1.SR9009 combined with indolepropionic acid alleviates inflammation in C2C12 myoblasts through the nuclear factor-kappa B signaling pathway
Huihui JI ; Xu JIANG ; Zhimin ZHANG ; Yunhong XING ; Liangliang WANG ; Na LI ; Yuting SONG ; Xuguang LUO ; Huilin CUI ; Ximei CAO
Chinese Journal of Tissue Engineering Research 2025;29(6):1220-1229
BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.
2.Research progress of novel intraocular lens in the treatment of posterior cataract
Xinran ZHAI ; Zhimin CHEN ; Yanhui XU ; Yue ZHANG
International Eye Science 2025;25(10):1611-1616
Posterior capsule opacification(PCO)is a common postoperative complication of cataract surgery, primarily caused by the proliferation and migration of residual lens epithelial cells(LECs). Although neodymium-doped yttrium aluminum garnet(Nd:YAG)laser posterior capsulotomy effectively treats PCO, it carries risks of complications such as cystoid macular edema(CME). Thus, preventing PCO formation is of critical clinical importance. Despite advancements in intraocular lens(IOL)materials and designs, achieving complete PCO eradication remains challenging. This review systematically examines recent advancements in surface-modified IOLs, including anti-biofouling IOL(reducing LECs adhesion), capsular adhesion-enhanced IOL(promoting capsular bag integration), micro-patterned IOL(physically inhibiting migration), photothermal/photodynamic IOL(inducing light-activated LECs apoptosis), and drug-eluting IOL(sustained drug release). These surface modification strategies demonstrate synergistic effects through complementary mechanisms(including physical barrier formation, chemical intervention, and bioactive regulation), effectively suppressing LECs proliferation while significantly reducing PCO incidence. Importantly, these approaches eliminate the risks associated with conventional Nd:YAG laser treatment, offering substantial advantages. By providing a comprehensive evaluation of these cutting-edge technologies, this review serves as a valuable reference for IOL design optimization. It represents a paradigm shift in cataract management strategies, transitioning from reactive therapeutic interventions to proactive preventive measures, and ultimately leads to improving long-term visual outcomes for patients.
3.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
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Male
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Female
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Coronary Artery Disease/drug therapy*
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Retrospective Studies
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Renal Dialysis/methods*
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Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
4.Mechanism of osteoarthritis treatment by exosomes.
Xiaofei WANG ; Jihang DAI ; Lei XU ; Zhimin WU ; Linbing LOU ; Cunyi XIA ; Haixiang MIAO ; Wenyong FEI ; Jingcheng WANG
Chinese Medical Journal 2025;138(3):367-369
5.The advances in the application of peripheral perfusion index in patients with septic shock.
Jiapan AN ; Xinqi XU ; Tingyu YANG ; Bin LI ; Zhimin DOU
Chinese Critical Care Medicine 2025;37(8):780-784
Septic shock, a prevalent critical condition in intensive care units (ICU) and a major cause of patient mortality, is fundamentally attributed to microcirculatory dysfunction. Traditional macrocirculatory parameters are often insufficiently sensitive to reflect microcirculatory status. Consequently monitoring peripheral microcirculatory function holds crucial significance for assessing disease progression and evaluating therapeutic efficacy in septic shock. The peripheral perfusion index (PPI), obtained from a standard pulse oximeter, is based on photoplethysmography (PPG). It calculates the differential absorption of red and infrared light emitted by the sensor between pulsatile arterial blood and non-pulsatile tissue, enabling real-time reflection of peripheral perfusion and thus providing non-invasive, continuous monitoring of microcirculatory function. Although often overlooked compared to other ICU monitoring parameters, PPI has demonstrated notable clinical advances in septic shock management. Specifically, in early identification, PPI combined with sequential organ failure assessment (SOFA) predicts disease progression, with its dynamic changes further aiding prognosis assessment. During fluid resuscitation, it guides fluid responsiveness evaluation and serves as a therapeutic target to optimize strategies. In circulatory support, it assists in determining vasoactive drug initiation timing and dosage titration. Additionally, PPI aids mechanical ventilation weaning and organ dysfunction evaluation. This article reviews the principles, influencing factors, and clinical application advances of PPI in septic shock, aiming to provide clinicians with a basis for individualized intervention, improved patient outcomes, and the advancement of precision medicine in septic shock management.
