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BACKGROUND: Foeniculum vulgare, F. vulgare, commonly known as fennel, is believed to be one of the worlds oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries, it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties. F. vulgare is used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD). METHODS: This study investigated the effects of fennel seed extract on intestinal epithelium barrier function and the Signal Transducer and Activator of Transcription (STAT) pathway. This pathway is active in inflammatory bowel disease. To study the protective effects of fennel seed extract in vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-γ) and monitored with and without fennel seed extract. To complement our in vitro studies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect of fennel seed extract can be recapitulated in vivo. RESULTS: Fennel seed extract was shown to exert a protective effect on transepithelial electrical resistance (TEER) in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated with fennel seed showed significantly lower ulcer indices than control mice. CONCLUSIONS: We conclude barrier function of the gastrointestinal tract is improved by fennel seed extract, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD.

Background: Despite advances in medical science, chronic obstructive pulmonary disease (COPD) continues to impact patients' lives significantly, due to symptom management limitations. Cheongsangboha-tang (CSBHT; Qing Shang Bu Xia Tang) and Hyunggaeyeongyo-tang (HGYGT; Jing Jie Lian Qiao Tang) have been used to treat respiratory diseases, including COPD. However, clinical data supporting their efficacy are lacking. We prospectively observed the response of patients with COPD to CSBHT and HGYGT as adjunctive therapies and assessed the feasibility of future research. Methods: Patients with COPD who were prescribed adjunctive HGYGT or CSBHT according to the COPD clinical practice protocol of Kyung Hee University Korean Medicine Hospital were recruited. Participants visited the hospital every month, for 6 months, to receive herbal preparations according to a Korean Medicine doctor's diagnosis and prescription and outcome evaluations. The primary outcome was the 6-min walking test (6-MWT). Secondary outcomes included the pulmonary function test (PFT), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and modified Medical Research Council (mMRC) score. Syndrome differentiation, adverse events, and patient adherence were recorded. Results: Thirty-seven patients were initially enrolled and followed up for a mean period of 154.1 days. CSBHT was prescribed to 36 patients, while one patient received either CSBHT or HGYGT, or both, throughout the entire period. During the herbal preparation treatment period, no statistically significant changes were observed in the 6-MWT. The CAT score (mean ± standard deviation) changed from 17.0 ± 5.0 to 12.5 ± 3.6, and the visual analogue scale score for dyspnea changed from 47.5 ± 18.9 to 28.4 ± 18.6 (both statistically significant from visit 5). The coronavirus disease 2019 pandemic precluded the PFT. SGRQ and mMRC scores did not change significantly. During the study period, seven patients dropped out, two experienced mild dyspepsia, and one experienced mild headache. No serious adverse effects were observed. Conclusion: We illustrated the therapeutic potential of CSBHT and provided preliminary clinical data on its efficacy and safety in patients with COPD. Our study highlights the need to derive optimal herbal formulations, which should be administered for an appropriate duration, based on the therapeutic goals for the treatment of COPD. [ABSTRACT FROM AUTHOR]

Quetiapine myristate (QM), an ester‐bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self‐assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200‐nm‐sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide‐co‐glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg−1 QTP), QMN undergoes pH‐responsive nanoaggregation to form the lipophilic prodrug, providing esterase‐oriented sustained release for five weeks compared with the two‐week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long‐acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long‐acting injectable to improve patient compliance and dosing frequency. [ABSTRACT FROM AUTHOR]

Background: Pathogenic variants of MYH7, which encodes the beta-myosin heavy chain protein, are major causes of dilated and hypertrophic cardiomyopathy. Methods: In this study, we used whole-genome sequencing data to identify MYH7 variants in 397 patients with various cardiomyopathy subtypes who were participating in the National Project of Bio Big Data pilot study in Korea. We also performed in silico analyses to predict the pathogenicity of the novel variants, comparing them to known pathogenic missense variants. Results: We identified 27 MYH7 variants in 41 unrelated patients with cardiomyopathy, consisting of 20 previously known pathogenic/likely pathogenic variants, 2 variants of uncertain significance, and 5 novel variants. Notably, the pathogenic variants predominantly clustered within the myosin motor domain of MYH7. We confirmed that the novel identified variants could be pathogenic, as indicated by high prediction scores in the in silico analyses, including SIFT, Mutation Assessor, PROVEAN, PolyPhen-2, CADD, REVEL, MetaLR, MetaRNN, and MetaSVM. Furthermore, we assessed their damaging effects on protein dynamics and stability using DynaMut2 and Missense3D tools. Conclusions: Overall, our study identified the distribution of MYH7 variants among patients with cardiomyopathy in Korea, offering new insights for improved diagnosis by enriching the data on the pathogenicity of novel variants using in silico tools and evaluating the function and structural stability of the MYH7 protein. [ABSTRACT FROM AUTHOR]

Tadalafil (TD) has poor water solubility but is well absorbed without affecting food intake when administered orally. Owing to patient adherence and therapeutic characteristics, a TD-loaded orodispersible film (TDF) is preferable. However, the mechanistic role of dietary status on the clinical pharmacokinetic analysis of TDF in human volunteers should be investigated because the gastrointestinal environment varies periodically according to meal intervals, although commercial 20 mg TD-loaded tablets (TD-TAB, Cialis® tablet) may be taken with or without food. TDF was prepared by dispersing TD in an aqueous solution and polyethylene glycol 400 to ensure good dispersibility of the TD particles. In the fasting state, each T/R of Cmax and AUC between TD-TAB and TDF showed bioequivalence with 0.936–1.105 and 1.012–1.153, respectively, and dissolution rates in 1000 mL water containing 0.5% SLS were equivalent. In contrast, TDF was not bioequivalent to TD-TAB under the fed conditions by the Cmax T/R of 0.610–0.798. The increased dissolution rate of TDF via the micronization of drug particles and the reduced viscosity of the second meal content did not significantly affect the bioequivalence. Interestingly, an increase in second meal intake time from 4 h to 6 h resulted in the bioequivalence by the Cmax T/R of 0.851–0.998 of TD-TAB and TDF. The predictive diffusion direction model for physical digestion of TD-TAB and TDF in the stomach after the first and second meal intake was successfully simulated using computational fluid dynamics modeling, accounting for the delayed drug diffusion of TDF caused by prolonged digestion of stomach contents under postprandial conditions. [ABSTRACT FROM AUTHOR]