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OBJECTIVES: This study aims to build a machine learning (ML) model to predict the recurrence probability for postoperative non-lactating mastitis (NLM) by Random Forest (RF) and XGBoost algorithms. It can provide the ability to identify the risk of NLM recurrence and guidance in clinical treatment plan. METHODS: This study was conducted on inpatients who were admitted to the Mammary Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine between July 2019 to December 2021. Inpatient data follow-up has been completed until December 2022. Ten features were selected in this study to build the ML model: age, body mass index (BMI), number of abortions, presence of inverted nipples, extent of breast mass, white blood cell count (WBC), neutrophil to lymphocyte ratio (NLR), albumin-globulin ratio (AGR) and triglyceride (TG) and presence of intraoperative discharge. We used two ML approaches (RF and XGBoost) to build models and predict the NLM recurrence risk of female patients. Totally 258 patients were randomly divided into a training set and a test set according to a 75%-25% proportion. The model performance was evaluated based on Accuracy, Precision, Recall, F1-score and AUC. The Shapley Additive Explanations (SHAP) method was used to interpret the model. RESULTS: There were 48 (18.6%) NLM patients who experienced recurrence during the follow-up period. Ten features were selected in this study to build the ML model. For the RF model, BMI is the most important influence factor and for the XGBoost model is intraoperative discharge. The results of tenfold cross-validation suggest that both the RF model and the XGBoost model have good predictive performance, but the XGBoost model has a better performance than the RF model in our study. The trends of SHAP values of all features in our models are consistent with the trends of these features' clinical presentation. The inclusion of these ten features in the model is necessary to build practical prediction models for recurrence. CONCLUSIONS: The results of tenfold cross-validation and SHAP values suggest that the models have predictive ability. The trend of SHAP value provides auxiliary validation in our models and makes it have more clinical significance.
Subject(s)
Machine Learning , Mastitis , Recurrence , Humans , Female , Adult , Middle Aged , Postoperative Complications , ChinaABSTRACT
Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem ⠡ (ФPS⠡), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.
Subject(s)
Plants, Medicinal , Scutellaria baicalensis , Scutellaria baicalensis/chemistry , Scutellaria baicalensis/metabolism , Photosynthesis , Flavonoids , Chlorophyll/metabolismABSTRACT
Purpose: To determine the risk factors, clinical characteristics, and prognosis of adolescent non-puerperal mastitis patients. Patients and methods: A retrospective analysis was conducted on 10 cases of NPM in adolescents who underwent surgical treatment at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from August 2021 to August 2023. We analyze the patient's general information, clinical characteristics, related medical history, laboratory indicators, breast magnetic resonance imaging examination, postoperative pathology, prognosis, etc. Results: The clinical manifestations of NPM in adolescents mainly included redness, swelling and pain in the breasts, congenital nipple retraction, and extensive lesion range. Inflammatory markers and prolactin were elevated. Magnetic resonance imaging showed circular enhancement with abscess formation as the main type. All patients underwent surgical treatment with a fast recovery time after surgery. No recurrence was observed during follow-up and the postoperative breast appearance was satisfactory. Multivariate Logistic regression analysis indicated that congenital nipple retraction, elevated prolactin levels and trauma were independent risk factors for adolescents non-puerperal mastitis. Conclusion: Adolescent non-puerperal mastitis is a rare and unique type. Summarizing its main risk factors, clinical characteristics, and prognosis provides a basis for further research.
