Inhibition of pancreatic lipase by coffee leaves-derived polyphenols: A mechanistic study.

The suppression of pancreatic lipase has been employed to mitigate obesity. This study explored the mechanism of coffee leaf extracts to inhibit pancreatic lipase. The ethyl acetate fraction derived from coffee leaves (EAC) exhibited the highest inhibitory capacity with a half-maximal inhibitory concentration (IC50) of 0.469 mg/mL and an inhibitor constant (Ki) of 0.185 mg/mL. This fraction was enriched with 3,5-dicaffeoylquinic acid (3,5-diCQA, 146.50 mg/g), epicatechin (87.51 mg/g), and isoquercetin (48.29 mg/g). EAC inhibited lipase in a reversible and competitive manner, and quenched its intrinsic fluorescence through a static mechanism. Molecular docking revealed that bioactive compounds in EAC bind to key amino acid residues (HIS-263, PHE-77, and SER-152) located within the active cavity of lipase. Catechin derivatives play a key role in the lipase inhibitory activity within EAC. Overall, our findings highlight the promising potential of coffee leaf extract as a functional ingredient for alleviating obesity through inhibition of lipase.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Mechanism of the Effect of Scopolamine on Breast Cancer: Determination by Network Pharmacology and Bioinformatics.

BACKGROUND: To a certain extent, traditional Chinese medicine (TCM)-based anesthesia has replaced opiate administration in recent years. Preliminary drug screening has revealed that scopolamine may affect breast cancer (BC) metastasis by an unknown mechanism. METHODS: Network pharmacology, bioinformatics, and protein-protein interaction (PPI) topological analysis were implemented to identify the core genes linking scopolamine and BC. The core genes were then subjected to gene expression profiling interactive analysis (GEPIA). The top ten pathways were detected by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The impact of immune infiltration on the core gene difference and survival analyses was then determined. Molecular docking was then performed on the core genes and the main active components. RESULTS: Protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), heat shock protein 90 alpha class A (HSP90AA1), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) were the key genes in the interaction between scopolamine and BC cells. The KEGG enrichment analysis disclosed that the top ten pathways significantly associated with the scopolamine response in BC included "protein glycosylation," "phosphoinositide 3-kinase (PI3K)-Akt signaling," "mitogen- activated protein kinase (MAPK) signaling" and others. The AKT1, EGFR, and especially the HSP90AA1 expression levels were correlated with survival in patients with BC. Immune infiltration also influenced the survival outcome. Molecular docking demonstrated that scopolamine bound and formed stable complexes with the protein products of all five aforementioned genes. CONCLUSION: Scopolamine has multiple targets regulating BC cell function and may increase the risk of metastasis during treatment. Therefore, it should be preoperatively administered with caution to patients with BC.

An Umbrella Insight into the Phytochemistry Features and Biological Activities of Corn Silk: A Narrative Review.

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.

Baduanjin Mind-Body Exercise for Cancer-Related Fatigue: Protocol for a Remotely Delivered Randomized Wait-List Controlled Feasibility Study.

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.

Genome assembly and microsatellite marker development using Illumina and PacBio sequencing in Persicaria maackiana (Polygonaceae) from Korea.

BACKGROUND: Persicaria maackiana (Regel) is a potential medicinal plant that exerts anti-diabetic effects. However, the lack of genomic information on P. maackiana hinders research at the molecular level. OBJECTIVE: Herein, we aimed to construct a draft genome assembly and obtain comprehensive genomic information on P. maackiana using high-throughput sequencing tools PacBio Sequel II and Illumina. METHODS: Persicaria maackiana samples from three natural populations in Gaecheon, Gichi, and Uiryeong reservoirs in South Korea were used to generate genomic DNA libraries, perform genome de novo assembly, gene ontology analysis, phylogenetic tree analysis, genotyping, and identify microsatellite markers. RESULTS: The assembled P. maackiana genome yielded 32,179 contigs. Assessment of assembly integrity revealed 1503 (93.12%) complete Benchmarking Universal Single-Copy Orthologs. A total of 64,712 protein-coding genes were predicted and annotated successfully in the protein database. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs, 13,778 genes were annotated into 18 categories. Genes that activated AMPK were identified in the KEGG pathway. A total of 316,992 microsatellite loci were identified, and primers targeting the flanking regions were developed for 292,059 microsatellite loci. Of these, 150 primer sets were randomly selected for amplification, and 30 of these primer sets were identified as polymorphic. These primers amplified 3-9 alleles. The mean observed and expected heterozygosity were 0.189 and 0.593, respectively. Polymorphism information content values of the markers were 0.361-0.754. CONCLUSION: Collectively, our study provides a valuable resource for future comparative genomics, phylogeny, and population studies of P. maackiana.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil.

