Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Angelica sinensis polysaccharides improve Th1/Th2 imbalance and protect pregnancy in threatened abortion model rats / 中国药房

OBJECTIVE To study the tocolysis effects of Angelica sinensis polysaccharides on threatened abortion model rats and their impacts on Th1/Th2 balance by regulating the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway. METHODS Pregnant rats were randomly grouped into the control group， model group， A. sinensis polysaccharide group （200 mg/kg）， PI3K/AKT signaling pathway inhibitor LY294002 group （5 mg/kg）， and A. sinensis polysaccharide+LY294002 group （200 mg/kg A. sinensis polysaccharide+5 mg/kg LY294002）， with 10 rats in each group. Except for the control group， rats in all other groups were given mifepristone （8.3 mg/kg） and misoprostol （100 μg/kg） intragastrically to establish a threatened abortion model， and intragastric or intraperitoneal injection of corresponding drugs. The serum levels of estrogen， progesterone， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， and interleukin-4 （IL-4） in each group of rats were detected， and the uterine ovarian index and embryonic mortality rate of rats in each group were measured； the morphology of uterine tissue in rats was observed in each group； Th1/Th2 balance in peripheral blood of rats as well as the expression of PI3K/AKT signaling pathway-related proteins in the uterine tissues of rats in each group were detected. RESULTS Compared with the control group， the uterine tissue of rats in the model group showed pathological damage； the serum levels of estrogen， progesterone and IL-4， uterine ovarian index， peripheral blood Th2 cell ratio， and the ratios of phosphorylated PI3K （p-PI3K）/PI3K and phosphorylated AKT （p-AKT）/AKT in uterine tissue were all decreased （P＜0.05）； the embryo mortality rate， Th1 cell ratio， Th1/Th2 ratio， and serum levels of IFN-γ and TNF-α were increased （P＜0.05）. Compared with the model group， the pathological damage of uterine tissue in the A. sinensis polysaccharide group was reduced， and the above indexes were all improved significantly （P＜0.05）； LY294002 could weaken the effect of A. sinensis polysaccharide on model rats （P＜0.05）. CONCLUSIONS A. sinensis polysaccharides can improve Th1/Th2 imbalance in threatened abortion model rats by activating the PI3K/AKT signaling pathway， thereby inhibiting immune inflammation， and promoting embryo survival.

Different Anesthesia and Sedation Depths of BIS-guided Closed-loop Target-controlled Infusion on Perioperative Th1/Th2 Balance in Elderly Patients Undergoing Laparoscopic Radical Gastrectomy / 肿瘤防治研究

Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H, n=36) and BIS value of 45(group L, n=37).Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4).IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array.We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P < 0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P < 0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P < 0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P < 0.05), IL-2 in group L at T4 was decreased (P < 0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4(P < 0.05).Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2(P < 0.05), IFN-γ/IL-6 in group H was significantly decreased (P < 0.05), IL-2 and IL-10 in group H were significantly increased at T4(P < 0.05).Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P > 0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop target-controlled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis.

Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.

Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.

Acupoint Autohemotherapy Attenuates Atopic Dermatitis Lesions by Regulating Th1/Th2 Balance in DNCB-Induced BALB/c Mice / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses.@*METHODS@#Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice.@*RESULTS@#Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05).@*CONCLUSION@#A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.

Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD.@*METHODS@#A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus.@*RESULTS@#There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.

Effect of short-And long-Term immunization of recombinant disorganized muscle protein-1 (rDIM-1) against human filarial parasite Brugia malayi in rodents

Objective: To evaluate the effect of short-Term and long-Term immunization of recombinant disorganized muscle protein-1 (rDIM-1) in rodents against human filarial parasite Brugia malayi. Methods: Recombinant Brugia malayi DIM-1 (rDIM-1bm) protein was cloned, expressed and purified using a Ni-NTA affinity column. Mastomys coucha were immunized with rDIM-1bm in three immunization schedules: short-Term (3-dose of rDIM-1bm), and long-Term (booster doses till 3-And 6-week) and subsequently challenged with infective third-stage larvae of filarial parasite Brugia malayi (L3). Microfilaraemia was monitored in L3 exposed groups on day 90 post larval inoculation (p.l.i.) and continued till day 205 p.l.i. On day 205 p.l.i. all the infected animals were killed and total worm burden was estimated. Cellular proliferative response, macrophage activity, nitric oxide (NO) release, specific IgG and its subtypes, IgE, IgA and Th1 (IFN-γ, TNF-α and IL-2) and Th2 (IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release were determined. Results: Of the 3 different immunization schedules, short-Term immunization (3-dose schedule) showed better reduction in microfilarial burden (36%-63%) in the peripheral circulation, adult worm load (52%), whereas long-Term immunization (3-And 6-week schedule) exerted less effect on peripheral microfilariae count (9%-58%), and adult worm burden (9%-12.5%). Short-Term immunization resulted in upregulation of cellular proliferation, macrophages activity, NO release, specific IgG, IgG1, IgG2a, IgG2b, IgE and IgA levels and both Th1 (IFN-γ, TNF-α and IL-2) and Th2 (IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release whereas long-Term immunization (3-And 6-week schedule) exerted less effect on parasite burden and showed mixed immunological responses. None of the rDIM-1bm administration schedules induced any pathology in lymphoid tissues, or alteration in mast cell number and granularity. Conclusions: The short-Term immunization with rDIM-1bm (3-dose schedule) induces robust immune responses and protects the host from filarial parasite infection.

