Platelet-derived biomaterial controls aspergillus fumigatus keratitis by decreasing fungal burden: an in vivo study.

Fungal keratitis is a severe corneal infection characterized by suppurative and ulcerative lesions. Aspergillus fumigatus is a common cause of fungal keratitis. Antifungal drugs, such as natamycin, are currently the first-line treatment for fungal keratitis, but their ineffectiveness leads to blindness and perforation. Additionally, the development of fungal resistance makes treating fungal keratitis significantly more challenging. The present study used platelet-derived biomaterial (PDB) to manage A. fumigatus keratitis in the animal model. Freezing and thawing processes were used to prepare PDB, and then A. fumigatus keratitis was induced in the mice. Topical administration of PDB, natamycin, and plasma was performed; quantitative real-time PCR (qPCR) and histopathologic examination (HE) were used to assess the inhibitory effect of the mentioned compounds against fungal keratitis. The qPCR results showed that PDB significantly decreased the count of A. fumigatus compared to the control group (P-value ≤ 5). Natamycin also remarkably reduced the count of fungi in comparison to the untreated animal, but its inhibitory effect was not better than PDB (P-value > 5). The findings of HE also demonstrated that treatment with PDB and natamycin decreased the fungal loads in the corneal tissue. However, plasma did not show a significant inhibitory effect against A. fumigatus. PDB is intrinsically safe and free of any infections or allergic responses; additionally, this compound has a potential role in decreasing the burden of A. fumigatus and treating fungal keratitis. Therefore, scientists should consider PDB an applicable approach to managing fungal keratitis and an alternative to conventional antifungal agents.

The role of viruses in human acute appendicitis: a systematic literature review.

BACKGROUND: There have been debates about the human appendix function, and while previous research suggested it might be a vestigial organ with no functional significance, recent studies have pointed out that it might have an important role in the immune system. Acute appendicitis (AA) is a common cause of emergency abdominal surgery in the world. Some epidemiologic investigations have found an association between appendicitis and viral infections. In this study, we have reviewed systematically articles to discover viral infections that cause appendicitis and find any possible correlations between the two. METHODS: This systematic review was performed by searching among electronic databases including Web of Science, PubMed, Scopus, and EMBASE on viruses and appendicitis topics. RESULTS: Conducted search leads to 983 results in all databases after the duplicate removal and screening by title, abstract, and full-text based on inclusion criteria lead to 19 studies. There were several assays to detect the viruses, which are thought to be AA causative agents. RT-PCR and immunoassays were the mainstay methods to detect the probable cause. CONCLUSION: Investigations suggested that some viruses including measles virus (MV), influenza virus, dengue fever virus (DFV), human immunodeficiency virus (HIV), human herpesviruses, rotavirus, and adenovirus are associated with acute appendicitis. Despite the available reports, the specific mechanisms behind the relationship between acute appendicitis and viral infections are yet to be understood. Therefore, further investigations are necessary to find out the pathogenesis and pathophysiology of viral complications in appendicitis.

Gastrointestinal mucormycosis: A periodic systematic review of case reports from 2015 to 2021.

BACKGROUND: GI mucormycosis (GI) is a rare but highly lethal infection in patients. There is no single comprehensive review of the literature that demonstrates the various clinical aspects of this infection. METHODS: A structured search of PubMed/Medline was used to collect case reports of GI mucormycosis in patients of all ages published between 2015 and November 2021. RESULTS: Eighty-seven cases were identified through PubMed bibliographic database searches, and final analyses were conducted on 70 adults and ten neonatal patients with GI mucormycosis. Asia had the highest number of reported cases, with 46 (57.5%). Neonatal cases had a mortality rate of 70%, while other cases had a mortality rate of 44%. Corticosteroid therapy and diabetes were the most significant risk factors in patients, while 11% were immunocompetent with no apparent underlying condition. COVID-19 positivity was detected in four adult patients. Moreover, neonatal cases included premature and low-weight infants, metabolic acidosis, and malnutrition. Abdominal pain, fever, and GI perforation were the most common signs of infection, while vomiting occurred in 40% of neonatal cases. In 97% of patients, a histopathologic examination was used to detect infection, whereas culture and molecular methods were used in only 28% and 17% of patients, respectively. Surgery plus anti-infection therapy, anti-infection therapy alone, and surgery alone were used in 61%, 28%, and 11% of patients, respectively. Nonetheless, all neonatal patients underwent surgery. Although used in a small number of patients, posaconazole (30%) and isavuconazole (11%) demonstrated high efficacy in treating patients. CONCLUSION: GI mucormycosis is a rare but highly lethal disease. Treatment of underlying conditions, the use of multiple diagnostic techniques, and appropriate antifungals in conjunction with surgery can all contribute to infection control.

