Effectiveness of a tissue conditioner containing antifungals in a rat model of denture stomatitis.

AIM: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis. METHODS AND RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for 4 days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or ß-cyclodextrin-complexed (ßCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices, one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After 4 days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:ßCD, and Chx groups presented a significant decrease in the microbial load compared with the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group. CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.

Antimicrobial activity of essential oils against biofilms formed in dental acrylic resin: a systematic review of in vitro studies.

This study aimed to answer the question formulated according to the PICO strategy: 'Which essential oils show antimicrobial activity against biofilms formed on dental acrylic resin?' composed by population (dental acrylic resin), intervention (application of essential oils), comparison (denture cleansers, antifungal drugs, chlorhexidine, and oral mouthwashes), and outcome (antibiofilm activity). In vitro experimental studies evaluating the activity of EOs on biofilm formed on acrylic resin were included. PRISMA guidelines were followed, and the search was performed in the PubMed, Science Direct, Embase, and Lilacs databases and in the gray literature using Google Scholar and ProQuest in December 2023. A manual search of the reference lists of the included primary studies was performed. Of the 1467 articles identified, 37 were selected for full-text reading and 12 were included. Twelve EOs were evaluated, of which 11 showed activity against Candida spp., 3 against Staphylococcus aureus, and 1 against Pseudomonas aeruginosa. The EOs of Cymbopogon citratus, Cinnamomum zeylanicum, and Cymbopogon nardus showed higher action than chlorhexidine, C. nardus higher than Listerine, C. citratus higher than nystatin, and Melaleuca alternifolia higher than fluconazole and nystatin. However, chlorhexidine was more effective than Lippia sidoides and Salvia officinalis, sodium hypochlorite was more effective than L. sidoides, nystatin was more effective than Zingiber officinale, Amphotericin B more effective than Eucalyptus globulus and M. alternifolia. In conclusion, the EOs of C. zeylanicum, C. citratus, C. nardus, and M. alternifolia showed antimicrobial activity to reduce biofilm on dental acrylic resin.

Anti-Candida activity and in vitro toxicity screening of antifungals complexed with ß-cyclodextrin.

The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with ß-cyclodextrin (ßCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl-thiazolyl-tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one-way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the ßCD-complexed antifungals were less toxic against A. salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5 mg/L; Nys:ßCD 4 mg/L; Chx 4 mg/L; and Chx:ßCD 8 mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with ßCD might be a biocompatible option for the treatment of Candida-related infections.

"Antimicrobial properties of tissue conditioner modified with chitosan and green-synthesized silver nanoparticles: a promising approach for preventing denture stomatitis".

BACKGROUND: Chitosan is known to inhibit the growth of many bacteria and fungi. Tissue conditioners are commonly used to prevent bone destruction under dentures. However, over time, these materials can become a suitable substrate for microbial growth. One approach to improving dental materials is the use of nanoparticles. This study examined the antifungal properties of chitosan and green technique-synthesized silver nanoparticles in combination with tissue conditioners. METHODS: Tissue conditioner materials were mixed with chitosan and silver nanoparticles at concentrations of 0.097%, 0.19%, and 0.37%, along with 1.25 ppm Nystatin, and their antimicrobial properties against Candida albicans were investigated. The growth rate was measured after 24 h of incubation at 37 °C. Non-parametric tests, such as the Kruskal-Wallis H test and Mann-Whitney U test with Bonferroni correction, were used for data analysis after verifying that the groups did not have a normal distribution. RESULTS: Compared with the control and Nystatin groups, the Chitosan-silver groups showed a significant decrease in the number of CFUs of Candida albicans. CONCLUSIONS: The combination of chitosan and silver nanoparticles with tissue conditioner materials is a promising alternative for preventing and treating denture stomatitis. These findings suggest that using very small amounts of nanoparticles in dental materials could effectively prevent microbial growth, which could improve the longevity and efficacy of dental prosthetics and materials.

Aspergillus welwitschiae; an otomycosis predominant agent, new epidemiological and antifungal susceptibility data from Iran.

