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1.
Breastfeed Med ; 19(6): 445-450, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38529934

ABSTRACT

Background: To investigate the efficacy of aloe gel in reducing pain and promoting wound healing in postpartum women with nipple trauma. Method: There were 80 postpartum women who took part in this study having developed nipple trauma during breastfeeding in the obstetrics department of a tertiary grade A hospital in Suzhou from January to December 2021. Postpartum women with nipple trauma whose hospital bed numbers ranged between 15 and 33 were included in the test group, whereas those whose hospital bed numbers ranged between 35 and 53 were included in the control group. Both groups received health education and breastfeeding guidance. The control group applied lanolin cream to their nipple trauma, whereas the test group used aloe gel. We used a nipple trauma severity assessment table to determine the severity of nipple trauma in lactating women and a Visual Analogue Scale (VAS) to determine the level of nipple pain and referred to the Traditional Chinese Medicine Standard for Diagnosis and Therapeutic Efficacy for Diseases and Syndromes to determine the healing time of their wounds. Results: The test group scored 3.70 ± 1.24 and 1.65 ± 0.74 points on the VAS on the first and third days following the intervention, whereas the control group scored 4.30 ± 0.94 and 2.23 ± 1.07 points, respectively. It took 3.75 ± 1.08 days and 4.45 ± 1.15 days for the nipple pain to completely disappear in the test group and the control group, respectively. The healing period for nipple trauma was 5.28 ± 1.26 days for the test group and 6.03 ± 1.61 days for the control group. All of the aforementioned distinctions were statistically significant (p < 0.05). Conclusions: Aloe gel can significantly alleviate the pain associated with nipple trauma in lactating women, accelerate wound healing, and reduce the duration of nipple trauma.


Subject(s)
Aloe , Breast Feeding , Gels , Lactation , Nipples , Wound Healing , Humans , Nipples/injuries , Female , Adult , Lactation/drug effects , Wound Healing/drug effects , Lanolin , Pain Measurement , Postpartum Period , Pain/drug therapy , Pain/etiology
2.
Fitoterapia ; 174: 105869, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38378132

ABSTRACT

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.


Subject(s)
Antineoplastic Agents , Asteraceae , Sesquiterpenes , Humans , Cell Line, Tumor , Molecular Structure , Reactive Oxygen Species , Antineoplastic Agents/pharmacology , Apoptosis , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry
3.
Eur J Clin Nutr ; 78(1): 19-26, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37653236

ABSTRACT

OBJECTIVE: To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach. METHODS: Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP). RESULTS: In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:ß = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: ß = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: ß = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: ß = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (ß = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association. CONCLUSIONS: Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.


Subject(s)
Diabetes Mellitus, Type 2 , Fatty Acids, Omega-3 , Sarcopenia , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Sarcopenia/genetics , Polymorphism, Single Nucleotide
4.
J Ethnopharmacol ; 315: 116653, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37236383

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.


Subject(s)
Caesalpinia , Diterpenes , NF-kappa B/metabolism , Caesalpinia/chemistry , Microglia/metabolism , Cyclooxygenase 2 , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Plant Leaves/metabolism , Diterpenes/pharmacology , Diterpenes/therapeutic use , Diterpenes/chemistry , Lipopolysaccharides/pharmacology
5.
Article in English | MEDLINE | ID: mdl-36865751

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a global health issue that lacks effective treatments. Dysfunction and/or death of pancreatic ß-cells (PBCs) are considered a major cause of T2DM. Therefore, elucidating the mechanisms underlying the death of PBCs might be helpful to develop novel strategies to treat T2DM. Ferroptosis is a newly identified form of cell death that has distinct features. However, knowledge regarding the role of ferroptosis in the death of PBCs remains limited. In the current study, we used high glucose (10 mM) (HG) levels to induce ferroptosis in PBC. We also observed that hispidin, a polyphenol compound that can be isolated from Phellinus linteus, could attenuate ferroptosis induced by HG in PBCs. Mechanistic investigations showed that hispidin led to the upregulation of miR-15b-5p, which directly inhibits the expression of glutaminase (GLS2) which plays an essential role in the glutamine metabolism. In addition, we found that overexpression of GLS2 could abrogate the protective effect of hispidin against ferroptosis caused by HG in PBCs. Therefore, our study provides novel insights into the mechanisms that regulate the death of PBCs.