The role of Staphylococcus aureus enterotoxin B in chronic rhinosinusitis with nasal polyposis.

CRS with nasal polyps (CRSwNP) is a multifactorial disease, and various etiological factors like bacterial superantigens are known to develop this disease. Recent studies reported that Staphylococcus aureus nasal colonization was detected in 67% of the patients with CRSwNP. Moreover, it was reported that specific IgE against S. aureus enterotoxins are discovered in almost half of the nasal tissue homogenates from nasal polyps. Thus, investigations have highlighted the role of staphylococcal enterotoxins, especially enterotoxin B (SEB), in pathogenesis of CRSwNP. The destruction of mucosal integrity was reported as a main SEB-related pathogenic mechanisms in CRSwNP. SEB activates Toll Like Receptor 2 and triggers the production of pro-inflammatory cytokines; furthermore, it induces reactive oxygen species and endoplasmic reticulum stress-induced inflammation that may cause epithelial cell integrity disruption and enhance their permeability. SEB-induced Type 2/Th2 pathway results in degranulation of eosinophils, cationic proteins production, and localized eosinophilic inflammation. Furthermore, SEB may be involved in the expression of RORC and HIF-1α in Tregs and by maintaining the inflammation in sinonasal mucosa that could have a main role in the pathogenesis of nasal polyposis. Different in vitro findings were confirmed in animal studies; however, in vivo analysis of SEB-induced nasal polyps and CRS remains unfulfilled due to the lack of appropriate animal models. Finally, after elucidating different aspects of SEB pathogenesis in CRSwNP, therapeutic agents have been tested in recent studies with some encouraging results. The purpose of this article is to summarize the most important findings regarding SEB-induced CRS and nasal polyposis. Video Abstract.

The effect of Ccnb1ip1 insulator on monoclonal antibody expression in Chinese hamster ovary cells.

BACKGROUND: The increasing need for therapeutic monoclonal antibodies (mAbs) entails the development of innovative and improved expression strategies. Chromatin insulators have been utilized for the enhancement of the heterologous proteins in mammalian cells. METHODS AND RESULTS: In the current study the Ccnb1ip1 gene insulator element was utilized to construct a novel vector system for the expression of an anti-CD52 mAb in Chinese hamster ovary (CHO) cells. The insulator containing (pIns-mAb) and control (pmAb) vectors were generated and stable cell pools were established using these constructs. The expression level in the cells created with pIns-mAb vector was calculated to be 233 ng/mL, and the expression rate in the control vector was 210 ng/mL, which indicated a 10.9% increase in mAb expression in pIns-mAb pool. In addition, analysis of mAb expression in clonal cells established from each pool showed a 10% increase in antibody productivity in the highest mAb producing clone derived from the pIns-mAb pool compared to the clone isolated from pmAb pool. CONCLUSIONS: More studies are needed to fully elucidate the effects of Ccnb1ip1 gene insulator on recombinant therapeutic protein expression in mammalian cells. The combination of this element with other chromatin-modifying elements might improve its augmentation effect which could pave the way for efficient and cost-effective production of therapeutic drugs.

Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis.

An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrug-resistant bacteria has severely restricted the application of antibiotics in recent years. Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm. However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients.

An overview of possible pathogenesis mechanisms of Alternaria alternata in chronic rhinosinusitis and nasal polyposis.

Chronic Rhinosinusitis (CRS) is a multifactorial disease, and different etiologies like metabolism and immunity disorders, bacterial superantigens, biofilms, and fungal allergens are known to develop this disease, especially the CRS with nasal polyps. Alternaria alternata (Alternaria) is one of the most prevalent airborne fungal species in the nasal discharge, which might have vigorous immunologic activities in nasal epithelial cells and play an essential role in the pathogenesis of CRS. Moreover, the interaction between this fungus and the innate and adaptive immune systems leads to the development of chronic inflammation. This inflammation may consequently instigate the CRS and nasal polyposis. The attenuation of surfactant protein synthesis or intracellular reserves and mucus hypersecretion could prevent the clearance of Alternaria from sinuses and may be correlated with colonization and re-infection of airborne fungi. Furthermore, higher expression of cathelicidin, thymic stromal lymphopoietin, toll-like receptors, and T helper 2-dominant immune responses can result in an IgE-mediated pathway activation and eosinophils degranulation. Moreover, higher local Alternaria-specific IgE was shown to be correlated with eosinophilic cationic proteins and might relate to nasal polyps. However, the role of genetic and environmental factors affecting CRS and nasal polyposis is not well studied. Likewise, further animal and clinical studies are required to better understand the role of Alternaria in CRS disease. The current article reviews the recent findings around the Alternaria-induced CRS and nasal polyposis.

Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: a systematic review of case reports.

BACKGROUND: Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). METHODS: Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline. RESULTS: Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%). CONCLUSION: CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.

A closer look at pathogenesis of cerebral mucormycosis in diabetic condition: A mini review.

Patients with diabetes are considered a high-risk group involved with cerebral mucormycosis (CM). Due to the potential of Mucorales to invade sinuses and its rapid progression into orbit and retro-orbital areas and even brain, in most cases, CM is fatal in patients with diabetes. In the last few decades, mucormycosis and background conditions responsible for the development of its infections have received a great deal of attention. Dysfunction of innate and adaptive immune system, the increased amount of available nutrition, expression of host factors, and free iron level in plasma in diabetic ketoacidosis are among the topics that have been mostly taken into account so far. Therefore, it is important to clarify the molecular mechanisms that let the Mucorales to involve the patients with diabetes, which even at early stages of diagnosis and treatment, there is minimum chance to control the disease.

Identification of opportunistic and nonopportunistic Exophiala species using high resolution melting analysis.

Exophiala is a genus comprising several species of opportunistic black yeasts. Exophiala species identification by morphological, physiological, and biochemical characteristics is challenging because of the low degree of phenotypic differences between species and its polyphyletic nature. We aimed to develop a high-resolution melting (HRM) assay based on the internal transcribed spacer (ITS) region to differentiate between pairs of clinical and environmental Exophiala species. HRM primers were designed based on the conserved ITS region of five Exophiala species (E. dermatitidis, E. phaeomuriformis, E. heteromorpha, E. xenobiotica, and E. crusticola). Environmental and clinical Exophiala isolates representing these five species (n = 109) were analyzed. The HRM assay was optimized using clinical and environmental reference isolates (n = 22), and then the results were compared with those obtained with nonreference isolates of Exophiala (n = 87) using two designed primer sets. The designed HRM assay was based on the normalized melting peak approach and two primer sets, and successfully distinguished between the five Exophiala species. The HRM1 primer set provided sufficient resolution, with a melting temperature (Tm) difference of approximately 2.5°C among the analyzed species and of approximately 1°C between E. dermatitidis and E. phaeomuriformis. HRM typing results were in agreement with those of ITS-sequence typing (100% sensitivity and specificity). The developed HRM assay can be used to ascertain the identity of Exophiala species, which may differ in clinical significance, with high accuracy. Its application to identify species directly in clinical samples and/or environmental niches may be possible in the future.

Epidemiology, clinical features, diagnosis and treatment of cerebral mucormycosis in diabetic patients: A systematic review of case reports and case series.

BACKGROUND: Patients with diabetes are known as an important high-risk group for cerebral mucormycosis (CM). METHOD: We conducted a structured search using PubMed/MEDLINE to collect both case reports and case series case (ie including at least two patients) onto CM in diabetic patient published between 2000 and March 2020. RESULTS: Forty-five reports of individual cases and eighteen case series articles were included. India accounted for the largest share of reports with 37.7% and 38.8% of individual cases and case series, respectively. Mortality ranged from 0% to 100% in the case series. The overall mortality in the individual cases was 46.3%, and 64.2% of deaths were reported in patients with ketoacidosis diabetes. Facial swelling (53.3%), headache (44.4%), loss of vision (35.5%) and ophthalmoplegia (35.5%) were the most frequently reported clinical symptoms. In all patients except 4 (91.1%), CM was treated surgically; however, in many cases (42%), despite the use of surgery, death occurred. Amphotericin B deoxycholate (AMB) and lipid-based AMB (LAMB) were used as the first lines of treatment for all patients; however, posaconazole, echinocandins, hyperbaric oxygen therapy (HBOT) and deferasirox were used in combination for a number of patients. Posaconazole has been shown to have positive therapeutic effect; however, posaconazole, LAMB and HBOT are not commonly used in low-income and health-challenged countries. CONCLUSION: Cerebral mucormycosis is a rapidly progressive infection in diabetic patients and carries immense morbidity despite early diagnosis and treatment. Low-income countries have had the highest number of reports of the disease in recent years, indicating the need to control diabetes in these countries.

In vitro activities of antifungal drugs against a large collection of Trichophyton tonsurans isolated from wrestlers.

