Neurofeedback Effect on Symptoms of Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis.

Posttraumatic stress disorder (PTSD) encompasses various psychological symptoms and a high early dropout rate due to treatment unresponsiveness. In recent years, neurofeedback has been implemented to control PTSD's psychological symptoms through physiological brain regulation. However, a comprehensive analysis concerning its efficacy is lacking. Therefore, we conducted a systematic review and meta-analysis to determine neurofeedback's effect on reducing PTSD symptoms. We analyzed randomized and non-randomized controlled trials (RCTs) from 1990 to July 2020, evaluating neurofeedback treatments for those diagnosed with PTSD and their symptoms. In addition, we calculated the standardized mean difference (SMD)using random-effects models to estimate effect sizes. We assessed ten articles comprising 276 participants, with a - 0.74 SMD (95% confidence interval = - 0.9230, - 0.5567), 42% I2, moderate effect size, and - 1.40 to -0.08 prediction intervals (PI). Neurofeedback was more effective for complex trauma PTSD patients than single trauma. Increasing and lengthening sessions are more effective than fewer, condensed ones. Neurofeedback positively affected arousal, anxiety, depression, and intrusive, numbing, and suicidal thoughts. Therefore, neurofeedback is a promising and effective treatment for complex PTSD.

Co-occurring Fatigue and Lymphatic Pain Incrementally Aggravate Their Negative Effects on Activities of Daily Living, Emotional Distress, and Overall Health of Breast Cancer Patients.

BACKGROUND: Fatigue and lymphatic pain are the most common and debilitating long-term adverse effects of breast cancer treatment. Fatigue and pain independently have negative effects on quality of life, physical functions, and cancer recurrence-free survival. The interactions between fatigue and pain may aggravate their negative effects. OBJECTIVES: Examine the effects of co-occurring fatigue and lymphatic pain on activities of daily living (ADLs), emotional distress, and overall health of breast cancer patients. METHODS: A cross-sectional and observational design was used to enroll 354 breast cancer patients. Valid and reliable instruments were used to assess fatigue, lymphatic pain, ADLs, emotional distress, and overall health. Descriptive statistics and multivariable regression models were used for data analysis. RESULTS: After controlling for demographic and clinical factors, patients with co-occurring fatigue and lymphatic pain had higher odds of having impaired ADLs (OR = 24.43, CI = [5.44-109.67], P < .001) and emotional distress (OR = 26.52, CI = [9.64-72.90], P < .001) compared to patients with only fatigue and only lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had 179% increase in impaired ADL scores (B = 8.06, CI = [5.54-10.59]) and 211% increase in emotional distress scores (B = 9.17, CI = [5.52-12.83]) compared to those without co-occurring fatigue and lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had a 34% decrease (B = -26.29, CI = [-31.90 to -20.69]) and patients with only fatigue had a 33% decrease in overall health scores (B = -25.74, 95% CI = [-34.14 to -17.33]), indicating poor overall health. CONCLUSIONS: Fatigue and lymphatic pain affected 66.4% of breast cancer patients. Findings from this study suggest that co-occurring fatigue and lymphatic pain have negative effects on breast cancer patients' ADLs, emotional distress, and overall health. The synergistic interactions between fatigue and lymphatic pain incrementally aggravated their negative effects on ADLs and emotional distress. Findings of the study highlight the need to evaluate the underlying mechanisms for co-occurring fatigue and lymphatic pain and develop interventions that target both fatigue and lymphatic pain to improve breast cancer patients' the quality of life.

The Effects of Kinect-Enhanced Lymphatic Exercise Intervention on Lymphatic Pain, Swelling, and Lymph Fluid Level.