Humans
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Shock, Septic/therapy*
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Microcirculation
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Perfusion Index
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Prognosis
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Photoplethysmography
6.Efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor in repairing facial trauma
Huibin LIAN ; Pingsong LI ; Kunjie RONG ; Gang XU ; Jie ZHOU ; Yi LUO ; Zhongyin ZHUFU ; Haibin JU ; Junjun JIN ; Rui JIAO ; Xiaowei ZHANG ; Zhimin YIN
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(6):571-575
Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People's Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.
7.Fuling Zexie Decoction Combined with Lifestyle for the Intervention of Metabolic Syndrome of Dampness Syndrome:A Clinical Randomized Trial
Shaoqin LIN ; Chengcheng WANG ; Qing XU ; Fei TAN ; Zhimin YANG ; Xinyan CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1453-1461
Objective To explore the clinical efficacy of Fuling Zexie Decoction combined with lifestyle intervention in patients with metabolic syndrome (MetS) of dampness syndrome. Methods A total of 40 patients with MetS of dampness syndrome were randomly divided into experimental group (n=20) and control group (n=20) according to a randomized double-blind placebo-controlled design. The experimental group was given oral administration of Fuling Zexie Decoction,the control group was given placebo,150 mL each time,twice a day. Both groups were given healthy lifestyle(healthy eating habits and exercise mode) education. The intervention period was 16 weeks. Traditional Chinese medicine dampness syndrome scale score and the diagnostic indexes of MetS,including waist circumference (WC),systolic blood pressure (SBP),diastolic blood pressure (DBP),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and fasting blood glucose (FBG),were evaluated before and after treatment. Other metabolic indexes such as body mass index(BMI),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),uric acid(UC),as well as inflammation related indexes including C-reactive protein (CRP),interleukin-6 (IL-6) and tumor necrosis factor(TNF-α) were also evaluated. Results A total of 33 people completed the trial,including 17 people in the experimental group and 16 people in the control group. Compared to the baseline period,FBG,BMI,LDL-C and dampness syndrome scale score in the experimental group were significantly decreased at the 8th and 16th week of intervention(P<0.05). WC was significantly decreased at the 8th week of intervention(P<0.05). CRP showed a downward trend at the 16th week of intervention(P<0.05). Moreover,SBP and IL-6 in control group decreased significantly at the 8th and 16th week of intervention(P<0.05). WC,DBP and HOMA-IR decreased significantly at the 8th week of intervention (P<0.05). There was no significant difference in other outcome indexes between the two groups at the 8th and 16th week of intervention (P>0.05). The safety indexes of all patients before and after intervention were not significantly abnormal,and no serious adverse events occurred. Conclusion This study initially shows the positive regulatory effect of Fuling Zexie Decoction combined with lifestyle on metabolism and inflammation-related indexes in people with MetS of dampness syndrome,which helps to improve the level of dampness syndrome and provides a basis for further research.
