Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Effect of Mollusca shell extracts on inhibition of kimchi over-acidification.

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro.

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.

Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Forsythiaside A Activates AMP-Activated Protein Kinase and Regulates Oxidative Stress via Nrf2 Signaling.

Forsythiaside A (FA) is an active constituent isolated from Forsythia suspensa, a beneficial herb used in traditional medicine known for its antioxidant and anti-inflammatory properties. Although various studies have suggested that FA has the protective effects, its impacts on arachidonic acid (AA) plus iron in vitro models and carbon tetrachloride (CCl4)-induced mouse liver damage in vivo have not been explored. In this study, HepG2 cells were subjected to AA + iron treatment to induce apoptosis and mitochondrial impairment and determine the molecular mechanisms. FA exhibited protective effects by inhibiting cell damage and reactive oxygen species (ROS) production induced by AA + iron, as assessed via immunoblot and flow cytometry analyses. Further molecular investigations revealed that FA resulted in the activation of extracellular-signal-related protein kinase (ERK), which subsequently triggered the activation of AMP-activated protein kinase (AMPK), a critical regulator of cellular oxidative stress. Additionally, FA modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is a significant antioxidant transcription factor regulated by the AMPK pathway. For in vivo studies, mice were orally administered FA and then subjected to induction of CCl4-based hepatotoxicity. The protective effect of FA was confirmed via blood biochemistry and immunohistochemical analyses. In conclusion, our findings demonstrated the protective effects of FA against oxidative stress both in vitro and in vivo, thus indicating that FA is a potential candidate for liver protection. Our study sheds light on the mechanistic pathways involved in the antioxidant effects of FA, highlighting the hepatoprotective potential of naturally occurring compounds in traditional herbs, such as FA.

Exploring the mechanism of action of total glucosides of paeony against autoimmune thyroiditis based on network pharmacology and molecular docking.

The objective of this study is to explore the potential mechanism of action of Total glucosides of paeony (TGP) in the treatment of autoimmune thyroiditis (AIT). The study utilized literature mining to obtain the active ingredients of TGP. Databases such as Super-PRED, similarity ensemble approach, and Swiss Target Prediction were utilized to predict the targets of the active ingredients. DisGeNET, Dangbank, GeneCards, online mendelian inheritance in man, and Pharmgkb databases were used to obtain the targets related to AIT. The Venn Online tool was used to screen the intersecting genes between the active ingredients and AIT targets. The STRING database was employed to analyze protein protein interaction. Gene ontology bio-enrichment and Kyoto encyclopedia of genes and genomes enrichment of common targets were analyzed using R language. Finally, molecular docking was performed using AutoDockTools-1.5.6 software for validation. The study identified 5 active ingredients of TGP, 283 ingredient targets, 7120 disease targets, 220 intersecting targets, 30 entries for gene ontology analysis, and 30 pathways for Kyoto encyclopedia of genes and genomes analysis. The important targets of the protein protein interaction network were identified as interleukin-6, proto-oncogene tyrosine-protein kinase, epidermal growth factor receptor, among others. The molecular docking validation results showed that Paeoniflorin, albiflorin, and benzoylpaeoniflorin and oxypaeoniflor all bind well to interleukin-6, epidermal growth factor receptor, and proto-oncogene tyrosine-protein kinase. This study reveals the multi-component, multi-target and multi-pathway mechanism of action of TGP in regulating AIT and provides a reference for subsequent basic research.

Anti-Inflammatory Effects of Alphitolic Acid Isolated from Agrimonia coreana Nakai Extracts Are Mediated via the Inhibition of ICRAC Activity in T Cells.

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.

Acupuncture Treatment for Emotional Problems in Women with Infertility: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of acupuncture in treating emotional problems in women with infertility. We searched for randomized controlled trials using acupuncture treatment for emotional problems in women with infertility using 11 databases from their inception to 30 June 2023. The control intervention included no treatment, sham acupuncture treatment, and conventional treatment. The primary outcome was emotion-related rating scales, and the secondary outcomes were total effectiveness rate, quality of life, clinical pregnancy rate, and adverse events. Twelve randomized controlled trials involving 1930 participants were included. A meta-analysis of these studies indicated that, as compared to the control treatment, acupuncture significantly improved the State-Trait Anxiety Inventory, Self-rating Anxiety Scale, Amsterdam Preoperative Anxiety and Information Scale, and Self-rating Depression Scale scores, which were the primary emotion-related outcomes. Furthermore, the meta-analysis demonstrated that acupuncture treatment had a significant effect on the clinical pregnancy rate, which was the secondary outcome. No adverse events were reported in any of the studies. Our findings demonstrate the potential of acupuncture for treating emotional problems in women with infertility. However, well-designed and high-quality randomized clinical trials are required to confirm the effectiveness and safety of acupuncture treatment. The protocol of the current study was registered in PROSPERO (registration number: CRD42020166119).

