ABSTRACT
OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.
Subject(s)
Homocysteine , Humans , Homocysteine/blood , Vitamins/blood , Hepatitis, Autoimmune/blood , Hepatitis, Autoimmune/immunology , Case-Control Studies , Autoimmune Diseases/blood , Autoimmune Diseases/immunologyABSTRACT
Background: The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature studies. Scientific articles are the direct achievements of theoretical research in this field and can reveal how current theories in basic research have developed. In this study, the progress and status of natural anticancer products in this field were summarized, and the research hotspots were explored through the analysis of the relevant patent literature and scientific articles. Methods: Patent data were retrieved from the incoPat patent retrieval database, and paper data were retrieved from the Web of Science core set and PubMed. GraphPad Prism 8, Microsoft Excel 2010, and CiteSpace 5.8.R3 were used to perform visual processing. The analyzed patent literature includes the patent applicant type, country (or region), and technical subject. The analyzed scientific article includes academic groups, subject areas, keyword clustering, and burst detection. Results: A total of 20,435 patent families and 38,746 articles were collected by 4 January 2022. At present, antitumor drugs derived from natural products mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, and gaillardin; 2) topoisomerase inhibitors such as camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, and evodiamine derivatives; 3) telomerase inhibitors such as camptothecin and isoquinoline alkaloids of Chelidonium majus, amentoflavone, and emodin; 4) microtubule inhibitors such as kolaflavanone, tanshinone IIA analog, eugenol, and millepachine; 5) immunomodulators such as fucoidan, myricetin, bergapten, and atractylenolide I; 6) tumor microenvironment regulators such as beta-escin and icaritin; 7) multidrug resistance reversal agents such as berberine, quercetin, and dihydromyricetin; and 8) antiangiogenic and antimetastatic agents such as epigallocatechin-3-gallate, lupeol, ononin, and saikosaponin A. Conclusion: Anticancer natural product technology was introduced earlier, but the later development momentum was insufficient. In addition, scientific research activities are relatively closed, and technical exchanges need to be strengthened. Currently, the development of medicinal plants and the research on the anticancer mechanism of natural active products are still research hotspots, especially those related to immune checkpoints, essential oils, and metastatic cancer. Theories of traditional Chinese medicine (TCM), such as "restraining excessiveness to acquire harmony," "same treatment for different diseases," "Meridian induction theory," and "Fuzheng Quxie," have important guiding significance to the research of anticancer mechanisms and the development of new drugs and can provide new ideas for this process. Systematic Review Registration: [https://sourceforge.net/projects/citespace/], identifier [000755430500001].
ABSTRACT
OBJECTIVE: To observe the clinical efficacy of Tiaoshen needling (dredging Governor Vessel and regulating mind)in the treatment of chronic insomnia (CI) and its effect on plasma melatonin (MT) and cortisol (CORT) levels, so as to explore its underlying mechanism. METHODS: Sixty patients with CI were randomly divided into the treatment group and the control group, with 30 cases in each group. Both groups were given sleep hygiene education before treatment. Patients in the treatment group received acupuncture or electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (GV29), bilateral Shenmen (HT7) and Sanyinjiao (SP6). Patients in the control group received acupuncture or electroacupuncture at bilateral Shousanli (LI10), Futu (ST32) and Feiyang(BL58). Both groups were treated every other day, 3 times a week, for a total of 4 weeks. Before and after treatment, Pittsburgh sleep quality index (PSQI) and fatigue severity scale (FSS) were used to evaluate sleep qua-lity and daytime fatigue, the plasma MT and CORT levels were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with before treatment, the PSQI scores and total FSS score of the treatment group decreased significantly (P<0.01ï¼P<0.05), and the plasma MT content increased and CORT decreased significantly in the treatment group (P<0.01)ï¼while the sleep-onset time score, sleep disturbance score and the PSQI total score of the control group decreased significantly (P<0.05). Compared with the control group, the PSQI sleep disorder score and total score, and the total FSS score as well as plasma CORT level were significantly down-regulated (P<0.01ï¼P<0.05), while the plasma MT content was up-regulated (P<0.05) in the treatment group. CONCLUSION: Tiaoshen acupuncture can significantly improve the sleep quality of patients with CI and relieve daytime fatigue, which may be related to the increase of plasma MT content in patients with CI, thereby inhibiting the excessive activation of the hypothalamic-pituitary-adrenal axis.
