1.MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation.
Limin TIAN ; Xiaohui HUYAN ; Sen YANG ; Mengjie WANG ; Yuenan YANG
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):26-32
Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4+CXCR5+IFN-γ+Tfh1 cells, CD4+CXCR5+IL-17A+Tfh17 and CD4+CXCR5+IL-21+Tfh21 cells, and a significant decrease in the percentage of CD4+CXCR5+IL-10+Tfh10 cells and CD4+CXCR5+FOXP3+Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Animals
;
Mice
;
Dermatitis, Atopic/drug therapy*
;
Interleukin-17
;
T Follicular Helper Cells
;
Janus Kinase 2
;
Dinitrochlorobenzene
;
Inflammation
;
Cell Differentiation
;
Signal Transduction
2.Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Zhibing FU ; Yajie XIE ; Liyue ZENG ; Lihua GAO ; Xiaochun YU ; Lina TAN ; Lu ZHOU ; Jinrong ZENG ; Jianyun LU
Journal of Central South University(Medical Sciences) 2023;48(1):1-14
OBJECTIVES:
Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.
METHODS:
Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.
RESULTS:
Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).
CONCLUSIONS
Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals
;
Mice
;
Dinitrochlorobenzene/metabolism*
;
Skin/metabolism*
;
Cytokines/metabolism*
;
Interleukin-17/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Dermatitis, Allergic Contact/pathology*
;
Dermatitis, Atopic/chemically induced*
;
Signal Transduction
;
RNA, Messenger/metabolism*
;
Mice, Inbred BALB C
3.Effect of acupuncture at neck-Jiaji (EX-B 2) and tuina on the cognitive function in the patients with subjective cognitive decline.
Yu ZHANG ; Xi YIN ; Zhao-Yang LIU ; Qing-Feng YANG ; Xu HAN ; Yi-di XU ; Xiao-Hui LU
Chinese Acupuncture & Moxibustion 2023;43(12):1379-1383
OBJECTIVES:
To observe the effects on cognitive function, sleep quality and hemodynamics in the patients with subjective cognitive decline (SCD) after treated with acupuncture at neck-Jiaji (EX-B 2) and tuina on the base of healthy lifestyle education and meta-memory training.
METHODS:
Sixty SCD patients were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 3 cases dropped out). In the control group, the healthy lifestyle education and meta-memory training was performed, twice daily, 15 min each time; the 5-day intervention was delivered a week, lasting consecutively 4 weeks. On the base of the intervention as the control group, in the observation group, acupuncture at neck-Jiaji (EX-B 2) and tuina was conducted. First, one-finger pushing and plucking method of tuina was exerted on the neck region along the running courses of the bladder meridian of foot-taiyang and the governor vessel, for 10 min to 15 min; afterwards, acupuncture was delivered at bilateral neck-Jiaji (EX-B 2), from C1 to C7; and the needles were retained for 30 min. This intervention was given once daily, 5 times a week, for consecutive 4 weeks. Before and after treatment, the score of the mini-mental state examination (MMSE), the score of full scale memory quotient (FSMQ) were assessed by Wechsler memory scale-fourth edition (WMS-Ⅳ) and the score of the Pittsburgh sleep quality index (PSQI) was compared between the two groups. Using transcranial Doppler ultrasound, the hemodynamic indexes (the mean velocity [Vm] and pulsatility index [PI] of the left vertebral artery [LVA], the right vertebral artery [RVA] and the basilar artery [BA]) were determined in the two groups.
RESULTS:
After treatment, the scores of MMSE and FSMQ increased compared with those before treatment in the two groups (P<0.05, P<0.001), PSQI score was lower (P<0.05) and Vm of BA was higher (P<0.001) in the observation group when compared with those before treatment. The scores of MMSE and FSMQ, as well as Vm of BA were higher (P<0.05, P<0.001), and PSQI score was decreased (P<0.05) in the observation group when compared with the control group.
CONCLUSIONS
The combined therapy of acupuncture at neck-Jiaji (EX-B 2) and tuina is more advantageous to improving cognitive function, relieving chronic emotional stress and ameliorating sleeping quality in the patients with subjective cognitive decline, which may be achieved by improving the blood supply of the basilar artery.
Humans
;
Acupuncture Therapy/methods*
;
Chlorophenols
;
Cognitive Dysfunction/therapy*
;
Cognition
;
Acupuncture Points
;
Treatment Outcome
4.Improvement of high-quality evaluation criteria of Chinese patent medicines based on whole process control.