6.
Phytomedicine ; 113: 154725, 2023 May.
Article in English | MEDLINE | ID: mdl-36867963

ABSTRACT

BACKGROUND: Regulating the microglial phenotype is an attractive strategy for treating diseases of the central nervous system such as depression and anxiety. Gastrodin can quickly cross the blood-brain barrier and mitigate microglia-mediated inflammation, which widely used to treat a variety of central nervous system diseases associated with microglial dysfunction. However, the molecular mechanism by which gastrodin regulates the functional phenotype of microglia remains unclear. PURPOSE: Since the transcription factor "nuclear factor erythroid 2-related factor 2″ (Nrf2) is associated with the anti-inflammatory effects of gastrodin, we hypothesized that gastrodin induces Nrf2 expression in microglia and thereby programs an anti-inflammatory phenotype. STUDY DESIGN: Male C57BL/6 mice, treated or not with gastrodin, were given lipopolysaccharide (LPS) at 0.25 mg/kg/d for 10 days to induce chronic neuroinflammation. The effects of gastrodin on microglial phenotypes, neuroinflammation and depression- and anxiety-like behaviors were evaluated. In another experiment, animals were treated with Nrf2 inhibitor ML385 throughout the 13-day gastrodin intervention period. METHODS: The effects of gastrodin on depression- and anxiety-like behaviors were evaluated through the sucrose preference test, forced swimming test, open field test and elevated plus-maze test; as well as its effects on morphology and molecular and functional phenotypes of hippocampal microglia through immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assays. RESULTS: Chronic exposure to LPS caused hippocampal microglia to secrete inflammatory cytokines, their somata to enlarge, and their dendrites to lose branches. These changes were associated with depression- and anxiety-like behaviors. Gastrodin blocked these LPS-induced alterations and promoted an Arg-1+ microglial phenotype that protected neurons from injury. The effects of gastrodin were associated with Nrf2 activation, whereas blockade of Nrf2 antagonized gastrodin. CONCLUSION: These results suggest that gastrodin acts via Nrf2 to promote an Arg-1+ microglial phenotype, which buffers the harmful effects of LPS-induced neuroinflammation. Gastrodin may be a promising drug against central nervous system diseases that involve microglial dysfunction.


Subject(s)
Depression , Microglia , Animals , Male , Mice , Anti-Inflammatory Agents/pharmacology , Anxiety/drug therapy , Anxiety/metabolism , Depression/drug therapy , Depression/metabolism , Hippocampus/metabolism , Lipopolysaccharides/pharmacology , Mice, Inbred C57BL , Neuroinflammatory Diseases , NF-E2-Related Factor 2/drug effects , NF-E2-Related Factor 2/metabolism , Phenotype
7.
Zhongguo Zhen Jiu ; 42(12): 1373-6, 2022 Dec 12.
Article in Chinese | MEDLINE | ID: mdl-36484190

ABSTRACT

OBJECTIVE: To observe the effect of acupuncture therapy based on "gut-brain axis" on clinical manifestations and gastrointestinal symptoms of children with autism spectrum disorder (ASD). METHODS: A total of 66 children with ASD were randomly divided into an observation group and a control group, 33 cases in each group. The control group was treated by routine rehabilitation training. On the basis of the control group, the observation group was treated with acupuncture based on "gut-brain axis", and the acupoints were Touwei (ST 8), Shenting (GV 24), Sishencong (EX-HN 1), Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36), etc. Both treatments were given once every other day, 3 times a week, 4 weeks as a course of treatment, consecutively for 3 courses. The scores of autism behavior checklist (ABC), TCM symptoms of gastrointestinal disease and childhood autism rating scale (CARS) were compared between the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of ABC, CARS and TCM symptoms of gastrointestinal disease in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate of the observation group was 90.9% (30/33), which was higher than 81.8% (27/33) in the control group (P<0.05). CONCLUSION: On the basis of routine rehabilitation training, acupuncture therapy based on "gut-brain axis" is effective in treating ASD, which can relieve the clinical manifestations and gastrointestinal symptoms.