Subject(s)
Acupuncture Therapy , Melatonin , Sleep Initiation and Maintenance Disorders , Acupuncture Points , Humans , Hydrocortisone , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Sleep Initiation and Maintenance Disorders/therapy , Treatment OutcomeABSTRACT
OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (P<0.01, P<0.05), among them, the sub-item scores of sleep quality, time to fall asleep, sleep time and sleep efficiency, daytime dysfunction and total score were all lower than those in the sham EA group (P<0.01, P<0.05). After treatment, the MoCA score and serum MT and DA levels in the EA group were higher than those before treatment (P<0.01), and the MoCA score and serum MT level in the EA group were higher than the sham EA group (P<0.01, P<0.05). CONCLUSION: Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.
Subject(s)
Electroacupuncture , Melatonin , Sleep Initiation and Maintenance Disorders , Acupuncture Points , Aged , Dopamine , Humans , Sleep Initiation and Maintenance Disorders/therapyABSTRACT
OBJECTIVE: To observe the clinical effect of acupuncture at Tiaoshen (regulating the spirit) acupoints on chronic insomnia and hyperarousal state, and explore its possible mechanism. METHODS: A total of 60 patients with chronic insomnia were randomly divided into an acupuncture group (30 cases, 1 case dropped off) and a sham acupuncture group (30 cases, 1 cases dropped off). Both groups were given basic sleep health education. The acupuncture group was treated with acupuncture at Tiaoshen acupoints including Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7) and Sanyinjiao (SP 6). The sham acupuncture group was treated with non-effective point shallow acupuncture. Both groups were treated once every other day, 3 times a week for 4 weeks. The Pittsburgh sleep quality index (PSQI) score, pre-sleep arousal scale (PSAS) score, hyperarousal scale (HAS) score, and serum gamma-aminobutyric acid (GABA) level before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group after treatment were decreased (P<0.05, P<0.01); in the sham acupuncture group, the time to fall asleep, daytime dysfunction scores and total score of PSQI, and cognitive arousal score of PSAS after treatment were decreased (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). Compared before treatment, the serum GABA level in the acupuncture group were increased (P<0.05), and the serum GABA level in the acupuncture group was higher than that in the sham acupuncture group after treatment (P<0.05). CONCLUSION: Acupuncture at Tiaoshen acupoints can obviously improve the sleep and hyperarousal state of patients with chronic insomnia, and up-regulating serum GABA content is one of its possible mechanisms.
Subject(s)
Acupuncture Therapy , Sleep Initiation and Maintenance Disorders , Acupuncture Points , Arousal , Humans , Sleep Initiation and Maintenance Disorders/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Perinatal depression is the most prevalent mental disorder during the perinatal period, and research suggests that it presents heterogeneously. We aimed to explore how subtypes of perinatal depression present in terms of multivariate patterns of stable characteristics. METHODS: A cohort study was conducted from March 2016 to March 2018 with Chinese women in the prenatal period (n = 3186). Of the participants, 682 (21.41%) women with Edinburgh Postnatal Depression Scale scores ≥10, indicating probable depression, were included, with the remaining 2504 (78.59%) representing the control group. We assessed mood distress, cognition, life history, emotional regulation, and personality, and used latent class analysis and latent transition analysis to identify perinatal depression subtypes. Of the 682 women with probable depression, only 598 were included in the full analyses, as they completed at least 10 questionnaires. A second, non-overlapping sample and a follow-up cohort were used. RESULTS: We identified four subtypes: 1) a highly distressed type characterized by distress across all domains, high levels of rumination and neuroticism, and reduced trait mindfulness; 2) two moderately distressed types: one with high trauma and low perceived social support, and another with low trauma, high perceived social support, and expressive suppression; and 3) a slightly distressed subtype. LIMITATIONS: We only collected cost and time spent in hospital from medical records. We only had a small follow-up sample. CONCLUSIONS: This multidimensional subtyping of women with perinatal depression could help reduce the apparent heterogeneity of perinatal depression. Distinguishing the subtype characteristics facilitates identifying underlying causes of perinatal depression.