BACKGROUND: The-Optimal-Lymph-Flow (TOLF) intervention aims to promote lymph flow through therapeutic lymphatic exercises to relieve lymphatic pain, swelling, lymphedema symptoms, and to decrease lymph fluid levels among breast cancer survivors. To enhance the efficacy of the TOLF intervention, an innovative, intelligent, Kinect-enhanced lymphatic exercise intervention (Kinect-TOLF) was developed to teach patients to perform the lymphatic exercises correctly. OBJECTIVES: This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels. METHODS: A single-arm feasibility trial with a pre- and post-test design was employed to recruit 30 breast cancer survivors with persistent lymphatic pain or swelling. Patients received a single training session to learn how to perform the lymphatic exercises using the Kinect-TOLF program. Descriptive statistics, Wilcoxon signed-rank tests, t-test, Spearman's rank correlation coefficients, linear regressions, and Cohen's d were performed for data analysis. Qualitative data were assessed for common themes. RESULTS: The Kinect-TOLF was effective in training patients to perform the lymphatic exercises correctly with high user satisfaction. Significant reductions were found in scores of lymphatic pain (MedΔ = -1.00, CI = [-1.5, -0.1], P = .004), arm/hand swelling (MedΔ = -1.00, CI = [-1.5, -0.5], P = .004), total swelling (MedΔ = -1.5, CI = [-2.0, -1.0], P = .003), number of lymphedema symptoms (MΔ = -3.8, CI = [-5.5, -2.1], P < .001), and lymphedema symptom severity (MΔ = -5.3, CI = [-9.5, -1.1], P = .016). A significant reduction in lymph fluid levels was found in mean L-Dex scores (MΔ = -2.68, CI = [-4.67, -0.69], P = .010). Greater decrease in mean L-Dex scores were found in patients with abnormal lymph fluid levels (L-Dex ≥ 7.1) (MΔ = -5.19, CI = [-1.75, -8.63], P = .008). Patients' qualitative feedback supported the results of the study. CONCLUSIONS: The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in ClinicalTrials.gov with US ClinicalTrials.gov Identifier: NCT03999177.

Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis.

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, in silico profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.

Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition.

Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and Leishmania infantum, is one of the major parasitic diseases worldwide. There is an urgent need for new drugs to treat VL, because current therapies are unfit for purpose in a resource-poor setting. Here, we describe the development of a preclinical drug candidate, GSK3494245/DDD01305143/compound 8, with potential to treat this neglected tropical disease. The compound series was discovered by repurposing hits from a screen against the related parasite Trypanosoma cruzi Subsequent optimization of the chemical series resulted in the development of a potent cidal compound with activity against a range of clinically relevant L. donovani and L. infantum isolates. Compound 8 demonstrates promising pharmacokinetic properties and impressive in vivo efficacy in our mouse model of infection comparable with those of the current oral antileishmanial miltefosine. Detailed mode of action studies confirm that this compound acts principally by inhibition of the chymotrypsin-like activity catalyzed by the ß5 subunit of the L. donovani proteasome. High-resolution cryo-EM structures of apo and compound 8-bound Leishmania tarentolae 20S proteasome reveal a previously undiscovered inhibitor site that lies between the ß4 and ß5 proteasome subunits. This induced pocket exploits ß4 residues that are divergent between humans and kinetoplastid parasites and is consistent with all of our experimental and mutagenesis data. As a result of these comprehensive studies and due to a favorable developability and safety profile, compound 8 is being advanced toward human clinical trials.

An Explorative Analysis for the Role of Serum miR-10b-3p Levels in Predicting Response to Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

The prognostic role of aberrant serum miRNA expression for predicting response to sorafenib treatment in advanced hepatocellular carcinoma (HCC) patients has not been well characterized. We aimed to identify specific serum miRNAs that are associated with positive radiologic responses or improved survival in sorafenib-treated HCC patients. miR-18a, miR-21, miR-139-5p, miR-221, miR-224, and miR-10b-3p, were selected for analysis. Serum samples from 24 patients with advanced stage HCC and 25 patients with liver cirrhosis (LC) were analyzed. All of the miRNAs except miR-21 were found to be upregulated in serum samples from HCC patients. None of the miRNAs assayed differed significantly in terms of expression between the responder and non-responder groups among HCC patients. However, miR-10b-3p levels were significantly higher in the subgroup of HCC patients with worse overall survival (fold change = 5.8, P = 0.008). Serum miRNA-10b-3p was upregulated in the presence of macrovascular invasion (MVI), and those with higher serum miRNA-10b-3p had significantly shorter survival during treatment (P = 0.042). Although no single serum miRNA was predictive of response to sorafenib treatment, analysis of serum miR-10b-3p levels may be valuable for diagnosis of HCC and prediction of survival of sorafenib-treated patients.

