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1.
Acta Pharmaceutica Sinica ; (12): 643-650, 2024.
Article in Chinese | WPRIM | ID: wpr-1016629

ABSTRACT

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC80 = 32 μg·mL-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

2.
Chinese Journal of Dermatology ; (12): 161-164, 2023.
Article in Chinese | WPRIM | ID: wpr-994457

ABSTRACT

Dermatomyositis, a common autoimmune disease in clinical practice, often involves muscles and lungs, and can be complicated by malignant tumors, and the lung involvement can be fatal. Therefore, early diagnosis and treatment of dermatomyositis is of great benefit for the reduction of muscle and lung injury, early recognition and management of malignant tumors, and improvement of prognosis and survival rate of patients. However, the heterogeneity and various clinical manifestations of dermatomyositis pose challenges to early diagnosis. This article describes risk factors for dermatomyositis complicated by rapidly progressive pulmonary interstitial fibrosis, dysphagia or malignant tumors, and proposes a mode of "rashes + nailfold capillary abnormalities + myositis antibodies" for the early diagnosis of dermatomyositis, early recognition of important visceral injury and tumors, and early management, in order to improve overall survival rate of patients.

3.
Journal of Experimental Hematology ; (6): 1469-1474, 2023.
Article in Chinese | WPRIM | ID: wpr-1009998

ABSTRACT

OBJECTIVE@#To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.@*METHODS@#Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.@*RESULTS@#The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.@*CONCLUSION@#Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.


Subject(s)
Humans , Child , Female , Fibrinogen/genetics , Pedigree , Afibrinogenemia/genetics , Mutation , Blood Transfusion
4.
China Journal of Orthopaedics and Traumatology ; (12): 798-803, 2023.
Article in Chinese | WPRIM | ID: wpr-1009139

ABSTRACT

OBJECTIVE@#To evaluate the needle puncture safety and clinical efficacy of manual reduction combined with external fixation of ankle frame in the treatment of trimalleolar fracture under the guidance of Chinese Osteosynthesis (CO) theory.@*METHODS@#The clinical data of 118 patients with trimalleolar fractures admitted from December 2010 to December 2021 were retrospectively analyzed. Fifty-three patients were treated with manual reduction combined with external fixation of ankle frame(observation group). Sixty-five patients were treated with open reduction and internal fixation with plate and screws(control group). The operation time, hospitalization days, non-weight-bearing time of the affected limb, clinical healing time of fracture, incidence of complications, visual analogue scale (VAS) before and 1 month after operation, and American Orthopedic Foot and Ankle Society(AOFAS) score of ankle joint before and 1 year after operation were compared between the two groups.@*RESULTS@#Patients in both groups were followed up for more than 1 year. All patients were followed up, and the duration ranged from 14 to 70 months, with an average of(35.28±14.66) months. There were statistically significant in operation time, hospitalization days, non-load-bearing time of affected limbs, clinical healing time of fractures and VAS score one month after operation between the two groups. One month after operation, the VAS score of the observation group was lower than that of the control group(t=3.343, P=0.001). The operation time of the observation group was significantly shorter than that of the control group(t=9.091, P=0.000). The hospitalization days in the observation group were significantly less than those in the control group(t=5.034, P=0.000). The non-load-bearing time of the affected limb in the observation group was significantly shorter than that in the control group(t=11.960, P=0.000). The clinical healing time of fracture in the observation group was significantly shorter than that in the control group(t=4.007, P=0.000). There was no significant difference in AOFAS score between the two groups one year after operation(t=0.417, P=0.678). In the observation group, there were 2 cases of pinhole infection and 3 cases of loss of reduction less than 2 mm. There were 3 cases of surgical incision infection in the control group. There was no significant difference in the incidence of complications between the two groups(χ2=0.446, P=0.504).@*CONCLUSION@#Manual reduction combined with external fixation is safe and effective in the treatment of trimalleolar fracture under the guidance of CO theory, and the function of ankle joint recovers well after operation. This therapy has good clinical value.


Subject(s)
Humans , Ankle Fractures/surgery , Ankle Joint/surgery , East Asian People , External Fixators , Lower Extremity , Retrospective Studies , Manipulation, Orthopedic/methods , Fracture Fixation/methods , Open Fracture Reduction/methods , Fracture Fixation, Internal/methods
5.
Chinese Journal of Dermatology ; (12): 1019-1020, 2022.
Article in Chinese | WPRIM | ID: wpr-957776

ABSTRACT

Pseudoangioedema, a new type of skin lesions of dermatomyositis, is characterized by localized or diffused, non-pitting, non-pruritic edema on the face, lips, and limbs, with or without erythema. Most dermatomyositis patients with pseudoangioedema are positive for anti-transcriptional intermediary factor 1γ antibodies, and experience severe muscle injuries, increase of serum creatine kinase levels, and refractory dysphagia. A small number of dermatomyositis patients with pseudoangioedema are positive for anti-melanoma differentiation-associated gene 5 antibodies, and have lung involvement. Therefore, high attention should be paid to the occurrence of pseudoangioedema in patients with dermatomyositis, and the screening of specific antibodies can facilitate early diagnosis and differential treatment, as well as improvement in symptoms and survival rates.