Subject(s)
Depression, Postpartum , Depressive Disorder , Mindfulness , Cohort Studies , Depression , Depression, Postpartum/epidemiology , Depressive Disorder/epidemiology , Female , Humans , Personality , PregnancyABSTRACT
OBJECTIVE: To investigate the clinical effect of Tongdu Tiaoshen needling in the treatment of chronic insomnia and its mechanism based on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: A total of 60 patients with chronic insomnia were randomly divided into treatment group and control group, with 30 patients in each group. In addition to the health education on sleep, the patients in the treatment group were given Tongdu Tiaoshen needling, iï¼e., electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), bilateral Shenmen (HT7), and bilateral Sanyinjiao (SP6), and those in the control group were given superficial acupuncture at Shousanli (LI10), Futu (ST32), and Feiyang (BL58) at both sides, once every other day and three times a week for 4 consecutive weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality and efficiency of sleep, and ELISA was used to measure the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). RESULTS: After treatment, the treatment group had significant reductions in the total PSQI score and the score of each component of PSQI (P<0.01), and the control group had significant reductions in the total PSQI score (P<0.01) and the scores of all components except sleep duration (P<0.05); compared with the control group, the treatment group had significantly lower total PSQI score and the score of each component (P<0.01). After treatment, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.05ï¼P <0.01), and compared with the control group, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.01ï¼P<0.05). CONCLUSION: Tongdu Tiaoshen needling has a good clinical effect in the treatment of chronic insomnia and can significantly improve the sleep condition of patients with chronic insomnia, possibly by reducing the hormones associated with the HPA axis.
Subject(s)
Sleep Initiation and Maintenance Disorders , Acupuncture Points , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal SystemABSTRACT
OBJECTIVE: To compare the clinical therapeutic effect and safety on insomnia among three acupuncture combinations, named Tongdu Tiaowei (promoting the circulation of the governor vessel and regulating the defensive system), Tongdu Yangxin (promoting the circulation of the governor vessel and nourishing the heart) and Tongdu Tiaozang (promoting the circulation of the governor vessel and regulating zang functions). METHODS: A total of 90 patients with insomnia were randomized into a Tongdu Tiaowei group (30 cases, 1 case dropped off ), a Tongdu Yangxin group (30 cases, 2 cases dropped off ) and a Tongdu Tiaozang group (30 cases, 1 case dropped off ). Besides electroacupuncture (EA) applied to Baihui (GV 20) and Yintang (GV 29) in all of the three groups, acupuncture was added at Shenmai (BL 62) and Zhaohai (KI 6), Shenmen (HT 7) and Sanyinjiao (SP 6) as well as back-shu points of five zang organs [Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23)] in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively. The treatment was given once every two days, 3 times weekly, consecutively for 4 weeks. The score of Pittsburgh sleep quality index (PSQI) before and after treatment was observed, the therapeutic effect was evaluated and the adverse reactions were recorded in the patients of each group. RESULTS: After treatment, the score of each of 6 factors, named sleep quality, sleep latency, sleep time, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total score of PSQI scale were all reduced as compared with the scores before treatment in the patients of each group (P<0.05). After treatment, the scores of sleep latency and daytime dysfunction in the Tongdu Tiaowei group were lower than the other two groups (P<0.05). The score of sleep time in the Tongdu Yangxin group was lower than the other two groups (P<0.05) and the score of sleep quality in the Tongdu Tiaozang group was lower than the other two groups (P<0.05). After treatment, the total effective rates were 96.6% (28/29), 96.4% (27/28) and 96.6% (28/29) in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively, without significant difference in comparison among the three groups (P>0.05). During treatment, 1 case of mild adverse reaction occurred in each group. CONCLUSION: All of the three acupuncture combinations, named Tongdu Tiaowei, Tongdu Yangxin and Tongdu Tiaozang can effectively improve the sleep conditions in the patients with insomnia and are satisfactory in safety. The acupuncture combinations of Tongdu Tiaowei has the potential advantage in shortening sleep latency and relieving daytime dysfunction, the combinations of Tongdu Yangxin has the potential advantage in increasing sleep time and the combinations of Tongdu Tiaozang has the potential advantage in improving sleep quality.
