1.Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis.
Kai-Fan HU ; Ling MO ; Hao ZHANG ; Dan XIA ; Gao-Xiang SHI ; Da-Qiang WU ; Tian-Ming WANG ; Jing SHAO ; Chang-Zhong WANG
China Journal of Chinese Materia Medica 2023;48(6):1578-1588
This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female
;
Animals
;
Humans
;
Mice
;
Candidiasis, Vulvovaginal/drug therapy*
;
Inflammasomes/genetics*
;
Interleukin-18
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
1-Butanol/pharmacology*
;
Fluconazole/therapeutic use*
;
Interleukin 1 Receptor Antagonist Protein/therapeutic use*
;
Mice, Inbred C57BL
;
Candida albicans
;
Cytokines
;
Drugs, Chinese Herbal/pharmacology*
;
Ethanol
;
RNA, Messenger
;
Calcium-Binding Proteins/therapeutic use*
2.Xianglian External Lotion Restored the Sensitivity of Drug-resistant Candida albicans Strains to Fluconazole: a Transcriptomics Study.
Ping WANG ; Zhi-qi FAN ; Rui-qiang FAN
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(12):1505-1509
OBJECTIVETo perform a transcriptomics study in differential genes after Xianglian External Lotion (XEL) induced the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole.
METHODSBroth microdilution antifungal susceptibility test was used to detect minimal inhibitory concentration (MIC) of drug-resistant Candida albicans strains induced by XEL. Transcriptome sequencing (RNA-Seq) was used to determine and compare the transcription of primary drug-resistant Candida aIbicans strains and sensitive strains induced by XEL. High expressed genes and signaling pathways strains were analyzed by gene ontology (GO) method.
RESULTSXEL could induce drug-resistant strains of the 6th generations to recover sensitivity. Transcriptome sequencing showed that, as compared with primary drug-resistant strains, there were 165 genes with up-regulated RPKM index and 144 genes with down-regulated RPKM index after XEL induction. GO analyses found that all genes were mainly classified as GO:0015903 (fluconazole transport).
CONCLUSIONSXEL could induce the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole. By analyzing transcriptomes, authors speculated that XEL could recover strain sensitivity to fluconazole by opening fluconazole transport pathway.
Antifungal Agents ; pharmacology ; therapeutic use ; Candida ; Candida albicans ; drug effects ; genetics ; Candidiasis ; drug therapy ; Drug Resistance, Fungal ; drug effects ; genetics ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluconazole ; pharmacology ; Microbial Sensitivity Tests
3.Comparison of the therapeutic effects of Garcin(®) and fluconazole on Candida vaginitis.
Farzaneh EBRAHIMY ; Mahrokh DOLATIAN ; Fariborz MOATAR ; Hamid Alavi MAJD
Singapore medical journal 2015;56(10):567-572
INTRODUCTIONThis study aimed to determine and compare the effects of garlic tablets (Garcin(®)) and fluconazole on Candida vaginitis in women who presented to a health centre in Koohdasht, Iran, from August 2011 to March 2012.
METHODSThe clinical trial was conducted on 110 married women (aged 18-44 years) who had complaints of itching or a burning sensation in the vaginal area. Candida vaginitis was diagnosed by pH measurement of vaginal secretions, direct microscopic evaluation and Sabouraud dextrose agar cultures of the vaginal discharge. On confirmation of diagnosis, the patients were randomly divided into two groups (n = 55). One group received 1,500 mg of Garcin tablets daily and the other received fluconazole tablets 150 mg daily, over a period of seven days. Four to seven days after the completion of treatment, patients were examined for treatment response and possible side effects.
RESULTSComplaints related to the disease improved by about 44% in the Garcin group and 63.5% in the fluconazole group (p < 0.05). The overall symptoms of the disease (i.e. redness of vulva and vagina, cheesy discharge, pustulopapular lesions and abnormal cervix) improved by about 60% in the Garcin group and 71.2% in the fluconazole group (p > 0.05). Results of microscopic evaluation and vaginal discharge culture showed significant differences before and after intervention in both groups (p < 0.05).
