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Objective:To analyze types of mucosal candidiasis and drug resistance of relevant pathogens in a dermatology outpatient clinic in Taiyuan.Methods:Clinical data were collected from 172 patients with mucosal candidiasis, who had positive fungal culture results, in the dermatology outpatient clinic of Shanxi Bethune Hospital from 2019 to 2020. Pathogens were identified by a molecular biological approach, and in vitro drug sensitivity test was performed. Results:Among the 172 patients with mucosal candidiasis, 142 (82.6%) had vulvovaginal candidiasis, 24 (14.0%) had candidal balanoposthitis, and 6 (3.5%) had oral candidiasis; 3 patients were aged ≤ 18 years, 155 were aged 19 - 59 years, and 14 were aged ≥ 60 years, and the proportion of patients with vulvovaginal candidiasis significantly differed among the above 3 age groups (2/3, 134/155[86.45%], 6/14, respectively; χ2 = 14.29, P < 0.05) . Molecular biological identification showed that all the 172 isolated strains belonged to the genus Candida, including 165 strains of Candida albicans (95.9%) , 5 strains of Candida glabrata (2.9%) , and 2 strains of Candida parapsilosis (1.2%) ; the sensitivity to common antifungal agents including flucytosine, amphotericin B, fluconazole, itraconazole and voriconazole was 95.9%, 100.0%, 62.2%, 47.1% and 56.4%, respectively. Conclusion:In the dermatology outpatient clinic of Shanxi Bethune Hospital, vulvovaginal candidiasis was the most common type of mucosal candidiasis, and the main pathogen was Candida albicans; the Candida isolates showed high sensitivity to flucytosine and amphotericin B.
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
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Bibenzyls, a kind of important plant polyphenols, have attracted growing attention for their broad and remarkable pharmacological activities. However, due to the low abundance in nature, uncontrollable and environmentally unfriendly chemical synthesis processes, these compounds are not readily accessible. Herein, one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes. Three types of efficiently post-modifying modular strains were engineered by employing methyltransferases, prenyltransferase, and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules. Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes. Especially, a prenylated bibenzyl derivative ( 12) was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke. RNA-seq, quantitative RT-PCR, and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor, mitochondria associated 3 (Aifm3), suggesting that Aifm3 might be a new target in ischemic stroke therapy. This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.
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Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability are hallmark features of several neurological disorders, including traumatic brain injury (TBI). However, there is no viable therapeutic strategy to rescue BBB function. Tissue inhibitor of metalloproteinase-1 (TIMP1) has been considered to be beneficial for vascular integrity, but the molecular mechanisms underlying the functions of TIMP1 remain elusive. Here, we report that TIMP1 executes a protective role on neuroprotective function ameliorating BBB disruption in mice with experimental TBI. In human brain microvessel endothelial cells (HBMECs) exposed to hypoxia and inflammation injury, the recombinant TIMP1 (rTIMP1) treatment maintained integrity of junctional proteins and trans-endothelial tightness. Mechanistically, TIMP1 interacts with CD63/integrin 1 complex and activates downstream FAK signaling, leading to attenuation of RhoA activation and F-actin depolymerization for endothelial cells structure stabilization. Notably, these effects depend on CD63/integrin 1 complex, instead of the MMP-inhibitory function. Together, our results identified a novel MMP-independent function of TIMP1 in regulating endothelial barrier integrity. Therapeutic interventions targeting TIMP1 and its downstream signaling may be beneficial to protect BBB function following brain injury and neurological disorders.
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Objective To analyze the precipitating factors for,clinical manifestations of,laboratory findings in and therapeutic effect on acute urticaria.Methods Clinical data were collected from 185 inpatients with acute urticaria in Shanxi Dayi Hospital from January 2013 to December 2016.Clinical features,laboratory examination results,treatment,prognosis and adverse reactions were analyzed retrospectively.Statistical analysis was carried out by chi-square test.Results There were 63 male patients and 122 female patients in this study,with an average age at onset of 32.87 ± 14.18 years.Of the 185 patients,78 (42.2％) were able to report the aetiological agents accurately,33 (17.8％) were induced by infection or drug therapy following infection,and 82 (44.3％) had fever.Blood cell analysis showed increased white blood cell count in 132 (71.4％) cases and increased proportion of neutrophils in 128 (69.2％) cases.The level of C reactive protein increased in 118 (69％) of 171 cases.A total of 185 patients received routine anti-anaphylactic treatment.Of 183 cured patients,153 (83.6％) were treated with antibiotics,26(14.2％)with antibiotics alone,and 24(13.1％) with azithromycin.There were 127 (69.4％) patients receiving combined treatment with glucocorticoids,antibiotics,and so on,and the antibiotic used in 111 (60.7％) cases was azithromycin.Of 88 cured patients with simultaneous signs of infection,85 (96.6％) showed increased levels of part or all of infection markers (including the white blood cell count,proportion of neutrophils and level of C reactive protein),and 69 (78.4％) were treated with azithromycin.Of 95 cured patients without signs of infection,83 (87.4％) showed increased levels of infection markers,and 61 (64.2％) were treated with azithromycin.Moreover,there were significant differences in the proportion of patients with increased levels of infection markers and that of patients treated with azithromycin between the cured patients with and without signs of infection (x2 =5.164,4.476,both P ＜ 0.05).Conclusions Infection is a common cause of acute urticaria,and laboratory examinations including white blood cell count,proportion of neutrophils and level of C reactive protein are of important reference value to the diagnosis of infection in patients with acute urticaria.Patients with signs of infection or increased levels of infection markers need to be treated with combined anti-infective therapy,and in the cured patients,the proportion of patients administrating azithromycin was higher than that of those administrating other antibiotics for the treatment of acute infectious urticaria.