Potential immunomodulatory role of sesamin in combating immune dysregulation associated with COVID-19

The ongoing outbreak of novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global health crisis. Development of a cure for this devastating disease is currently at full speed, with several vaccines against COVID-19 already authorized and administered. Currently, demand for these vaccines far exceeds supply. As such, boosting immunity represents a viable route to halt the rapid spread of SARS-CoV-2 and limit fatalities until vaccines become more readily and widely available. The use of phytochemicals appears to be a promising panacea. Sesamin, a lignan isolated from Sesamum indicum seeds, is known for its potent pharmacological properties, and is therefore hypothesized as a potential candidate in the therapeutic regimen against COVID-19. Herein, we highlight the confirmed therapeutic anti-inflammatory and immune-modulatory potential of sesamin against myriads of respiratory disorders, and tentatively suggest that sesamin may exert similar potent effects against COVID-19. Precisely, we speculate that sesamin may help alleviate COVID-19 via restoring Th1/Th2 balance and preventing inflammation and cytokine storm development. Additionally, we further support the promising role of sesamin against COVID-19 by underscoring the direct evidence, which suggests that sesamin may demonstrate promising inhibitory potential against three important SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Although preliminary, there is ample evidence to propose sesamin as a potential phytotherapeutic and prophylactic candidate against COVID-19. Further in vitro, in vivo, and preclinical studies are required to further substantiate the role of sesamin in the prevention and/or treatment of COVID-19.

Regulatory effects of miR-138 and RUNX3 on Th1/Th2 balance in peripheral blood of children with cough variant asthma / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.

Immunomodulatory effect of Quercetin on dysregulated Th1/Th2 cytokine balance in mice with both type 1 diabetes and allergic asthma

T-helper subtype imbalance is intricate in type 1 diabetes (T1D) and asthma initiation. The role of quercetin in immunedysregulation in comorbid conditions of T1D and asthma is not available. In this study, it was thought worthy toevaluate the role of quercetin on modulating Th1/Th2 cytokine dysregulation in comorbid diabetic asthma. Male Balb/cmice were injected intravenously with alloxan (80 mg/kg) to persuade T1D. Succeeding diabetes introduction, twointraperitoneal sensitizing doses of ovalbumin emulsion (50 µg ovalbumin blended with 2.5 mg alum/sensitization) weregiven on days 3 and 8. Mice were given intranasal challenges of ovalbumin (100 µg ovalbumin/25 µl of sterile saline) ondays 13–15. Oral quercetin treatment (10–30 mg/kg) was given daily on days 3–15. Nasal hyperresponsiveness (NHR)was recorded immediately after Ova challenge on day 16. Bronchoalveolar lavage fluid (BALF), blood, and lungs werecollected 1-hour post NHR for further analysis. Quercetin treatment significantly decreased eosinophils, interleukin-4while increasing interferon-gamma in blood, and BALF and reduced the allergic airway inflammation by inhibitinginflammatory cell infiltration and mucous cell metaplasia. Furthermore, quercetin with a dose of 30 mg/kg demonstrateda significant glucose reduction. Thus, quercetin exerted dose-dependent anti-asthma activity by modulating Th1/Th2balance with glucose-lowering potential in comorbid mice.

Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift / 中草药·英文版

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high mortality. The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously. This study aimed to evaluate the effect of Jinbei Oral Liquid (JBOL) on IPF and its relationship with Th1/Th2 shift. Methods: Rats were divided into six groups: control group, model group (bleomycin), pirfenidone group (positive group, 54 mg/kg, i.g.) and JBOL (5.4, 10.8 and 21.6 mL/kg, i.g.) groups. The rat model was established by an intratracheal instillation of bleomycin (BLM, 5 mg/kg). One day after injection of BLM, pirfenidone or JBOL was given to rats once daily within 28 consecutive days, respectively. Positron emission tomography/computed tomography (PET/CT) was performed on the treated rats. The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining. The contents of TGF-β1, TNF-α, IL-4 and IFN-γ were further quantified by ELISA assay. Results: PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycin-induced alveolitis and fibrosis extent, and the alveolitis lesion score was markedly decreased compared with the model group. The increased expression of inflammatory cytokines TGF-β1 and TNF-α induced by bleomycin was also suppressed by JBOL. The Th1 response was limited by the reduced IFN-γ after BLM administration, and the Th2 response predominated significantly marked by the increased IL-4. JBOL could increase the level of IFN-γ and markedly increased the ratio of IFN-γ/IL-4. Conclusion: These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration, pro-inflammatory cytokine release and excessive collagen deposition in rats. One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.

The Th1-th2 profile in immune responses to Human papillomavirus (HPV) in vitro in men from the city of São Paulo, Brazil / Perfil Th1-Th2 nas respostas imunes ao Papilomavírus Humano (HPV) in vitro em homens da cidade de São Paulo, Brasil

Introduction: The cell-mediated immune response plays an important role in the control of HPV-induced cancers. Cytokines play an important function in host defense against HPV infection by modulating viral infection and polarizing the immune response towards Th1 or Th2 cells. Objective: To evaluate the specific immune response to HPV in vitro in men with and without lesions caused by HPV. Methods: We recruited 31 patients and 11 volunteers and divided them into the following four groups: 12 patients in Group A (HIV+/HPV+); 9 patients in Group B (HIV-/HPV+); 10 patients in Group C (HIV+/ HPV-); and 11 healthy subjects in Group D (HIV-/HPV-). PBMCs culture assays were performed to measure the levels of Th1/Th2/Th17 cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10 and IL-17) in cells from patients stimulated with a quadrivalent HPV vaccine (HPV 6, 11, 16 and 18) and the E7 protein of HPV16. Results: The coinfected group A (HIV+/HPV+) showed higher levels of cytokines, especially Th2 cytokines, compared with the other study groups. The coinfected group had significantly higher levels of IL-6 and IL-10, which are Th2 cytokines, compared to the control group (HIV-/HPV-) (p<0.0001 and p<0.0001, respectively). Conclusion: This study reports a high production of cytokines in the coinfected group, suggesting strong immunomodulatory effects by HIV/HPV coinfection. However, further studies should be conducted to confirm these data. Because this group had high levels of Th2 cytokines, especially IL-6 and IL-10, these data suggest that these two cytokines may serve as biomarkers for viral persistence because HIV seropositive patients have a higher HPV persistence and may allow for the progression to more serious injuries to be monitored.

Introdução: A resposta imune celular exerce um importante papel no controle dos cânceres induzidos pela infecção por HPV. As citocinas desempenham um papel importante na defesa do hospedeiro contra a infecção pelo HPV pela modulação da infecção viral e a polarização da resposta imune para células Th1 ou Th2. Objetivo: Avaliar a resposta imune específica in vitro ao HPV em homens com e sem lesões causadas pelo HPV. Métodos: Foram recrutados 31 pacientes e 11 voluntários, divididos em quatro grupos: 12 pacientes no grupo A (HIV+/HPV+); 9 pacientes no grupo B (HIV-/HPV+); 10 pacientes no Grupo C (HIV+/HIV-); e 11 sujeitos saudáveis no grupo D (HIV-/HPV-). Uma cultura de PBMCs foi realizada para medir os níveis de citocinas Th1/ Th2/Th17 (IFN-γ, IL-2, TNF-α, IL-4, IL-10 e IL-17) de células de pacientes estimulados com a vacina quadrivalente para HPV (HPV 6, 11, 16 e 18) e a proteína E7 de HPV-16. Resultados: O grupo A coinfectado (HIV+/HIV+) apresentou altos níveis de citocinas, especialmente citocinas do perfil Th2, comparados com os demais grupos estudados. O grupo coinfectado apresentou níveis significativamente mais elevados de IL-6 e IL-10, citocinas do perfil Th2, comparados ao grupo controle (HIV-/HPV-) (p<0,0001 e p<0,0001, respectivamente). Conclusão: Este estudo reportou uma elevada produção de citocinas no grupo de coinfectados, sugerindo um forte efeito imunomodulatório pela coinfecção HIV/HPV. Entretanto, outros estudos devem ser conduzidos para confirmar estes dados. Devido este grupo apresentar altos níveis de citocinas Th2, especialmente IL-6 e IL-10, esses dados sugerem que essas duas citocinas podem servir como biomarcadores para a persistência viral, uma vez que pacientes soropositivos para HIV apresentam níveis mais altos de persistência pelo HPV e podem permitir que a progressão para lesões mais graves possa ser monitorada.