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ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla, as a traditional Chinese herbal medicine, was often used to relieve inflammation and pain. Rhizoma Paridis saponins (RPS) as the main active components of Paris polyphylla have excellent analgesic effects. AIM OF THE STUDY: Determine the analgesic material basis of RPS. MATERIALS AND METHODS: LC-MS/MS was used to analyze RPS, plasma after intravenous injection of RPS, and oral administration of RPS. H22 plantar pain model was established to explore the analgesic material basis of RPS. Moreover, correlation analysis, network pharmacology, RT-PCR and molecular docking were applied in this research. RESULTS: RPS had dose-dependently analgesic effects in acetic acid- and formalin-induced pain models. LC-MS/MS detection indicated that diosgenin as the metabolite of RPS mainly distributed in brain tissues. The addition of antibiotics increased the anti-tumor effect of RPS, but reduced its analgesic effect. Network pharmacology, RT-PCR and molecular docking showed that diosgenin exerted its analgesic effect through SRC and Rap1 signaling pathway. CONCLUSION: Diosgenin exhibited analgesic effects, while saponins had good anti-tumor effects in RPS. This discovery provided a better indication for the later application of RPS in anti-tumor and analgesic settings.
Subject(s)
Diosgenin , Liliaceae , Melanthiaceae , Neoplasms , Saponins , Saponins/pharmacology , Saponins/therapeutic use , Saponins/metabolism , Chromatography, Liquid , Molecular Docking Simulation , Tandem Mass Spectrometry , Rhizome/metabolism , Neoplasms/drug therapy , Pain/drug therapy , Analgesics/pharmacology , Analgesics/therapeutic useABSTRACT
OBJECTIVES: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway. METHODS: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-ß (Aß), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence. RESULTS: Compared with the control group, the escape latency of the mice in the model group was prolonged (P<0.001, P<0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced (P<0.001), the positive expression of both Aß and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased (P<0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased (P<0.05, P<0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened (P<0.001, P<0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased (P<0.001), the positive expression of Aß and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased (P<0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aß and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.
Subject(s)
Alzheimer Disease , Moxibustion , Mice , Male , Animals , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Interleukin-33/genetics , Interleukin-33/metabolism , Interleukin-1 Receptor-Like 1 Protein/metabolism , Microglia/metabolism , Mice, Inbred C57BL , Hippocampus/metabolism , Amyloid beta-Peptides/metabolism , Mice, TransgenicABSTRACT
China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health. In this study, we investigated the toxic effects of YCl3 on mouse testes and four types of testicular cells, including Sertoli, Leydig, spermatogonial and spermatocyte cells. The results showed that YCl3 exposure causes substantial damage to mouse testes and induces apoptosis and autophagy, but not pyroptosis or necrosis, in testicular cells. Genome-wide gene expression analysis revealed that YCl3 induced significant changes in gene expression, with Ca2+ and mitochondria-related genes being the most significantly altered. Mechanistically, YCl3 exposure induced mitochondrial dysfunction in testicular cells, triggering the overproduction of reactive oxygen species (ROS) by impairing the Nrf2 pathway, regulating downstream Ho-1 target protein expression, and increasing Ca2+ levels to activate the CamkII/Ampk signaling pathway. Blocking ROS production or Ca2+ signaling significantly attenuates apoptosis and autophagy, while supplementation with Ca2+ reverses the suppression of apoptosis and autophagy by ROS blockade in testicular cells. Notably, apoptosis and autophagy induced by YCl3 treatment are independent of each other. Thus, our study suggests that YCl3 may impair the antioxidant stress signaling pathway and activate the calcium pathway through the ROS-Ca2+ axis, which promotes testicular cell apoptosis and autophagy independently, thus inducing testicular damage and impairing male reproductive function.
Subject(s)
Metals, Rare Earth , Yttrium , Humans , Animals , Mice , Male , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Reactive Oxygen Species , Apoptosis , Autophagy , DNA, Mitochondrial , Genitalia, MaleABSTRACT
Objective: To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa. Method: The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR P. aeruginosa. Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen via traditional infusion (TI)/optimized two-step-administration therapy (OTAT). Results: We found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B). P. aeruginosa isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine ß-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDR P. aeruginosa achieved 100% PTA when the MIC was ≤32 mg/L. Conclusion: AZA has been considered as an option for the treatment of infections caused by XDR/PDR P. aeruginosa producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDR P. aeruginosa with a high-level MIC of CZA/AZA.