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Objective To study the effects of different stimulators on the production of matrix metalloproteinases (MMPs) by peripheral blood mononuclear cells (PBMCs),and to evaluate the effects of the culture supernatant of activated PBMCs,named conditioned media (CM),on the proliferation of and production of MMPs by cultured human fibroblasts.Methods PBMCs were isolated from the venous blood samples of healthy volunteers and divided into three groups to be stimulated by phytohemagglutinin (PHA group),the combination of antibodies against CD3 and CD28 (double-antibody group),or the RPMI 1640 medium containing 10％ fetal calf serum (control group).After 72-hour stimulation,CM was collected from all the three groups,diluted to several different degrees.Cultured human fibroblasts were classified into several groups to be treated with different dilutions of CM from the three groups for 48 or 24 hours,with the fibroblasts untreated with CM serving as the control group.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cellular proliferative activity,semi-quantitative reverse transcription (RT)-PCR to detect the expressions of MMP-1,MMP-3 and MMP-9 mRNAs in cells,and enzyme-linked immunosorbent assay (ELISA) to measure the levels of interleukin (IL)-6,MMP-1,MMP-3 and MMP-9 proteins in the culture supernatant of cells.Statistical analysis was carried out mainly by using one-way analysis of variance (ANOVA),Tukey HSD test,and GamesHowell test.Results Compared with the control group,the PHA group showed increased cellular proliferative activity,IL-6 and MMP-3 protein levels in the culture supernatant of activated PBMCs (all P ＜ 0.05).Significant differences were observed among the PHA group,double-antibody group and control group in the relative mRNA expression level (expressed as the ratio of target mRNA to β-actin mRNA) of MMP-1 in activated PBMCs (0.083 ± 0.016 vs.0.188 ± 0.030 vs.0.714 ± 0.104,F =85.905,P ＜ 0.05),but neither MMP-3 nor MMP-9 mRNA was expressed by activated PBMCs.MMP-3 protein was detectable in the culture supernatant of fibroblasts after the treatment with CM,and the level of MMP-3 protein was highest in that of fibroblasts treated with undiluted CM,and lowest with 1/10 diluted CM;at the same dilutions,the level of MMP-3 protein was highest in the culture supernatant of fibroblasts treated with CM from the PHA group,but lowest with that from the control group.Neither MMP-1 nor MMP-9 protein was detected in the culture supernatant of activated PBMCs or treated fibroblasts.There were no significant differences in cellular proliferative activity of and mRNA expressions of MMP-1 or MMP-3 in fibroblasts among these groups (all P ＞ 0.05),and MMP-9 mRNA expression was undetected in the treated fibroblasts.Conclusions PBMCs can be induced to express MMP-1 mRNA and secret MMP-3 protein after activation.However,the culture supernatant of activated PBMCs has no capacity to stimulate the expressions of MMP-1,MMP-3 and MMP-9 mRNAs or proteins by fibroblasts,suggesting that inflammatory cells may function through self-production of MMPs.
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Objective To investigate the role of infiltrating inflammatory cells in photoaging process by comparing the type and number of these cells in sun-exposed and-unexposed skin.Methods The expression of CD3,CD45RO and CD68 were detected by immunohistochemieal staining in 46 paraffin-embeded skin samples from the extensor forearms(sun-exposed)and upper-inner arms(sun-unexposed) of 23 healthy female volunteers.The number of positive cells in sun-exposed and -unexposed sites was counted and statistically tested by paired samples t test,and Pearson correlation analysis was performed to assess the relationship between the number of positive cells and age of these volunteers.Results The number of cells positive for CD3,CD45RO and CD68 per square millimetre in sun-exposed skin was significantly higher than that in sun-unexposed skin(48.91±13.173 vs.40.61±11.571,46.83±12.915 vs.38.00±10.109,85.43±22.346 vs.73.48±16.208,respectively,P<0.01 or 0.05).The number of cells positive for CD3 and CD45RO increased significantly with age (r=0.557,0.555,respectively,both P<0.01) in the sun-exposed skin but not in sun-unexposed skin,and the number of CD68-positive cells was uncorrelated with age in either sunexposed or -unexposed skin.Conclusion T lymphocytes and macrophages may play a role in the process of photoaging.
