The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition.

Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.

A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells.

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.

Research status and prospects of acupuncture for prevention and treatment of chemo- and radiotherapy-induced salivary gland dysfunction in head and neck cancer.

Salivary gland dysfunction (SGD) induced by chemo- and radiotherapy for head and neck cancer (HNC) has always been a difficult problem in modern medicine. The quality of life of a large number of HNC patients is severely impaired by SGD such as xerostomia and dysphagia. In recent years, several studies have found that acupuncture can improve patients' salivary secretion, but it has not yet been approved as an alternative therapy for SGD. For this reason, we collected the clinical study reports on acupuncture in the treatment of SGD induced by chemo- and radiotherapy in HNC patients in the past 20 years, and analyzed and discussed the advantages and disadvantages of these studies with respect to tumor types, group setting, intervention modality, acupoints selection, outcome evaluation, and safety. We believed that acupuncture is beneficial for SGD, but the existing objective evidence is insufficient to support its effectiveness. Therefore, improving the Standards for Reporting Interventions in Clinical Trials of Acupuncture, selecting the optimal combination of acupoints through scientific and rigorous study design, and exploring the potential mechanism of acupuncture in the treatment of diseases combined with the meridian theory may be effective ways to promote the acceptance of acupuncture as an alternative therapy for SGD in future. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of SGD in future from the perspective of the combination of modern medicine and traditional Chinese medicine.

Association between referral source and duration of untreated psychosis in pathways to care among first episode psychosis patients in Northern Malawi.

AIMS: To examine the association between referral source and duration of untreated psychosis (DUP) and explore determinants of referral source; when adjusting for pathways to care, positive and negative symptoms, diagnosis and socio-demographic characteristics. METHODS: A total of 140 subjects with first episode psychosis (FEP) were enrolled from a pilot early intervention service for psychosis in Northern Malawi between June 2009 and September 2012. Logistic regression analyses were used to quantify the associations between variables of interest. RESULTS: Age ranged between 18 and 65 at assessment, with median, 33. Median DUP was 12.5 months. First contact did not independently determine DUP. Long DUP (>6 months) was associated with referral from community based volunteer (CBV) or traditional healer (TH), a unit increase in severity of negative symptoms and having schizophrenia, which was also associated with referral from CBV or TH. Additionally, being unemployed was associated with referral from CBV or TH. However, a unit increase in the number of times religious advice (RA) was sought, GP was contacted and severity of positive symptoms was associated with referral by GP. CONCLUSIONS: Mental health awareness is justified for this population and collaboration with THs in identifying and treating patients with psychosis may help reduce treatment delays. Access to mental health services ought to improve, particularly for the unemployed group. Future studies should consider adjusting for referral source when ascertaining first contact source as a predictor of DUP.

Artificial Intelligence Approach To Investigate the Longevity Drug.

Longevity is a very important and interesting topic, and Klotho has been demonstrated to be related to longevity. We combined network pharmacology, machine learning, deep learning, and molecular dynamics (MD) simulation to investigate potent lead drugs. Related protein insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (IR) were docked with the traditional Chinese medicine (TCM) database to screen out several novel candidates. Besides, nine different machine learning algorithms were performed to build reliable and accurate predicted models. Moreover, we used the novel deep learning algorithm to build predicted models. All of these models obtained significant R2, which are all greater than 0.87 on the training set and higher than 0.88 for the test set, respectively. The long time 500 ns molecular dynamics simulation was also performed to verify protein-ligand properties and stability. Finally, we obtained Antifebrile Dichroa, Holarrhena antidysenterica, and Gelsemium sempervirens, which might be potent TCMs for two targets.

Artificial Intelligence Approach to Find Lead Compounds for Treating Tumors.

It has been demonstrated that MMP13 enzyme is related to most cancer cell tumors. The world's largest traditional Chinese medicine database was applied to screen for structure-based drug design and ligand-based drug design. To predict drug activity, machine learning models (Random Forest (RF), AdaBoost Regressor (ABR), Gradient Boosting Regressor (GBR)), and Deep Learning models were utilized to validate the Docking results, and we obtained an R2 of 0.922 on the training set and 0.804 on the test set in the RF algorithm. For the Deep Learning algorithm, R2 of the training set is 0.90, and R2 of the test set is 0.810. However, these TCM compounds fly away during the molecular dynamics (MD) simulation. We seek another method: peptide design. All peptide database were screened by the Docking process. Modification peptides were optimized the interaction modes, and the affinities were assessed with ZDOCK protocol and Refine Docked protein protocol. The 300 ns MD simulation evaluated the stability of receptor-peptide complexes. The double-site effect appeared on S2, a designed peptide based on a known inhibitor, when complexed with BCL2. S3, a designed peptide referred from endogenous inhibitor P16, competed against cyclin when binding with CDK6. The MDM2 inhibitors S5 and S6 were derived from the P53 structure and stable binding with MDM2. A flexible region of peptides S5 and S6 may enhance the binding ability by changing its own conformation, which was unforeseen. These peptides (S2, S3, S5, and S6) are potentially interesting to treat cancer; however, these findings need to be affirmed by biological testing, which will be conducted in the near future.