Subject(s)
Acupuncture Therapy , Autism Spectrum Disorder , Gastrointestinal Diseases , Child , Humans , Autism Spectrum Disorder/therapy , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy
8.
Semin Arthritis Rheum ; 57: 152095, 2022 12.
Article in English | MEDLINE | ID: mdl-36126568

ABSTRACT

OBJECTIVE: Multiple observational studies have reported the close associations of obstructive sleep apnea (OSA) with serum uric acid (SUA) levels and gout. However, the causal nature and direction remains unclear. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was performed, based on publicly available genome-wide association studies (GWAS) summary statistics, to investigate whether OSA is causally related to SUA levels, gout and vice versa. The inverse-variance weighted (IVW) was used as the primary analysis approach, supplemented with four sensitive analysis methods applied to assess the robustness of the results. Moreover, multivariable MR (MVMR) was utilized to evaluate the independent causal effect of OSA on SUA and gout after adjusting for body mass index (BMI), hypertension, type 2 diabetes (T2D), coronary artery disease (CAD), and chronic kidney disease (CKD). RESULTS: Genetically predicted OSA liability was significantly associated with increased levels of SUA (IVW method: ß = 0.19, 95% CI = 0.11 - 0.26, P = 7.24 × 10-7) and risk of gout [IVW method: odds ratio (OR) = 1.75 95% CI = 1.13 - 2.69, P = 0.01] in univariable MR. The MVMR results suggested that OSA retained its significant association with increased SUA levels, whereas the significant association between OSA and gout was attenuated to null after adjusting for BMI and T2D. No causal effect of OSA on SUA levels and gout was found in the reverse direction. CONCLUSIONS: Our findings suggest that OSA was causally associated with increased levels of SUA, but was not independently associated with gout risk.


Subject(s)
Diabetes Mellitus, Type 2 , Gout , Sleep Apnea, Obstructive , Humans , Uric Acid , Mendelian Randomization Analysis , Genome-Wide Association Study , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Gout/genetics , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/genetics , Polymorphism, Single Nucleotide
9.
Sci Total Environ ; 844: 157215, 2022 Oct 20.
Article in English | MEDLINE | ID: mdl-35809728

ABSTRACT

Phosphorus (P) is essential for crop growth as an indispensable nutrient; however, there has been growing concern over the low use efficiency of P used in current fertilizers. We synthesized and characterized a potential P fertilizer nanohydroxyapatite/biochar/sodium humate (nHAP/BC/HANa) composite. To study the impact of the composite on soil chemical properties and microbial community in sandy soils, we set up four treatments as follows: (1) biochar (BC), (2) nanohydroxyapatite (nHAP), (3) nHAP/BC/HANa composite, and (4) sodium humate (HANa) was added separately into soils amended with nHAP/BC (nHAP/BC + HANa) to compare its performance with that of the nHAP/BC/HANa composite. A key finding was that the nHAP/BC/HANa composite not only significantly increased the soil available P content and alkaline phosphatase activity but also the increased organic matter content compared to the control. Additionally, leaching losses of P in soils amended with the nHAP/BC/HANa composite were lower than those in soils amended with the nHAP/BC + HANa, which suggested that the nHAP/BC/HANa composite had great potential to decrease P loss in sandy soils. Moreover, bacterial communities were more sensitive than fungal communities to all treatments. The bacterial communities showed the most significant changes in the nHAP/BC/HANa treatments. Results from Mantel tests further indicated that the strongest correlation between bacterial communities and soil properties occurring in the nHAP/BC/HANa treatments. Random forest analysis was conducted to identify the dominant microbial taxa, such as Proteobacteria, Acidobacteria, and Gemmatimonadetes, for predicting changes in soil properties. There was an asymptotical transition in bacterial community assembly processes from stochastic to deterministic in the nHAP/BC/HANa treatments. In conclusion, we demonstrated that nHAP/BC/HANa composite had the remarkable contribution to soil P availability in sandy soils, and simultaneously promoted the bacterial functions potential for P cycling, which present valuable insights to the development of potential P fertilizer.


