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Bietti’s crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-β-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-β-CyD. Our results suggest that HP-β-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-β-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-β-CyD alone. Furthermore, the slow release of HP-β-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-β-CyD, and that HP-β-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.

Tablets are the most commonly used dosage form in the pharmaceutical industry, and their properties such as disintegration, dissolution, and portability are influenced by their strength. However, in industry, the mixing fraction of powders to obtain a tablet compact with sufficient strength is determined based on empirical rules. Therefore, a method for predicting tablet strength based on the properties of a single material is required. The objective of this study was to quantitatively evaluate the relationship between the compression properties and tablet strength of powder mixtures. The compression properties of the powder mixtures with different plasticities were evaluated based on the force-displacement curves obtained from the powder compression tests. Heckel and compression energy analyses were performed to evaluate compression properties. During the compression energy analysis, the ratio of plastic deformation energy to elastic deformation energy (E_p/E_e) was assumed to be the plastic deformability of the powder. The quantitative relationship between the compression properties and tensile strength of the tablets was investigated. Based on the obtained relationship and the compression properties of a single material, a prediction equation was put forward for the compression properties of the powder mixture. Subsequently, a correlation equation for tablet strength was proposed by combining the values of K and E_p/E_e obtained from the Heckel and compression energy analyses, respectively. Finally, by substituting the compression properties of the single material and the mass fraction of the plastic material into the proposed equation, the tablet strength of the powder mixture with different plastic deformabilities was predicted.

Obesity is known to be associated with increased inflammation and dysregulated autophagy, both of which contribute to insulin resistance. Saikosaponin-A (SSA) has been reported to exhibit anti-inflammatory and lipid-lowering properties. In this research, we employed a combination of computational modeling and animal experiments to explore the effects of SSA. Male C57BL/6 mice were categorized into four groups: normal diet, high-fat diet (HFD), HFD + atorvastatin 10 mg/kg, and HFD + SSA 10 mg/kg. We conducted oral glucose and fat tolerance tests to assess metabolic parameters and histological changes. Furthermore, we evaluated the population of Kupffer cells (KCs) and examined gene expressions related to inflammation and autophagy. Computational analysis revealed that SSA displayed high binding affinity to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, fibroblast growth factor 21 (FGF21), and autophagy-related 7 (ATG7). Animal study demonstrated that SSA administration improved fasting and postprandial glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) index, as well as triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C)-cholesterol, and high-density lipoprotein cholesterol (HDL-C)-cholesterol levels in HFD-fed mice. Moreover, SSA significantly reduced liver weight and fat accumulation, while inhibiting the infiltration and M1 activation of KCs. At the mRNA level, SSA downregulated TNF-α and NF-κB expression, while upregulating FGF21 and ATG7 expression. In conclusion, our study suggests that SSA may serve as a therapeutic agent for addressing the metabolic complications associated with obesity. This potential therapeutic effect is attributed to the suppression of inflammatory cytokines and the upregulation of FGF21 and ATG7.

Batrachotoxin (1) is a potent cardio- and neurotoxic steroid isolated from certain species of frogs, birds, and beetles. We previously disclosed two synthetic routes to 1. During our synthetic studies toward 1, we explored an alternative strategy for efficiently assembling its 6/6/6/5-membered steroidal skeleton (ABCD-ring). Here we report the application of intermolecular Weix and intramolecular pinacol coupling reactions. While Pd/Ni-promoted Weix coupling linked the AB-ring and D-ring fragments, SmI₂-mediated pinacol coupling did not cyclize the C-ring. Instead, we discovered that SmI₂ promoted a 1,4-addition of the α-alkoxy radical intermediate to produce the unusual 11(9→7)-abeo-steroid skeleton. Thus, this study demonstrates the convergent assembly of the skeleton of the natural product matsutakone in 11 steps from 2-allyl-3-hydroxycyclopent-2-en-1-one.

Amine-free phosphorylation of various alcohols was developed with 4-methylpyridine N-oxide in the presence of 4 Å molecular sieves at room temperature. This mild method gave various phosphorylated products in high yield and could be applied to acid- or base-sensitive substrates. Furthermore, this method was also effective for the chemoselective phosphorylation of diols or polyols.

