ABSTRACT
The anti-inflammatory role of lutein has been widely recognized, however, the underlying mechanism is still not fully elucidated. Hence, the effects of lutein on the intestinal health and growth performance of broilers and the action of mechanism were investigated. 288 male yellow-feathered broilers (1-day old) were randomly allocated to 3 treatment groups with 8 replicates of 12 birds each, and the control group was fed a broken rice-soybean basal diet, while the test groups were fed a basal diet added with 20 mg/kg and 40 mg/kg of lutein (LU20, LU40), respectively. The feeding trial lasted for 21 d. The results showed that 40 mg/kg lutein supplementation tended to increase ADFI (P = 0.10) and ADG (P = 0.08) of broilers. Moreover, the addition of lutein caused a decreasing trend of gene expression and concentration of proinflammatory cytokines IL-1ß (P = 0.08, P = 0.10, respectively) and IL-6 (P = 0.06, P = 0.06, respectively) and also tended to decrease the gene expression of TLR4 (P = 0.09) and MyD88 (P = 0.07) while increasing gene expression and concentration of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05) in the jejunum mucosa of broilers. Additionally, lutein supplementation increased the jejunal villi height of broilers (P < 0.05) and reduced villi damage. The experiment in vitro showed that lutein treatment reduced the gene expression of IL-1ß, IL-6, and IFN-γ in chicken intestinal epithelial cells (P < 0.05). However, this effect was diminished after knock-down of TLR4 or MyD88 genes using RNAi technology. In conclusion, lutein can inhibit the expression and secretion of proinflammatory cytokines in the jejunum mucosa and promote intestinal development of broilers, and the anti-inflammatory effect may be achieved by regulating TLR4/MyD88 signaling pathway.
Subject(s)
Chickens , Toll-Like Receptor 4 , Male , Animals , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Chickens/physiology , Myeloid Differentiation Factor 88 , Lutein/pharmacology , Lutein/metabolism , Interleukin-6/metabolism , Diet/veterinary , Signal Transduction , Cytokines/metabolism , Cell Differentiation , Animal Feed/analysisABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.
Subject(s)
Colitis, Ulcerative , Colitis , Animals , Mice , PPAR alpha/genetics , AMP-Activated Protein Kinases , Scutellaria baicalensis , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Dextran Sulfate/toxicity , RNA, Ribosomal, 16S , Colon , Disease Models, Animal , Fatty Acids , Mice, Inbred C57BLABSTRACT
Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.
Subject(s)
Asteraceae , Chrysanthemum , Alkynes , Antimalarials , Antioxidants/pharmacologyABSTRACT
BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.
Subject(s)
Colitis, Ulcerative , Colitis , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Amino Acids/metabolism , Animals , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Colon/pathology , Dextran Sulfate/adverse effects , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Mice , Mice, Inbred C57BL , Scutellaria baicalensis/chemistry , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Astragalus membranaceus (AM, family: Leguminosae) exerts significant therapeutic effect on gastric ulcer (GU); however, there are scarce studies on its molecular mechanism against GU. This study aims to explore the key ingredients, key targets, and potential mechanisms of AM in the treatment of GU by utilizing network pharmacology and molecular docking. METHODS: Several public databases were used to predict the targets of AM and GU, respectively, and the drug and disease targets were intersected to obtain the common targets. Next, the key ingredients and key targets were identified by constructing ingredient-target network and protein-protein-interaction (PPI) network. Gene Ontology biological processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the common targets in order to ascertain the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between the key ingredients and key targets. RESULTS: A total of 552 predicted targets were obtained from 23 screened active ingredients, of which 203 targets were the common targets with GU. Quercetin, kaempferol, and isorhamnetin were identified as the key ingredients by constructing ingredient-target network, and TP53, AKT1, VEGFA, IL6, TNF, CASP3, and EGFR were selected as the key targets by constructing PPI network. GOBP and KEGG pathway enrichment analysis suggested that the therapeutic effect of AM on GU involved multiple biological processes and signaling pathways related to inflammation, oxidative stress, apoptosis, cell proliferation, and angiogenesis. Molecular docking validation demonstrated that all key ingredients had good binding affinity with the key targets. CONCLUSION: This study revealed the key ingredients, key targets, and potential mechanisms of AM against GU, and these data may provide some crucial references for subsequent research and development of drugs for treating GU.