BACKGROUND: Black aspergilli (section Nigri) are predominate etiologic agents of otomycosis, however, there is controversy in the exact differentiation of species. For several decades Aspergillus niger is considered the main otomycosis etiologic agent. Recently calmodulin gene has been accepted as a more suitable gene for the accurate assignment of Aspergillus species. Therefore, it is found that A. welwitschiae and A. tubingensis are the main otomycosis agents based on calmodulin gene sequencing. AIMS: The objective of the study was to isolate and identify black aspergilli from otomycosis using the calmodulin gene and their susceptibility was evaluated against several antifungals. METHODS: 134 clinically confirmed patients with otomycosis were sampled and specimens were cultured on Sabouraud dextrose agar (SDA) at ambient temperature. Black aspergilli were screened based on colony morphology on SDA and microscopy features and then subjected to sequencing using calmodulin primers. Moreover, antifungal susceptibility for isolates was applied based on CLSI M38 3rd edition. RESULTS: 132 (98.5%) of patients had positive cultures for different species of molds or yeasts. Most of the patients (30.3%) ranged from 31 to 40 years, and 56.1% of them were female. Aspergillus section Nigri was the most prevalent fungal pathogen and of 86 isolates, 60.5% isolates were identified as A. welwitschiae, A. tubingensis, 31 (36.0%), A. niger (sensu stricto), 2 (2.3%), and A. neoniger 1 (1.2%). According to the maximum likelihood method, all isolates of A. tubingensis and one isolate of A. neoniger were included in the A. tubingensis clade. On the other hand, the clade of A. niger/A. welwitschiae contains, all isolates of A. welwitschiae, two A. niger (sensu stricto) isolates, and 36 isolates from other countries. Aspergillus welwitschiae was more sensitive to luliconazole, voriconazole, and amphotericin B compared to A. tubingensis. 78.8% of A. welwitschiae strains were classified as non-wild type to nystatin compared to 35.5% of A. tubingensis. Moreover, 3.2% of A. tubingensis strains were non-wild type against amphotericin B. The isolates of A. tubingensis were more sensitive to itraconazole than A. welwitschiae. CONCLUSIONS: It is concluded that in contrast, to the previous study A. welwitschiae from section Nigri is the most causative agent of otomycosis followed by A. tubingensis. In addition, the isolates of A. welwitschiae were more sensitive to luliconazole, voriconazole, and amphotericin B compared to A. tubingensis. Whereas, the isolates of A. tubingensis were more sensitive to itraconazole than A. welwitschiae. On the other hand, 78.8% and 35.5% of A. welwitschiae and A. tubingensis strains were classified as a non-wild type against nystatin. Also, 3.2% of A. tubingensis strains were non-wild type against amphotericin B. All A. welwitschiae were included in the A. niger/A. welwitschiae clade, associated with different clinical and environmental species from different countries.

Cyclic and Linear Peptides Containing Alternate WW and RR Residues as Molecular Cargo Delivery Tools.