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

BACKGROUND: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. METHODS: Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. RESULTS: The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. CONCLUSIONS: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

Extraction, structural characterization and biological activities of polysaccharides from mulberry leaves: A review.

In recent years, plant polysaccharides have garnered attention for their impressive biological activity. Mulberry leaves have a long history of medicinal and edible use in China, polysaccharide is one of the main active components of mulberry leaves, mainly consist of xylose, arabinose, fructose, galactose, glucose and mannose, etc. The extraction methods of mulberry leaves polysaccharides (MLPs) mainly include hot water extraction, microwave-assisted extraction, ultrasonic extraction, enzyme-assisted extraction, and co-extraction. The separation and purification of MLPs involve core steps such as decolorization, protein removal, and chromatographic separation. In terms of pharmacological effects, MLPs exhibit excellent activity in reducing blood glucose, anti-oxidation, immune regulation, anti-tumor, antibacterial, anti-coagulation, and regulation of gut microbiota. Currently, there is a considerable amount of research on MLPs, however, there is a lack of systematic summarization. This review summarizes the research progress on the extraction, structural characterization, and pharmacological activities of MLPs, and points out existing shortcomings and suggests reference solutions, aiming to provide a basis for further research and development of MLPs.

Genome Assembly and Microsatellite Marker Development Using Illumina and PacBio Sequencing in the Carex pumila (Cyperaceae) from Korea.

This study is the first to report the characterization of Carex pumila genomic information. Assembly of the genome generated a draft of C. pumila based on PacBio Sequel II and Illumina paired-end sequencing, which was assembled from 2941 contigs with an estimated genome size of 0.346 Gb. The estimate of repeats in the genome was 31.0%, and heterozygosity ranged from 0.426 to 0.441%. The integrity evaluation of the assembly revealed 1481 complete benchmarked universal single-copy orthologs (BUSCO) (91.76%), indicating the high quality of the draft assembly. A total of 23,402 protein-coding genes were successfully predicted and annotated in the protein database. UpsetR plots showed that 7481 orthogroups were shared by all species. The phylogenetic tree showed that C. pumila is a close but distant relative of Ananas comosus. C. pumila had greater contraction (3154) than expansion (392). Among the extended gene families, aquaporins have been found to be enriched. Primers for microsatellite markers determined 30 polymorphic markers out of 100. The average number of alleles amplified by these 30 polymorphic markers was 4 to 12, with an average polymorphism information content (PIC) value of 0.660. In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of C. pumila.

Eye Rubbing in Chinese Patients With Keratoconus: A Multicenter Analysis.

PURPOSE: To investigate the eye rubbing habits of Chinese patients with keratoconus. METHODS: This study was carried out from 2018 to June 2022 at Shandong Eye Hospital, Qingdao Eye Hospital, and Henan Eye Hospital. The study compared the number of patients who rubbed their eyes between medical records and second time questionnaires, eye rubbing of patients with myopia and patients with keratoconus, and disease severity between patients with keratoconus. A questionnaire survey of ophthalmologists was conducted to determine their degree of awareness that eye rubbing is a risk factor for keratoconus. RESULTS: The study assessed 799 patients with keratoconus and 798 control patients, and 97 ophthalmologists. The average proportion of patients with keratoconus who rubbed their eyes was 31.0% in the medical records with an increasing trend related to the increase in ophthalmologists' awareness, 66.6% after the second follow-up, and 25.4% among patients with myopia. After multivariate analysis, the following variables showed significant results: eye rubbing frequency more than 10 times/day (odds ratio [OR], 9.168; P < .001); rubbing with knuckles (OR, 9.804; P = .001); and prone sleep position (OR, 12.427; P < .001). The proportion of patients who rubbed their eyes with stage IV keratoconus was 71.9%, 18.9% higher than those with stage I, 4.8% higher than stage II, and 17.8% higher than stage III. CONCLUSIONS: The proportion of Chinese patients with keratoconus who rubbed their eyes was relatively high. The main reasons for the low proportions reported were lack of attention. Clinical attention should be paid to eye rubbing in patients with keratoconus who should be educated to avoid it. [J Refract Surg. 2023;39(10):712-718.].

