Transformative Outcomes With Paliperidone Long-Acting Injection in Severe Treatment-Resistant Schizophrenia: A Case Report and Literature Review.

Treatment-resistant schizophrenia (TRS) presents considerable challenges in contemporary psychiatric practice due to inadequate response to conventional antipsychotic treatments. Paliperidone, the primary active metabolite of risperidone, particularly in its long-acting injectable (LAI) form, has emerged as a promising option for TRS due to its consistent medication delivery, reducing symptom exacerbation and relapse associated with oral dosing fluctuations. This case report presents the clinical journey of a 42-year-old female diagnosed with schizophrenia at age 15. Despite numerous hospital admissions and trials of various oral and injectable antipsychotics, including clozapine and electroconvulsive therapy (ECT), her symptoms persisted. During her last admission, her condition showed minimal improvement despite extensive pharmacological interventions. Introducing paliperidone LAI while tapering off other antipsychotics led to significant improvements within four weeks. The patient exhibited reduced hallucinatory behaviour, delusions, and disorganized behaviour. Follow-up assessments confirmed sustained progress, with the patient showing increased engagement in daily activities and reduced irritability and suspiciousness. This case underscores the potential efficacy of paliperidone LAI in managing TRS. The patient's notable improvement highlights the importance of personalized treatment plans and continuous monitoring in complex psychiatric conditions. Its favourable safety and tolerability profile further supports its use as a long-term treatment option for TRS, potentially leading to enhanced patient compliance and overall quality of life. The significant symptomatic relief and functional improvement observed advocate for the consideration of paliperidone LAI as a promising therapeutic option for TRS, with the potential to be considered in the future among the first-line treatments for TRS.

Clinical effectiveness of paliperidone palmitate 3-monthly and 1-monthly as monotherapy in patients with schizophrenia: A retrospective cohort study based on the Medicaid claims database.

AIM: Real-world data (RWD) for paliperidone palmitate (PP) three-monthly (PP3M) is lacking based on Japan label requirements. This study evaluated the clinical effectiveness of PP3M versus PP once-monthly (PP1M) in patients with schizophrenia administered according to Japan label requirements. METHODS: Retrospective analyses were conducted using RWD from Merative™ MarketScan® Multi-State Medicaid (MDCD) claims database (June 2015-December 2022). Adult patients with schizophrenia switching from PP1M to PP3M were included. Patients transitioning to PP3M were matched with patients who continued with PP1M using propensity score matching (PSM) at 1:1 ratio. Primary hypothesis aimed to investigate non-inferiority of PP3M versus PP1M in terms of relapse-free status at 24 months from index PP injection. Outcome measures were proportions of relapse-free patients at 24 months, time to relapse, treatment persistence, and adherence. RESULTS: Total 4252 eligible adult schizophrenia patients on PP (PP3M:582; PP1M:3670) were identified. After PSM, each PP cohort comprised 562 matched individuals. Estimated proportion of relapse-free patients was higher in PP3M (85.7%) versus PP1M (77.9%), per Japan PP label. PP3M demonstrated superiority to PP1M after testing for non-inferiority in terms of achieving relapse-free status at 24 months, with an estimated difference of 7.8% (95% CI: 1.7%-13.9%). PP3M cohort had lower risk of relapse (HR: 0.605; CI: 0.427-0.856), longer treatment persistence, and higher treatment adherence versus PP1M cohort. CONCLUSIONS: Findings suggests that patients who switched to PP3M might be able to reduce risk of relapse compared to those who continued PP1M after aligning particularly with Japan's label requirements.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K/AKT/mTOR axis.

OBJECTIVE: This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). METHODS: Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated ß-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. RESULTS: Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence.

An A2 ß-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial.

The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 ß-casein cow's milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow's milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 ß-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM. Clinical trial registration: https://clinicaltrials.gov/, NCT04749290.