Subject(s)
Acupuncture Therapy , Sleep Initiation and Maintenance Disorders , Acupuncture Points , Humans , Sleep , Sleep Initiation and Maintenance Disorders/therapy , Treatment OutcomeABSTRACT
N-acyl-homoserine lactone quorum sensing (AHL-QS) has been shown to regulate many physiological behaviors in Serratia marcescens MG1. In the current study, the effects of AHL-QS on the biosynthesis of acid and neutral products by S. marcescens MG1 and its isogenic ∆swrI with or without supplementing exogenous N-hexanoyl-L-homoserine lactone (C6-HSL) were systematically investigated. The results showed that swrI disruption resulted in rapid pH drops from 7.0 to 4.8, which could be restored to wild type by supplementing C6-HSL. Furthermore, fermentation product analysis indicated that ∆swrI could lead to obvious accumulation for acidogenesis products such as lactic acid and succinic acid, especially excess acetic acid (2.27 g/l) produced at the early stage of fermentation, whereas solventogenesis products by ∆swrI appeared to noticeably decrease by an approximate 30% for acetoin during 32-48 h and by an approximate 20% for 2,3-butanediol during 24-40 h, when compared to those by wild type. Interestingly, the excess acetic acid produced could be removed in an AHL-QS-independent manner. Subsequently, quantitative real-time PCR was used to determine the mRNA expression levels of genes responsible for acidogenesis and solventogenesis and showed consistent results with those of product synthesis. Finally, by close examination of promoter regions of the analyzed genes, four putative luxI box-like motifs were found upstream of genes encoding acetyl-CoA synthase, lactate dehydrogenase, α-acetolactate decarboxylase, and Lys-like regulator. The information from this study provides a novel insight into the roles played by AHL-QS in switching from acidogenesis to solventogenesis in S. marcescens MG1.
Subject(s)
Acyl-Butyrolactones/pharmacology , Carbohydrate Metabolism/drug effects , Fermentation , Quorum Sensing , Serratia marcescens/drug effects , Serratia marcescens/metabolism , Acetic Acid/metabolism , Acetoin/metabolism , Bacterial Proteins/genetics , Biomass , Butylene Glycols/metabolism , Carbohydrate Metabolism/genetics , Carboxy-Lyases/genetics , Gene Expression Profiling , Gene Expression Regulation, Bacterial/drug effects , Genes, Bacterial/genetics , Glucose/metabolism , Hydrogen-Ion Concentration , L-Lactate Dehydrogenase/genetics , Lactic Acid/metabolism , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , RNA, Messenger/metabolism , Sequence Alignment , Serratia marcescens/genetics , Serratia marcescens/growth & development , Succinic Acid/metabolism , Time FactorsABSTRACT
OBJECTIVES: Jie-Du-Hua-Yu (JDHY) granule is a combination of six traditional Chinese medicines with known therapeutic effect in treating acute liver failure (ALF). The aim of this study was to investigate the amelioration efficacy of JDHY in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF in rat and explore the possible molecular mechanism underlying the therapeutic efficacy. MATERIALS AND METHODS: The efficacy of JDHY was determined by assessing hepatic pathology and function in LPS and D-GalN challenged Wistar rat. We also evaluated the effect of JDHY on LPS-induced Kupffer cells by measuring inflammatory cytokines and determining the phenotypic function. By means of bioinformatics analysis of liver tissue and validation in Kupffer cells, we identified possible pathways involved in the pharmacologic action of mechanism of JDHY. RESULTS: JDHY could attenuate LPS-induced liver injury in rat by inhibiting apoptosis and increasing hepatic activity. In vitro study showed that JDHY could decrease the production of proinflammatory cytokines (tumor necrosis factor-α, IL6, and interferon-γ), increase anti-inflammatory cytokines (IL10, IL13), and promote cell survival and proliferation, possibly due to inhibition of IκB/nuclear factor-κB (NF-κB) signaling pathway and expression of CD14 and CXCL2, which was consistent with the findings from bioinformatics analysis. CONCLUSION: Our results revealed that JDHY protected against LPS-induced liver damage both in vitro and in vivo, by inhibiting the NF-κB-mediated inflammatory pathway, indicating its potential function to treat liver diseases.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Liver Failure, Acute/prevention & control , Medicine, Chinese Traditional , Animals , Cell Proliferation/drug effects , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Galactosamine/pharmacology , Lipopolysaccharides/pharmacology , Liver Failure, Acute/chemically induced , Liver Failure, Acute/pathology , Male , Rats , Rats, WistarABSTRACT