Subject(s)
Microbiota , Soil , Bacteria , Charcoal/chemistry , Fertilizers , Phosphorus , Sand , Sodium , Soil/chemistry , Soil Microbiology
10.
Zhongguo Zhen Jiu ; 42(6): 625-8, 2022 Jun 12.
Article in Chinese | MEDLINE | ID: mdl-35712945

ABSTRACT

OBJECTIVE: To compare the clinical efficacy between Wei's triple nine needling combined with esculin and digitalis glycosides eye drops and esculin and digitalis glycosides eye drops alone for presbyopia complicated with visual fatigue of liver depression and spleen deficiency. METHODS: Forty-six cases (92 eyes) with presbyopia complicated with visual fatigue of liver depression and spleen deficiency were randomly divided into an observation group (23 cases) and a control group (23 cases, 2 cases dropped off). The cases in the observation group were treated with Wei's triple nine needling and esculin and digitalis glycosides eye drops. The acupoints included Shangming (Extra), Chengqi (ST 1), Cuanzhu (BL 2) to Jingming (BL 1), Sizhukong (TE 23) to Taiyang (EX-HN 5), etc; the needling was given once every other day, three times a week, and the eye drops were given one drop each time, three times a day. The cases in the control group were only treated with the eye drops. Both groups were treated for 7 days as one course of treatment, and 2 courses of treatment were given. The visual fatigue core symptoms score, adjustment amplitude, adjustment lag and best average corrected visual acuity were observed in the two groups before treatment, 1 week and 2 weeks into treatment, respectively. RESULTS: Compared before treatment, the visual fatigue core symptoms scores in the two groups were decreased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment amplitude was increased after 2-week treatment (P<0.05), while in the control group, the adjustment amplitude was increased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment lag was decreased after 1-week and 2-week treatment (P<0.05). After 2-week treatment, the visual fatigue core symptoms score in the observation group was lower than that in the control group, and the adjustment amplitude was higher than that in the control group (P<0.05). There were no significant differences in adjustment lag and best average corrected visual acuity between the two groups after 1-week and 2-week treatment (P>0.05). CONCLUSION: Wei's triple nine needling combined with esculin and digitalis glycosides eye drops could improve the visual fatigue and eye regulation ability in patients with presbyopia complicated with visual fatigue of liver depression and spleen deficiency, and the effect is better than esculin and digitalis glycosides eye drops alone.


Subject(s)
Acupuncture Therapy , Asthenopia , Presbyopia , Acupuncture Points , Depression , Digitalis Glycosides , Esculin , Humans , Liver , Ophthalmic Solutions , Spleen , Treatment Outcome
11.
J Mater Chem B ; 10(27): 5154-5164, 2022 07 13.
Article in English | MEDLINE | ID: mdl-35666635

ABSTRACT

Tumor-triggered targeting ammonium bicarbonate (TTABC) liposomes were proposed to improve the uptake of ammonium bicarbonate (ABC) liposomes in tumor cells and retain their long circulation in vivo in our previous study. However, it must be solved how to precisely release the loaded drugs of the TTABC liposomes into tumor cells. In addition, synergistic multimodal therapy could result in better tumor treatment outcomes than monomodal chemotherapy. In the research, we prepared indocyanine green (ICG) and doxorubicin (DOX) encapsulated TTABC liposomes (ICG&DOX@TTABC) to achieve near-infrared (NIR) light-controlled chemo/photothermal/photodynamic multimodal therapy guided by fluorescence and photothermal imaging. In vitro and vivo studies show that ICG&DOX@TTABC can specifically accumulate in tumor tissues, effectively transform NIR light into local thermo-therapy, and have excellent anti-tumor ability without obvious side effects. ICG&DOX@TTABC could be promising for fluorescence and photothermal imaging-guided chemo/photothermal/photodynamic tumor treatment.