Subject(s)
Pseudomonas Infections , Respiratory Tract Infections , Sepsis , Humans , Aztreonam/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas aeruginosa , Pharmaceutical Preparations , Drug Combinations , Respiratory Tract Infections/drug therapy , Sepsis/drug therapy , beta-Lactamases , Microbial Sensitivity Tests , Pseudomonas Infections/drug therapyABSTRACT
Bacillus cereus, a Gram-positive bacterium, is a food contaminant that threatens the health of thousands of people around the world. Because of the continuous emergence of drug-resistant strains, the development of new classes of bactericides from natural products is of high priority. In this study, two novel cassane diterpenoids (pulchins A and B) and three known ones (3-5) were elucidated from the medicinal plant Caesaplinia pulcherrima (L.) Sw. Pulchin A, with a rare "6/6/6/3" carbon skeleton, showed significant antibacterial activity against B. cereus and Staphylococcus aureus, with MIC values of 3.13 and 6.25 µM, respectively. Further investigation of its mechanism of antibacterial activity against B. cereus is also discussed in detail. The results revealed that the antibacterial activity of pulchin A against B. cereus may be caused by pulchin A interfering with bacterial cell membrane proteins, affecting membrane permeability and causing cell damage or death. Thus, pulchin A may have a potential application as an antibacterial agent in the food and agricultural industries.
Subject(s)
Bacillus cereus , Plants, Medicinal , Humans , Anti-Bacterial Agents , Cell Membrane , Gram-Positive Bacteria , Microbial Sensitivity TestsABSTRACT
Objectives: To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products Aß and Tau protein via decreasing N6-methyladenosine (m6A). Methods: APP/PS1 mice were randomly divided into model group (APP/PS1) and moxibustion group (APP/PS1+Mox). C57BL/6J mice were used as a control group (Control). Learning and memory abilities were assessed by the Morris water maze. Aß, Tau, phosphorylated Tau (p-Tau), and YTHDF1 proteins were detected in the mouse cortex and hippocampus by immunofluorescence and western blot. Altered m6A expression levels in hippocampal and cortical tissues were measured with the m6A RNA methylation quantification assay kit. RNA transcript levels of YTHDF1, METTL3, and FTO in the hippocampus and cortex were measured by q-PCR. Results: Moxibustion shortened the escape latency, increased the number of platform crossings, and increased the percentage of swimming time in the target quadrant of APP/PS1 mice. Meanwhile, moxibustion reduced the levels of Aß, Tau, and p-Tau proteins both in the hippocampal and cortical regions of APP/PS1 mice. In addition, the total amount of m6A in the hippocampal and cortical regions of APP/PS1 mice was significantly reduced after moxibustion. The expression of YTHDF1 in the hippocampal region of APP/PS1 mice increased and that in the cortical region decreased after moxibustion treatment. Conclusion: Moxibustion improves the learning and memory abilities and reduces the deposition of Aß and Tau protein pathological products in APP/PS1 mice. This may be related to the fact that moxibustion reduces the total amount of m6A and inhibits its binding enzyme YTHDF1 in the hippocampus and cortex of APP/PS1 mice.
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Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.