Cell-impermeable and negatively charged compounds' cellular uptake across the cell membranes remains challenging. Herein, the synthesis of four linear [(WWRR)2, (WWRR)3, (WWRR)4, and (WWRR)5] and four cyclic ([WWRR]2, [WWRR]3, [WWRR]4, and [WWRR]5) peptides containing alternate two tryptophan (WW) and two arginine (RR) residues and their biological evaluation as molecular transporters are reported. The peptides did not show any significant cytotoxicity in different cell lines (MDA-MB-23, SK-OV-3, and HEK 293) at a concentration of 5 µM and after 3 h of incubation time. The uptake of fluorescence-labeled cargo molecules (F'-GpYEEI, F'-siRNA, and F'-3TC) in the presence of the peptides was monitored in different cell lines (SK-OV-3 and MDA-MB-231) with fluorescence-activated cell sorting. Among all the peptides, [WWRR]5 (C4) showed the highest cellular uptake of cargo molecules, indicating it can act as effective molecular transporter. Confocal microscopy in MDA-MB-231 cells showed the cellular uptake of F'-GpYEEI in the presence of C4 and the intracellular localization of fluorescence-labeled C4 (F'-C4) in the cytosol. The F'-C4 cellular uptake was found to be concentration- and time-dependent, as shown by flow cytometry in MDA-MB-231 cells. Confocal microscopy and flow cytometry of F'-C4 in MDA-MB-231 cells were examined alone and in the presence of different endocytosis inhibitors (chlorpromazine, methyl-ß-cyclodextrin, chloroquine, and nystatin). The data showed that the cellular uptake of F'-C4 in the presence of chlorpromazine, chloroquine, and methyl-ß-cyclodextrin was reduced but not completely eliminated, indicating that both energy-independent and energy-dependent pathways contributed to the cellular uptake of F'-C4. Similar results were obtained using the confocal microscopy of C4 and F'-GpYEEI in the presence of endocytosis inhibitors (chlorpromazine, methyl-ß-cyclodextrin, chloroquine, and nystatin). These data indicate that C4 has the potential to be used as a cell-penetrating peptide and cargo transporter.

Emergence of microbial infections in some hospitals of Cairo, Egypt: studying their corresponding antimicrobial resistance profiles.

BACKGROUND: Antimicrobial resistance is one of the ten major public health threats facing humanity, especially in developing countries. Identification of the pathogens responsible for different microbial infections and antimicrobial resistance patterns are important to help clinicians to choose the correct empirical drugs and provide optimal patient care. METHODS: During the period from November 2020 to January 2021, one hundred microbial isolates were collected randomly from different specimens from some hospitals in Cairo, Egypt. Sputum and chest specimens were from COVID-19 patients. Antimicrobial susceptibility testing was performed according to CLSI guidelines. RESULTS: Most microbial infections were more common in males and in elderly people over 45 years of age. They were caused by Gram-negative, Gram-positive bacteria, and yeast isolates that represented 69%, 15%, and 16%, respectively. Uropathogenic Escherichia coli (35%) were the most prevalent microbial isolates and showed high resistance rates towards penicillin, ampicillin, and cefixime, followed by Klebsiella spp. (13%) and Candida spp. (16%). Of all microbial isolates, Acinetobacter spp., Serratia spp., Hafnia alvei, and Klebsiella ozaenae were extremely multidrug-resistant (MDR) and have resisted all antibiotic classes used, except for glycylcycline, in varying degrees. Acinetobacter spp., Serratia spp., and Candida spp. were secondary microbial infections in COVID-19 patients, while H. alvei was a bloodstream infection isolate and K. ozaenae was recorded in most infections. Moreover, about half of Staphylococcus aureus strains were MRSA isolates and reported low rates of resistance to glycylcycline and linezolid. In comparison, Candida spp. showed high resistance rates between 77 and 100% to azole drugs and terbinafine, while no resistance rate towards nystatin was reported. Indeed, glycylcycline, linezolid, and nystatin were considered the drugs of choice for the treatment of MDR infections. CONCLUSION: The prevalence of antimicrobial resistance in some Egyptian hospitals was high among Gram-negative, Gram-positive bacteria, and candida spp. The high resistance pattern -especially in secondary microbial infections in COVID-19 patients- to most antibiotics used is a matter of great concern, portends an inevitable catastrophe, and requires continuous monitoring to avoid the evolution of new generations.

CYP broth: a tool for Yersinia pestis isolation in ancient culture collections and field samples.