ABSTRACT
Cuscuta species (dodders) are agriculturally destructive, parasitic angiosperms. These parasitic plants use haustoria as physiological bridges to extract nutrients and water from hosts. Cuscuta campestris has a broad host range and wide geographical distribution. While some wild tomato relatives are resistant, cultivated tomatoes are generally susceptible to C. campestris infestations. However, some specific Heinz tomato (Solanum lycopersicum) hybrid cultivars exhibit resistance to dodders in the field, but their defense mechanism was previously unknown. Here, we discovered that the stem cortex in these resistant lines responds with local lignification upon C. campestris attachment, preventing parasite entry into the host. Lignin Induction Factor 1 (LIF1, an AP2-like transcription factor), SlMYB55, and Cuscuta R-gene for Lignin-based Resistance 1, a CC-NBS-LRR (CuRLR1) are identified as factors that confer host resistance by regulating lignification. SlWRKY16 is upregulated upon C. campestris infestation and potentially negatively regulates LIF1 function. Intriguingly, CuRLR1 may play a role in signaling or function as an intracellular receptor for receiving Cuscuta signals or effectors, thereby regulating lignification-based resistance. In summary, these four regulators control the lignin-based resistance response in specific Heinz tomato cultivars, preventing C. campestris from parasitizing resistant tomatoes. This discovery provides a foundation for investigating multilayer resistance against Cuscuta species and has potential for application in other essential crops attacked by parasitic plants.
Subject(s)
Cuscuta , Solanum lycopersicum , Solanum , Cuscuta/physiology , Host Specificity , Lignin , Solanum lycopersicum/geneticsABSTRACT
OBJECTIVE: To observe the clinical effect of Modified Shenqi Dihuang Decoction (MSDD) on bone metastasis of hormone-sensitive PCa after castration. METHODS: Seventy-six hormone-sensitive PCa patients with bone metastasis were randomly divided into a control and an MSDD group of an equal number, the former treated by maximal androgen blockade (MAB) and the latter with MSDD in addition to MAB, both for 6 months. Comparisons were made between the two groups of patients in their TCM symptom scores, quality of life (QOL) scores and the incidence rates of castration resistance, bone metastasis and adverse events. RESULTS: Totally, 64 of the patients were included in the statistical analysis. Compared with the controls, the MSDD group showed significantly lower rates of castration resistance (71.87% vs 28.12%, P < 0.05) and new bone and visceral metastases (40.63% vs 18.75%, P < 0.05) and level of serum alkaline phosphatase after treatment (ï¼»328.5 ± 170.6ï¼½ vs ï¼»318.5 ± 165.8ï¼½ U/L, P < 0.05), as well as lower scores in the TCM symptoms of frequent micturition (2.05 ± 0.51 vs 1.64 ± 0.66, P < 0.05), loss of appetite (1.95 ± 0.48 vs 1.41 ± 0.39, P < 0.05), fatigue (2.59 ± 0.68 vs 1.39 ± 0.58, P < 0.05), back pain (1.76 ± 0.41 vs 1.26 ± 0.38, P < 0.05), weight loss (1.88 ± 0.75 vs 1.26 ± 0.80, P < 0.05) and self-evaluation (1.89 ± 0.58 vs 1.54 ± 0.63, P < 0.05), but a higher score in the physical status (Karnofsky Performance Scale) (70.45 ± 12.16 vs 79.87 ± 11.23, P < 0.05). There were no statistically significant differences in the Numeric Rating Scale for Pain score and the incidence of adverse events between the two groups of patients. CONCLUSIONS: Modified Shenqi Dihuang Decoction can effectively improve the QOL and TCM symptom scores of the patients with hormone-sensitive PCa after androgen castration, enhance the efficacy of modern drugs in the treatment of hormone-sensitive PCa, decrease the incidence of metastasis, improve the patient's serum indicators, reduce the pain associated with bone metastasis, and improve the patient's quality of life.