Subject(s)
Pueraria , Pharmacognosy , Plant Roots/geneticsABSTRACT
CONTEXT: Pomelo peel oil (PPO) [Citrus maxima (Burm.) Merr. (Rutaceae)] is reported to possess antioxidant and antimelanogenic activities. OBJECTIVE: To investigate the effect of PPO [Citrus maxima (Burm.) Merr. cv. Shatian Yu] on tumour necrosis factor-α (TNF-α)-induced necroptosis in cerebral ischaemia-reperfusion injury (CIRI) after cardiac arrest (CA). MATERIALS AND METHODS: Male Sprague Dawley rats were randomly assigned to six groups: sham group, PP0-L (10 mg/kg), PPO-M (20 mg/kg), PPO-H (40 mg/kg) and two control groups (CA, 0.9% saline; Gly, 10% glycerol). All drugs were administered intravenously to the CA/CPR rats within 10 min after return of spontaneous circulation (ROSC). After 24 h, rats were assessed for neuronal injury via the neurological deficit score (NDS), cerebral cortex staining and transmission electron microscopy (TEM) and expression levels of TNF-α and necroptosis-related proteins by immunoreactivity staining and western blotting. RESULTS: Compared to those in the sham group (survival rate, 100% and NDS, 80), the survival rate and NDS were significantly reduced in the model groups (CA, 56.25%, 70; Gly, 62.5%, 71; PPO-L, 75%, 72; PPO-M, 87.5%, 75; PPO-H, 81.25%, 74). In the PPO-M group, Nissl bodies were significantly increased (43.67 ± 1.906 vs. 17 ± 1.732), the incidence of pathomorphological injury was lower and the necroptosis markers (TNF-α, RIPK1, RIPK3, p-MLKL/MLKL) expression was downregulated compared to those in the CA group (p < 0.05). DISCUSSION AND CONCLUSIONS: The neuroprotective effects of PPO in the CA rats suggested that PPO possibility as a health product enhances the resistance ability against brain injury for humans.
Subject(s)
Citrus/chemistry , Heart Arrest/drug therapy , Plant Oils/pharmacology , Reperfusion Injury/drug therapy , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Heart Arrest/physiopathology , Male , Necroptosis/drug effects , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Oils, Volatile/administration & dosage , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology , Plant Oils/administration & dosage , Plant Oils/isolation & purification , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury/physiopathology , Survival Rate , Tumor Necrosis Factor-alpha/administration & dosageABSTRACT
After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients' health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Bone Neoplasms/drug therapy , Hydrogels/pharmacology , Ketones/pharmacology , Osteosarcoma/drug therapy , Polyethylene Glycols/pharmacology , 3T3 Cells , Animals , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Benzophenones , Bone Neoplasms/pathology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Drug Screening Assays, Antitumor , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Hydrogels/chemistry , Ketones/chemistry , Mice , Mice, Inbred Strains , Microbial Sensitivity Tests , Osteogenesis/drug effects , Osteosarcoma/pathology , Particle Size , Photothermal Therapy , Polyethylene Glycols/chemistry , Polymers , Rats , Rats, Sprague-Dawley , Surface PropertiesABSTRACT
OBJECTIVES: To study how thermal energy is converted after moxibustion at local skin from the view of mitochondrial respiratory chain and its key regulatory elements of sirtuins 1 (SIRT1) and sirtuins 3 (SIRT3). METHODS: Two moxibustion temperatures usually used in clinical practice (38°C and 46°C) were applied to Zusanli (ST36) acupoint for 30 minutes in C57BL/6J mice. Local skin samples were harvested at 30 min and 72 h after moxibustion intervention, respectively. The activity of mitochondrial respiratory chain complexes I-V was detected by spectrophotometry. The expression of SIRT1 and SIRT3 protein was detected by immunofluorescence staining or western blot. RESULTS: Moxibustion at 38°C triggered more significant increase of mitochondrial respiratory chain complexes I-V expression. However, the protein expression of SIRT1 and SIRT3 at 46°C showed more obvious enhancement. In addition, the effect of mitochondrial respiratory chain complexes I-V activity on local skin of ST36 acupoint was more obvious at 30 min after moxibustion, while the expression of SIRT1 and SIRT3 protein was more significant at 72 h after moxibustion. CONCLUSION: Mitochondrial respiratory chain and its key regulatory element proteins SIRT1 and SIRT3 play important role in the initial process of thermal energy conversion stimulated by different moxibustion temperatures in local skin.