Subject(s)
Liposomes , Neoplasms , Bicarbonates , Combined Modality Therapy , Doxorubicin , Humans , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Liposomes/therapeutic use , Neoplasms/drug therapy , Phototherapy/methods
12.
J Asian Nat Prod Res ; 23(11): 1023-1029, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33118374

ABSTRACT

A phytochemical investigation on the 90% ethanol aqueous extract of the bulbs of Crinum latifolium led to the isolation of three new crinane-type alkaloids, designated as crinumlatines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. As a result, compounds 1-3 exhibited some antimicrobial activity against the tested Gram negative bacteria with minimum inhibitory concentration values less than 50 µg/ml.


Subject(s)
Alkaloids , Amaryllidaceae Alkaloids , Anti-Infective Agents , Crinum , Alkaloids/pharmacology , Molecular Structure , Plant Extracts
13.
Cancer Biol Med ; 17(3): 676-692, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32944399

ABSTRACT

Objective: In this study, we aimed to develop an amino-terminal fragment (ATF) peptide-targeted liposome carrying ß-elemene (ATF24-PEG-Lipo-ß-E) for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: The liposomes were prepared by ethanol injection and high-pressure microjet homogenization. The liposomes were characterized, and the drug content, entrapment efficiency, and in vitro release were studied. The targeting efficiency was investigated using confocal microscopy, ultra-fast liquid chromatography, and an orthotopic bladder cancer model. The effects of ATF24-PEG-Lipo-ß-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model. Results: ATF24-PEG-Lipo-ß-E had small and uniform sizes (˜79 nm), high drug loading capacity (˜5.24 mg/mL), high entrapment efficiency (98.37 ± 0.95%), and exhibited sustained drug release behavior. ATF24-PEG-Lipo-ß-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol (PEG)ylated ß-elemene liposomes (PEG-Lipo-ß-E). DDP, combined with ATF24-PEG-Lipo-ß-E, exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways. Furthermore, the in vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors, using the combined strategy. Conclusions: The present study provided an effective strategy for the targeted delivery of ß-elemene (ß-E) to bladder cancer, and a combined strategy for bladder cancer treatment.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cisplatin/pharmacology , Sesquiterpenes/pharmacology , Urinary Bladder Neoplasms/drug therapy , Animals , Apoptosis/drug effects , CDC2 Protein Kinase , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cyclin B1/metabolism , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Liposomes/metabolism , Mice , Mice, Nude , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays
14.
Signal Transduct Target Ther ; 5(1): 51, 2020 05 08.
Article in English | MEDLINE | ID: mdl-32382060

ABSTRACT

Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca2+/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca2+/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.


Subject(s)
Bibenzyls/pharmacology , Calcium Signaling/drug effects , Calcium/metabolism , Calmodulin/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Dendrobium/chemistry , Ferroptosis/drug effects , Lung Neoplasms/metabolism , Neoplasm Proteins/metabolism , Phenol/pharmacology , Plant Extracts/chemistry , Animals , Bibenzyls/chemistry , Cell Line, Tumor , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Phenol/chemistry
15.
Theranostics ; 10(11): 5107-5119, 2020.
Article in English | MEDLINE | ID: mdl-32308771