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Objective To study the expression of matrix metalloproteinase(MMP)-1,-3 and-9 in sun-exposed and-unexposed skin as weil as its significance in the mechanism of skin photoaging.Methods Skin samples were resected from the exmnsor side of forearm(sun-exposed area)and flexor side of upper arm(sun-unexposed area)of 23 healthy female volunteers.The expression of MMP-1,-3 and-9 was detected by immunohistochemical staining in 46 skin samples.Immunoreactive intensity distribution index (IRIDI)was calculated to assess the expression of MMP-1,-3 and-9.Wilcoxon signed ranks test,Mann-Whitney U-test and Spearman rank correlation analysis were performed.Results MMP-1,-3 and-9 were expressed in both sun-exposed and -unexposed skin.The average IRIDI value for MMP-1,-3 and-9 was 7.70(range,3 to 12).9.22(range,6 to 12),8.30(range,6 to 12)in sun-exposed skin,and 4.26 (range,2 to 6),5.39(range,2 to 9),4.04(range,1 to 6)in sun-unexposed skin,respectively;significant difierence existed between sun.exposed and-unexposed skin in the three parameters(all P＜0.01).A significant inerease was observed in the average IRIDI value for MMP-1,-3 and-9 in sun-exposed skin vs.sun-unexposed skin in women above 50 years of age (9.17 vs 4.75,10.58 vs 6.42,8.92 vs 4.33,respectively,all P＜0.05).In women younger than 50 years,the average IRIDI value for MMP-1,-3 and-9 was 6.09(range,3 to 8),7.73(range,6 to 9),7.64(range,6 to 12)in sun-exposed skin,significantly higher than that in sun-unexposed skin[3.73(range,2 to 6),4.27(range,2 to 8),3.73(range,1 to 6),all P＜0.05].Increased IRIDI scores of MMP-1,-3 and -9 were noticed in sun-exposed skin in women above 50 years of age vs.those younger than 50 years.but there was no statistical difrerence in MMP-I or MMP-9 between the two aged groups in sun-unexposed skin(all P＞0.05).The IRIDI scores of MMP-1,MMP-3 and MMP-9 were positively correlated with age(r=0.66,0.69,0.74,all P＜0.01)in sun-exposed skin,but the IRIDI scores of MMP-1 and MMP-9 uncorrelated with age in sun-unexposed skin.Conclusions There isan elevated expression of MMP-1,-3 and.9 in sun-exposed skin VS.SUn.unexposed skin.hinting that these three MMPs play a role in the occurrence and development of photoaging,but their biological mechanism may be different.
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Objective To summarize the experience with adapalene in the treatment of ache vulgaris and to provide a clue to improve the clinical use of adapalene in ache vulgaris. Methods Chinese literature over the past ten years related to the evaluation of efficacy and safety of 0.1% adapalene gel in acne vulgaris were searched and assessed. Results Combination therapy with 0.1% adapalene was more effective than monotherapy with it. The efficacy of adapalene gel was higher than that of non-tretinoin topical agents, but equivalent to that of other tretinoins. Furthermore, the incidence of adverse events was lower for adapalene than for other tretinoin formulations. Conclusions Adapalene is safe and effective for the treatment of mild to moderate acne vulgaris, and can be used as monotherapy, maintenance treatment, or in combination therapy of acne vulgaris.
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Objective To analyse the clinical and therapeutic features as well as laboratory findings in bullous pemphigoid with non-bullous lesions as initial manifestation. Methods Clinical data on 34 cases of bullous pemphigoid with non-bullous lesions as initial manifestation were retrospectively analyzed. Results The male to female ratio was 1.83 :1, with a mean age of onset at 59.79±15.63 years. Before typical bullae appeared, patients presented with erythema, papules, papulovesicles' plaques" wheals, nodules,or erythema muitiforme-like lesions, with the most common lesions being erythematous papules and plaques (occumng in 35.29% of these patients). Conclusions Among these patients, nearly 1/3 displayed various skin lesions at the onset; simultaneous erythematous papules and plaques are the most common initial manifestation.
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Objective To investigate the mechanism of abnormal epidermal proliferation induced by psoriatic T lymphocytes.Methods Skin organ culture was established with psoriatic T cells mixed with epi-dermal cells.The expressions of c-myc,bcl-2and p53protein were examined with immunohistochemical method in epidermis before culture,on the3rd day and the6th day after culture.Results Significant up-regulation of c-myc and p53protein was found in psoriatic lesions,but bcl-2protein expression was rarely observed.The expressions of those proteins were normal in non-lesional psoriatic skin.The p53protein ex-pression was increased in normal skin and non-lesional psoriatic skin on the3rd day after culture with psori-atic T cells,and c-myc protein expression was enhanced while bcl-2was decreased on the6th day of co-culture.There was no significant difference of those proteins' expression between normal skin and non-lesion-al psoriatic skin stimulated by psoriatic T cells.Conclusions The abnormal expressions of c-myc,bcl-2and p53protein play an important role in abnormal epidermal proliferation and differentiation in psoriasis.Psoriatic T lymphocytes can influence c-myc,bcl-2and p53protein expression in normal skin and non-le-sional psoriatic skin.Pathogenic T cells rather than keratinocytes might be vital for initiation of psoriasis.