 months (27 ± 15 vs. 19 ± 17, p < 0.001) respectively. No major adverse events were observed. CONCLUSIONS: Intra-arterial injection of IPM/CS is a feasible treatment option for DIP/PIP-OA.

Molybdophyllysin, a toxic metalloendopeptidase from the tropical toadstool, Chlorophyllum molybdites.

A toxic protein, dubbed molybdophyllysin, was isolated from the tropical toadstool Chlorophyllum molybdites by following its lethal effect in mice. Analysis of the protein using SDS-PAGE revealed a single 23-kDa band. Sequence analysis of molybdophyllysin tryptic fragments showed that this protein is highly homologous to metalloendopeptidases (MEPs) obtained from edible mushrooms, such as Grifola frondosa, Pleurotus ostreatus, and Armillaria mellea. These proteins include a HEXXH+D zinc-binding motif known as aspzincin. Accordingly, molybdophyllysin is a member of the deuterolysin family of zinc proteases. Molybdophyllysin retained its proteolytic activity at temperatures up to 60°C with an optimum pH of 7.0. The activity was inhibited by both 1,10-phenanthroline and N-bromosuccinimide, but molybdophyllysin exhibited strong resistance to SDS.

Identification of the toxic trigger in mushroom poisoning.

We have isolated the small, highly strained carboxylic acid cycloprop-2-ene carboxylic acid from the Asian toxic mushroom Russula subnigricans. This compound is responsible for fatal rhabdomyolysis, a new type of mushroom poisoning that is indicated by an increase in serum creatine phosphokinase activity in mice. We found that polymerization of the compound at high concentrations via ene reaction abolishes its toxicity.

Synthetic studies on polymaxenolides: synthesis and structure elucidation of nominal epoxyafricanane and other africane-type sesquiterpenoids.

A racemic total synthesis of the sesquiterpenoid unit of the hybrid marine natural product polymaxenolide has been achieved based on a three-component assembly followed by ring-closing metathesis as the key steps. However, the spectral data of our product synthesized from Δ(9(15))-africanene by epoxidation were not identical with those of the natural product named epoxyafricanane. The structure confirmation of the synthetic nominal epoxyafricanane is described.

Synthetic studies on lactonamycins: synthesis of the model BCDEF aglycon.

The lactonamycin model aglycon 4 was synthesized from the trihalogenated benzene derivative 10. Ethynyltetraol 6 was prepared from 10 via carbon elongations, oxidative demethylation, a cycloaddition reaction with the diene derived from homophthalic anhydride, and dihydroxylation. Final E- and F-ring constructions from 6 were realized via a palladium-catalyzed cyclization-methoxycarbonylation, a stereoselective methanol addition, and lactonization, leading to the production of 4.

Pigment chemistry: the red sweat of the hippopotamus.

Within a few minutes of perspiration, the colourless, viscous sweat of the hippopotamus gradually turns red, and then brown as the pigment polymerizes. Here we isolate and characterize the pigments responsible for this colour reaction. The unstable red and orange pigments turn out to be non-benzenoid aromatic compounds that are unexpectedly acidic and have antibiotic as well as sunscreen activity.

Total synthesis of methyl sarcophytoate, a marine natural biscembranoid.

The total synthesis of methyl sarcophytoate (1), a marine natural biscembranoid, has been achieved by the thermal Diels-Alder reaction between the 14-membered dienophile unit, methyl sarcoate (2), and the 14-membered diene unit 64. Methyl sarcoate (2) was prepared using n-BuLi-Bu(2)Mg-mediated dithiane coupling, Kosugi-Migita-Stille coupling, and Grubbs ring-closing metathesis. The diene unit 64 was prepared using Sharpless asymmetric epoxidation, Grubbs ring-closing metathesis, 6-exo-tet epoxide opening, and n-BuLi-Bu(2)Mg-mediated Ito-Kodama cyclization. The final Diels-Alder reaction between 2 and 64 proceeded with high site, endo/exo, pi-face, and regioselectivities. During this reaction, partial E --> Z isomerization at the C4 position was observed.

Total Synthesis of Pactalactam, an Imidazolidinone-Type Pactamycin Analogue.

The first total synthesis of pactalactam was accomplished using substrate-controlled stereoselective aziridination and regioselective aziridine ring-opening to construct three continuous amino groups on an octasubstituted cyclopentane core. The cyclopentane framework was obtained by ring-closing metathesis and aldol coupling using a l-threonine-derived oxazoline compound. Cyclic urea formation, m-acetylphenyl group introduction by Chan-Lam coupling, and primary alcohol-selective acylation yielded the reported pactalactam structure. The presence of pactalactam in the fermentation broth of pactamycin-producing bacteria was also confirmed.

Diastereoselective synthesis of useful building blocks by crotylation of beta-branched alpha-methylaldehydes with potassium crotyltrifluoroborates.

The diastereoselective construction of stereotriads having consecutive methyl, hydroxy, and methyl substituents was realized by the substrate-controlled crotylation of beta-branched alpha-methylaldehydes with potassium crotyltrifluoroborates. Especially, crotylation of 2-(1,3-dithian-2-yl)propanal with potassium ( E)-crotyltrifluoroborate afforded, in good yield and with excellent diastereoselectivity, a useful building block that has different and potential functional groups on both ends.

Bolevenine, a toxic protein from the Japanese toadstool Boletus venenatus.

A toxic protein, called bolevenine, was isolated from the toxic mushroom Boletus venenatus based on its lethal effects on mice. On SDS-PAGE, in either the presence or absence of 2-mercaptoethanol, this protein showed a single band of approximately 12 kDa. In contrast, based on gel filtration and MALDI-TOFMS, its relative molecular mass was estimated to be approximately 30 kDa and approximately 33 kDa, respectively, indicating that the protein consists of three identical subunits. This toxin exhibited its lethal activity following injection at 10mg/kg into mice. The N-terminal amino acid sequence was determined up to 18, and found to be similar to the previously reported bolesatine, a toxic compound isolated from Boletus satanas.