Extract of Phyllanthus emblica L. fruit stimulates basal glucose uptake and ameliorates palmitate-induced insulin resistance through AMPK activation in C2C12 myotubes.

BACKGROUND: The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. METHODS: Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. RESULTS: In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. CONCLUSIONS: WEPE significantly stimulated basal glucose uptake though CaMKKß/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

Evaluation and comparison of sensitivity of alcohol biomarkers PEth, EtG and EtPa in civil cases in England 2022-2023.

This study details trends in direct alcohol biomarker concentrations from civil cases within the United Kingdom (UK). Our subject cohort in this study related to family law litigation, where an individual was subject to an alcohol monitoring order by the court. This monitoring was conducted by quantification of alcohol biomarkers Phosphatidlyethanol (PEth) in dried blood spots (DBS) and Ethyl Glucuronide (EtG) and Ethyl Palmitate (EtPa) from hair segments. In total 298 PEth cases predominantly from the South East of England during the period July 2022 to August 2023 were analysed for alcohol biomarkers in DBS and hair. Subjects alcohol intake was classified as abstinence/low alcohol consumption, moderate or excessive alcohol consumption, based on a combination of Society for Hair Testing and PEth Net guidelines. Our results indicate that 33 % of PEth concentrations were consistent with excessive alcohol use (>200 ng/mL DBS), with 36 % consistent with social or moderate alcohol use (20-200 ng/mL DBS). In relation to EtG and EtPa 23 % and 31 % of subjects were classified as excessive alcohol users respectively. This study indicates that DBS sampling of PEth is a more sensitive predictor of alcohol use, in particular, at differentiating between moderate and excessive alcohol use compared to EtG and EtPa testing in hair. The authors suggest that increased frequency in the sampling of PEth in DBS (multiple occasions per month) may provide a more accurate assessment and simplification of the interpretation criteria of alcohol patterns rather than the combined hair testing and DBS sampling that are typically requested by UK courts.

Human cardiac metabolism.

The heart is the most metabolically active organ in the human body, and cardiac metabolism has been studied for decades. However, the bulk of studies have focused on animal models. The objective of this review is to summarize specifically what is known about cardiac metabolism in humans. Techniques available to study human cardiac metabolism are first discussed, followed by a review of human cardiac metabolism in health and in heart failure. Mechanistic insights, where available, are reviewed, and the evidence for the contribution of metabolic insufficiency to heart failure, as well as past and current attempts at metabolism-based therapies, is also discussed.

Ethnobotany, phytochemistry, pharmacology and quality control of Peucedanum decursivum (Miq.) Maxim: A critical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dried roots of Peucedanum decursivum, a traditional Chinese medicine (TCM), has historically respiratory diseases such as cough, thick phlegm, headache, fever, and gynecological diseases, rheumatoid arthritis, and nasopharyngeal carcinoma. AIM OF THE STUDY: Made an endeavor to evaluate the research trajectory of P. decursivum, comprehensively discern its developmental status, and offer a guideline for future investigations. MATERIALS AND METHODS: A meticulous search of literatures and books from 1955 to 2024 via databases like PubMed, Web of Science and CNKI was conducted, including topics and keywords of " P. decursivum" "Angelica decursivum" and "Zihua Qianhu". RESULTS: P. decursivum and its prescriptions have traditionally been used for treating phlegm-heat cough, wind-heat cough, gastrointestinal diseases, pain relief and so on. It contains 234 identified compounds, encompassing coumarins, terpenes, volatile oils, phenolic acids, fatty acids and derivatives. It exhibits diverse pharmacological activities, including anti-asthmatic, anti-inflammatory, antioxidant effects, anti-hypertensive, anti-diabetic, anti-Alzheimer, and anti-cancer properties, primarily attributed to coumarins. Microscopic identification, HPLC fingerprinting, and bioinformatics identification are the primary methods currently used for the quality control. CONCLUSION: P. decursivum demonstrates anti-asthmatic, anti-inflammatory, and antioxidant effects, aligning with its traditional use. However, experimental validation of its efficacy against phlegm and viruses is needed. Additionally, analgesic effects mentioned in historical texts lack modern pharmacological studies. Numerous isolated compounds exhibit highly valuable medicinal properties. Future research can delve into exploring these substances further. Rigorous of heavy metal contamination, particularly Cd and Pb, is necessary. Simultaneously, investigating its pharmacokinetics and toxicity in humans is crucial for the safety.