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Two-dimensional (2D) MXene nanomaterials have explored as a great potential candidate for tumor therapy during recent decades, especially for photothermal therapeutic applications. However, MXene-based drug-carriers cannot be elaborately controlled in cancer therapy. To solve the problem, a heterostructured titanium carbide-cobalt nanowires (Ti3C2-CoNWs) nanocarrier is developed for synergetic anticancer with magnetic controlling ability, dual stimuli-responsive drug release, and chemo-photothermal therapy. The structure, drug loading/release behavior, magnetic controlling capacity, photothermal performance, and synergistic therapeutic efficiency of the Ti3C2-CoNWs nanocarrier heterojunction are investigated. The heterostructured Ti3C2-CoNWs nanocarrier exhibits excellent photothermal conversion efficiency under 808 nm laser irradiation and high drug loading ability (225.05%). The doxorubicin (DOX) release behavior can be triggered by acid pH value (4-6) or near-infrared (NIR) irradiation. The Ti3C2-CoNWs nanocarrier heterojunction with synergistic chemo-photothermal therapeutic effect exhibits strong lethality for cancer cells than that of chemotherapy or photothermal therapy (PTT) alone. Therefore, Ti3C2-CoNWs nanocarrier heterojunction will be a promising choice for improving the efficiency of cancer treatment.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Nanowires , Cell Line, Tumor , Cobalt , Doxorubicin/pharmacology , Drug Delivery Systems , Drug Liberation , Phototherapy , Photothermal TherapyABSTRACT
Paeonol, a major ingredient isolated from Moutan Cort, has various pharmacological effects. Our previous studies have shown that paeonol can exert antioxidant and anti-inflammatory therapeutic effects on ethanol-induced experimental gastric ulcer (GU). Therefore, in this study, we designed two GU models in rats induced by pyloric ligation (PL) and acetic acid and evaluated the protective effects of paeonol and gastroretention tablets of paeonol (GRT-Ps; 24, 48, and 96 mg/kg) on GU in rats and the effect of paeonol (48 mg/kg) on the intestinal flora. In vivo experiments showed that paeonol or GRT-Ps remarkably reduced gastric mucosal damage in a dose-dependent manner in the different types of models and improved the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content. And in fact, the sustained-release effect of GRT-Ps is more conducive to the improvement of GU compared with the rapid clearance of free drugs. In the PL-induced model, gastric secretion parameters, that is, pH and total acid, showed significant differences compared with the model group. In addition, paeonol treatment can improve the richness and diversity of the intestinal flora and increase the amount of beneficial bacteria, such as Lactobacillus. Paeonol and its stable sustained-release tablet GRT-Ps can promote ulcer healing by inhibiting oxidative stress and regulating the intestinal flora. This study can provide basis for the clinical treatment of GU with paeonol. Graphical Abstract.
Subject(s)
Acetophenones/pharmacology , Gastric Mucosa/drug effects , Gastrointestinal Microbiome/drug effects , Stomach Ulcer/drug therapy , Tablets , Acetic Acid , Animals , Antioxidants/metabolism , Catalase/pharmacology , Gastric Acid/metabolism , Inflammation , Intestines , Male , Malondialdehyde/metabolism , Oxidative Stress , Phytotherapy , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species , Superoxide DismutaseABSTRACT
Omeprazole (OME) is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, OME may cause some inevitable side effects and the long-term consequences of OME could increase the risk of diarrhea. Patchouli Alcohol (PA), the main extract of Pogostemonis Herba, have demonstrated benefits in treating gastric ulcer (GU) with low toxicity. The present study aimed to investigate the synergistically protective effects of OME and PA against ethanol-induced GU in rats to study the involvement of antioxidant and anti-inflammatory activities. Moreover, the anti-apoptosis, anti-oxidant and anti-inflammatory effects in H2O2-induced gastric epithelial cells (GES-1) and LPS-induced RAW264.7 cells were determined, as well as the modulation of signaling proteins. The results demonstrated that PA alone or combined with OME provided remarkable benefits by reducing ulcer areas, modulating oxidant stress and inflammatory factors and the therapeutic efficacy was showed to be dose-dependent, which were partly superior to that of high-dose OME only. Additionally, co-treated regimen could superiorly down-regulate cell apoptosis and regulate the levels of oxidant activities and inflammatory cytokines on H2O2-induced GES-1 cells and LPS-induced RAW264.7 cells, which involved with cleaved caspase 3, Bcl-2 and BAX protein expressions and MAPK pathway. We provided a new understanding that the combination of OME and PA possessed gastroprotective effects on modulating cell apoptosis, antioxidant stress and anti-inflammatory responses against GU. Therefore, PA was inferred to take a potential and critic role in gastric mucosa protection.