Opportunities and challenges for ribosome-inactivating proteins in traditional Chinese medicine plants.

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

Isorhamnetin and anti-PD-L1 antibody dual-functional mesoporous silica nanoparticles improve tumor immune microenvironment and inhibit YY1-mediated tumor progression.

BACKGROUND: The immune checkpoint inhibitor (ICI) anti-PD-L1 monoclonal antibody can inhibit the progress of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transformation (EMT) can promote tumor migration and the formation of immune-suppression microenvironment, which affects the therapeutic effect of ICI. Yin-yang-1 (YY1) is an important transcription factor regulating proliferation, migration and EMT of tumor cells. This work proposed a drug-development strategy that combined the regulation of YY1-mediated tumor progression with ICIs for the treatment of HCC. METHODS: We first studied the proteins that regulated YY1 expression by using pull-down, co-immunoprecipitation, and duo-link assay. The active compound regulating YY1 content was screened by virtual screening and cell-function assay. Isorhamnetin (ISO) and anti-PD-L1 antibody dual-functional mesoporous silica nanoparticles (HMSN-ISO@ProA-PD-L1 Ab) were prepared as an antitumor drug to play a synergistic anti-tumor role. RESULTS: YY1 can specifically bind with the deubiquitination enzyme USP7. USP7 can prevent YY1 from ubiquitin-dependent degradation and stabilize YY1 expression, which can promote the proliferation, migration and EMT of HCC cells. Isorhamnetin (ISO) were screened out, which can target USP7 and promote YY1 ubiquitin-dependent degradation. The cell experiments revealed that the HMSN-ISO@ProA-PD-L1 Ab nanoparticles can specifically target tumor cells and play a role in the controlled release of ISO. HMSN-ISO@ProA-PD-L1 Ab nanoparticles inhibited the growth of Hepa1-6 transplanted tumors and the effect was better than that of PD-L1 Ab treatment group and ISO treatment group. HMSN-ISO@ProA-PD-L1 Ab nanoparticles also exerted a promising effect on reducing MDSC content in the tumor microenvironment and promoting T-cell infiltration in tumors. CONCLUSIONS: The isorhamnetin and anti-PD-L1 antibody dual-functional nanoparticles can improve tumor immune microenvironment and inhibit YY1-mediated tumor progression. This study demonstrated the possibility of HCC treatment strategies based on inhibiting USP7-mediated YY1 deubiquitination combined with anti-PD-L1 monoclonal Ab.

[Effect of deep needling "Tianshu" (ST25) on colonic motility in rats with slow transit constipation].

OBJECTIVE: To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC．. METHODS: Fifty male Wistar rats were selected and randomly divided into control，STC model，conventional acupuncture，deep needling group 1 and deep needling group 2 groups，with 10 rats in each group．The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage．EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days．Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry. RESULTS: Compared with the control group，the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased (P<0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group (P<0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit (P<0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain (P<0.05), lowering the amplitude of EMG of the gut smooth muscle (P<0.05) and in increasing the frequency of EMG (P<0.05) and the expressions of SP and c-kit (P<0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group (P>0.05), except the excretion time of the first black stool grain (P<0.05). CONCLUSION: Deep needling at ST25 at depth of 4.5 mm and 10 mm，especially at depth of 10 mm，has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.

SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity.

Cancer cells evade T cell-mediated killing through tumour-immune interactions whose mechanisms are not well understood1,2. Dendritic cells (DCs), especially type-1 conventional DCs (cDC1s), mediate T cell priming and therapeutic efficacy against tumours3. DC functions are orchestrated by pattern recognition receptors3-5, although other signals involved remain incompletely defined. Nutrients are emerging mediators of adaptive immunity6-8, but whether nutrients affect DC function or communication between innate and adaptive immune cells is largely unresolved. Here we establish glutamine as an intercellular metabolic checkpoint that dictates tumour-cDC1 crosstalk and licenses cDC1 function in activating cytotoxic T cells. Intratumoral glutamine supplementation inhibits tumour growth by augmenting cDC1-mediated CD8+ T cell immunity, and overcomes therapeutic resistance to checkpoint blockade and T cell-mediated immunotherapies. Mechanistically, tumour cells and cDC1s compete for glutamine uptake via the transporter SLC38A2 to tune anti-tumour immunity. Nutrient screening and integrative analyses show that glutamine is the dominant amino acid in promoting cDC1 function. Further, glutamine signalling via FLCN impinges on TFEB function. Loss of FLCN in DCs selectively impairs cDC1 function in vivo in a TFEB-dependent manner and phenocopies SLC38A2 deficiency by eliminating the anti-tumour therapeutic effect of glutamine supplementation. Our findings establish glutamine-mediated intercellular metabolic crosstalk between tumour cells and cDC1s that underpins tumour immune evasion, and reveal glutamine acquisition and signalling in cDC1s as limiting events for DC activation and putative targets for cancer treatment.