Solid Lipid Nanoparticles Loaded with Dexamethasone Palmitate for Pulmonary Inflammation Treatment by Nebulization Approach.

Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.

Liposomal Encapsulation of Ascorbyl Palmitate: Influence on Skin Performance.

L-ascorbic acid represents one of the most potent antioxidant, photoprotective, anti-aging, and anti-pigmentation cosmeceutical agents, with a good safety profile. However, the main challenge is the formulation of stable topical formulation products, which would optimize the penetrability of L-ascorbic acid through the skin. The aim of our research was to evaluate the performance of ascorbyl palmitate on the skin, incorporated in creams and emulgels (2%) as carriers, as well as to determine the impact of its incorporation into liposomes on the penetration profile of this ingredient. Tape stripping was used to study the penetration of ascorbyl palmitate into the stratum corneum. In addition, the sensory and textural properties of the formulations were determined. The liposomal formulations exhibited a better penetration profile (p < 0.05) of the active substance compared to the non-liposomal counterpart, leading to a 1.3-fold and 1.2 fold-increase in the total amount of penetrated ascorbyl palmitate in the stratum corneum for the emulgel and cream, respectively. Encapsulation of ascorbyl palmitate into liposomes led to an increase in the adhesiveness and density of the prepared cream and emulgel samples. The best spreadability and absorption during application were detected in liposomal samples. The obtained results confirmed that liposomal encapsulation of ascorbyl palmitate improved dermal penetration for both the cream and emulgel formulations.

The Impact of Phospholipid-Based Liquid Crystals' Microstructure on Stability and Release Profile of Ascorbyl Palmitate and Skin Performance.

The drug delivery potential of liquid crystals (LCs) for ascorbyl palmitate (AP) was assessed, with the emphasis on the AP stability and release profile linked to microstructural rearrangement taking place along the dilution line being investigated by a set of complementary techniques. With high AP degradation observed after 56 days, two stabilization approaches, i.e., the addition of vitamin C or increasing AP concentration, were proposed. As a rule, LC samples with the lowest water content resulted in better AP stability (up to 52% of nondegraded AP in LC1 after 28 days) and faster API release (~18% in 8 h) as compared to the most diluted sample (29% of nondegraded AP in LC8 after 28 days, and up to 12% of AP released in 8 h). In addition, LCs exhibited a skin barrier-strengthening effect with up to 1.2-fold lower transepidermal water loss (TEWL) and 1.9-fold higher skin hydration observed in vitro on the porcine skin model. Although the latter cannot be linked to LCs' composition or specific microstructure, the obtained insight into LCs' microstructure contributed greatly to our understanding of AP positioning inside the system and its release profile, also influencing the overall LCs' performance after dermal application.

Dexamethasone Palmitate Encapsulated in Palmitic Acid Modified Human Serum Albumin Nanoparticles for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.

Saturated fatty acids negatively affect musculoskeletal tissues in vitro and in vivo.

Fish oils rank among the world's most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Infant Formula with 50% or More of Palmitic Acid Bound to the sn-2 Position of Triacylglycerols Eliminate the Association between Formula-Feeding and the Increase of Fecal Palmitic Acid Levels in Newborns: An Exploratory Study.