8.Comparison of the effects of different sizes of capsular tension ring on the stability of capsular bag in patients with high myopia and cataract after sur-gery
Xiaojing LIU ; Yue ZHANG ; Yanhui XU ; Zhimin CHEN
Recent Advances in Ophthalmology 2024;44(10):796-801
Objective To investigate the effect of different sizes of capsular tension ring(CTR)on the stability of the capsular bag of patients with high myopia accompanied by cataract after surgery.Methods In this prospective study,75 patients(150 eyes)with high myopia and cataract visited our hospital from January 2022 to June 2022 were selected.These patients were divided into the large-size group,small-size group and control group using the random number table,with 25 patients(50 eyes)in each group.All affected eyes underwent phacoemulsification combined with intraocular lens(IOL)implantation.CTR1311(with an open diameter of 13mm)was implanted in patients of the large-size group,CTR1210(with an open diameter of 12mm)was implanted in patients of the small-size group,and no CTR was implanted in patients of the control group.The uncorrected visual acuity(UCVA),best corrected visual acuity(BCVA),intraocular pressure(IOP),corneal endothelial cell density(ECD),effective lens position(ELP),mean absolute refractive error,an-terior capsular area and complications of patients in the three groups were compared before,1 month,3 months,6 months and 1 year after the surgery.Results One year after the surgery,the UCVA and BCVA of patients in the three groups im-proved than those before surgery(all P<0.05),and the IOP and corneal ECD had no significant difference from those be-fore surgery(all P>0.05).At different times after the surgery,the IOL tilt in patients who underwent CTR implantation was significantly lower than that of patients in the control group(all P<0.05),and the IOL tilt in the small-size group was higher than that in the large-size group(all P<0.05);the IOL eccentricity in patients of the three groups had no significant difference(all P>0.05).At 6 months after the surgery,the postoperative IOL eccentricity and tilt of patients with an axial length>30 mm in the large-size group were smaller than those of patients in the small-size group(both P<0.05).At dif-ferent times after the surgery,the anterior capsular area of patients in the control group was significantly smaller than that of the large-size group and small-size group(all P<0.05),and there was no significant difference in the anterior capsular area between the large-size group and small-size group(all P>0.05).At 6 months after the surgery,the mean absolute re-fractive error of patients in the control group was greater than that of the large-size group and small-size group(both P<0.05),and there was no significant difference in the mean absolute refractive error between the large-size group and small-size group(P>0.05).During the 1-year follow-up,there were no severe complications in the three groups.Conclusion Phacoemulsification combined with CTR implantation is effective for patients with high myopia and cataract.The postop-erative IOL of patients who received large-size CTR implantation is more stable than that of patients who underwent small-size CTR implantation.For patients with an axial length>30mm,large-size CTR implantation is recommended.
9.HPLC fingerprint and three main components determination of Modified Zengye Decoction
Shiqi LIU ; Chuang WU ; Zhimin ZHU ; Feng XU ; Yaowen CHANG ; Haiyan ZHANG ; Xiaojun GOU
China Pharmacist 2024;27(6):928-936
Objective To establish a method for HPLC fingerprint analysis and determine three main components of Modified Zengye Decoction.Methods The chromatographic column was Shimadzu WondaSil C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-0.3%aqueous phosphoric acid with a gradient elution procedure,the volume flow rate was 1.0 mL/min,the detection wavelengths were 265,203,310 and 290 nm,the column temperature was 25 ℃,and the injection volume was 20 μL.The HPLC fingerprints of the 10 batches of Modified Zengye Decoction were established,and the similarity analysis was performed by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine(version 2012A).The common peaks were identified and assigned,and the contents of the three main components were quantitatively determined.Results There were 17 common peaks in the fingerprints of 10 batches of Modified Zengye Decoction with similarities ranging from 0.872-0.989.The fingerprints recognized peak 9,14 and 17 as ferulic acid,aurantiamarin and harpagoside,respectively.The contents of ferulic acid,aurantiamarin and harpagoside were 0.067 3-0.174 8,0.498 8-1.522 7,0.270 9-0.802 4 mg/g,and the transfer rate were 30.74%-55.63%,11.77%-35.94%,23.15%-68.56%,respectively.Conclusion The established HPLC fingerprint analysis method combined with main components quantitative analysis method can be used for the quality analysis and control of Modified Zengye Decoction with simple analysis method and reliable results.