OBJECTIVE: To observe the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer, and study its anti-tumor mechanism. METHOD: In vitro, MTT assay and scratch assay were adopted to detect the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer cells. The cell autophagy was detected by the acridine orange staining. The gap-junction intercellular communication (GJIC) was investigated by the fluorescent yellow transfer. The expression of aquaporin 1 (AQP1) was analyzed by the Western blotting. In vivo, the subcutaneous implant model and the experimental pulmonary metastasis model of Lewis lung cancer in mice were established to evaluate the anti-tumor and anti-metastasis effects of alcohol extract from Pharbitidis Semen. The serum carcinoembryonic antigen (CEA) and beta2 microglobulin (beta2-MG) of mice bearing Lewis lung cancer were detected by the electrochemiluminesence immunoassay. The expressions of lung AQP1 and Connexin 43 (Cx43) were examined by the immunohistochemical method. RESULT: In vitro, alcohol extracts from Pharbitidis Semen inhibited the cell proliferation in a dose-dependent matter, significantly prevented the cell migration, down-regulated AQP1 proteins of cells, promoted GJIC, and decreased the serum-free autophagy of tumor cells. In vivo, compared with untreated model mice, alcohol extracts from Pharbitidis Semen inhibited the tumor growth in a dose-dependent matter, prevented the tumor metastasis and prolonged the life span of mice bearing Lewis lung cancer, while decreasing serum CEA and beta2-MG of mice bearing Lewis lung cancer, enhancing the immumohistochemical staining intensity of Cx43 and weakening aquaporins AQP1 positive intensity. CONCLUSION: Alcohol extracts from Pharbitidis Semen could prevent the proliferation and metastasis in Lewis lung cancer cells. Its mechanism may be related to the promotion of GJIC and the down-regulation of AQP1.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Lewis Lung/drug therapy , Drugs, Chinese Herbal/administration & dosage , Ipomoea/chemistry , Lung Neoplasms/drug therapy , Seeds/chemistry , Animals , Aquaporin 1/genetics , Aquaporin 1/metabolism , Carcinoma, Lewis Lung/genetics , Carcinoma, Lewis Lung/metabolism , Carcinoma, Lewis Lung/pathology , Cell Line, Tumor , Connexin 43/genetics , Connexin 43/metabolism , Disease Models, Animal , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Neoplasm MetastasisABSTRACT
There are diverse immunosuppressive factors in the tumor microenvironment, but the main reason for these factors is unclear. Because hypothermia induces micronuclei in mouse bone marrow cells and because alterations in body temperature may influence immune system function, we aimed to investigate whether the hypothermic microenvironment is associated with the presence of diverse immunosuppressive factors. We found that hypothermic culture (34°C) decreased lymphocyte proliferation, cytotoxic CD8+ T cell function and Th1 cell expression of IFN-γ and IL-2 in vitro, with a concomitant increase in Th2 and Treg cell populations. Whole-body hypothermia at a temperature less than 34°C produced an immunosuppressive microenvironment, resulting in an increase in splenic Treg and Th2 cell populations as well as increased serum IL-4 and IL-10 levels in vivo. As a result of whole-body hypothermia, less than one of two cells in a conventional syngeneic tumor model was capable of tumor formation. In contrast, febrile-range hyperthermia (39-40°C) promoted a T cell-mediated immune response, resulting in an increase in splenic Th1 and Tc1 cell populations, which caused more than a two-fold increase in the number of nontumorigenic cells in a conventional syngeneic tumor model. Similarly, local hypothermia induced by microcirculatory dysfunction or the application of a cold compress increased intratumor Treg cells and TGF-ß1 levels, which promote lung metastasis, whereas local hyperthermia induced by capsaicin stimulation or a hot compress had the opposite effect. These results confirmed the hypothesis that tumor hypothermia determines the immunosuppressive microenvironment and suggested a novel treatment strategy for solid tumors.