The binding ratio of palmitic acid (PA) at the sn-2 position of triacylglycerols in infant formulas is lower than that in breast milk, resulting in higher levels of fecal PA. Even if the ratio is increased to 40-50%, fecal PA levels in formula-fed infants remain higher than those in breast-fed infants. In Japan, infant formulas with 50% or more of PA bound to sn-2 (high sn-2 PA milk) are commercially available; however, their effects on PA excretion have not been investigated. Therefore, this observational study aimed to preliminarily evaluate whether the feeding volume of high sn-2 PA milk is significantly associated with fecal total/soaped PA levels in newborns. Infant formulas were classified as high (≥50% of PA bound to sn-2) or low sn-2 (<50%) PA milk. Associations between feeding volume of high or low sn-2 PA milk and fecal PA levels were evaluated using multiple regression analysis models. The results showed that the feeding volume of low sn-2 PA milk was positively associated with fecal total/soaped PA levels, while there was no significant association between those of high sn-2 PA milk and fecal total/soaped PA levels. Our preliminary study suggests that high sn-2 PA milk may reduce increased fecal PA levels in formula-fed newborns.

Phytochemical analysis, physicochemical, pharmacokinetic properties and molecular docking studies of bioactive compounds in Ottelia alismoides (L.) pers. Against breast cancer proteins.

Plants provide compounds that can be used to treat diseases, and in silico methods help to expedite drug discovery while reducing costs. This study explored the phytochemical profile of methanol extract of O. alismoides using GC-MS to identify potential bioactive compounds. Autodock 4.2.6. was employed for molecular docking evaluation of the efficacy of these identified compounds against Estrogen Receptor Alpha (ERα), Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor (EGFR), proteins. Additionally, the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of the compounds were predicted using the SwissADME online tool. The preliminary phytochemical analysis revealed the presence of alkaloids, carbohydrates, glycosides, and steroids. During the GC-MS analysis, seven compounds were identified, and drug-likeness prediction of these compounds showed good pharmacokinetic properties having high gastrointestinal absorption, and orally bioavailable. The molecular docking studies exhibited promising binding affinities of bioactive compounds against all target proteins. Specifically, the compounds Tricyclo[5.2.1.0(2,6)]decan-10-ol and 2,2,6-Trichloro-7-oxabicyclo[4.1.0]heptane-1-carboxamide demonstrated the highest binding affinities with the ERα (-6.3 and - 6.0 k/cal), HER2 (-5.6 and - 6.1 k/cal), and EGFR (-5.4 and - 5.4 k/cal), respectively. These findings suggest the potential of O. alismoides as a source for developing new cancer therapeutics. The study highlights the effectiveness of in silico approaches for accelerating drug discovery from natural sources and paves the way for further exploration of these promising compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00227-y.

Effects of ethyl palmitate on the release of aroma compounds in propanediol-ethanol solution and its mechanisms.

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment.

Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to these symptoms, leading to a USD 50 billion annual loss of salary. Neurological symptoms associated with long COVID result from persistent infection with SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous system (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in olfactory mucosa. Recently published clinical data demonstrate that only 5% of long COVID anosmia patients have fully recovered during the past 2 years, and 10.4% of COVID patients are still symptomatic 18 months post-infection. Our group demonstrated that epigallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activity against human coronavirus, suggesting that this green-tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to restoration of neurologic functions. The objective of the current study was to evaluate the mucociliary safety of the EC16m nasal nanoformulations and their efficacy against human coronavirus. METHODS: Nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using the MucilAir human nasal model; contact antiviral activity and post-infection inhibition against the OC43 viral strain were assessed by the TCID50 assay for cytopathic effect on MRC-5 cells. RESULTS: The saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference compared to saline (0.9% NaCl) with respect to tissue integrity, cytotoxicity, and cilia beat frequency. A 5 min contact resulted in 99.9% inactivation of ß-coronavirus OC43. OC43 viral replication was inhibited by >90% after infected MRC-5 cells were treated with the formulations. CONCLUSION: The saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety properties comparable to saline, a solution widely used for nasal applications.