Gene Expression Profile of the Hypothalamus in DNP-KLH Immunized Mice Following Electroacupuncture Stimulation.

Clinical evidence indicates that electroacupuncture (EA) is effective for allergic disorder. Recent animal studies have shown that EA treatment reduces levels of IgE and Th2 cytokines in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). The hypothalamus, a brain center of the neural-immune system, is known to be activated by EA stimulation. This study was performed to identify and characterize the differentially expressed genes in the hypothalamus of DNP-KLH immunized mice that were stimulated with EA or only restrained. To this aim, we conducted a microarray analysis to evaluate the global gene expression profiles, using the hypothalamic RNA samples taken from three groups of mice: (i) normal control group (no treatments); (ii) IMH group (DNP-KLH immunization + restraint); and (iii) IMEA group (immunization + EA stimulation). The microarray analysis revealed that total 39 genes were altered in their expression levels by EA treatment. Ten genes, including T-cell receptor alpha variable region family 13 subfamily 1 (Tcra-V13.1), heat shock protein 1B (Hspa1b) and 2'-5' oligoadenylate synthetase 1F (Oas1f), were up-regulated in the IMEA group when compared with the IMH group. In contrast, 29 genes, including decay accelerating factor 2 (Daf2), NAD(P)H dehydrogenase, quinone 1 (Nqo1) and programmed cell death 1 ligand 2 (Pdcd1lg2) were down-regulated in the IMEA group as compared with the IMH group. These results suggest that EA treatment can modulate immune response in DNP-KLH immunized mice by regulating expression levels of genes that are associated with innate immune, cellular defense and/or other kinds of immune system in the hypothalamus.

The genome-wide expression profile of 1,2,3,4,6-penta-O-galloyl-ß-D-glucose-treated MDA-MB-231 breast cancer cells: molecular target on cancer metabolism.

1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a polyphenolic compound isolated from Rhus chinensis Mill. PGG has been known to have anti-tumor, anti-angiogenic and anti-diabetic activities. The present study revealed another underlying molecular target of PGG in MDA-MB-231 breast cancer cells by using Illumina Human Ref-8 expression BeadChip assay. Through the Beadstudio v3 micro assay program to compare the identified genes expressed in PGG-treated MDA-MB-231 cells with untreated control, we found several unique genes that are closely associated with pyruvate metabolism, glycolysis/gluconeogenesis and tyrosine metabolism, including PC, ACSS2, ACACA, ACYP2, ALDH3B1, FBP1, PRMT2 and COMT. Consistent with microarray data, real-time RT-PCR confirmed the significant down-regulation of these genes at mRNA level in PGG-treated MDA-MB-231 cells. Our findings suggest the potential of PGG as anticancer agent for breast cancer cells by targeting cancer metabolism genes.

Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray.

BACKGROUND: The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. RESULTS: We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFß, was significantly enhanced. CONCLUSIONS: These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

The genome-wide expression profile of Curcuma longa-treated cisplatin-stimulated HEK293 cells.

AIM: The rhizome of turmeric, Curcuma longa (CL), is a herbal medicine used in many traditional prescriptions. It has previously been shown that CL treatment showed greater than 47% recovery from cisplatin-induced cell damage in human kidney HEK 293 cells. This study was conducted to evaluate the recovery mechanisms of CL that occur during cisplatin induced nephrotoxicity by examining the genome wide mRNA expression profiles of HEK 293 -cells. METHOD: Recovery mechanisms of CL that occur during cisplatin-induced nephrotoxicity were determined by microarray, real-time PCR, immunofluorescent confocal microscopy and Western blot analysis. RESULTS: The results of microarray analysis and real-time PCR revealed that NFκB pathway-related genes and apoptosis-related genes were down-regulated in CL-treated HEK 293 cells. In addition, immunofluorescent confocal microscopy and Western blot analysis revealed that NFκB p65 nuclear translocation was inhibited in CL-treated HEK 293 cells. Therefore, the mechanism responsible for the effects of CL on HEK 293 cells is closely associated with regulation of the NFκB pathway. CONCLUSION: CL possesses novel therapeutic agents that can be used for the prevention or treatment of cisplatin-induced renal disorders.