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Antioxidants/therapeutic use , Omeprazole/therapeutic use , Sesquiterpenes/therapeutic use , Stomach Ulcer/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line , Cytokines/metabolism , Drug Combinations , Ethanol , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Hydrogen Peroxide , Male , Mice , Omeprazole/pharmacology , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Sesquiterpenes/pharmacology , Stomach Ulcer/chemically induced , Stomach Ulcer/pathologyABSTRACT
BACKGROUND: Reducing cerebral ischemia-reperfusion injury is crucial for improving survival and neurologic outcomes after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The purpose of this study is to investigate the neuroprotective effects of green tea polyphenols (GTPs) concern with the modulation of endogenous antioxidation and endoplasmic reticulum stress. METHODS: After subjecting to CA/CPR, rats were randomized into the saline group (NS, n = 40) and the GTPs group (GTPs, n = 40) and the GTPs group (GTPs, n = 40) and the GTPs group (GTPs. RESULTS: Comparing with that in NS group, GTPs increased the expression of SOD1 and SOD2 at 12 h, 24 h, 48 h, 72 h, and the expression of GRP78 at 24 h and 48 h (p < 0.05) butdecreased caspase-12, CHOP, caspase-3 level, and apoptotic number of neurons (p < 0.05) butdecreased caspase-12, CHOP, caspase-3 level, and apoptotic number of neurons (. CONCLUSION: GTPs exert neuroprotective effects via mechanisms that may be related to the enhancement of endogenous antioxidant capacity and inhibition of endoplasmic reticulum stress in CA/CPR rat models.
Subject(s)
Cardiopulmonary Resuscitation/methods , Endoplasmic Reticulum Stress/drug effects , Heart Arrest/metabolism , Neuroprotective Agents/pharmacology , Polyphenols/pharmacology , Superoxide Dismutase/metabolism , Tea/chemistry , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Caspase 12/metabolism , Caspase 3/metabolism , Cerebral Cortex/metabolism , Disease Models, Animal , Heat-Shock Proteins/metabolism , Male , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Superoxide Dismutase-1/metabolism , Transcription Factor CHOP/metabolismABSTRACT
BACKGROUND: Various and opposite roles of epigallocatechin gallate (EGCG) have been reported in different studies. We aimed to investigate how EGCG affects the cerebral injury in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) model of rat. METHODS: The rats which were subjected to CA/CPR randomly received low dose of EGCG (3 mg/kg, Low-EGCG group, n=16), high dose of EGCG (9 mg/kg, High-EGCG group, n=16) and equal volume of 0.9% saline solution (NS group, n=16) at the first minute after return of spontaneous circulation (ROSC). The rats underwent anesthesia and intubation were defined as Sham group (n=16). Twenty-four hours after ROSC, neural defect score (NDS), ROS fluorescence intensity, degree of mitochondrial permeability transition pore (mPTP) opening, ATP contents and mitochondrial ATP synthase expression were evaluated in the four groups. The expression of extracellular signal-regulated kinase (ERK) activity and cleaved-caspase 3 were also detected by Western blot. RESULTS: CA/CPR induced severe ischemia-reperfusion injury (IRI), resulted in mitochondrial dysfunction and upregulated phosphorylation of ERK. EGCG dose-dependently alleviated the IRI after CA/CPR, inhibited ERK activity and restored mitochondrial function and, as indicated by improved NDS, reduced ROS level, decreased mPTP opening, elevated ATP content, increased ATPase expression and downregulated cleaved-caspase 3 level. CONCLUSION: EGCG alleviated global cerebral IRI by restoring mitochondrial dysfunction and ERK modulation in a rat CA/CPR model, which might make it a potential candidate agent against IRI after CA/CPR in the future. Further study is needed to determine whether higher dosage of EGCG might aggravate cerebral IRI post-CA/CPR.