Exploring intrusions without awareness: A preliminary study of the characteristics and influences of meta-awareness failures.

BACKGROUND AND OBJECTIVES: Research shows that people can lack meta-awareness (i.e., being explicitly aware) of their trauma-related thoughts, which impacts our understanding of re-experiencing symptoms, a key symptom type in posttraumatic stress disorder (PTSD), assessed through self-report. This preliminarily study explored differences between (meta-)aware and unaware intrusion characteristics to understand why some intrusions are not immediately apparent to individuals. METHODS: Trauma-exposed participants (N = 78) were recruited from online crowd-sourcing platforms to complete an online meta-awareness task. During a reading task, participants were intermittently probed to index the occurrence of unreported (i.e., unaware) trauma-related intrusions. Once participants indicated trauma-related intrusions were present, they then completed a questionnaire that indexed intrusion characteristics. RESULTS: Although unaware intrusions did occur in a subset of the sample, there were no fundamental differences between aware and unaware intrusions in terms of modality of experience (imagery vs. non-imagery), meaningfulness, accessibility, or other characteristics (e.g., vividness). LIMITATIONS: There was potential for lower participant engagement and attention due to the online delivery of the meta-awareness task, which may have minimized meta-awareness failure. Future research could consider using a continuous measure to index levels of meta-awareness. In addition, recruiting clinical samples (e.g., individuals with PTSD) who typically experience multiple daily intrusions would allow generalizability of the current findings to be tested. CONCLUSIONS: Our findings from this preliminary study suggest that unaware and aware intrusions show more commonality than not in their characteristics, with further research required to improve our understanding of the mechanisms leading to meta-awareness or lack of in PTSD.

Systems biology strategy through integrating metabolomics and network pharmacology to reveal the mechanisms of Xiaopi Hewei Capsule improves functional dyspepsia.

Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei Capsule (XPHC) is a classic formula originated from the Chinese Miao minority. Clinical studies have demonstrated that XPHC can effectively alleviate the symptoms of FD, but the molecular mechanism has not been elucidated. The purpose of this work is to investigate the mechanism of XPHC on FD by integrating metabolomics and network pharmacology. The mice models of FD were established, and gastric emptying rate, small intestine propulsion rate, serum level of motilin and gastrin were evaluate to study the interventional effect of XPHC on FD. Next, a metabolomics strategy has been developed to screen differential metabolites and related metabolic pathways induced by XPHC. Then, prediction of active compounds, targets and pathways of XPHC in treating FD were carried out by commonly used network pharmacological method. Finally, two parts of the results were integrated to investigate therapeutic mechanism of XPHC on FD, which were preliminary validated based on molecular docking. Thus, twenty representative different metabolites and thirteen related pathways of XPHC in treating FD were identified. Most of these metabolites were restored using modulation after XPHC treatment. The results of the network pharmacology analysis showed ten crucial compounds and nine hub genes related to the treatment of FD with XPHC. The further integrated analysis focused on four key targets, such as albumin (ALB), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF) and roto-oncogene tyrosine-protein kinase Src (SRC), and three representative biomarkers such as citric acid, L-leucine and eicosapentaenoic acid. Furthermore, molecular docking results showed that ten bioactive compounds from XPHC have good binding interactions with the four key genes. The functional enrichment analysis indicated that the potential mechanism of XPHC in treating FD was mainly associated with energy metabolism, amino acid metabolism, lipid metabolism, inflammatory reactions and mucosal repair. Our work confirms that network pharmacology-integrated metabolomics strategyis a powerful means to reveal the therapeutic mechanisms of XPHC improves FD, which contribute its further scientific research.