CONCLUSIONThe present study shows that Garcin tablets could be a suitable alternative to fluconazole for the treatment of Candida vaginitis.
Adolescent ; Adult ; Antifungal Agents ; therapeutic use ; Candida ; drug effects ; Candidiasis, Vulvovaginal ; drug therapy ; Female ; Fluconazole ; therapeutic use ; Garlic ; chemistry ; Humans ; Iran ; Plant Extracts ; therapeutic use ; Tablets ; Treatment Outcome ; Young Adult
4.Three Cases of Candidiasis Misidentified as Candida famata by the Vitek 2 System.
Hyun Young KIM ; Hee Jae HUH ; Rihwa CHOI ; Chang Seok KI ; Nam Yong LEE
Annals of Laboratory Medicine 2015;35(1):175-177
No abstract available.
Adult
;
Aged
;
Antifungal Agents/therapeutic use
;
Candida/*genetics/isolation & purification
;
Candidiasis/diagnosis/drug therapy/*microbiology
;
*Diagnostic Errors
;
Female
;
Fluconazole/therapeutic use
;
Humans
;
Infant
;
Lymphoma, T-Cell/diagnosis/microbiology
;
Male
;
Reagent Kits, Diagnostic/*standards
5.First Case of Continuous Ambulatory Peritoneal Dialysis-Related Peritonitis Caused by Cryptococcus arboriformis.
Hyungjun IM ; Jeong Don CHAE ; Minseok YOO ; So Young LEE ; Eun Ju SONG ; Su Ah SUNG ; Young Hwan HWANG ; Jeong Hwan SHIN ; Young Uk CHO
Annals of Laboratory Medicine 2014;34(4):328-331
No abstract available.
Amphotericin B/therapeutic use
;
Antifungal Agents/pharmacology/therapeutic use
;
Cryptococcosis/*diagnosis/drug therapy/microbiology
;
Cryptococcus/classification/drug effects/*isolation & purification
;
DNA, Ribosomal/chemistry/metabolism
;
Fluconazole/therapeutic use
;
Humans
;
Male
;
Microbial Sensitivity Tests
;
Middle Aged
;
Peritoneal Dialysis, Continuous Ambulatory
;
Peritonitis/*diagnosis/etiology
;
Phylogeny
;
Saccharomyces cerevisiae/drug effects/isolation & purification
;
Sequence Homology, Nucleic Acid
6.Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation.
Zhixiang QIU ; Hanyun REN ; Xinan CEN ; Jinping OU ; Weilin XU ; Mangju WANG ; Lihong WANG ; Yujun DONG ; Yuan LI ; Wei LIU ; Yuhua SUN ; Zeyin LIANG ; Qian WANG
Chinese Journal of Hematology 2014;35(7):577-580
OBJECTIVETo investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODSAt the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10⁹/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.
RESULTSOf the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.
CONCLUSIONIntravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.
Administration, Intravenous ; Adolescent ; Adult ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Female ; Fluconazole ; administration & dosage ; therapeutic use ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Mycoses ; etiology ; prevention & control ; Postoperative Complications ; prevention & control ; Treatment Outcome ; Voriconazole ; administration & dosage ; therapeutic use ; Young Adult
7.Case 136th--intermittent fever for over 20 days and coughing for 2 days.
Sainan SHU ; Sanqing XU ; Yaqin WANG ; Feng YE ; Hua ZHOU ; Feng FANG
Chinese Journal of Pediatrics 2014;52(1):72-74
Amphotericin B
;
administration & dosage
;
therapeutic use
;
Antifungal Agents
;
administration & dosage
;
therapeutic use
;
Biomarkers
;
blood
;
Child
;
Cough
;
diagnosis
;
drug therapy
;
etiology
;
Cryptococcosis
;
Fever
;
diagnosis
;
drug therapy
;
etiology
;
Fluconazole
;
administration & dosage
;
therapeutic use
;
Humans
;
Lung
;
diagnostic imaging
;
pathology
;
Lung Diseases, Fungal
;
complications
;
diagnosis
;
drug therapy
;
Male
;
Radiography, Thoracic
;
Tomography, X-Ray Computed
8.Treatment of invasive fungal diseases in children.