Subject(s)
Cardiopulmonary Resuscitation , Catechin/analogs & derivatives , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Mitochondrial Membrane Transport Proteins/drug effects , Protein Kinase Inhibitors/pharmacology , Animals , Catechin/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Heart Arrest/drug therapy , Male , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Phosphorylation/drug effects , Rats , Rats, Sprague-DawleyABSTRACT
Imbalances between cellular K+ efflux and influx are considered to be involved in cerebral ischemia-reperfusion (I/R) injury. High-potassium pretreatment alleviates this injury, but the underlying molecular mechanism is unclear. In this study, we sought to investigate whether high-potassium preconditioning enhances cerebral tolerance to I/R injury through an anti-apoptotic mechanism. Adult male Sprague-Dawley rats were randomly divided into four groups (n = 40/group): a sham-operated group, normal saline group (3.2 ml/kg saline, intravenous (IV)), and low-dose and high-dose potassium chloride (KCl) groups (40 and 80 mg/kg KCl solution, IV, respectively). Subsequently, the rats underwent 90 min of middle cerebral artery occlusion (MCAO) followed by 24 hr of reperfusion (MCAO/R). Neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining, and TUNEL assay were used to assess neural injury. The expression of apoptotic proteins, brain potassium levels, mitochondrial function and oxidative stress were detected to explore the potential mechanism. After 24 hr of reperfusion, in both KCl treatment groups, neurological deficits and the cerebral infarct volume were reduced, and the apoptosis index of neurons was decreased. Furthermore, high-potassium preconditioning increased brain K+ , adenosine triphosphate (ATP), cytochrome c oxidase (COX) levels, reduced malondialdehyde level, improved Na+ /K+ -ATPase, succinic dehydrogenase and superoxide dismutase activities, upregulated anti-apoptotic protein expression, and downregulated pro-apoptotic protein expression. This study suggests that high-potassium preconditioning enhanced cerebral tolerance to I/R injury in a rat MCAO/R model. The protective mechanism may involve apoptosis inhibition via preservation of intracellular K+ and improvement of mitochondrial function.
Subject(s)
Brain Ischemia/physiopathology , Brain/blood supply , Potassium Chloride/pharmacology , Reperfusion Injury/physiopathology , Animals , Apoptosis/drug effects , Apoptosis/physiology , Ischemic Preconditioning/methods , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Natural Cordyceps cicadae (C. cicadae) has been utilized extensively in traditional Chinese medicine to treat chronic renal diseases, heart palpitations, infantile convulsions, and dizziness. However, given its slow growth and immoderate exploitation, C. cicadae resources have been severely depleted. By contrast, Paecilomyces cicadae (P. cicadae), as the anamorph stage of C. cicadae, is easy to cultivate, and this kind of cultivated P. cicadae has good and controllable quality. PURPOSE: This study aimed to compare the therapeutic effects of C. cicadae and P. cicadae on adenine-induced chronic renal failure (CRF) rats. In accordance with the aforementioned studies, our work subsequently analyzed the intrinsic relationships between the efficacy and pharmacodynamic substances of C. cicadae and P. cicadae to conclude whether or not P. cicadae could be used as an alternative to C. cicadae in treating CRF. METHODS: Rats were administered with C. cicadae (1.0 g/kg) or P. cicadae (1.0 g/kg) by gavage for 4 weeks. Furthermore, we applied Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, and ultraviolet spectrophotometry to comprehensively detect and analyze the chemical constituent differences from ten batches each of C. cicadae and P. cicadae. RESULTS: This study revealed that both C. cicadae and P. cicadae exerted obvious therapeutic effects on CRF and were more consistent with their chemical compositions. CONCLUSION: P. cicadae can be used as an alternative to C. cicadae for treating CRF to cater to market demands.