Subject(s)
Prostatic Neoplasms , Quality of Life , Castration , Drugs, Chinese Herbal , Hormones , Humans , Male , Prostatic Neoplasms/drug therapyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.
Subject(s)
Colitis, Ulcerative/drug therapy , Drugs, Chinese Herbal/pharmacology , Endothelium/metabolism , Estrogen Receptor alpha/metabolism , Scutellaria baicalensis/chemistry , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Cyclooxygenase 2/metabolism , Dextran Sulfate/toxicity , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Endothelium/drug effects , ErbB Receptors/metabolism , Male , Mice, Inbred BALB C , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , Protein Interaction Maps , STAT1 Transcription Factor/metabolism , STAT2 Transcription Factor/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-β-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg
ABSTRACT
OBJECTIVE: To investigate the effect of varicocelectomy (VCE) combined with medication of Qilin Pills (QLP) in the treatment of varicocele (VC)-associated male infertility. METHODS: We retrospectively analyzed the clinical data on 180 cases of VC-associated male infertility treated in our hospitals between October 2017 and March 2019, 67 by VCE ( the control group) and 113 by VCE in combination with 6-month medication of QLP after operation (the VCE+QLP group). We obtained the semen parameters from the patients before and at 1, 2, 3 and 6 months after surgery, measured their sperm DNA fragmentation index (DFI) before and at 6 months after operation, and recorded the rate of pregnancy at months postoperatively. RESULTS: There were no severe complications in any of the cases after surgery or during the whole course of medication. Compared with the baseline, the patients in control group showed significant increases at 6 months postoperatively in sperm concentration (ï¼»17.1 ± 12.4ï¼½ vs ï¼»29.5 ± 14.4ï¼½ ×106/ml, P < 0.01), sperm motility (ï¼»33.6±13.5ï¼½% vs ï¼»54.5±12.0ï¼½% , P <) and the percentage of progressively motile sperm (PMS) (ï¼»22.8 ± 10.9ï¼½% vs ï¼»43.7 ± 11.7ï¼½%, P <) but a remarkable decrease in sperm DFI (16.5 ± 7.6ï¼½% vs ï¼»13.3 ± 4.4ï¼½% , P <), and so did those in the VCE+QLP group in sperm concentration (ï¼»16.8 ± 10.7ï¼½ vs ï¼»38.9 ± 24.1)×106/ml, P < 0.01), sperm motility (ï¼»32.8 ± 14.0ï¼½% vs ï¼»50.1 ± 15.0)%, P <), PMS (ï¼»21.8 ± 11.3ï¼½% vs ï¼»39.6 ± 13.3ï¼½% , P <) and sperm DFI (ï¼»17.8 ± 9.0ï¼½% vs ï¼»11.8 ± 4.8ï¼½%, P <). There were even more statistically significant differences between the control and VCE+QLP groups at 6 months in the above semen parameters (P < 0.01) and in the rate of natural pregnancy (32.8% ï¼»22/67ï¼½ vs 48.7% ï¼»55/113ï¼½, P < 0.05). CONCLUSIONS: Varicocelectomy combined with medication of Qilin Pills can effectively improve semen quality and increase the rate of natural pregnancy in the treatment of VC-associated male infertility.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Infertility, Male , Varicocele , Female , Humans , Infertility, Male/drug therapy , Infertility, Male/etiology , Male , Pregnancy , Pregnancy Rate , Retrospective Studies , Semen Analysis , Sperm Count , Sperm Motility , Spermatozoa , Varicocele/complications , Varicocele/surgeryABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.
Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Diet, High-Fat , Lipogenesis , Liver , Pogostemon , RatsABSTRACT
OBJECTIVE@#To observe the effect of electroacupuncture (EA) of " acupoint combination" on appetite, body fat, insulin sensitivity and central sensitivity of cholecystokinin (CCK) in obese rats with insulin resistance (IR), and to explore the mechanism of EA on improving obesity with insulin resistance.@*METHODS@#Among the fifty 8-week-old healthy SPF male Wistar rats, 10 rats were randomly selected and fed with normal diet; after 8 weeks, 8 rats were randomly selected as a normal group. The remaining 40 rats were fed with high-fat diet to establish the model of obsesity IR; after 8 weeks, 24 rats with successful model of obsesity IR were randomly divided into a model group, an EA group and a sham EA group, 8 rats in each group. Eight weeks after model establishment, the rats in the EA group were intervened with EA at "Fenglong" (ST 40), "Zhongwan" (CV 12), "Guanyuan" (CV 4) and "Zusanli" (ST 36), with continuous wave, in frequency of 2 Hz, and current intensity of 1 mA, for 10 min each time. The rats in the sham EA group were intervened with EA at the points 5 mm next to the acupoints used in the EA group and no electricity was given; the sham EA was given for 10 min each time. Both the treatments were given once every other day for 8 weeks. The Lee's index and food intake were observed before the intervention as well as 2 weeks, 4 weeks, 6 weeks and 8 weeks into intervention; after the intervention, serum insulin (INS) and glucose infusion rate (GIR) were detected; serum cholecystokinin (CCK) level was detected by ELISA; c-fos expression in the area postrema (AP) and nucleus tractus solitarius (NTS) of medulla oblongata was detected by immunohistochemistry.@*RESULTS@#Before the intervention as well as 2 weeks, 4 weeks, 6 weeks and 8 weeks into intervention, the Lee's index and food intake in the model group were higher than those in normal group (<0.01). The Lee's index (6 weeks and 8 weeks into intervention) and food intake (4 weeks, 6 weeks and 8 weeks into intervention) in the EA group were lower than those in the model group and the sham EA group (<0.05, <0.01). After intervention, compared with the normal group, serum level of INS was increased (<0.01), while GIR, serum CCK level, c-fos expression in AP and NTS in the model group were decreased (<0.01, <0.05). Compared with the model group and the sham EA group, serum level of INS in the EA group was decreased (<0.01), and GIR, serum CCK level, c-fos expression in AP and NTS were increased (<0.01, <0.05).@*CONCLUSION@#EA of " acupoint combination" could effectively reduce appetite, body fat and enhance insulin sensitivity in obese rats with IR. The mechanism may be related to the regulation of central sensitivity of CCK.
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Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. △9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.
ABSTRACT
Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. Δ9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.
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OBJECTIVE@#To explore the clinical effect of acupuncture and the potential effect mechanism in patients with premature ovarian failure.@*METHODS@#A total of 104 patients with premature ovarian failure were randomized into an acupuncture group and a western medication group, 52 cases in each one. In the western medication group, the conjugated estrogens tablets were prescribed for oral administration, 0.625 mg each time, once a day, consecutively for 21 days. On the 16th day of medication with conjugated estrogens tablets, the oral administration of medroxyprogesterone acetate tablets were supplemented, 10 mg each time, once a day, consecutively for 5 days, and then, these two kinds of western medication were discontinued for 1 week. A total of 3 cycles were required in treatment with 28 days as an artificial cycle. In the acupuncture group, acupuncture was applied. Two groups of acupoints were selected. The first group of acupoints were stimulated before ovulation and the acupoints were Guanyuan (CV 4), Guilai (ST 29), Taichong (LR 3), Taixi (KI 3), Xuehai (SP 10), Sanyinjiao (SP 6), Zigong (EX-CA 1), Yinlingquan (SP 9), Zusanli (ST 36), Shuidao (ST 28), Dahe (KI 12) and Tianshu (ST 25). The second group of acupoints were stimulated after ovulation and the acupoints included Ciliao (BL 32), Shiqizhui (EX-B 8), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Pishu (BL 20). The therapeutic effect was observed and compared in the patients between the two groups, as well as the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and the levels of serum luteinizing hormone (LH), follicule stimulating hormone (FSH) and estradiol (E) before and after treatment.@*RESULTS@#The total effective rate was 90.4% (47/52) in the acupuncture group, higher than 67.3% (35/62) in the western medication group (<0.05). After treatment, the expressions of IFN-γ and TNF-α in the acupuncture group were obviously lower than the western medication group (<0.05). Except for serum LH after treatment, at the end of treatment and in 30 days and 90 days after treatment, the levels of serum E in the acupuncture group were higher obviously than the western medication group and the levels of serum LH and FSH were lower obviously than the western medication group (all <0.05).@*CONCLUSION@#Acupuncture promotes the regular menstruation, effectively regulates the levels of serum LH, FSH and E and improves the pituitary gland and the ovary endocrine in the patients with premature ovarian failure. Such effect may be related to the the improvements in the expressions of IFN-γ and TNF-α, the inhibition of the apoptosis of ovarian granulosa cells, the recovery of ovarian function and the enhancement of reserve capacity.