ABSTRACT

Background and Purpose: RAS mutations limit the effectiveness of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in combination with chemotherapy for metastatic colorectal cancer (mCRC) patients. Therefore, new cell death forms have focused on identifying indirect targets to inhibit Ras-induced oncogenesis. Recently, emerging evidence has shown the potential of triggering ferroptosis for cancer therapy, particularly for eradicating aggressive malignancies that are resistant to traditional therapies. Methods: KRAS mutant CRC cell HCT116 and Lovo were treated with cetuximab and ß-elemene, a bioactive compound isolated from Chinese herb Curcumae Rhizoma. Ferroptosis and epithelial-mesenchymal transformation (EMT) were detected in vitro and in vivo. Orthotopic CRC animal model were established and the tumor growth was monitored by IVIS bioluminescence imaging. Tumor tissues were collected to determine ferroptosis effect and the expression of EMT markers after the treatment. Results: CCK-8 assay showed that synergetic effect was obtained when 125 µg/ml ß-elemene was combined with 25 µg/ml cetuximab in KRAS mutant CRC cells. AV/PI staining suggested a non-apoptotic mode of cell death after the treatment with ß-elemene and cetuximab. In vitro, ß-elemene in combination with cetuximab was shown to induce iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of HO-1 and transferrin, and downregulation of negative regulatory proteins for ferroptosis (GPX4, SLC7A11, FTH1, glutaminase, and SLC40A1) in KRAS mutant CRC cells. Meanwhile, combinative treatment of ß-elemene and cetuximab inhibited cell migration and decreased the expression of mesenchymal markers (Vimentin, N-cadherin, Slug, Snail and MMP-9), but promoted the expression of epithelial marker E-cadherin. Moreover, ferroptosis inhibitors but not other cell death suppressors abrogated the effect of ß-elemene in combination with cetuximab on KRAS mutant CRC cells. In vivo, co-treatment with ß-elemene and cetuximab inhibited KRAS mutant tumor growth and lymph nodes metastases. Conclusions: Our data for the first time suggest that the natural product ß-elemene is a new ferroptosis inducer and combinative treatment of ß-elemene and cetuximab is sensitive to KRAS mutant CRC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for CRC patients with RAS mutations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Colorectal Neoplasms/drug therapy , Ferroptosis/drug effects , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Cell Line, Tumor , Cell Proliferation , Cetuximab/administration & dosage , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Drug Therapy, Combination , Epithelial-Mesenchymal Transition/drug effects , ErbB Receptors/antagonists & inhibitors , Female , Humans , Mice, Inbred BALB C , Mice, Nude , Proto-Oncogene Proteins p21(ras)/metabolism , Sesquiterpenes/administration & dosage , Xenograft Model Antitumor Assays
16.
Medicine (Baltimore) ; 99(11): e19481, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32176081

ABSTRACT

BACKGROUND: Elemene is a natural compound extracted from Zingiberaceae plants, and is used in various cancer. However, the efficacy and safety elemene combined with chemotherapy in advanced gastric cancer (GC) are lack of systematic assessment. METHODS: we searched the PubMed, EMBASE, Web of Science, Cochrane Library, China Academic Journals (CNKI), Chinese Science and Technology Journals (CQVIP) and Chinese Biomedical Literature databases. Randomized controlled trials (RCTs) comparing elemene plus chemotherapy with chemotherapy alone in participants with advanced GC and reporting at least one of the following outcomes were selected and assessed for inclusion. JADAD scale was used to assess the quality. Data was screened and extracted by two independent investigators. The primary clinical outcome was overall response rate (ORR); the secondary outcomes were quality of life (QOL) and adverse events (AEs). Analysis was performed using Review Manager 5.3. RESULTS: Sixteen RCTs matched the selection criteria, which reported on 969 subjects. Risk ratios (RR) and corresponding 95% confidence intervals (CIs) were pooled for ORR, life quality based on KPS, and risk of AEs. Compared to chemotherapy alone, elemene combined with chemotherapy in the treatment of GC may increase the efficiency of ORR(RR: 1.41; 95% CI: 1.23-1.60; P < .0001), improve their life quality based on KPS (RR: 1.84; 95% CI: 1.45-2.34; P < .00001), and reduce the adverse reactions, including leukopenia(RR: 0.73; 95% CI: 0.62-0.85; P < .00001), neutropenia (RR: 0.75; 95% CI: 0.60-0.95; P = .02), anemia (RR: 0.76; 95% CI: 0.60-0.95; P = .02), thrombocytopenia (RR: 0.56; 95% CI: 0.43-0.73; P < .00001). Nausea and vomiting (RR: 0.84; 95% CI: 0.84-1.07; P = .39), diarrhea (RR: 0.69; 95% CI: 0.41-1.15; P = .15), neurotoxicity (RR: 0.77; 95% CI: 0.59-1.00; P = .05) and hepatic dysfunction (RR: 0.95; 95% CI: 0.58-1.54; P = .83) were similar between two groups. CONCLUSIONS: Elemene may have the potential to improve the efficacy and reduce the AEs of chemotherapy for gastric cancer. However, the long-term, high-quality researches with a large sample size in different populations are required.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Sesquiterpenes/therapeutic use , Stomach Neoplasms/drug therapy , Humans , Randomized Controlled Trials as Topic
17.
Front Mol Biosci ; 7: 602282, 2020.
Article in English | MEDLINE | ID: mdl-33585556