Herbal Medicine for Postpartum Pain: A Systematic Review of Puerperal Wind Syndrome (Sanhupung).

Mothers in the postpartum period often experience musculoskeletal disorders and pain, impacting their ability to care for themselves and their infants. Conventional treatments have limitations, prompting interest in alternative options like herbal medicine. This systematic review aimed to confirm the effectiveness and safety of herbal medicine treatment to improve maternal health in patients with postpartum pain (puerperal wind syndrome). We searched eight electronic databases for randomized controlled trials (RCTs) to evaluate the effects of herbal medicines on puerperal wind syndrome. Nine RCTs, including 652 patients, were selected. Following a meta-analysis of RCTs, both herbal medicine and combination treatments improved the visual analog scale scores, total effective rate, scores of Traditional Chinese Medicine syndromes, Oswestry Disability Index, and quality of life in patients with role-emotional puerperal wind syndrome. All adverse events were minor, and the incidence rate was not high compared with that of the control group. In conclusion, herbal medicine supports the improvement in pain, other systemic symptoms, and the quality of life of patients with puerperal wind syndrome. Moreover, no serious side effects were observed; therefore, herbal medicines appear to be safe. It can be the preferred treatment option for puerperal wind syndrome, which is currently managed symptomatically.

Comparative study of the mechanism of natural compounds with similar structures using docking and transcriptome data for improving in silico herbal medicine experimentations.

Natural products have successfully treated several diseases using a multi-component, multi-target mechanism. However, a precise mechanism of action (MOA) has not been identified. Systems pharmacology methods have been used to overcome these challenges. However, there is a limitation as those similar mechanisms of similar components cannot be identified. In this study, comparisons of physicochemical descriptors, molecular docking analysis and RNA-seq analysis were performed to compare the MOA of similar compounds and to confirm the changes observed when similar compounds were mixed and used. Various analyses have confirmed that compounds with similar structures share similar MOA. We propose an advanced method for in silico experiments in herbal medicine research based on the results. Our study has three novel findings. First, an advanced network pharmacology research method was suggested by partially presenting a solution to the difficulty in identifying multi-component mechanisms. Second, a new natural product analysis method was proposed using large-scale molecular docking analysis. Finally, various biological data and analysis methods were used, such as in silico system pharmacology, docking analysis and drug response RNA-seq. The results of this study are meaningful in that they suggest an analysis strategy that can improve existing systems pharmacology research analysis methods by showing that natural product-derived compounds with the same scaffold have the same mechanism.

Levo-tetrahydropalmatine ameliorates neuropathic pain by inhibiting the activation of the Clec7a-MAPK/NF-κB-NLRP3 inflammasome axis.

BACKGROUND: Because of the complex pathogenesis of neuropathic pain (NP), the therapeutic efficacy of existing drugs is not satisfactory. Accumulating studies have indicated that neuroinflammation may play a key role in NP onset and progression. Levo-tetrahydropalmatine (l-THP) has been extensively used for relieving chronic pain for decades. However, its potential mechanisms against NP have not yet been fully elucidated. PURPOSE: Exploring and elucidating the therapeutic effect and pharmacological mechanism of l-THP in treating NP. METHODS: RNA-seq and bioinformatics analyses were carried out to identify effective target profiling of I-THP in chronic constrictive injury (CCI) rats. The I-THP related hub targets and signaling pathways were obtained via bioinformatics analysis, then subjected to in-depth analyses through experiments in vivo. A gain-of-function study further confirmed the role of Clec7a in l-THP-mediated pain relief. Finally, the interaction between l-THP and Clec7a was verified through molecular docking and surface plasmon resonance (SPR). RESULTS: l-THP treatment effectively alleviated mechanical and thermal allodynia in NP model rats. Functionally, the I-THP effective targets were mainly enriched in inflammatory response-related pathways. Furthermore, Clec7a-MAPK/NF-κB-NLRP3 inflammasome axis was selected as one of the potential pathways of l-THP against NP. Mechanically, l-THP markedly reduced CCI-induced Clec7a overexpression, significantly inhibited the Clec7a-triggered phosphorylation of MAPK and NF-κB-p65, and decreased the expression of pyroptosis-related protein NLRP3 and Caspase-1-p20. The analgesic effect of l-THP on NP was partly eliminated when transfecting the overexpression vector virus pLVSO5Clec7a. Importantly, molecular docking and SPR data revealed that l-THP directly binds with the Clec7a protein. CONCLUSION: This study is the first to indicate that l-THP may exert an analgesic effect through inhibiting neuroinflammation via the Clec7a-MAPK/NF-κB-NLRP3 inflammasome axis, supporting the clinical utility of l-THP in NP therapy.