Subject(s)
Female , Humans , Acupuncture Points , Acupuncture Therapy , Interferon-gamma , Blood , Primary Ovarian Insufficiency , Blood , Therapeutics , Tumor Necrosis Factor-alpha , BloodABSTRACT
OBJECTIVE@#To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models.@*METHODS@#PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review.@*RESULTS@#CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate.@*CONCLUSION@#CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.
Subject(s)
Animals , Mice , Drugs, Chinese Herbal , Therapeutic Uses , Osteosarcoma , Drug Therapy , Publication Bias , Risk Factors , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
Objective@#To observe the effects of a combination treatment with narrow-spectrum intense pulsed light and fractional carbon dioxide laser on hypertrophic scar pruritus in clinic.@*Methods@#A prospective randomized controlled study was conducted. A total of 90 patients with hypertrophic scars conforming to the inclusion criteria who were hospitalized in our ward from March to December 2017 were divided into combination treatment group and control group according to the random number table, with 45 patients in each group. For scar pruritus, patients in control group were treated twice by narrow-spectrum intense pulsed light with a one-month interval, while patients in combination treatment group were firstly treated by narrow-spectrum intense pulsed light combined with fractional carbon dioxide laser once, and with narrow-spectrum intense pulsed light once one month later. Before and 3 months after treatment, scar pruritus was evaluated by the Visual Analogue Scale and the Four-item Itch Questionnaire, and the improvement of scar was assessed by photography. Three months after treatment, the treatment satisfaction of scar pruritus was self-rated by patients. Meanwhile, adverse effects were recorded during the procedures and follow-up periods. Data were processed with Chi-square test, paired t test, Wilcoxon rank-sum test, and Fisher′s exact probability test.@*Results@#Before treatment, there was no statistically significant difference in scar pruritus degree evaluated by the Visual Analogue Scale and score distribution of scar pruritus location, extent, frequency, and sleep effect of the Four-item Itch Questionnaire between patients of two groups (Z=-1.08, -0.91, -0.03, -0.69, -1.49, P>0.05). Three months after treatment, there was reducing degree of scar pruritus of patients evaluated by the Visual Analogue Scale in control group or combination treatment group compared with before treatment within the same group (Z=-1.98, -4.65, P<0.05 or P<0.01), while the latter was more obvious than the former (Z=-2.14, P<0.05). There were reducing scores of scar pruritus extent and frequency of patients in control group, along with location, extent, frequency, and sleep effect of patients in combination treatment group compared with those before treatment within the same group (Z=-2.33, -2.34, -3.53, -4.96, -3.32, -4.84, P<0.05 or P<0.01). However, scores of scar pruritus location and sleep effect of patients in control group were similar to those before treatment within the same group (Z=-0.58, -1.34, P>0.05). The scores of scar pruritus location, extent, frequency, and sleep effect of patients were obviously lower in combination treatment group compared with control group (Z=-2.09, -2.69, -1.99, -2.23, P<0.05 or P<0.01). It was much better of scar improvement of patients in combination treatment group compared with control group (Z=-4.00, P<0.01). The percentages of treatment satisfaction of scar pruritus of patients with 0, 1%-25%, 26%-50%, 51%-75%, 76%-100% were 0, 2.2% (1/45), 17.8% (8/45), 48.9% (22/45), and 31.1% (14/45) respectively in combination treatment group, which were obviously better than 0, 11.1% (5/45), 53.3% (24/45), 28.9% (13/45), and 6.7% (3/45) in control group (Z=-4.42, P<0.01). During the treatment and follow-up periods, the adverse effect ratio of patients in control group was 6.7% (3/45), similar to 2.2% (1/45) of combination treatment group (P>0.05).@*Conclusions@#The combination of narrow-spectrum intense pulsed light and fractional carbon dioxide laser can greatly reduce pruritus, improve effect of scar treatment, and bring higher patient satisfaction compared with narrow-spectrum intense pulsed light alone in treating hypertrophic scar pruritus.@*Clinical trial registration@#Chinese Clinical Trial Registry, ChiCTR-ONH-17012350.