Core Target and Key Signal Pathway of Xiaoluo in the Treatment of Thyroid Cancer.

Context: At present, hormone therapy and surgery are the main treatments for thyroid cancer, and they have a quick effect but a high recurrence rate. Also, the side effects are significant. it's extremely urgent to explore treatments that can take into account both therapeutic benefits and side effects. Objective: The study intended to explore whether Xiaoluo has an inhibitory effect on the proliferation of thyroid-cancer cells in vitro and to examine the core target and key signaling pathway of Xiaoluo in the treatment of thyroid cancer, using the thyroid-cancer cell line SW579. Design: The research team performed an in-vitro study. Setting: The study took place at the College of Pharmacy at Harbin University of Commerce in Harbin, China. Outcome Measures: The research team used a Western blot analysis to detect the expression of apoptosis proteins-B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3-and the activity related to the signaling pathways phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin 1 (mTORC1). The team measured optical densities and inhibition rates for the 1, 2, 5, 10, and 15 mg/mL Xiaokuo groups and for a negative control group. The research team measured apoptosis, expression of Bcl-2, Bax, and Caspase-3, and expression of P13K, AKT, and mTor for the 10 µmol/L LY294002, 10 mg/mL Xiaoluo, 100 ng/mL IGF-1, and 100 ng/mL IGF-1+10 mg/mL Xiaoluo groups and for the blank control group. Results: The inhibition of SW579 cell proliferation increased with each increase in the Xiaoluo concentration from 1-15 mg/mL, and the inhibition rate reached 49.63% when the concentration was 15 mg/ml. The Xiaoluo group's late and total apoptosis rates were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expression of the Bcl-2 protein was significantly lower (P < .05), and its expressions of Bax and Caspase-3 were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expressions of P-PI3K, P-Akt, and P-MTOR were significantly lower than those of the blank group (all P < .01). These findings were comparable to those that occurred with use of the PI3K/AKT/mTORC1 signaling pathway inhibitor LY294002. Conclusions: Xiaoluo exerts its antithyroid-cancer effects through the induction of apoptosis in thyroid cancer cells through the inhibition of the PI3K/AKT/mTORC1 signaling pathway. Xiaoluo may serve as a potential therapeutic agent for the treatment of thyroid cancer.

Effects of roasting on the chemical compositions, color, aroma, microstructure, and the kinetics of changes in coffee pulp.

Roasting is a critical process that affects the quality attributes of coffee beans; however, how roasting conditions affect the physical, chemical, biological, and organoleptic changes of coffee pulp needs more research. In the present study, we investigated the effects of roasting temperatures and times on chemical compositions and quality attributes of coffee pulp. The results showed that the contents of total soluble sugar (TSS) and free amino acid (FAA) followed a temporal pattern of first increasing and then decreasing under the roasting temperatures between 100 and 160°C. Total phenolic content (TPC) and antioxidant activity of coffee pulp significantly (p < 0.05) increased after roasting, reaching the maximum values of 83.09 mg gallic acid equivalent (GAE) /g and 360.45 µM 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) /g, respectively, when coffee pulp was roasted at 160°C for 18 min. Drying rates of coffee pulp fitted the Logarithmic kinetic model, while color (L*, a*, and b*) changes and 5-caffeoylquinic acid degradation followed the first-order kinetic model. Electronic nose analysis showed that the main aroma compounds of the coffee pulp are sulfur-containing organics that were reduced with the extended roasting time. Scanning electronic microscopy analysis presented the loosened, shrunk, and cracked microstructure on the surface of the roasted coffee pulp, which might contribute to the increased TSS, FAA, TPC, and antioxidant activity of coffee pulp roasted under specific conditions. In conclusion, our research provides valuable information for preparing high-quality coffee pulp tea. PRACTICAL APPLICATION: This article investigates the effects of roasting on the chemical composition, color, flavor, microstructure, and the kinetics of changes in the moisture, color, and 5-caffeoylquinic acid (5-CQA) of the coffee pulp. We have found that high-temperature and short-time roasting helps retain the total phenolic contents, antioxidant activity, and aroma. The drying kinetic fits the Logarithmic model, and the changes in color and 5-CQA fit the first-order kinetic model. This study provides meaningful information for preparing coffee pulp tea with high-quality attributes and antioxidant activity.