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OBJECTIVES: Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions. METHODS: A total of 79 subjects with either treatment-refractory MDD (n = 60) or BD (n = 19) were included in a clinical ketamine study. The Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively. RESULTS: At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p's > 0.05). Only the 'wish to die' and 'desire to make a suicide attempt' items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p's < 0.05). CONCLUSION: Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions.KEY POINTSSerial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression.The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear.Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Ketamina/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Ideação Suicida , Anedonia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Escalas de Graduação PsiquiátricaRESUMO
The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1ß, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1ß, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1ß, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1ß, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.
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Colite Ulcerativa , Medicamentos de Ervas Chinesas , Animais , Camundongos , Caspase 1/genética , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Interleucina-10/genética , Interleucina-6/genética , Mesalamina/farmacologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Scutellaria baicalensis/química , Fator de Necrose Tumoral alfa/metabolismo , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.
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Adenoma , Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Humanos , Adenoma/diagnóstico , Adenoma/prevenção & controle , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Baseada em Evidências , Medicina Tradicional ChinesaRESUMO
The efficacy and safety of adjunctive nonconvulsive electrotherapy (NET) for patients with depression are undetermined. This systematic review was conducted to examine the efficacy and safety of adjunctive NET for patients with depression. Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO and the Cochrane Library) databases were systematically searched from their inception until Jan 27, 2021 by three independent investigators. One randomized controlled trial (RCT) with 3 treatment arms (n = 108) and two observational studies (single-group, before-after design, n = 31) were included. In the RCT, the antidepressant efficacy of NET on depression was similar to that of electroconvulsive therapy (ECT) (P > 0.05) but with significantly fewer neurocognitive impairments as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (P < 0.05). In two observational studies, the 17-item Hamilton Depression Rating Scale (HAMD-17) scores decreased significantly from baseline to post-NET (all Ps < 0.05), without adverse neurocognitive effects. In the RCT, adverse drug reactions (ADRs) were not separately reported among the 3 treatment arms but a similar rate of discontinuation was reported. The currently available limited evidence from 3 studies suggests that NET as an adjunctive treatment may be a safe, well-tolerated, effective therapy for depression without serious neurocognitive impairments.
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Terapia por Estimulação Elétrica , Eletroconvulsoterapia , Antidepressivos , Depressão/terapia , HumanosRESUMO
Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.
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Antígeno B7-H1/genética , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismoRESUMO
OBJECTIVE: To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS). METHODS: The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively. RESULTS: LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups. CONCLUSION: HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.
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Antioxidantes , Colite , Camundongos , Animais , Antioxidantes/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Scutellaria baicalensis/química , Scutellaria baicalensis/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espectrometria de Massas em Tandem , Camundongos Endogâmicos C57BL , Colite/complicações , Colite/tratamento farmacológico , Colite/metabolismo , Transdução de Sinais , Carcinogênese , Azoximetano/farmacologia , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α). METHODS: In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1ß and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot. RESULTS: In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1ß, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05). CONCLUSION: HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.
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Colite Ulcerativa , NF-kappa B , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Scutellaria baicalensis , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVES: Patents with anxious depression have poor treatment outcomes compared to their nonanxious counterparts. Ketamine has a rapid and robust antianhedonic effect, independent of depressive symptoms. The difference in the antianhedonic effect of ketamine between patients with anxious versus nonanxious depression remains unknown. METHODS: One hundred thirty-five Chinese individuals with anxious depression (n = 92) and nonanxious depression (n = 43) received six intravenous infusions of ketamine (0.5 mg/kg). Post hoc analyses compared changes in anhedonic symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), between patients with anxious depression (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) and nonanxious depression. RESULTS: In this study, 68.1 % of patients were found to have anxious depression. Anxious depressed patients were associated with a relatively lower antianhedonic response (47.8 % versus 51.2 %, p > 0.05) and remission (17.4 % versus 27.9 %, p > 0.05) than their nonanxious counterparts. When compared to baseline, a significant reduction in anhedonic symptoms was observed from the first infusion to the last infusion and 2-week follow-up in both groups (all p < 0.05). A linear mixed model did not find a significant group main effect on the MADRS anhedonia subscale scores (F = 0.5, p = 0.46). CONCLUSION: This preliminary study shows that repeated intravenous infusions of ketamine rapidly ameliorate anhedonic symptoms in individuals experiencing anxious depression, but these individuals displayed a weaker antianhedonic response to ketamine than nonanxious depressed patients.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Antidepressivos/uso terapêutico , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Depressão , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Infusões Intravenosas , Resultado do TratamentoRESUMO
Objectives: Subanaesthetic ketamine (0. 5 mg/kg/40 min intravenous infusion) produces rapid and robust antianhedonic effects in subjects with mood disorders, independent of other depressive symptoms. The objective of this study was to examine potential differences in rate of antianhedonic response to ketamine in males and females, which has not been previously examined. Methods: A total of 135 patients with depression (68 males, 67 females) who received six intravenous infusions of ketamine (0.5 mg/kg/40 min) during 2 weeks were enrolled. The anhedonia subscale of the Montgomery-Åsberg Depression Rating Scale (MADRS) was utilized to measure anhedonic symptoms. Antianhedonic remission and response were defined as ≥75 and ≥50% improvement of anhedonic symptoms at 24 h after the sixth ketamine infusion (day 13). Results: Antianhedonic response (50 vs. 47.8%, p > 0.05) and remission (26.5 vs. 14.9%, p > 0.05) rates did not differ significantly between males and females. A linear mixed model revealed a nonsignificant between-group difference in MADRS anhedonia subscale scores [F(1, 132.5) = 1.1, p = 0.30]. Females reported a significantly larger reduction in anhedonic symptoms than males at the 2-week follow-up (p < 0.05). Conclusion: The rates of antianhedonic response and remission to multiple ketamine infusions for the treatment of depression were similar between males and females. These findings should be verified by future studies, preferably randomized controlled trials (RCTs).