We developed a simple new selective LB-based medium, named CYP broth, suitable for recovering long-term stored Y. pestis subcultures and for isolation of Y. pestis strains from field-caught samples for the Plague surveillance. It aimed to inhibit the growth contaminating microorganisms and enrich Y. pestis growth through iron supplementation. The performance of CYP broth on microbial growth from different gram-negative and gram-positive strains from American Type Culture Collection (ATCC®) and other clinical isolates, field-caught rodent samples, and more importantly, on several vials of ancient Y. pestis subcultures was evaluated. Additionally, other pathogenic Yersinia species such as Y. pseudotuberculosis and Y. enterocolitica were also successfully isolated with CYP broth. Selectivity tests and bacterial growth performance on CYP broth (LB broth supplemented with Cefsulodine, Irgasan, Novobiocin, nystatin and ferrioxamine E) were evaluated in comparison with LB broth without additive; LB broth/CIN, LB broth/nystatin and with traditional agar media including LB agar without additive, and LB agar and Cefsulodin-Irgasan-Novobiocin Agar (CIN agar) supplemented with 50 µg/mL of nystatin. Of note, the CYP broth had a recovery twofold higher than those of the CIN supplemented media or other regular media. Additionally, selectivity tests and bacterial growth performance were also evaluated on CYP broth in the absence of ferrioxamine E. The cultures were incubated at 28 °C and visually inspected for microbiological growth analysis and O.D.625 nm measurement between 0 and 120 h. The presence and purity of Y. pestis growth were confirmed by bacteriophage and multiplex PCR tests. Altogether, CYP broth provides an enhanced growth of Y. pestis at 28 °C, while inhibiting contaminant microorganisms. The media is a simple, but powerful tool to improve the reactivation and decontamination of ancient Y. pestis culture collections and for the isolation of Y. pestis strains for the Plague surveillance from various backgrounds. KEY POINTS: • The newly described CYP broth improves the recuperation of ancient/contaminated Yersinia pestis culture collections • CYP broth was also efficient in reducing environmental contamination in field-capture samples, improving Y. pestis isolation • CYP broth can also be used for the isolation of Y. enterocolitica and Y. pseudotuberculosis.

Assessing nystatin cream treatment efficacy against Leishmania (L.) amazonensis infection in BALB/c model.

The current scenario for cutaneous leishmaniasis treatment includes the use of first and second-choice drugs, both therapeutic strategies presenting several adverse effects and being related to an increment of treatment-refractory parasite strains. These facts encourage the search for new treatment approaches, including repositioning drugs, such as nystatin. Although in vitro assays show that this polyene macrolide compound has leishmanicidal activity, no in vivo evidence for a similar activity has been shown so far for the commercial nystatin cream formulation. This work assessed the effects of nystatin cream (25,000 IU/g) administered on mice in an amount to completely cover the paw surface of BALB/c mice infected with Leishmania (L.) amazonensis once a day, until a total of up to 20 doses. The data presented herein points to unequivocal evidence that treatment with this formulation causes a statistically significant reduction of swelling/edema in mice paws when compared to animal groups not submitted to this treatment regimen after the fourth week of infection: lesion sizes at the sixth (p = 0.0159), seventh (p = 0.0079) and eighth (p = 0.0079) week. Furthermore, swelling/edema reduction relates to a decrease in parasite load in the footpad (∼48%) and in draining lymph nodes (∼68%) at eight weeks post-infection. This is the first report of the effectiveness of nystatin cream used as a topical treatment in BALB/c model for cutaneous leishmaniasis.

Otomycosis: The foremost aetiological agent causing otitis externa and the antifungal susceptibility pattern in North-Western Iran.

BACKGROUND: Otomycosis is considered a recurring fungal ear infection. The external auditory canal provides an appropriate and optimal situation for fungal growth. OBJECTIVES: The study aimed to identify the causative agents of otomycosis and determine corresponding antifungal drug susceptibility patterns in north-western Iran. METHODS: From October 2020 until November 2021, 200 patients attended an otolaryngology referral centre with otitis externa, and their ear discharge and debris were examined and cultured. The identification of the fungal agents was implemented by polymerase chain reaction-restriction fragment length polymorphism and sequencing. In vitro antifungal susceptibility testing of the isolates was conducted in accordance with the CLSI broth microdilution protocols. RESULTS: The prevalence of otomycosis was measured 50.5% (n = 101/200). The majority of patients were in their forties (n = 35, 34.6%) and female (n = 57, 56.4%), and the most prevalent symptom was otalgia (56.4%). The most underlying factor was remarked manipulation employing a cotton swab (65.3%). Regarding fungus, Aspergillus section Nigri (58.57%) was the foremost isolate, followed by Aspergillus section Flavi (19.23%) and Candida parapsilosis (14.96%). The predominance of Aspergillus isolates had minimal in vitro sensitivity to tioconazole and nystatin. Candida species represented higher geometric mean minimum inhibitory concentrations (MIC) against nystatin. The MIC of three Aspergillus species isolates shown above the epidemiologic cut-off values (ECV) against itraconazole. CONCLUSIONS: Otomycosis incidence surpassed in comparison with the previous study as the most common cause of otitis externa. The MIC distribution of Aspergillus species isolates against triazole antifungals is close to the defined ECVs and likely outrun it over time.