Guided isolation of secondary metabolites from Nectria sp. MHHJ-3 by molecular network strategy.

The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.

Effects of a Meaning-Centered Spiritual Care Training Program for Hospice Palliative Care Teams in South Korea: A Nonrandomized Controlled Trial.

BACKGROUND: Spiritual care is an essential part and a core component of quality palliative care, as identified by the World Health Organization. However, spiritual care training for hospice palliative care teams (HPCTs) is infrequent. OBJECTIVE: The aim of this study was to investigate the effects of a meaning-centered spiritual care training program for HPCTs (McSCTP-HPCT). METHODS: This study used a nonrandomized controlled design. The McSCTP-HPCT comprised 5 modules. The participants were HPCTs working in 15 national hospice institutions and were allocated to either the experimental group (n = 33) or the control group (n = 27) based on the participating institutions' preference. Three outcome variables were tested: spiritual care competency, spiritual care therapeutics, and compassion fatigue. Data were analyzed using descriptive statistics, χ 2 test, 1-way analysis of variance, and repeated-measures analysis of variance. RESULTS: There was a significant difference in the interaction between measurement time and group assignment in spiritual care competency ( P = .002) and spiritual care therapeutics ( P = .038), whereas no significant difference was found for compassion fatigue ( P = .716). CONCLUSION: The McSCTP-HPCT conducted in this study shows effectiveness in increasing the spiritual care competency and spiritual care therapeutics of HPCTs and may support the importance of spiritual care training. IMPLICATIONS FOR PRACTICE: The McSCTP-HPCTs adds to the scientific evidence on spiritual care and has the capacity to improve the quality of care for patients with a life-threatening illness.

Identifying target organ location of Radix Achyranthis Bidentatae: a bioinformatics approach on active compounds and genes.

Background: Herbal medicines traditionally target organs for treatment based on medicinal properties, and this theory is widely used for prescriptions. However, the scientific evidence explaining how herbs act on specific organs by biological methods has been still limited. This study used bioinformatic tools to identify the target organ locations of Radix Achyranthis Bidentatae (RAB), a blood-activating herb that nourishes the liver and kidney, strengthens bones, and directs prescription to the lower body. Methods: RAB's active compounds and targets were collected and predicted using databases such as TCMSP, HIT2.0, and BATMAN-TCM. Next, the RAB's target list was analyzed based on two approaches to obtain target organ locations. DAVID and Gene ORGANizer enrichment-based approaches were used to enrich an entire gene list, and the BioGPS and HPA gene expression-based approaches were used to analyze the expression of core genes. Results: RAB's targets were found to be involved in whole blood, blood components, and lymphatic organs across all four tools. Each tool indicated a particular aspect of RAB's target organ locations: DAVID-enriched genes showed a predominance in blood, liver, and kidneys; Gene ORGANizer showed the effect on low body parts as well as bones and joints; BioGPS and HPA showed high gene expression in bone marrow, lymphoid tissue, and smooth muscle. Conclusion: Our bioinformatics-based target organ location prediction can serve as a modern interpretation tool for the target organ location theory of traditional medicine. Future studies should predict therapeutic target organ locations in complex prescriptions rather than single herbs and conduct experiments to verify predictions.

Research on the Chemical Constituents against Alzheimer's Disease of the Fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Physalis alkekengi L. var. franchetii (Mast.) Makino (PA) is a natural plant which is utilised as a traditional herbal medicine. It has properties that make it effective against inflammation and free radical damage. In the present study, the major constituents of four extraction parts of the fruits of PA (PAF) were investigated by combining ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The mice model of Alzheimer's disease (AD) induced by aluminum chloride (AlCl3 ) combined with D-galactose (D-gal) was established to comprehend the mechanism behind PAF's anti-AD activity from both behavioural and pathological perspectives. The results showed that four extraction parts of PAF (PAFE) had favorable anti-AD effects and the ethyl acetate (EA) group showed the best activity. UPLC-Q-TOF-MS analysis identified Physalin B, Nobiletin and Caffeic acid as the main anti-AD active constituents in EA extract. This study reveals that PAF can reduce neuroinflammatory damage by inhibiting p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which is the theoretical basis for clinical development and utilization of PAF in AD therapy.

PLM-101 is a novel and potent FLT3/RET inhibitor with less adverse effects in the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.