The genome-wide expression profile of electroacupuncture in DNP-KLH immunized mice.

Previously, we demonstrated that electoracupuncture (EA) suppressed allergic reactions in DNP-KLH immunized mice. In this study, the mechanisms by which EA induces immunomodulation in the immunized mice were evaluated by genome-wide microarray analysis. The anti-allergic effects of EA in DNP-KLH immunized mice were confirmed by analyzing antigen specific IgE using ELISA. Microarray analysis, followed by real time RT-PCR validation, revealed that Th1 and Th17 cytokine-, opioid peptide-, and anti-apoptosis-related genes were up-regulated upon treatment with EA. In addition, significant decreases in Th2 cytokine-, MAPK signaling pathway-, and apoptosis-related genes were observed following EA treatment.

Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells.

BACKGROUND: Vitex rotundifolia has long been used in traditional medicine to treat asthma and other allergic diseases. OBJECTIVE: To evaluate the anti-inflammatory mechanisms of V rotundifolia in cultured A549 human alveolar epithelial cells. METHODS: In the present study, A549 cells were stimulated with tumor necrosis factor alpha, interleukin 4, and interleukin 1beta to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. The anti-inflammatory effects of V rotundifolia on stimulated A549 cells were then evaluated by analyzing eotaxin secretion and eosinophil migration. In addition, the effects of V rotundifolia on gene expression profiles in stimulated A549 cells were evaluated by oligonucleotide microarray and real-time reverse transcription-polymerase chain reaction (RTRP). RESULTS: The V rotundifolia-treated A549 cells had significantly suppressed eotaxin secretion and eosinophil migration in a dose-dependent manner. In addition, the results of the microarray analysis and RTRP revealed that inflammation-related genes and cell adhesion-related genes were down-regulated in V rotundifolia-treated A549 cells. Furthermore, several genes related to the mitogen-activated protein kinase pathway were down-regulated in V rotundifolia-treated A549 cells. CONCLUSIONS: The mechanism responsible for the effects of V rotundifolia on A549 cells is closely associated with regulation of the mitogen-activated protein kinase pathway. Thus, V rotundifolia may be useful in the treatment of asthma and other allergic diseases.

Global gene analysis of Erigeron canadensis-treated TNF-alpha-, IL-4- and IL-1beta-stimulated A549 human epithelial cells.

BACKGROUND/AIMS: This study was conducted to evaluate the anti-inflammatory mechanisms of Erigeron canadensis (EC) on the tumor necrosis factor-alpha (TNF-alpha)-, interleukin (IL)-4- and IL-1beta-induced stimulation of A549 cells. METHODS: In the present study, the anti-inflammatory effects of EC on TNF-alpha-, IL-4- and IL-1beta-induced A549 cells were determined by analyzing eotaxin secretion using ELISA. In addition, the effects of ECon gene expression profiles in stimulated A549 cells were evaluated by microarray analysis. RESULTS: Oligonucleotide microarray analysis revealed that inflammatory-related genes such as NOS1, NOS2A, IL-1beta, IL-8 and CSF2 and cell adhesion-related genes such as SELE, MMP3, VCAM1, ICAM1, ITGA7 and ITGB2 were downregulated in EC-treated A549 cells that had been pretreated with TNF-alpha, IL-4 and IL-1beta. In addition, significant decreases in Eotaxin, ICAM, VCAM and IL-8 gene expression were observed in EC-treated A549 cells. CONCLUSIONS: EC has an anti-inflammatory effect in stimulated A549 cells. Microarray-based genomic survey is a high-throughput approach that is suitable for the evaluation of gene expression in cell lines that have been treated with EC.

The genome-wide expression profile of Nelumbinis semen on lipopolysaccharide-stimulated BV-2 microglial cells.