A Network Pharmacology-Based Approach to Investigate the Novel TCM Formula against Huntington's Disease and Validated by Support Vector Machine Model.

Several pathways are crucial in Huntington's disease (HD). Based on the concept of multitargets, network pharmacology-based analysis was employed to find out related proteins in disease network. The network target method aims to find out related mechanism of efficacy substances in rational design way. Traditional Chinese medicine prescriptions would be used for research and development against HD. Virtual screening was performed to obtain drug molecules with high binding capacity from traditional Chinese medicine (TCM) database@Taiwan. Quantitative structure-activity relationship (QSAR) models were conducted by MLR, SVM, CoMFA, and CoMSIA, constructed to predict the bioactivities of candidates. The compounds with high-dock score were further analyzed compared with control. Traditional Chinese medicine reported in the literature could be the training set provided for constructing novel formula by SVM model. We tried to find a novel formula that can bind well with these targets at the same time, which indicates our design could be highly related to the HD. Additionally, the candidates would validate by a long-term molecular dynamics (MD) simulation, 5 microseconds. Thus, we suggested the herbs Brucea javanica, Holarrhena antidysenterica, Dichroa febrifuga, Erythrophleum guineense, etc. which contained active compounds might be a novel medicine formula toward Huntington's disease.

[Protection of oxymatrine against ischemia-reperfusion injury of liver and mechanism thereof: experiment with rats].

OBJECTIVE: To investigate the effects of oxymatrine on protecting the liver against ischemia-reperfusion injury (IRI) and explore the mechanism thereof. METHODS: Thirty male Wistar rats were randomly divided into 3 equal groups: IRI group (2 ml normal saline was injected into the dorsal vein of penis, 30 min later laparotomy was performed, arterial clamp was used to grip the hepatic artery and portal vein for 30 minutes and then removed, the vessels were reperfused for 90 min, and 4 ml blood was collected from the aorta; parts of the liver were resected); oxymatrine group (oxymatrine 40 mg/kg was injected into the dorsal vein of penis, and the other procedures were the same as in the IRI group); and sham operation group (2 ml normal saline was injected into the dorsal vein of penis, laparotomy was performed, 150 min after the injection 4 ml blood was collected from the aorta and parts of the liver were resected). The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. The liver tissues underwent HE staining and TUNEL staining for pathological examination. Suspension of single hepatocytes was prepared to observe the ratio of apoptotic cells and cell cycles by flow cytometry (FCM). Western blotting was used to examine the Fas protein expression. RESULTS: The AST and ALT levels of the IRI group were 1326 U/L +/- 211 U/L and 768 U/L +/- 175 U/L respectively, significantly higher than those of the sham operation group (112 U/L +/- 53 U/L and 55 U/L +/- 17 U/L, both P < 0.05) and those of the oxymatrine group (513 U/L +/- 96 U/L and 352 U/L +/- 72 U/L respectively, both P < 0.01). The liver cells of the sham operation group were normal, those of the IRI group showed remarkable edema and cytoplasm degeneration. TUNEL staining showed remarkably more apoptotic cells in the IRI group. FCM showed that the apoptotic rate of hepatocytes was 42.8% +/- 5.2% in the IRI group, significantly higher than in the oxymatrine group (8.8% +/- 1.8%, P < 0.01), and that the ratio of hepatocytes in G(0)/G(1) stage of the IRI group was 99.2% +/- 1.8%, significantly higher than that of the sham operation group (77.0% +/- 2.1%), and that of the oxymatrine group (87.6% +/- 2.8%) (both P < 0.05); the ratio of hepatocytes in the S stage of the IRI group was 0.52% +/- 0.25%, significantly lower than those of the sham operation group (23.94% +/- 1.84%) and oxymatrine group (12.42% +/- 0.46%) (both P < 0.01). The Fas protein expression was significantly highly in the IRI group than in the oxymatrine group. CONCLUSION: Remarkably reducing the IRI of hepatocytes, oxymatrine has potential to protect the liver against IRI during surgical intervention.