OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

OBJECTIVESix1 and Six4 are expressed in several tumors, and associated with tumor progress and poor prognosis. The aim of this study was to investigate the expression of Six1 and Six4 in esophageal squamous cell carcinoma (ESCC), and to evaluate their correlation with the clinicopathological factors and prognosis.

METHODSTissue microarray technology and immunohistochemical method (EnVision) were used to detect the expression of Six1 and Six4 in the tumor tissues and corresponding adjacent normal epithelium of esophagus from 292 ESCC patients.

RESULTSAmong the 292 ESCC patients, the positive rates of Six1 and Six4 protein expression in tumor tissues were 72.9% (213/292) and 56.2% (164/292), respectively, significantly higher than the expression rate of 33.2% (97/292) and 32.5% (95/292) in adjacent normal epithelium of esophagus (P < 0.05). Chi square test showed that the expression of Six1 protein was related to tumor size, depth of tumor invasion and patient survival status; higher Six4 protein expression level was related to poor differentiation and increased depth of invasion. Single factor Log-rank analysis revealed that gender, TNM stage, Six1 protein expression level were related to the overall survival of ESCC patients (P < 0.05), while the five-year survival rate was significantly higher in the Six1-negative group than the Six1-positive group [51.9% (41/79) vs. 43.7% (93/213)]. Multi-factor Cox proportional risk model analysis showed that TNM stage and positive expression of Six1 were independent prognostic factors for ESCC patients (P < 0.05).

CONCLUSIONSSix1 and Six4 are highly expressed in ESCC. Their expression levels are closely related to the progress and prognosis of ESCC. Over-expression of Six1 is related to poor prognosis in ESCC patients. Thus, Six1 could be used as an important prognostic indicator for ESCC patients.

Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Esophageal Neoplasms ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Homeodomain Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Trans-Activators ; metabolism ; Tumor Burden

Background and purpose:Coventional radiation has been used for decades,but the 3D dose distribution has not been studied as yet.In this study,different treatment plans of conventional irradiation technique for esophageal carcinoma have been evaluated by 3-D TPS.Methods:Five patients with esophageal carcinoma at upper-thoracic and five patients at middle-thoracic were enrolled in this study.Three conventional treatment plans were created for each patient,with a prescribed dose of 70 Gy.For tumor at upper-thoracic,plan 1 consisted of one anterior field and bilateral posterior oblique fields with wedges,plan 2 consisted of anterior bilateral oblique fields with wedges ,plan 3 consisted of a pair of AP-PA portals,then followed by right anterior oblique portals and left posterior oblique portals to spare spine cord.For tumor at middle thoracic,plan 1 consisted of one anterior field and bilateral posterior oblique fields.Plan 2 consisted of a pair of AP-PA portals and followed by another pair of parallel-opposed lateral off- cord fields as boost.Plan 3 used the same plan as for the lesion at upper-thoracic.The evaluation of each treatment plan was carried out by dose-volume histogram(DVH).Results:For tumor at upper-thoracic,on average,the maximum dose to spinal-cord in plan 3 was (57.1?4.9)Gy,and was higher than that in plan 1 and plan 2.Plan 1 increased mean lung dose from (12.8?2.1)Gy to (18.2?4.1)Gy(P=0.045)compared with plan 2,but it improved the homogenous dose of PTV2,especially in the patient with long tumor.For tumor at middle-thoracic,on average,plan 2 increased mean lung dose from (11.9?1.1)Gy to (13.0?0.6)Gy(P=0.045) compared with plan 3.Plan 2 increased V_(20) and V_(30) from (23.6?2.3)% to (29.2?1.9)%(P=0.004) and (13.9?2.3)% to (20.9?1.3)%(P=0.006) compared with plan 1.The trachea volume of(?)70 Gy(V_(70))in plan 3 was larger than that in plan 1[(20.3?15.9)% VS (10.5?9.8)%,P=0.058].Conclusion:For tumor at upper-thoracic,plan 1 and 2 were superior to plan 3.Irradiation to lung in plan 2 was lower than that in plan 1,but plan 1 improved the homogenous dose of PTV2 compared with plan 2,especially for patient with longer lesion.For tumor at upper-thoracic,plan 2 increased irradiation dose to lung compared with plan 1 and plan 3.Plan 1 was comparable with plan 3,but the dose of trachea in plan 1 may lower than that in plan 3.

Twenty-nine cases of fasciitis of back muscles were treated by acupuncturing the main acupoints, including Ashi acuponit, Jianjing (GB 21), Tianzhu (BL 10) and Tianzong (SI 11), plus cupping on the painful part of back. After 2 courses of treatment, 26 cases were cured and 3 cases improved.

Objective To evaluate the role of late course accelerated fractions.ted irradiation(LCAF) combined with concurrent chemotherapy in the management of esophageal carcinoma.Methods From March 1998 to July 2000,111 eligible patients were randomized into LCAF alone group(LCAF,57 patients)or LCAF plus concurrent chemotherapy group(LACF-CT,54 patients).The radiotherapy regimen was identical in the two groups,consisting of conventional fractionation in the first 2/3 course and accelerated fractionation in the second 1/ 3 course to a total dose of 68.4 Gy/41 Fx/44 d.Chemotherapy regimen consisted of four eycles of cisplatin 25 mg/ (m~2?d)plus fluorouracil 600 mg/(m~2?d)on day 1 to 3 every 4 weeks and was delivered on the first day of radiotherapy.Results The median follow-up time was 67.1 months(range 47.6-76.4 months).The 1-,3-,5- year survival rate was 67%,44% ,40% and 77%,39% 28% in LACF-CF and LEAF group,respectively(P =0.310).Grade 3+4 acute side-effact was 42% and 25% in LCAF-CT and LCAF group,respectively(P＜0. 05),with 3 treatment-related deaths in the LCAF-CT group.Conclusions Late course accelerated fractionated irradiation combined with concurrent chemotherapy has a trend towards improving the survival,at the cost of increasing acute side-effect.Its role needs further confirmation by larger sample studied in randomization.