The Persistence of Nystatin Use for Dermatophyte Infections.

BACKGROUND: Despite the limited use of nystatin for tinea infections, physicians may continue to use it. METHODS: We assessed the National Ambulatory Medical Care Survey for all to determine the extent of topical nystatin use in tinea infections. RESULTS: Topical nystatin was used at 4.3% (2.1%, 6.0%) of all tinea infection visits. It was not used at visits with dermatologists and was most common among family medicine physicians (P=.02). DISCUSSION: Physicians are continuing to use nystatin for the treatment of tinea infections. Dermatologists have discontinued this treatment regimen, whereas other specialties have an opportunity to further improve their knowledge in this regard. J Drugs Dermatol. 2023;22(12):e49-e50.     doi:10.36849/JDD.5606e.

Effects of Nystatin oral rinse on oral Candida species and Streptococcus mutans among healthy adults.

OBJECTIVES: To examine the effect of Nystatin oral rinse on oral Candida species and Streptococcus mutans carriage. MATERIALS AND METHODS: Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, and 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline and 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test. RESULTS: Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p < 0.05). Periodontal status reflected by bleeding-on-probing was significantly improved at 1-week and 3-month follow-ups (p < 0.05). Plaque accumulation was significantly reduced at 1-week follow-up (p < 0.05). Interestingly, the responses to Nystatin oral rinse were not associated with race, gender, age, oral hygiene practice, adherence to Nystatin rinse, or sweet consumption (p > 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokine eotaxin and fractalkine were significantly reduced at 3-month follow-up among participants who responded to Nystatin rinse (p < 0.05). CONCLUSIONS: The study results indicate that oral antifungal treatment had an effect on S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida. CLINICAL RELEVANCE: Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective.

Curcumin nanoparticles: the topical antimycotic suspension treating oral candidiasis.

Phytotherapeutics is widely used nowadays as an alternative to the current antifungal drugs to reduce their side effects. Curcumin, with its wide therapeutic array as antioxidant and anti-inflammatory agent, is one of the natural compounds that ha..s an antifungal effect, especially when being used at nanoscale to increase its bioavailability. Our research aimed to evaluate clinically and microbiologically the effect of using topical nanocurcumin suspension to treat oral candidiasis. After 4 days from induction of oral candidiasis (baseline), we randomly divided 39 female BALB/c mice into three groups of 13 animals; nanocurcumin, nystatin, and sham groups. All animals in nanocurcumin and nystatin groups received topical treatment twice daily for 10 days. Then, we performed clinical and microbiological evaluations at baseline, day 5, and day 10. By the end of treatment, our results revealed that nanocurcumin promoted a significant reduction in the number of candida colonies. There was no statistically significant difference neither clinically nor microbiologically between nanocurcumin and nystatin groups. In conclusion, nanocurcumin has a good antifungal effect as nystatin, however, its therapeutic efficacy takes a longer time to appear than nystatin. The enhanced bioavailability of curcumin at the nanoscale qualifies this nano-herb as a promising alternative therapy for oral candidiasis, evading nystatin-associated morbidity.

Antifungal Properties of Biogenic Selenium Nanoparticles Functionalized with Nystatin for the Inhibition of Candida albicans Biofilm Formation.