10.Molecular mechanisms underlying the inflammatory response induced by Cutibacterium acnes biofilms in keratinocytes
Lu PEI ; Nana ZHENG ; Rong ZENG ; Yuanyuan XIE ; Haoxiang XU ; Zhimin DUAN ; Yuzhen LIU ; Min LI
Chinese Journal of Dermatology 2024;57(4):302-308
Objective:To investigate molecular mechanisms underlying the inflammatory response induced by Cutibacterium acnes ( C. acnes) biofilms in human primary keratinocytes. Methods:A C. acnes biofilm model was established in vitro, and confocal fluorescence microscopy was performed to examine its three-dimensional structure. The cultured human primary keratinocytes were divided into 3 groups: a dimethyl sulfoxide (DMSO) control group (treated with 0.01% DMSO alone), a C. acnes suspension group (co-incubated with C. acnes suspensions), and a C. acnes biofilm group (co-incubated with C. acnes biofilms). Real-time fluorescence-based quantitative PCR (RT-qPCR) was performed to determine the relative mRNA expression of interleukin (IL) -6, IL-8, and tumor necrosis factor (TNF) -α in the groups after 6-hour culture, enzyme-linked immunosorbent assay to detect the free protein levels of IL-6, IL-8, and TNF-α in the groups after 24-hour culture, and Western blot analysis to determine the protein expression of Toll-like receptor 2 (TLR2) in keratinocytes. In addition, some human primary keratinocytes were pretreated with key molecular blockers targeting the TLR2/mitogen-activated protein kinase (MAPK) /nuclear factor (NF) -κB signaling pathway (C29, ST2825, BAY11-7082, SB203580, U0126-EtOH), and then co-incubated with C. acnes biofilms; the DMSO control group and the C. acnes biofilm group receiving no pretreatment were simultaneously set as negative and positive controls, respectively. The mRNA and free protein expression levels of IL-6, IL-8, and TNF-α were then detected in the above groups. One-way analysis of variance was used for comparisons among multiple groups, and the Bonferroni method was used for multiple comparisons. Results:Confocal fluorescence microscopy demonstrated a three-dimensional C. acnes biofilm structure resembling a lawn, and the biofilm grew well. RT-qPCR and ELISA showed significant differences in the mRNA and free protein expression levels of IL-6, IL-8, and TNF-α among the C. acnes biofilm group, C. acnes suspension group and DMSO control group (mRNA: F = 89.70, 312.17, 46.09, respectively, all P < 0.001; free protein: F = 886.12, 634.25, 307.01, respectively, all P < 0.001) ; in detail, the mRNA and free protein expression levels of IL-6, IL-8, and TNF-α were significantly higher in the C. acnes biofilm group than in the C. acnes suspension group and DMSO control group (all P < 0.001) ; the C. acnes suspension group showed significantly increased expression levels of IL-6 mRNA and TNF-α free protein compared with the DMSO control group ( P < 0.001, = 0.003, respectively), while there were no significant differences in the expression of IL-6 free protein, TNF-α mRNA, or IL-8 mRNA and free protein between the 2 groups (all P > 0.05). Western blot analysis showed that the TLR2 protein expression was significantly higher in the C. acnes suspension group and C. acnes biofilm group than in the DMSO control group. After the pretreatment with molecular blockers targeting the MAPK/NF-κB signaling pathway and co-incubation with C. acnes biofilms, the mRNA and free protein expression levels of IL-6, IL-8 and TNF-α were all significantly lower in the C29 group, ST2825 group, BAY11-7082 group, SB203580 group, U0126-EtOH group, as well as in the DMSO control group compared with the C. acnes biofilm group (all P < 0.05) . Conclusion:The C. acnes biofilms exhibited a strong ability to induce inflammatory responses in human keratinocytes, possibly through the activation of the TLR2/MAPK/NF-κB signaling pathway.

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