Yan LIU ; Cong GUO ; Jun ZHANG ; Qing-Xia XU ; An-Yi ZHAO ; Yong-Zhen LAO ; Jiang-Min SU ; Zhi-Guang WANG ; Yu-Zhen LIU ; Sha CHEN ; An LIU
China Journal of Chinese Materia Medica 2023;48(6):1700-1704
Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/therapeutic use*
;
Nonprescription Drugs
;
Chlorobenzenes
;
China
5.Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats.
Dina TUCOVIC ; Jelena KULAS ; Ivana MIRKOV ; Dusanka POPOVIC ; Lidija ZOLOTAREVSKI ; Marta DESPOTOVIC ; Milena KATARANOVSKI ; Popov Aleksandrov ALEKSANDRA
Biomedical and Environmental Sciences 2022;35(11):1038-1050
OBJECTIVE:
The effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it disturbs homeostasis, thus resulting in inflammation and injury.
METHODS:
Male rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS:
Orally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production).
CONCLUSION
These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.
Male
;
Rats
;
Animals
;
Allergens/toxicity*
;
Cadmium/toxicity*
;
Dinitrochlorobenzene/toxicity*
;
Interleukin-17
;
Cytokines
6.Four Chinese patent medicines for regulating stomach for functional dyspepsia: a rapid health technology assessment.
Si-Min XU ; Ze-Qi DAI ; Xue WU ; Miao-Miao LI ; Xing LIAO
China Journal of Chinese Materia Medica 2022;47(17):4778-4788
This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.
Capsules
;
China
;
Chlorobenzenes
;
Domperidone/therapeutic use*
;
Drugs, Chinese Herbal/therapeutic use*
;
Dyspepsia/drug therapy*
;
Humans
;
Nonprescription Drugs/therapeutic use*
;
Stomach
;
Sulfides
;
Tablets
;
Technology Assessment, Biomedical
7.Research and development of an air sampling tube for chlorobenzene compounds and its supporting determination method.
Wei Jie LING ; Wei Feng RONG ; Shi Hua WU ; Guan Hao GUO ; Jiu CHEN ; Yi Min LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(8):613-619
Objective: To establish a GDH-3 air sample tube for simultaneous determination of twelve kinds of chlorobenzene compounds (CBs) in workplace air by gas chromatography. And to established a matching determination method. Methods: In October 2020, the vapor and aerosol CBs in workplace air were collected by GDH-3 air sampling tube, and desorption and elution with 3.00 ml toluene for 15 min, then the solution separated by DB-23 capillary column, and finally detected with microcell electron capture detector. Results: The quantitative determination ranges of twelve isomers of CBs were 0.71×10(-3)-2000.00 mg/L, with the correlative coefficients were 0.99967-0.99998. The minimum detectable concentrations were 0.04-112.63 μg/m(3), and the minimum quantification concentrations were 0.14-375.42 μg/m(3) (15.00 L sample, 3.00 ml sample solution) . The average elution efficiencies were 96.00%-104.00%. The within-run relative standard deviations (RSDs) were 2.54%-6.12%, and the between-run RSDs were 3.85%-7.87%. Sealed samples could be stable at room temperature for at least 15 days. Conclusion: GDH-3 air sample tube can be used for simultaneous determination of twelve kinds of CBs in workplace air by gas chromatography. The established supporting measurement method meets the measurement requirements of the occupational health standard detection method, and the it's suitable for the simultaneous determination of 12 kinds of CBS in the air.
Air Pollutants, Occupational/analysis*
;
Chlorobenzenes/analysis*
;
Chromatography, Gas/methods*
;
Research
;
Workplace
8.Determination of chlorobenzene metabolite-p-chlorophenol in urine by solid phase extraction-gas chromatography.