In the present study, biogenic selenium nanoparticles (SeNPs) have been prepared using Paenibacillus terreus and functionalized with nystatin (SeNP@PVP_Nystatin nanoconjugates) for inhibiting growth, morphogenesis, and a biofilm in Candida albicans. Ultraviolet-visible spectroscopy analysis has shown a characteristic absorption at 289, 303, and 318 nm, and X-ray diffraction analysis has shown characteristic peaks at different 2θ values for SeNPs. Electron microscopy analysis has shown that biogenic SeNPs are spherical in shape with a size in the range of 220-240 nm. Fourier transform infrared spectroscopy has confirmed the functionalization of nystatin on SeNPs (formation of SeNP@PVP_Nystatin nanoconjugates), and the zeta potential has confirmed the negative charge on the nanoconjugates. Biogenic SeNPs are inactive; however, nanoconjugates have shown antifungal activities on C. albicans (inhibited growth, morphogenesis, and a biofilm). The molecular mechanism for the action of nanoconjugates via a real-time polymerase chain reaction has shown that genes involved in the RAS/cAMP/PKA signaling pathway play an important role in antifungal activity. In cytotoxic studies, nanoconjugates have inhibited only 12% growth of the human embryonic kidney cell line 293 cells, indicating that the nanocomposites are not cytotoxic. Thus, the biogenic SeNPs produced by P. terreus can be used as innovative and effective drug carriers to increase the antifungal activity of nystatin.

Miconazole for the treatment of vulvovaginal candidiasis. In vitro, in vivo and clinical results. Review of the literature.

At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in C. albicans, in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.

Efficacy of photodynamic therapy in the treatment of oral candidiasis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of photodynamic therapy (PDT) as an adjunct or alternative to traditional antifungal drugs in the treatment of oral candidiasis, and to provide evidence-based medical evidence for its use in the treatment of oral candidiasis. METHODS: Computer combined with manual retrieval of China Academic Journals Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Science and Technology Journal Database (VIP), Wanfang Database, PubMed, Web of Science, Cochrane Library, Embase, Scopus retrieval for articles published before January 2023, basic information and required data were extracted according to the inclusion and exclusion criteria, and the Revman V5.4 software was used to conduct Meta-analysis of the included literature. RESULTS: A total of 11 articles were included, 7 of which used nystatin as an antifungal drug, 2 of which were combined treatment of PDT and nystatin, 2 of the remaining 4 articles were treated with fluconazole, and 2 were treated with miconazole. Meta results showed that PDT was superior to nystatin in reducing the number of oral candida colonies in the palate of patients MD = -0.87, 95%CI = (-1.52,-0.23), P = 0.008, the difference was statistically significant, and the denture site MD = -1.03, 95%CI = (-2.21, -0.15), P = 0.09, the difference was not statistically significant; compared with the efficacy of fluconazole, RR = 1.01, 95%CI = (0.56,1.83), P = 0.96; compared with miconazole RR = 0.55, 95%CI = (0.38, 0.81), P = 0.002; PDT combined with nystatin RR = 1.27, 95%CI = (1.06, 1.52), P = 0.01; recurrence rate RR = 0.28, 95%CI = (0.09, 0.88), P = 0.03. CONCLUSIONS: PDT was effective in the treatment of oral candidiasis; PDT was more effective than nystatin for the treatment of denture stomatitis in the palate, while there was no significant difference between the two for the denture site; The efficacy of PDT for oral candidiasis was similar to that of fluconazole; PDT was less effective than miconazole for oral candidiasis; Compared with nystatin alone, the combination of PDT and nystatin is more effective in treating oral candidiasis with less risk of recurrence.

Effect of Nystatin with and without DMAHDM on Antifungal and Mechanical Properties of Acrylic Resins.

