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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]

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]

We conducted this single-center, retrospective, cohort study to examine whether insulin resistance (IR) and high-sensitivity C-reactive protein (hsCRP) have a relationship with metabolic abnormalities in patients with type 2 diabetes mellitus (T2DM). In a total of 3758 patients (n = 3758) with T2DM, we analyzed medical records and thereby evaluated their baseline characteristics such as age, sex, duration of T2DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference, body mass index (BMI), visceral fat thickness (VFT), fasting plasma insulin levels, C-peptide levels, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), albuminuria, intima-media thickness (IMT) and hsCRP. The patients were stratified according to the tertile of the K index of the insulin tolerance test (KITT) or hsCRP. Thus, they were divided into the lowest (≥2.37), middle (1.54–2.36) and highest tertile (0–1.53) of KITT and the lowest (0.00–0.49), middle (0.50–1.21) and highest tertile (≥1.22) of hsCRP. Moreover, associations of KITT and hsCRP with metabolic abnormalities, such as steatotic liver disease (SLD), metabolic syndrome (MetS), albuminuria, diabetic retinopathy and carotid atherosclerosis, were also analyzed. There was a significant positive correlation between the prevalence of SLD, MetS, albuminuria and diabetic retinopathy and KITT (p < 0.001). Moreover, there was a significant positive association between the prevalence of SLD, MetS and albuminuria and hsCRP (p < 0.001). In conclusion, our results indicate that clinicians should consider the relationships of IR and hsCRP with metabolic abnormalities in the management of patients with T2DM. However, further large-scale, prospective, multi-center studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Fexuprazan (Fexuclue®; Daewoong Pharmaceutical Co., Ltd., Seoul, Korea) is a novel potassium-competitive acid blocker (P-CAB). This multi-center, randomized, double-blind, active-controlled, parallel-group, therapeutic confirmatory, phase III study was conducted to assess its efficacy and safety compared with esomeprazole (Nexium®; AstraZeneca, Gothenburg, Mölndal, Sweden) in Korean patients with erosive esophagitis (EE). Methods: This study evaluated patients diagnosed with EE at a total of 25 institutions in Korea between 13 December 2018 and 7 August 2019. After voluntarily submitting a written informed consent form, the patients were evaluated using a screening test and then randomized to either of the two treatment arms. The proportion of the patients who achieved the complete recovery of mucosal breaks at 4 and 8 weeks, the proportion of those who achieved the complete recovery of heartburn at 3 and 7 days and 8 weeks, and changes in the GERD–Health-Related Quality of Life Questionnaire (GERD-HRQL) scores at 4 and 8 weeks from baseline served as efficacy outcome measures. The incidence of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) and the serum gastrin levels served as safety outcome measures. Results: The study population comprised a total of 231 patients (n = 231) with EE, including 152 men (65.80%) and 79 women (34.20%); their mean age was 54.37 ± 12.66 years old. There were no significant differences in the efficacy and safety outcome measures between the two treatment arms (p > 0.05). Conclusions: It can be concluded that the efficacy and safety of Fexuclue® are not inferior to those of esomeprazole in Korean patients with EE. [ABSTRACT FROM AUTHOR]

Recognizing the growing interests and benefits of technology-assisted interactive telerehabilitation in various populations, the aim of this review is to systematically review the effects of interactive telerehabilitation with remote monitoring and guidance for improving balance and gait performance in older adults and individuals with neurological conditions. The study protocol for this systematic review was registered with the international prospective register of systematic reviews (PROSPERO) with the unique identifier CRD42024509646. Studies written in English published from January 2014 to February 2024 in Web of Science, Pubmed, Scopus, and Google Scholar were examined. Of the 247 identified, 17 were selected after initial and eligibility screening, and their methodological quality was assessed with the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. All 17 studies demonstrated balance and gait performance improvement in older adults and in individuals with stroke, Parkinson's disease, and multiple sclerosis following 4 or more weeks of interactive telerehabilitation via virtual reality, smartphone or tablet apps, or videoconferencing. The findings of this systematic review can inform the future design and implementation of interactive telerehabilitation technology and improve balance and gait training exercise regimens for older adults and individuals with neurological conditions. [ABSTRACT FROM AUTHOR]

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss‐of‐function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self‐mutilating behavior, and intellectual disability. Methods: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing. Results: CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3–8 years). Two patients exhibited self‐mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851‐33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574‐156_850+1113del (exons 5‐7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851‐33T>A (p.?) mutations and compound heterozygous for c.851‐33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574‐156_850+1113del (exons 5‐7 del) displayed a late onset and milder clinical manifestation. Conclusion: All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity. [ABSTRACT FROM AUTHOR]