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OBJECTIVES: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. METHODS: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. RESULTS: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval = 38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. CONCLUSION: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.
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Transtorno Bipolar , Transtorno Depressivo Maior , Ketamina , Anedonia , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Infusões Intravenosas , Ketamina/uso terapêuticoRESUMO
Objectives: Melancholic depression may respond differently to certain treatments. The aim of this study was to compare the antianhedonic effects of six intravenous injections of 0.5 mg/kg ketamine in patients with melancholic and non-melancholic depression, which remain largely unknown. Methods: Individuals experiencing melancholic (n = 30) and non-melancholic (n = 105) depression were recruited and assessed for anhedonic symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS). The presence of melancholic depression was measured with the depression scale items at baseline based on DSM-5 criteria. Results: A total of 30 (22.2%) patients with depression fulfilled the DSM-5 criteria for melancholic depression. Patients with melancholic depression had a non-significant lower antianhedonic response (43.3 vs. 50.5%, t = 0.5, p > 0.05) and remission (20.0 vs. 21.0%, t = 0.01, p > 0.05) to repeated-dose ketamine infusions than those with non-melancholic depression. The melancholic group had significantly lower MADRS anhedonia subscale scores than the non-melancholic group at day 26 (p < 0.05). Conclusion: After six ketamine infusions, the improvement of anhedonic symptoms was found in both patients with melancholic and non-melancholic depression, and the efficacy was similar in both groups.
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Objectives: Accumulating evidence supports a role for vascular endothelial growth factor (VEGF) in the pathogenesis of depression, but its relationship with the antisuicidal effects of ketamine is not clear. Our objective was to determine whether there was an association between the plasma VEGF (pVEGF) concentrations and the antisuicidal response to serial ketamine infusions. Methods: Six ketamine infusions (0.5 mg/kg) over a 12-day period were administered to sixty depressed individuals suffering from suicidal ideation. The Hamilton Depression Rating Scale (HAMD) suicide item, the Montgomery-Åsberg Depression Rating Scale (MADRS) suicide item, and the Beck Scale for Suicide Ideation (SSI-part I) were used to assess suicidal ideation at baseline, 1 day after the first infusion (day 1), 1 day following the last infusion (day 13), and again 2 weeks post-infusion (day 26). For this purpose, plasma was obtained at baseline, day 13 and 26. Results: The rates of antisuicidal response to ketamine were 61.7% (37/60), 81.7% (49/60), and 73.3% (44/60) at days 1, 13, and 26, respectively. The linear mixed model revealed significant time effects on suicidal ideation and pVEGF concentrations over time (all Ps < 0.05). Antisuicidal responders did not have significantly altered pVEGF concentrations compared with non-responders on day 13 and day 26 (all Ps > 0.05). No significant correlation was found between the baseline pVEGF concentration and suicidal ideation as measured by the SSI part 1, HAMD suicide item and MADRS suicide item on days 1, 13, and 26 (all ps > 0.05). Conclusion: This preliminary finding does not support a role for VEGF in the antisuicidal effects of serial ketamine treatments in individuals with depression and suicidal ideation. Further research is needed to confirm and expand these findings.
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OBJECTIVE: To examine whether early symptom improvement can predict eventual remission following electroconvulsive therapy (ECT) with ketamine plus propofol (ketofol) anesthesia in patients with treatment-resistant depression (TRD). METHODS: Thirty Han Chinese subjects suffering from TRD were administered ketofol anesthesia during ECT. Remission was defined as a score of ≤7 on the 17-item Hamilton Depression Rating Scale (HAMD-17). Receiver operating characteristic (ROC) curves were applied to identify the number of ECT sessions (i.e., 1, 2, 3, or 4 ECT sessions) that had the best discriminative capacity for eventual remission. The best definition of early improvement to predict final remission was determined by using the Youden index. RESULTS: Of the 30 patients with TRD, 16 (53.3%) and 30 (100%) were classified as remitters and responders, respectively. A 45% reduction in the HAMD-17 score after 3 ECT sessions was the optimum definition of early improvement in the prediction of eventual remission, with relatively good sensitivity (88%) and specificity (93%). Patients with than without early improvement had a greater possibility of achieving favorable ECT outcomes. CONCLUSION: Final remission of TRD following ECT with ketofol anesthesia appeared to be predicted by early improvement, as indicated by a 45% reduction in HAMD-17 score after 3 ECT sessions.
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Anestesia , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Depressão , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Resultado do TratamentoRESUMO
Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in SpragueDawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow. Compared with the DGP group, atractylenolide1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZinduced group compared with the vehicle control group. Moreover, the STZinduced group displayed downregulated expression levels of the DGP indicator KIT protooncogene, receptor tyrosine kinase (ckit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stressrelated markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide1 significantly counteracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZinduced DGP model rats. Further research indicated that atractylenolide1 regulated oxidative stress reactions and improved gastric function by activating the SCF/ckit signaling pathway. Collectively, the results of the present study suggested that atractylenolide1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/ckit signaling pathway, providing novel insights for the treatment of DGP.
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Diabetes Mellitus Experimental/metabolismo , Gastroparesia/tratamento farmacológico , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Neuropatias Diabéticas , Mucinas Gástricas , Heme Oxigenase-1/metabolismo , Células Intersticiais de Cajal/metabolismo , Masculino , Estresse Oxidativo , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Células-Tronco , Estômago , Estreptozocina/farmacologia , Superóxido DismutaseRESUMO
Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD). Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS. Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05). Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.