6.
Chinese Journal of Medical Education Research ; (12): 1458-1461, 2022.
Article in Chinese | WPRIM | ID: wpr-955689

ABSTRACT

Objective:To explore the application value of humanistic literacy and clinical practice ability training in postgraduate courses of geriatrics.Methods:Postgraduates in Zhejiang University School of Medicine were taken as research objects. The teaching curriculum combining humanistic literacy and clinical practice ability training was set as the course of experimental group, and the teacher-led teaching course was set as the course of control group. The questionnaire survey was conducted to the evaluate the teaching effect among the postgraduates from three aspects: classroom situation, knowledge application and ability training. SPSS 17.0 was used for t-test. Results:The teaching of combining humanistic literacy and clinical practice ability training in classroom atmosphere, participation, teacher-student communication, helping memory, knowledge comprehension, knowledge application, collaboration ability, expression ability, organizational ability, knowledge acquisition ability, and autonomous learning ability scores of the experimental group were (3.96±0.20), (3.92±0.28), (3.75±0.44), (3.92±0.28), (3.96±0.20), (3.96±0.20), (3.83±0.38), (3.92±0.28), (3.79±0.41), (3.88±0.34), and (3.83±0.38), which were better than those of the control group, especially in classroom atmosphere, participation, knowledge application, expression ability, and autonomous learning ability.Conclusion:The combination of humanistic literacy and clinical practice ability training can significantly improve the classroom atmosphere of geriatric postgraduate courses, enhance students' medical humanistic literacy, familiarize students with the core skills of geriatrics, and improve students' ability to express and learn independently.

7.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 142-145, 2022.
Article in Chinese | WPRIM | ID: wpr-935763

ABSTRACT

A patient with paraquat poisoning was followed up for five years, and it was showed that the interstitial lesion areas in chest CT of this patient gradually decreased after acute period of the poisoning and no significant changes were found six months later. After that the density of the lesions gradually reduced, while the cystic air cavities slowly increased. In addition, the patient's exercise endurance gradually improved over time, and the lung function was close to the normal level five years after poisoning. The follow-up report helps clinicians to have a deeper understanding of the long-term outcome of paraquat poisoning.


Subject(s)
Humans , Follow-Up Studies , Lung/pathology , Paraquat , Poisoning , Tomography, X-Ray Computed
8.
Chinese Journal of Dermatology ; (12): 308-315, 2022.
Article in Chinese | WPRIM | ID: wpr-933549

ABSTRACT

Objective:To determine classification and clinical features of morphea.Methods:A retrospective analysis was conducted on epidemiological information about clinical manifestations of and laboratory data from 180 patients with morphea, who visited Zhongshan Hospital, Fudan University from January 2010 to July 2021. Two-independent-sample t test was used to compare the age at onset between genders, and chi-square test to analyze differences in clinical characteristics between different genders and subtypes. Results:Among the 180 patients, 123 were females and 57 were males, with a male-to-female ratio of 1∶2.16. The age at onset of morphea was 28.69 ± 17.97 years for female patients, and 29.90 ± 20.67 years for male patients. Among them, linear morphea was the most common type in this study (68 cases, 37.78%), followed by plaque morphea (63 cases, 35.00%), mixed morphea (28 cases, 15.56%) and deep morphea (21 cases, 11.67%). The disease occurred in all age groups, but the age at onset significantly varied among different clinical subtypes ( F = 5.95, P < 0.001). No significant difference was observed in the age at onset or proportion of clinical subtypes between genders ( F = 0.15, P = 0.696; χ2 =2.88, P = 0.410). Atrophoderma of Pasini and Pierini (APP) was very common (62 cases, 34.44%) in the 180 patients, which mainly manifested as plaques or linear lesions, and 26 out of 45 patients with plaque APP and 11 out of 17 with linear APP were both accompanied by other subtypes of morphea. Among the 75 patients tested for autoantibody profiles, 34 (45.33%) presented with positive results. More diverse types of autoantibodies were found in female patients compared with male patients, and antinuclear antibodies, anti-SSA and anti-SSB antibodies were the most common types. There were various types of comorbidities in female patients, but lichen sclerosus et atrophicus and vitiligo were the most common comorbidities in both genders. Conclusion:High incidence and frequent co-occurrence with other subtypes of APP may be the characteristics of Chinese patients with morphea, and it is recommended to classify morphea into plaque, linear, deep and mixed subtypes.