ABSTRACT
The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1β, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF-α, and IFN-γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity.
Subject(s)
Animals , Humans , Male , Mice , Antimalarials , Pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Hepcidins , Pharmacology , Interleukin-10 , Allergy and Immunology , Interleukin-17 , Allergy and Immunology , Malaria , Drug Therapy , Allergy and Immunology , Mortality , Parasitology , Plasmodium berghei , Genetics , MetabolismABSTRACT
Objective To explore the therapeutic efficacy of the water soluable photosensitizer D-galactopyranosyl zinc phthalocyanines (T1)-mediated photodynamic therapy (PDT) applied to HepG2 human hepatocellular carcinoma cells in vitro and in vivo,as well as its mechanism.Methods HepG2 cells in their logarithmic growth phase were cultured and divided into different concentrations ofT1 (0 μM,0.06 μM,0.125 μM,0.25 μM,0.5 μM and 1 μM).Methyl thiazolyl tetrazolium (MTT) assays were employed to determine the effect of the T1-PDT on the proliferation of the HepG2 cells.Cell apoptosis and necrosis were measured using a cell analyzer with Annexin VFITC/PI/Hochest33342 triple-staining.The reactive oxygen species (ROS) and the mitochondrial membrane potentials of the HepG2 cells were detected using fluorescence microscopy.Confocal microscopic assays were used to observe T1's subcellular localization on the HepG2 cells.Real-time quantitative polymerase chain reactions (RT-PCRs)were used to detect any apoptosis of Bcl-2-and Bax-related genes.H-22-bearing mice were used to calculate the antitumor rate of T1-PDT,and the expression levels of Bcl-2 and Bax mRNA were detected using RT-PCRs.Twenty-four healthy mice were randomly divided into a control group,a low-dose group,a middle-dose group and a high-dose group,each of 6.Each group was given different doses of T1-PDT and the tumor inhibition rate was calculated.Results The MTT assays showed that T1-PDT could significantly inhibit HepG2 cell growth,but T1 or PDT alone had little effect.The confocal microscope assay showed that T1 was mainly localized in the mitochondria in HepG2 cells with little in the lysosome.Cell analyzer results showed that T1-PDT could induce HepG2 apoptosis.The ROS levels of HepG2 cells increased after T1-PDT.The RT-PCR results showed that T1-PDT could increase the expression of Bax and decrease the expression of Bcl-2.The in vivo experiments demonstrated that T1-PDT significantly inhibited the growth of H-22-xenografied tumors.Conclusions T1-mediated PDT has a significant lethal effect on HepG2 cells in vitro and in vitro.The lethal effect of PDT on cancer cells is shown in the apoptosis and can be attributed to T1's subcellular localization in the mitochondria,increasing ROS levels,and regulating apoptosis-related genes.
ABSTRACT
Blue light is commonly used to kill Propionibacterium acnes in clinic. Furthermore, blue light exhibits a good bactericidal effect against Helicobacter pylori, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and many oral bacteria in laboratory studies. The bactericidal mechanism of blue light as commonly accepted consists photo-excitation of intracellular porphyrins resulting in production of cytotoxic reactive oxygen species which can inactivate bacteria. Blue light can kill bacteria without additional exogenous photosensitizers. In addition, it produces little harm to mammalian cells. Therefore, as the increasing emergence of antibiotic resistant microorganisms, blue light might be a good antibacterial tool.