Chinese Journal of Pediatrics 2013;51(4):241-245
Amphotericin B
;
administration & dosage
;
therapeutic use
;
Antifungal Agents
;
administration & dosage
;
therapeutic use
;
Child
;
Child, Preschool
;
Fluconazole
;
administration & dosage
;
therapeutic use
;
Humans
;
Mycoses
;
drug therapy
;
epidemiology
;
prevention & control
;
Practice Guidelines as Topic
;
standards
9.Clinical analysis of invasive laryngeal mycosis.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(21):1174-1176
OBJECTIVE:
To summarize the clinical datas of thepatients with invasive laryngeal fungal infections in, discuss pathogenesis and treatment methods.
METHOD:
Eleven cases of invasive laryngeal fmycosis who were collected from September 2006 to February 2010 with electronic laryngoscopy, aspirate smear and culture and tissue biopsy for pathological diagnosis, were restrospectively analyzed. Those patients were received iv fluconazole, treatment of Oxygen Atomization of amphotericin B solution and taking itraconazole orally. The hepatic and renal functions of the patients were monitored in the course of treatment.
RESULT:
All the cases were diagnosed of invasive laryngeal mycosis. 1 patient showed liver dysfunction in the second week during treatment. And continuing the treatment after using liver protection drugs. All symptoms of the patients were improved and no recurrence happened during the 1-6 years of follow-up.
CONCLUSION
Invasive laryngeal fmycosis was correlated with occupation exposure, abusing of antibiotics and low immunity. Laryngeal mycosis was Diagnosised mainly depended on the pathological examination. The positive rates of the secretion smear was low. The effects of iv fluconazole, Oxygen Atomization of amphotericin B 2-4 weeks, and 4 weeks of taking itraconazole orally were safety and reliable.
Administration, Oral
;
Amphotericin B
;
therapeutic use
;
Antifungal Agents
;
therapeutic use
;
Chemical and Drug Induced Liver Injury
;
prevention & control
;
Fluconazole
;
therapeutic use
;
Humans
;
Itraconazole
;
therapeutic use
;
Laryngeal Diseases
;
drug therapy
;
etiology
;
pathology
;
Mycoses
;
drug therapy
;
etiology
;
pathology
10.The First Korean Case of Candidemia due to Candida dubliniensis.
Nae YU ; Hye Ryoun KIM ; Mi Kyung LEE
Annals of Laboratory Medicine 2012;32(3):225-228
Candidemia due to uncommon Candida spp. appears to be increasing in incidence. C. dubliniensis has been increasingly recovered from individuals not infected with HIV. Identification of C. dubliniensis can be problematic in routine clinical practice due to its phenotypic resemblance to C. albicans. We report the first case of C. dubliniensis candidemia in Korea, which occurred in a 64-yr-old woman who presented with partial seizure, drowsiness, and recurrent fever. Germ-tube positive yeast that was isolated from blood and central venous catheter tip cultures formed smooth, white colonies on sheep blood agar and Sabouraud agar plates, indicative of Candida spp. C. dubliniensis was identified using the Vitek 2 system (bioMerieux, USA), latex agglutination, chromogenic agar, and multiplex PCR. The blood isolate was susceptible to flucytosine, fluconazole, voriconazole, and amphotericin B. After removal of the central venous catheter and initiation of fluconazole treatment, the patient's condition gradually improved, and she was cleared for discharge from our hospital. Both clinicians and microbiologists should be aware of predisposing factors to C. dubliniensis candidemia in order to promote early diagnosis and appropriate treatment.
Amphotericin B/pharmacology
;
Antifungal Agents/pharmacology/therapeutic use
;
Candida/drug effects/*isolation & purification
;
Candidemia/*diagnosis/drug therapy
;
Catheterization, Central Venous
;
Female
;
Fluconazole/pharmacology/therapeutic use
;
Flucytosine/pharmacology
;
Humans
;
Microbial Sensitivity Tests
;
Middle Aged
;
Pyrimidines/pharmacology
;
Triazoles/pharmacology

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