This study was conducted to evaluate the protective mechanisms of Nelumbinis semen (NS) on lipopolysaccharide (LPS)-induced activation of BV-2 microglial cells. The anti-inflammatory effects of NS were determined by analyzing nitric oxide production and proinflammatory cytokines using enzyme-linked immunosorbent assay. The mechanism was evaluated in BV-2 cells with or without NS treated with LPS for various lengths of time using oligonucleotide microarray and real time reverse transcription-polymerase chain reaction. The oligonucleotide microarray analysis revealed that mitogen activated protein kinase (MAPK) signaling pathway-related genes such as Fgfr3, Fgf12, Rasal2, Nfkb2, Map2k5, Mapk1, Map3k7, and NFatc2 were down-regulated in LPS activated BV-2 cells by pretreatment with NS. In addition, significant decreases in Nos1ap gene expression were observed with NS pretreatment. Cluster linked pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that the effects of NS were closely associated with the regulation of mitochondria functions. These results suggested that NS can affect the MAPK signaling pathway and mitochondrial functions in BV-2 cells activated with LPS.

The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells.

The endoplasmic reticulum (ER) is a principal site for protein synthesis, protein folding, calcium storage, and calcium signaling. Thapsigargin (TG), an inducer of ER stress, inhibits ER-associated Ca(2+)-ATPase and disrupts Ca(2+) homeostasis. ER stress plays an important pathogenetic role in Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease, and prion protein diseases. This study was conducted to evaluate the protective mechanisms of Scrophularia ningpoensis (SN) extracts and chemicals on TG-stimulated U-87MG cells. In this study, the recovery activities of E-harpagoside (EHA), harpagide (HA), 8-O-E-p-methoxycinnamoylharpagide (MH), aucubin (AB), cinnamic acid (CA), p-coumaric acid (pCA), p-methoxycinnamic acid methyl ester (MME), caffeic acid (CFA), ferulic acid (FA), and (E)-p-methoxycinnamic acid (MA) on TG-stimulated U-87MG cells were evaluated. The results revealed that SN, MME, CFA, and MH showed considerable recovery effects. Therefore, SN, MME, CFA, and MH were selected to evaluate the gene expression profile of U-87MG cells by using microarray analysis and real-time RT-PCR. The results of this analysis revealed that cell cycle, proliferation, protein folding, and anti-apoptosis-related genes were up-regulated in SN, MME, CFA, and MH-treated U-87MG cells. In addition, significant decreases in apoptosis, the MAPK signaling pathway, and mitochondria-related gene expressions were observed in SN-, MME-, CFA-, and MH-treated U-87MG cells. Thus, SN, MME, CFA, and MH might affect neurodegenerative diseases.

Microarray analysis of gene expression profiles in response to treatment with bee venom in lipopolysaccharide activated RAW 264.7 cells.

AIM OF THE STUDY: The therapeutic application of bee venom (BV) has been used in traditional medicine to treat diseases such as arthritis, rheumatism and pain. Macrophages produce molecules that are known to play roles in inflammatory responses. MATERIAL AND METHODS: We performed microarray analysis to evaluate the global gene expression profiles of RAW264.7 macrophage cells treated with BV. In addition, six genes were subjected to real-time PCR to confirm the results of the microarray. The cells were treated with lipopolysaccharide (LPS) or BV plus LPS for 30 min or 1h. RESULTS: 124 genes were found to be up-regulated and 158 were found to be down-regulated in cells that were treated with BV plus LPS for 30 min, whereas 211 genes were up-regulated and 129 were down-regulated in cells that were treated with BV plus LPS for 1h when compared with cells that were treated with LPS alone. Furthermore, the results of real-time PCR were similar to those of the microarray. BV inhibited the expression of specific inflammatory genes that were up-regulated by nuclear factor-kappa B in the presence of LPS, including mitogen-activated protein kinase kinase kinase 8 (MAP3K8), TNF, TNF-alpha-induced protein 3 (TNFAIP3), suppressor of cytokine signaling 3 (SOCS3), TNF receptor-associated factor 1 (TRAF1), JUN, and CREB binding protein (CBP). CONCLUSIONS: These results demonstrate the potent activity of BV as a modulator of the LPS-mediated nuclear factor-kappaB (NF-kappaB)/MAPK pathway in activated macrophages. In addition, these results can be used to understand other effects of BV treatment.

Molecular changes in remote tissues induced by electro-acupuncture stimulation at acupoint ST36.