Effect of melatonin on the expression of Th1/Th2/Th17 cytokines of gastric cancer in vitro and in vivo / 解剖学报

Objective: To investigate the effect of melatonin(MLT) on the expression of type Thl/Th2/Thl7 cytokines such as interferon(IFN)-Î3, tumor necrosis factor(TNF), interleukin(IL)-2,IL-4,IL-6,IL-10,IL-17a and so on of gastric cancer in vitro and in vivo. Methods: 1. Model of gastric cancer-bearing mice was established. Then 32 male 615 mice were all inoculated with murine foregastric carcinoma cells and randomly divided into 4 groups, and injected intraperitoneally with melatonin at doses of 0, 25, 50 and 100 mg/kg, and measureed long and short diameter of tumor, respectively. After a week of intervention, peripheral blood was taken and the tumor tissue was removed for weighing and measurement. 2. Murine foregastric carcinoma (MFC) cells were inoculated into a six-well cell culture plate and routinely cultured. After 24 hours of adherence, they were treated with melatonin at different concentrations of 0, 2, 4, 6, 8 and 10 mmol/L. After 24 hours again, the cells morpology were observed and the corresponding supematants were collected. 3. The expressions of melatonin concentrations in peripheral blood serum was detected by enzyme -linked imm unosorbent assay (ELISA). The expressions of Thl/Th2/Thl7 cytokines in peripheral blood serum and cell supematants were detected by cytometric bead array (CBA) respectively. Results: 1. Tumor-bearing mice models were successfully established. Compared with the negative control group, the melatonin concentration in peripheral blood serum of the middle and high dose MLT group which increased significantly, and the tumor volume significantly decreased. Compared with the negative control group, the concentration of 1L-10 in the middle dose group increased significantly. And the concentration of IFN-y, IL-2 and IL-10 in the high dose group increased significantly too. 2. Compared with the 0 mmol/L MLT group, the concentrations of IFN-Î3 in the 6 and 10 mmol/L MLT group were significantly decreased; the concentrations of IL-6 in the 4, 6, 8 and 10 mmol/L MLT group were significantly decreased, and the concentration of IL-10 in 6 mmol/L MLT group was significantly increased. All the difference were statistically significant (P<0. 05). Conclusion: Melatonin inhibits the proliferation of murine foregastric carcinoma cell MFC both in vitro and in vivo, and may enhance tumor immunity by adjust the expression of IFN-Î3, IL-2, IL-6 and IL-10 cytokines of type Thl/Th2/Thl7 cells.

Influence of fire needle stimulation at Sihua acupoints on performance status and Th1/Th2 ba-lance in the patients with advanced non-small cell lung cancer after chemotherapy / 针刺研究

OBJECTIVE: To observe the influence of fire needle stimulation at Sihua acupoints combined with chemotherapy on Th1/Th2 imbalance and performance status in the patients with advanced non-small cell lung cancer (NSCLC) so as to investigate its immunological mechanism underlying the improvement of lung cancer. METHODS: Sixty eligible NSCLC inpatients were randomly assigned to a control group and a treatment group (n＝30 cases in each one). The control group was treated with paclitaxel combined with cisplatin (TP) or gemcitabine plus cisplatin (GP) of chemotherapy, and the treatment group was treated with fire needle stimulation at Sihua acupoints (i.e. bilateral Geshu [BL17] and Danshu [BL19]) and with chemotherapy simultaneously. The fire needle stimulation was given once daily for successive 7 days. One day before and 14 days after chemotherapy, the patients' blood samples were collected for assaying the concentrations of Th1 related cytokines (IL-2, IFN-γ) and Th2 related cytokines (IL-4, IL-10) with ELISA. The Karnofsky performance status (KPS) score was used to assess the patient's physical conditions before and 14 days after chemotherapy. RESULTS: Compared with the results before treatment, the levels of IL-2 and IFN-γ concentration increased obviously and the levels of IL-4 and IL-10 concentration as well as KPS score decreased significantly in the treatment group and the control group after treatment (all P<0.01). After treatment, compared with the control group, the levels of IL-2 and IFN-γ concentration in the treatment group increased and the levels of IL-4 and IL-10 concentration decreased (P<0.01); and the decrease amplitude of KPS score in the treatment group was less than that in the control group (P<0.01). CONCLUSION: Fire needle stimulation at Sihua acupoints improves the function of Th1 cells, and reduces the function of Th2 cells. As a result, the balance between Th1 and Th2 has been modified and the deterioration degree of the performance status been alleviated in the patients after chemotherapy.