9.
Chinese journal of integrative medicine ; (12): 116-123, 2022.
Article in English | WPRIM | ID: wpr-922576

ABSTRACT

OBJECTIVE@#To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H@*METHODS@#Sprague-Dawley rats were exposed to H@*RESULTS@#The morphological investigation showed that XBJ attenuated H@*CONCLUSIONS@#XBJ ameliorated H


Subject(s)
Animals , Rats , Claudin-5 , Drugs, Chinese Herbal , Endothelial Cells , Hydrogen Sulfide , Phosphatidylinositol 3-Kinases , Rats, Sprague-Dawley , Respiratory Distress Syndrome, Newborn/drug therapy
10.
Braz. J. Pharm. Sci. (Online) ; 58: e19685, 2022. graf
Article in English | LILACS | ID: biblio-1383966

ABSTRACT

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Integrins/analysis , Keratinocytes/classification , Patients/classification , Psoriasis/pathology , Blotting, Western/instrumentation , Cytokines/agonists , Interleukins/analysis
11.
Chinese Journal of Dermatology ; (12): 639-641, 2021.
Article in Chinese | WPRIM | ID: wpr-911500

ABSTRACT

Seborrheic dermatitis-distributed dermatomyositis, a special type of dermatomyositis, is characterized by facial seborrheic dermatitis-distributed rashes, usually accompanied by Gottron papules, inverse Gottron papules, mechanic′s hands and skin ulcers, seldom accompanied by muscle involvement. Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients with seborrheic dermatitis-distributed dermatomyositis are prone to interstitial lung disease/rapidly progressive interstitial lung disease. Early diagnosis of seborrheic dermatitis-distributed dermatomyositis can be made through the combination of rashes and antibody detection, and early and active combined treatment with glucocorticoids and immunosuppressors can improve the survival rate of patients.

12.
World Journal of Emergency Medicine ; (4): 303-308, 2021.
Article in English | WPRIM | ID: wpr-904312

ABSTRACT

@#BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

13.
Chinese Journal of Hepatobiliary Surgery ; (12): 114-117, 2021.
Article in Chinese | WPRIM | ID: wpr-884624

ABSTRACT

Objective:To study the use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma.Methods:A retrospective analysis of clinical data was conducted on patients with hilar cholangiocarcinoma admitted to the Department of General Surgery, the First Affiliated Hospital of the University of Science and Technology of China from January 1, 2017 to July 31, 2019. The classification of hilar cholangiocarcinoma, vascular invasion and surgical resectability were determined by preoperative three-dimensional reconstruction. These data were then compared with the findings obtained during operations, by comparing with the three-dimensional reconstruction technology findings in classification of hilar cholangiocarcinoma, vascular invasion, and hilar extent of biliary and vasculature involvement.Results:Of 65 patients included in this study, there were 35 males and 30 females, with an age of (60.35±10.70) years. After operation, these 65 patients were classified into type I ( n=7), type II ( n=4), type III ( n=14), and type IV ( n=40) using the Bismuth classification. The accuracy rates of preoperative three-dimensional reconstruction for hilar cholangiocarcinoma classification, portal vein invasion, hepatic artery invasion, and diagnosis of hilar cholangiocarcinoma vasculature involvement were 90.7% (59/65), 90.7% (59/65), 86.1% (56/65) and 80.0% (52/65) respectively. Conclusions:The three-dimensional computer reconstruction technology could visually and accurately display the shape and spatial extent of hilar cholangiocarcinoma. It has an important clinical use in accurately diagnosing hilar cholangiocarcinoma preoperatively.

14.
International Journal of Traditional Chinese Medicine ; (6): 511-516, 2021.
Article in Chinese | WPRIM | ID: wpr-882618

ABSTRACT

The clinical effect of Traditional Chinese Medicine (TCM) in the treatment of primary bronchial lung cancer is good. To a certain extent, TCM can control the progress of the disease and improve quality of life by the treatment of syndrome differentiation, disease-modified prescription, experience prescription, Chinese patent medicine, TCM injection, acupuncture and acupoint application, which have been combined with chemotherapy. The mechanism of TCM in the treatment of primary bronchial lung cancer mainly includes inhibition of lung cancer cell proliferation, induction of lung cancer cell apoptosis, improvement of body immunity and overcoming chemotherapy resistance.