Aiming to synthesize a cyclic hexaamide, 4-bromo-3-(isobutylamino)benzoic acid was subjected to self-condensation reactions in the presence of either dichlorotriphenylphosphorane in 1,1,2,2-tetrachloroethane or tetrachlorosilane in pyridine. However, instead of the targeted cyclic hexaamide, the cyclic triamide and the cyclic tetraamide were obtained. The cyclic hexaamide was successfully synthesized via the self-condensation of the dimer, which was synthesized in five steps from 4-bromo-3-(isobutylamino)benzoic acid. A thorough screening of the self-condensation conditions was performed to improve the yield of the target macrocycle. In addition, the linear hexamer was synthesized by stepwise deprotection and condensation, and its cyclization afforded the cyclic hexaamide in good yield.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

To explore drug interactions involving sodium zirconium cyclosilicate hydrate (SZC) and concomitant drugs like calcium antagonists (amlodipine and nifedipine) and β-blockers (carvedilol and bisoprolol), we investigate how these concomitant drugs influenced the administration of SZC in an artificial intestinal juice. Initially, we assessed the potassium ion adsorption capacity, ranking it as follows: calcium polystyrene sulfonate (CPS, 54.9 mg/g) < sodium polystyrene sulfonate (SPS, 62.1 mg/g) < SZC (90.8 mg/g). However, the adsorption equilibrium was achieved in the order of CPS ≒ SPS (within 1 min) < SZC (within 1 h). Subsequently, we determined the residual percentages of amlodipine, nifedipine, carvedilol, and bisoprolol, finding them to be 79.0–91.9% for SZC, 0.38–38.4% for SPS, and 0.57–29.0% for CPS. These results suggest the efficacy of SZC in managing hyperkalemia alongside concomitant drugs in an artificial intestinal juice, with particular emphasis on amlodipine (calcium antagonist) and carvedilol (β-blocker). Additionally, we identified the presence of carbon, nitrogen, and oxygen components from both drugs on the SZC surface following interaction. We also evaluated how amlodipine, nifedipine, carvedilol, and bisoprolol affected the administration of SZC in the presence of potassium ions. Our results indicate that potassium ions and concomitant drugs did not interfere with each other in the artificial intestinal juice. These results offer valuable insights into the administration of SZC in conjunction with concomitant drugs. Lastly, the presented data shows qualitative results in this study.

This study focused on the electrochemical properties of tetrazolium salts to develop a simple method for evaluating viable bacterial counts, which are indicators of drug susceptibility. Considering that the oxidized form of tetrazolium, which has excellent cell membrane permeability, changes to the insoluble reduced form formazan inside the cell, the number of viable cells was estimated based on the reduction current of the tetrazolium remaining in the bacterial suspension. Dissolved oxygen is an important component of bacterial activity. However, it interferes with the electrochemical response of tetrazolium. We estimated the number of viable bacteria in the suspension based on potential-selective current responses that were not affected by dissolved oxygen. Based on solubility, cell membrane permeability, and characteristic electrochemical properties of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium, we developed a method for rapidly measuring viable bacteria within one-fifth of the time required by conventional colorimetric methods for drug susceptibility testing.

Codeine is a common analgesic drug that is a pro-drug of morphine. It also has a high risk of abuse as a recreational drug because of its extensive distribution as an OTC drug. Therefore, sensitive and selective screening methods for codeine are crucial in forensic analytical chemistry. To date, a commercial analytical kit has not been developed for dedicated codeine determination, and there is a need for an analytical method to quantify codeine in the field. In the present work, potential modulation was combined with electrochemiluminescence (ECL) for sensitive determination of codeine. The potential modulated technique involved applying a signal to electrodes by superimposing an AC potential on the DC potential. When tris(2,2′-bipyridine)ruthenium(II) ([Ru(bpy)₃]²⁺) was used as an ECL emitter, ECL activity was confirmed for codeine. A detailed investigation of the electrochemical reaction mechanism suggested a characteristic ECL reaction mechanism involving electrochemical oxidation of the opioid framework. Besides the usual ECL reaction derived from the amine framework, selective detection of codeine was possible under the measurement conditions, with clear luminescence observed in an acidic solution. The sensitivity of codeine detection by potential modulated-ECL was one order of magnitude higher than that obtained with the conventional potential sweep method. The proposed method was applied to codeine determination in actual prescription medications and OTC drug samples. Codeine was selectively determined from other compounds in medications and showed good linearity with a low detection limit (150 ng mL⁻¹).