Effect of Modified Renseng Yangrong Tang Combined with Chemotherapy on Serum Tumor Markers and Th1/Th2-type Cytokines Expression in Cervical Cancer Patients / 中国实验方剂学杂志

Objective: To investigate the effect of modified Renseng Yangrong Tang combined with chemotherapy on serum tumor markers and Th1/Th2 type cytokines expression in cervical cancer patients. Method: A total of 114 patients with cervical cancer admitted in our hospital from December 2014 to December 2017 were selected as the study subjects. According to the random number table method, the patients were divided into two groups. The control group (57 cases) was treated with conventional chemotherapy. The treatment group (57 cases) was treated with modified Renseng Yangrong Tang in addition to the conventional chemotherapy. Traditional Chinese medicine (TCM) symptom scores, serum tumor markers[carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125)]and Th1/Th2 type cytokine[interferon gamma-interferon (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), interleukin-6 (IL-6) levels], clinical efficacy after treatment 3 months, and adverse reaction rate of two groups were observed. Result: There was no significant difference in TCM symptom scores, serum tumor markers and Th1/Th2 cytokines between the two groups before treatment. After treatment, the TCM symptom scores, CEA, SCCA, CA125, IL-6, and IL-4 levels in the treatment group were lower than those in control group and before treatment (Pγ were higher than those in the control group and before treatment (PPχ2=4.524, 4.150, PConclusion: Modified Renseng Yangrong Tang can significantly relieve clinical symptoms, reduce the level of serum tumor markers, improve cellular immunity, improve the recent therapeutic effect, and reduce adverse reactions in patients with cervical cancer chemotherapy.

Effect of Jiawei Changfengyin with Retention Enema Therapy on Th1/Th2 in Patients with Acute Radiation Proctitis / 中国实验方剂学杂志

Objective: To discuss the efficacy of Jiawei Changfengyin with retention enema therapy for acute radiation proctitis and investigate its influence on regulating levels of helper T cell(Th)1/Th2. Method: One hundred and twenty-eight patients were randomly divided into control group and observation group by random number table. Patients in control group (64 cases) got montmorillonite powder (3.0 g), dexamethasone (10 mg) and normal saline (100 mL), with retention enema therapy. Patients in observation group (64 cases) got Jiawei Changfengyin(Changfengyin+Xileisan+pearl powder), with retention enema therapy. Both groups of patients received enema once every night, and the treatment course was 4 weeks in both groups. Before and after treatment, scores of main symptoms, proctoscopy, routine examination of stool+occult blood, and KPS scores of quality of life were graded. Levels of Th1 cell factors[interleukin(IL)-1β, IL-8 and interferon-γ(IFN-γ)], Th2 cell factors (IL-4 and IL-10) were detected. Result: The total effective rate for comprehensive clinical efficacy was 95.31% in observation group, higher than 82.81% in control group (χ2=5.132, PPZ=2.764, PPPβ, IL-8 and IFN-γ in observation group were lower than those in control group, while levels of IL-4 and IL-10 were higher than those in control group (PConclusion: Jiawei Changfengyin can relieve symptoms of acute radiation proctitis, promote healing of rectal mucosa, improve quality of life, and regulate Th1/Th2 cytokines, with good repairing effect for intestinal mucosa.

Attach importance to the immunological mechanism of preeclampsia / 中国医师杂志

Preeclampsia is one of the main causes of high morbidity and mortality of pregnant women and perinatal infants worldwide. Affected by many factors, preeclampsia has a complex pathogen-esis and can cause involvement of multiple organs and systems. Its pathogenesis is still unclear. Current research suggests that maternal immune system indirectly involved in the pathophysiology of preeclampsia change, that is, abnormal activation of innate immune cells and unbalanced differentiation of T helper cell subsets interfere with normal immune regulation, and interact with inflammatory response of the body, which produces cytotoxic environment at the maternal-fetal interface and affects trophoblast inva-sion. Therefore, clarifying the role of the immune system can not only clarify the pathogenesis of pre-eclampsia, but also contribute to the development of diagnosis and treatment of preeclampsia. This paper reviews the research status of immune system in preeclampsia, including innate immunity and adaptive immunity . The immune mechanism of preeclampsia is elaborated mainly from immune regulation mediated by T lymphocyte, natural killer ( NK) cell, macrophage and human leukocyte antigen.