15.
Chinese Herbal Medicines ; (4): 381-388, 2021.
Article in Chinese | WPRIM | ID: wpr-953636

ABSTRACT

Objective: Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south China. In this study, we aimed to explore its bioactive constituent which contributes to the anti-inflammatory activity. Methods: Polyphenol-enriched and polyphenol-deprived fractions (PRF and PDF, respectively) were separated from the ethanolic extract by HPD300 macroporous resin-based method, and their anti-inflammatory activities were investigated on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats. The possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 cells. Results: Both Folin-Ciocalteu and

16.
Chinese Journal of Traumatology ; (6): 328-332, 2021.
Article in English | WPRIM | ID: wpr-922351

ABSTRACT

PURPOSE@#Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone.@*METHODS@#From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests.@*RESULTS@#A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ@*CONCLUSION@#PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Altitude , China , Decompressive Craniectomy , Drainage , Encephalocele/surgery , Hematoma , Intracranial Hemorrhage, Hypertensive/surgery , Prognosis , Punctures , Retrospective Studies , Treatment Outcome
17.
International Eye Science ; (12): 1125-1129, 2021.
Article in Chinese | WPRIM | ID: wpr-876768

ABSTRACT

@#AIM: To identify pathogenic mutations of <i>CYP4V2</i> gene in two Chinese families with Bietti crystalline corneoretinal dystrophy(BCD)by Sanger sequencing. <p>METHODS: The relevant clinical examination of BCD patients were collected. Peripheral blood of patients and their family members was collected. Then DNA was extracted from peripheral blood, and Sanger sequencing was used to identify mutation sites.<p>RESULTS: Two probands of BCD from different families were collected. All the probands showed progressive decrease of visual acuity and typical crystal-like material deposition could be seen in the fundus. Sanger sequencing showed that proband 1 and her brother and sister all had homozygous mutation of c.802-8_810del17insGC in <i>CYP4V2</i> gene. On the other hand, proband 2 had a compound heterozygous mutation of c.219T>A(p.F73L)and c.802-8_810del17insGC in <i>CYP4V2</i> gene. <p>CONCLUSION: The most common mutation was c.802-8_810del17insGC in Chinese BCD patients. The homozygous c.802-8_810del17insGC mutation was the cause of BCD in the proband 1 family. On the other hand, proband 2 had c.802-8_810del17insGC heterozygous mutation and c. 219T>A(p.F73L)heterozygous missence mutation, all of which affected the normal coding of <i>CYP4V2</i> gene and led to disease.

18.
Chinese Journal of Dermatology ; (12): 66-71, 2020.
Article in Chinese | WPRIM | ID: wpr-870224

ABSTRACT

Systemic sclerosis (SSc) is a rare,chronic connective tissue disease with internal organ fibrosis,and interstitial lung disease (ILD) is the leading cause of death in patients with SSc.The onset of SSc-associated ILD is usually latent,and delayed treatment may lead to rapid progression,and markedly decrease the quality of life and survival rate of patients.This review summarizes approaches to the early diagnosis of SSc-associated ILD and the time-to-treatment,and provides an overview of its treatment,including traditional immunosuppressive agents,newly emerging targeted therapies,hematopoietic stem cell transplantation,lung transplantation,and so on.

19.
Immune Network ; : e26-2020.
Article | WPRIM | ID: wpr-835459

ABSTRACT

Cereblon (CRBN), a negative modulator of AMP-activated protein kinase (AMPK), is highly expressed in the retina. We confirmed the expression of CRBN in ARPE-19 human retinal cells by Western blotting. We also demonstrated that CRBN knock-down (KD) could effectively downregulate IL-6 and MCP-1 protein and gene expression in LPS-stimulated ARPE-19 cells. Additionally, CRBN KD increased the phosphorylation of AMPK/acetyl-coenzyme A carboxylase (ACC) and the expression of heme oxygenase-1 (HO-1) in ARPE-19 cells. Furthermore, CRBN KD significantly reduced LPS-induced nuclear translocation of NF-κB p65 and activation of NF-κB promoter activity. However, these processes could be inactivated by compound C (inhibitor of AMPK) and zinc protoporphyrin-1 (ZnPP-1; inhibitor of HO-1). In conclusion, compound C and ZnPP-1 can rescue LPS-induced levels of proinflammatory cytokines (IL-6 and MCP-1) in CRBN KD ARPE-19 cells. Our data demonstrate that CRBN deficiency negatively regulates proinflammatory cytokines via the activation of AMPK/HO-1 in the retina.

20.
Acta Pharmaceutica Sinica ; (12): 1647-1660, 2020.
Article in Chinese | WPRIM | ID: wpr-823317

ABSTRACT

In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.

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