Peng WANG ; Yi Yao CAO ; Hong REN ; Xiang Jing GAO ; Qiu Liang XU ; Zhen ZHOU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(9):703-706
Objective: A method to determine chlorobenzene metabolite-p-chlorophenol in urine by solid phase extraction-gas chromatography was established. Methods: In May 2021, the urine sample was hydrolyzed at 100 ℃ for 1.5 h with 2 ml concentrated hydrochloric acid. After cooling and filtering, the sample was enriched and purified by Oasis(®)MAX 6cc SPE column. Drip washing with 0.01 mol/L hydrochloric acid solution and elution with acetonitrile, the eluent was volumized to 5 ml with acetonitrile and determined by gas chromatography, and quantify by standard curve method. Results: Calibration curve of the method was linear within the range of 1.61-80.30 μg/ml and showed good linearity with r=0.9997, the regression equation was y=1.51602x-0.10234. The determination limit was 0.17 μg/ml, and the limit of quantitation was 0.55 μg/ml. Recovery rates were between 89.3%-104.4%, the relative standard deviation (RSD) of intra-day measurements ranged from 4.3% to 6.7%, and the RSD of inter-day measurements ranged from 4.5% to 6.7%. Conclusion: This method could optimize sample pretreatment, and eliminate the interference of impurities, which is sensitive, efficient and accurate for the determination of chlorobenzene metabolite-p-chlorophenol in urine.
Acetonitriles
;
Chlorophenols
;
Chromatography, Gas
;
Chromatography, High Pressure Liquid
;
Hydrochloric Acid
;
Solid Phase Extraction/methods*
9.Acupoint Autohemotherapy Attenuates Atopic Dermatitis Lesions by Regulating Th1/Th2 Balance in DNCB-Induced BALB/c Mice.
Zhi-Wen ZENG ; Jin-Quan HUANG ; Yong CHEN ; Xiao YU ; Wei ZHU ; Dong-Shu ZHANG
Chinese journal of integrative medicine 2022;28(7):612-619
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 Points
;
Animals
;
Dermatitis, Atopic/therapy*
;
Dinitrobenzenes
;
Dinitrochlorobenzene
;
Immunoglobulin E
;
Interferon-gamma
;
Interleukin-4
;
Mice
;
Mice, Inbred BALB C
;
Saline Solution
10.Effect of panlong needling at Jiaji (EX-B 2) on motor dysfunction in patients with Parkinson's disease of liver and kidney deficiency: a randomized controlled trial.
Lin HAN ; Xiu-Zhen SU ; Zhong-Yuan ZHANG ; Ying LIU ; Zhong-Xiang WEI ; Qing-Lan ZHANG ; Jun-Ping ZHANG ; Chen-Xi WANG ; Quan-de SU
Chinese Acupuncture & Moxibustion 2022;42(5):493-497
OBJECTIVE:
To compare the curative effect of panlong needling at Jiaji (EX-B 2) combined with western medication and western medication alone on motor dysfunction in patients with Parkinson's disease (PD) of liver and kidney deficiency.
METHODS:
A total of 98 patients with PD were randomly divided into an acupuncture and medication group (49 cases, 1 case dropped off) and a western medication group (49 cases,1 case was removed). The patients in the western medication group were given oral of levodopa and benserazide hydrochloride tablets, 125 mg each time, three times a day in the 1st week, and the dose was increased according to the needs of the patients' condition from the 2nd week until 250 mg each time, three times a day, for 16 consecutive weeks. On the basis of the same western medication treatment as the western medication group, panlong needling was applied at Jiaji (EX-B 2) from C2 to L5 in the acupuncture and medication group, once a day, 20 times as a course of treatment, for 4 consecutive courses. The scores of unified Parkinson's disease rating scale (UPDRS-Ⅲ, UPDRS-Ⅳ), TCM symptoms score, and 39-item Parkinson's disease questionnaire (PDQ-39) score were evaluated before treatment, after treatment and during follow-up of 1 month after treatment, respectively. The safety of the two groups was compared.
RESULTS:
After treatment and during follow-up, except the PDQ-39 score of the western medication group, the scores of UPDRS-Ⅲ, UPDRS-Ⅳ, TCM syndrome and PDQ-39 were lower than those before treatment in the two groups (P<0.05), and the scores of above indexes in the acupuncture and medication group were lower than those of the western medication group (P<0.05). The total incidence of adverse reactions in the acupuncture and medication group was 10.4% (5/48), which was lower than 29.2% (14/48) in the western medication group (P<0.05).
CONCLUSION
Panlong needling at Jiaji (EX-B 2) combined with western medication could significantly improve the motor dysfunction and clinical symptoms, improve the quality of life and has high safety, and the efficacy is superior to western medication alone.
Acupuncture Points
;
Acupuncture Therapy
;
Chlorophenols
;
Humans
;
Kidney
;
Liver
;
Parkinson Disease/therapy*
;
Quality of Life
;
Treatment Outcome

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