To investigate the effects of electro-acupuncture (EA) treatment on regions remote from the application, we measured cellular, enzymatic, and transcriptional activities in various internal tissues of healthy rats. The EA was applied to the well-identified acupoint ST36 of the leg. After application, we measured the activity of natural killer cells in the spleen, gene expression in the hypothalamus, and the activities of antioxidative enzymes in the hypothalamus, liver and red blood cells. The EA treatment increased natural killer cell activity in the spleen by approximately 44%. It also induced genes related to pain, including 5-Hydroxytryptamine (serotonin) receptor 3a (Htr3a) and Endothelin receptor type B (Ednrb) in the hypothalamus, and increased the activity of superoxide dismutase in the hypothalamus, liver, and red blood cells. These findings indicate that EA mediates its effects through changes in cellular activity, gene expression, and enzymatic activity in multiple remote tissues. The sum of these alterations may explain the beneficial effects of EA.

Suppression of IgE production and modulation of Th1/Th2 cell response by electroacupuncture in DNP-KLH immunized mice.

Effects of electroacupuncture (EA) on Th1/Th2 cell response were investigated in BALB/c mice immunized intraperitoneally with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). Successive electroacupuncture stimulation on the ST36 acupoint was performed just after immunization. Serum levels of antigen-specific IgE and total IgE were significantly decreased compared with non-acupunctured controls. Production of the Th2-specific cytokines IL-4 and IL-13 in the anti-CD3 mAb-activated splenocytes was significantly suppressed in ST36 electroacupunctured mice compared with non-acupunctured mice. These results imply that successive electroacupuncture on ST36 can decrease the serum level of antigen-specific IgE and total IgE by suppression of the Th2 lineage development.

So-Cheong-Ryong-Tang, tradititional Korean medicine, suppresses Th2 lineage development.

The present study was designed to evaluate the effect of So-Cheong-Ryong-Tang (SCRT, also called Sho-Seiryu-To or Xiao-Qing-Long-Tang) on helper T cell development by monitoring Th1/Th2-specific cytokine secretion patterns in artificially induced Th1 or Th2 polarized conditions. The results demonstrated that Th2 cells were dramatically underpopulated in the Th2-driven condition triggered by SCRT treatment, while the Th1 cells were not altered in the Th1-skewed condition. Furthermore, under Th2-skewed conditions the levels of interleukin-4 were considerably decreased with SCRT treatment. The expression of GATA-3, a transcription factor that plays a pivotal role in Th2 lineage programming, did not change with SCRT treatment, while the expression of another Th2 transcription factor, c-Maf, was dramatically suppressed. These data suggest that SCRT modulates Th2 development by suppressing c-Maf expression. This study implies that the SCRT effect on CD4(+) T cells is a key pharmacologic point of effect for treating IgE-mediated allergic asthma. These results also suggest that SCRT might be a useful agent for the correction of Th2-dominant pathologic disorders.

Chung-Yeul-Gue-Soup-Sa-Gan-Tang, traditional Korean medicine, enhances CD4(+) T cell activities and modulates Th1/Th2 lineage development.

Chung-Yeul-Gue-Soup-Sa-Gan-Tang (CYT), a traditional Korea herbal medicine, has been widely used in Korea for the treatment of various immunological disorders, including allergic asthma. In this study, CYT was examined in vitro and tested for possible immunological effects. The results demonstrated that CYT had no mitogenic effects on unstimulated CD4(+) T cells, but rather increased CD4(+) T cell proliferation upon activation with anti-CD3/CD28 antibody. Under the Th0 condition, CYT also enhanced expression of interleukin (IL)-2 in purified murine CD4(+) T cells assayed by real-time PCR, suggesting that CYT moderately increases the activity of helper T cells upon T cell receptor ligation under the neutral condition. However, the Th1 cells were overpopulated following CYT treatment under the Th1 condition, while Th2 cells were under-populated in the Th2 driven condition. In addition, under Th1/Th2-skewed conditions, the levels of IL-4 were considerably decreased, while the expression of T-bet and interferon-gamma were increased with CYT treatment. Thus, CYT enhances Th1 lineage development from naive CD4(+) T cells both by increasing Th1 specific cytokine secretion and repressing Th2 specific cytokine production. These results suggest that CYT is a desirable agent for the correction of Th2 dominant pathological disorders.