ABSTRACT

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

18.
Front Pharmacol ; 10: 1139, 2019.
Article in English | MEDLINE | ID: mdl-31649531

ABSTRACT

Background: Primary intracerebral hemorrhage (ICH) is the most harmful subtype of stroke, but there have yet been no specific proven therapies. Chinese herbal medicine (CHM) has been used for ICH for more than a thousand years; however, currently it is still lacking of available evidence. The objective of this study is to assess the current available evidence of CHM for acute ICH according to randomized controlled trials. Methods: Eight databases were searched from the year of their respective inception to November 2017. Only the studies that assessed at least four domains with "yes" according to the Cochrane risk of bias tool were selected for analysis. All the data were analyzed by using Review Manager 5.3 software. P < 0.05 was considered to be statistically significant. Results: Forty-five studies with 4,517 individuals were identified. CHM paratherapy can improve dependency, neurological function deficit, volume of hematoma, clinical effective rate, and volume of perihematomal edema compared with CHM alone or placebo (all P < 0.05). By contrast, it was not significant for improving the mortality rate of ICH patients (P > 0.05). In addition, adverse events were reported in 16 studies, whereas 29 studies did not mention it. The frequency of adverse events was 70/972 in the trial group and 48/944 in the control group. Conclusion: The present study provided supportive evidence of CHM for improving dependency of ICH and showed generally safety; however, there is still lack of evidence for improving mortality rate, and it opens for further study.

19.
Front Pharmacol ; 10: 277, 2019.
Article in English | MEDLINE | ID: mdl-31001112

ABSTRACT

Wilson's disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Randomized-controlled clinical trials (RCTs), which compared CHM with Western conventional medicine or placebo for WD, were searched in six databases from inception to July 2017. The methodological quality was assessed using 7-item criteria from the Cochrane's collaboration tool. All the data were analyzed using Rev-Man 5.3 software. Eighteen studies involving 1,220 patients were identified for the final analyses. A score of study quality ranged from 2/7 to 4/7 points. Meta-analyses showed that CHM could significantly increase 24-h urinary copper excretion and improve liver function and the total clinical efficacy rate for WD compared with control (p < 0.05). Additionally, CHM was well tolerated in patients with WD. The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects. In conclusion, despite the apparent positive results, the present evidence supports, to a limited extent because of the methodological flaws and CHM heterogeneity, that CHM paratherapy can be used for patients with WD but could not be recommended as monotherapy in WD. Further rigorous RCTs focusing on individual CHM formula for WD are warranted.

20.
Ann Transl Med ; 7(6): 123, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31032278

ABSTRACT

BACKGROUND: There is increasing evidence demonstrating the highly inadequate reporting of preclinical research in multiple scientific publications. The purpose of this study is to systematically investigate the reporting quality of acupuncture for neurogenesis in animal models of acute ischemic stroke. METHODS: We searched eight databases, including PubMed, EMBASE, CINAHL, AMED, Chinese National Knowledge Infrastructure, VIP information database, Wanfang data Information Site, and Chinese Biomedical Literature Database. The methodological quality of included studies was assessed by using the CAMARADES 10-item checklist. The STRICTA statement was modified to gear to animal acupuncture research. The reporting quality was assessed according to the ARRIVE guidelines and the modified STRICTA statement. Data were analyzed with descriptive statistics. RESULTS: Ultimately, 44 studies containing 2,411 subjects were identified. The overall compliance with the CAMARADES 10-item checklist has a mean of 4.3. The reporting quality indicated that the overall compliance with ARRIVE guidelines has a mean of 59.9% and with the modified STRICTA statement a mean of 71.8%. The findings suggest that the reporting quality of acupuncture for preclinical stroke was generally poor. CONCLUSIONS: Full compliance with ARRIVE guidelines and/or modified STRICTA statement in designing, conducting and reporting preclinical acupuncture research is urgently needed in the future.

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