PURPOSE: To investigate antifungal and mechanical properties after the impregnation of Dimethyl Amino-ethyl Hexa-decyl Di-methacrylate (DMAHDM) alone or in combination with Nystatin in polymethylmethacrylate. METHODOLOGY: The control group was fabricated by mixing powder and liquid of PMMA at the ratio of 2.5:1 g/mL. The DMAHDM was added to PMMA liquid and were mixed with PMMA powder. The Nystatin (500,000 International Units (IU)) was mixed with PMMA powder, whereby the composite powder was mixed with the DMAHDM-based liquid. The prepared specimens were tested for fungal adhesion testing (at days 1 and 30), impact strength and flexural strength. Oneway ANOVA post-hoc Tukey's test were used for statistical analysis. RESULTS: Statistical analysis for the adhesion assay revealed that the antifungal activities of unaged and aged specimens in experimental groups were statistically significant as compared to control group A. The groups containing DMAHDM with Nystatin have shown statistically reduced flexural strength. The impact strength test revealed that groups containing 20% DMAHDM alone and DMAHDM with Nystatin showed statistically reduced impact strength compared to the control group. CONCLUSION: Antifungal activities of experimental PMMA resin was increased. The addition of DMAHDM alone in PMMA resin has no deleterious effects on impact and flexural strength, however, at higher concentration values were reduced.

FXYD3 facilitates Na+ and liquid absorption across human airway epithelia by increasing the transport capacity of the Na/K ATPase.

Na/K ATPase activity is essential for ion transport across epithelia. FXYD3, a γ subunit of the Na/K ATPase, is expressed in the airway, but its function remains undetermined. Single-cell RNA sequencing and immunohistochemistry revealed that FXYD3 localizes within the basolateral membrane of all airway epithelial cells. To study FXYD3 function, we reduced FXYD3 expression using siRNA. After permeabilizing the apical membrane with nystatin, epithelia pretreated with FXYD3-targeting siRNA had lower ouabain-sensitive short-circuit currents than control epithelia. FXYD3-targeting siRNA also reduced amiloride-sensitive short-circuit currents and liquid absorption across intact epithelia. These data are consistent with FXYD3 facilitating Na+ and liquid absorption. FXYD3 may be needed to maintain the high rates of Na+ and fluid absorption observed for airway and other FXYD3-expressing epithelia.

Prolonged ethanol exposure modulates constitutive internalization and recycling of 5-HT1A receptors.

Alcohol exposure alters the signaling of the serotoninergic system, which is involved in alcohol consumption, reward, and dependence. In particular, dysregulation of serotonin receptor type 1A (5-HT1AR) is associated with alcohol intake and withdrawal-induced anxiety-like behavior in rodents. However, how ethanol regulates 5-HT1AR activity and cell surface availability remains elusive. Using neuroblastoma 2a cells stably expressing human 5-HT1ARs tagged with hemagglutinin at the N-terminus, we found that prolonged ethanol exposure (18 h) reduced the basal surface levels of 5-HT1ARs in a concentration-dependent manner. This reduction is attributed to both enhanced receptor internalization and attenuated receptor recycling. Moreover, constitutive 5-HT1AR internalization in ethanol naïve cells was blocked by concanavalin A (ConA) but not nystatin, suggesting clathrin-dependent 5-HT1AR internalization. In contrast, constitutive 5-HT1AR internalization in ethanol-treated cells was blocked by nystatin but not by ConA, indicating that constitutive 5-HT1AR internalization switched from a clathrin- to a caveolin-dependent pathway. Dynasore, an inhibitor of dynamin, blocked 5-HT1AR internalization in both vehicle- and ethanol-treated cells. Furthermore, ethanol exposure enhanced the activity of dynamin I via dephosphorylation and reduced myosin Va levels, which may contribute to increased internalization and reduced recycling of 5-HT1ARs, respectively. Our findings suggest that prolonged ethanol exposure not only alters the endocytic trafficking of 5-HT1ARs but also the mechanism by which constitutive 5-HT1AR internalization occurs.

Novel Meso-Benzothiazole-Substituted BODIPY-Based AIE Fluorescent Rotor for Imaging Lysosomal Viscosity and Monitoring Autophagy.

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.