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Lung Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , CD8-Positive T-Lymphocytes/drug effects , Capsaicin/administration & dosage , Cell Proliferation/drug effects , Cells, Cultured , Cold Temperature/adverse effects , Cytokines/metabolism , Cytotoxicity, Immunologic/drug effects , Epinephrine/administration & dosage , Hot Temperature/therapeutic use , Hyperthermia, Induced/methods , Hypothermia, Induced/methods , Immunosuppression Therapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mice , Mice, Inbred C57BL , Microcirculation/drug effects , Neoplasm Transplantation , T-Lymphocytes, Regulatory/drug effects , Th1 Cells/drug effects , Th1-Th2 Balance/drug effects , Th2 Cells/drug effects , Tumor Escape/drug effects , Tumor Microenvironment/drug effectsABSTRACT
OBJECTIVE: To study Chinese medicine (CM) signs and symptoms of urethane-induced lung cancer in mice, and observe the effect of Aconiti Lateralis Radix Praeparata and Taraxaci Herba on symptoms in mice and tumor progress. METHOD: The mice were intraperitoneally injected with urethane twice a week for consecutively five weeks to establish a lung cancer model. The changes in their appearance, body temperature and auricle microcirculation were observed in carcinogenic process. CM signs and symptoms of urethane-induced lung cancer in mice were evaluated with energy metabolism, erythrocytic ATP emzymatic activity and hemorrheological index. During the tumor model was induced, Aconiti Lateralis Radix Praeparata and Taraxaci Herba were used to treat the mice and observe their effect on symptoms in mice and tumor progress. RESULT: During urethane was used to induce lung cancer, the mice had gradually become chill, lazy, hunched, with reduction in temperature, cyanosis in auricle and tail. Meanwhile, their energy metabolism and erythrocytic ATP enzymatic activity reduced, whereas their whole blood viscosity and erythrocytic aggregate index increased. Taraxaci Herba showed an effect on enhancing above symptoms and signs but had no effect on tumor progress. Aconiti Lateralis Radix Praeparata showed an effect on reducing above symptoms and signs and preventing tumor progress. CONCLUSION: Mice with urethane-induced lung cancer show CM signs and symptoms of congealing cold with blood stasis. The treatment with Aconiti Lateralis Radix Praeparata can alleviate symptoms and signs in mice and prevent tumor progress.
Subject(s)
Aconitum/chemistry , Drugs, Chinese Herbal/administration & dosage , Lung Neoplasms/drug therapy , Taraxacum/chemistry , Animals , Blood Circulation/drug effects , Female , Humans , Lung Neoplasms/chemically induced , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Mice , Mice, Inbred BALB C , Neoplastic Processes , Urethane/adverse effectsABSTRACT
Relieving pulmonary edema is the key of a successful treatment to seawater drowning. Sodium tanshinone IIA sulfonate (STS) has been observed to reduce lung edema from lipopolysaccharide (LPS)-induced lung injury. In this study the authors investigated whether STS attenuates seawater aspiration-induced acute pulmonary edema, and examined the effects of sodium-potassium adensosine triphosphatase (Na(+),K(+)-ATPase) on it. Seawater was instilled through an endotracheal tube. The anesthetized and spontaneously breathing rats received STS intraperitoneally after seawater aspiration. Pao(2), lung wet-to-dry weight ratio, and pulmonary microvascular permeability were tested. The authors explored the effects of STS on the expression and activity of Na(+),K(+)-ATPase in vivo and in vitro. Additionally, the authors investigated the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in the stimulation of Na(+),K(+)-ATPase by STS. The results showed that STS significantly improved hypoxemia, attenuated lung edema, and alleviated seawater-induced lung injury in vivo. Both in vivo and in vitro, it was observed that STS up-regulated the expression and activity of Na(+),K(+)-ATPase. ERK1/2 inhibitor partially blocked the effects of STS on Na(+),K(+)-ATPase activity in alveolar type II cells following seawater incubation. These results indicated that STS could improve seawater aspiration-induced acute pulmonary edema by up-regulating Na(+),K(+)-ATPase activity, and the ERK1/2 signaling pathway may be involved in it.