BACKGROUND: Trichophyton tonsurans is the most common agent causing tinea gladiatorum in wrestlers, and limited data on susceptibility profiles of Trichophyton tonsurans are available. OBJECTIVES: We aimed to assess the in vitro activity of the common antifungal drug against a large collection of T tonsurans. MATERIALS/METHODS: The in vitro activities to eight common antifungal drugs (sertaconazole, itraconazole, clotrimazole, fluconazole, butenafine, tolnaftate, terbinafine and griseofulvin) against 128 clinical isolates of T tonsurans strains, obtained from wrestlers with dermatophytosis, were performed according to CLSI M38-A2 broth microdilution document. RESULTS: The geometric mean minimum inhibitory concentration was the lowest for tolnaftate (0.022 µg/mL), followed by itraconazole (0.026 µg/mL), terbinafine (0.033 µg/mL), butenafine (0.088 µg/mL), griseofulvin (0.566 µg/mL), sertaconazole (2.875 µg/mL), clotrimazole (3.419 µg/mL) and fluconazole (12.540 µg/mL). CONCLUSIONS: Evaluation of antifungal susceptibility of dermatophytes showed that tolnaftate and itraconazole were the most effective drugs against T tonsurans and fluconazole had the least effect.

Effect of competition between petroleum-degrading bacteria and indigenous compost microorganisms on the efficiency of petroleum sludge bioremediation: Field application of mineral-based culture in the composting process.

The effect of competition between isolated petroleum-degrading bacteria (PDB) and indigenous compost microorganisms (ICM) on the efficiency of composting process in bioremediation of petroleum waste sludge (PWS) was investigated. After isolating two native PDB (Acinetobacter radioresistens strain KA5 and Enterobacter hormaechei strain KA6) from PWS, their ability for growth and crude oil degradation was examined in the mineral-based culture (MBC). Then, the PDB isolate were inoculated into the composting experiments and operated for 12 weeks. The results showed that the PDB degraded 21.65-68.73% of crude oil (1-5%) in the MBC after 7 days. The PDB removed 84.30% of total petroleum hydrocarbon (TPHs) in the composting bioreactor containing the initial TPH level of 20 g kg-1. Removal of petroleum hydrocarbons (PHCs) in the composting experiments proceeded according to the first-order kinetics. The computed values of degradation rate constants and half-lives showed a better performance of the PDB than ICM for TPHs removal. This finding suggests that simultaneous application of the PDB and ICM in the composting reactors resulted in a decline in the effectiveness of the PDB which is due to competition between them. The study also verified that the capability of PDB in degrading PHCs can be successfully scaled-up from MBC to composting process.

Biodegradation of high concentrations of petroleum compounds by using indigenous bacteria isolated from petroleum hydrocarbons-rich sludge: Effective scale-up from liquid medium to composting process.

The scale-up of petroleum hydrocarbons-rich sludge (PHRS) bioremediation from liquid medium to a composting method bioaugmentated with two indigenous bacteria, capable of degrading high levels of crude oil, was surveyed. After isolating the strains (Sphingomonas olei strain KA1 and Acinetobacter radioresistens strain KA2) and determining their biomass production, emulsification index (E24), bacterial adhesion to hydrocarbon (BATH), and crude oil degradation in liquid medium, they were inoculated into the composting experiments. In liquid medium, the removal rate of crude oil were 67.25, 70.86, 61.77, 42.13, and 27.92%, respectively for the initial oil levels of 1, 2, 3, 4, and 5% after 7 days. Degradation of 10, 20, 30, 40 and 50 g kg-1 concentrations of total petroleum hydrocarbons (TPH) were also calculated to be 91.24, 87.23, 84.69, 74.08, and 60.14%, respectively after a composting duration of 12 weeks. The values of the rate constants (k) and half-lives (t1/2) of petroleum hydrocarbons degradation were 0.083-0.212 day-1 and 3.27-8.35 days for the first-order and 0.003-0.089 g kg-1day-1 and 1.12-6.67 days for the second-order model, respectively. This study verified the suitability of the isolated strains for PHRS bioremediation. Successful scale-up of PHRS bioremediation from a liquid medium to a composting process for degrading high amounts of TPH was also confirmed.

In vitro activity of new azoles luliconazole and lanoconazole compared with ten other antifungal drugs against clinical dermatophyte isolates.

In vitro susceptibilities of 100 clinical dermatophyte isolates belonging to five species from Iran toward lanoconazole and luliconazole were compared with ten other antifungal agents including econazole, itraconazole, miconazole, fluconazole, griseofulvin, butenafine, terbinafine, caspofungin, anidulafungin and tolnaftate. MIC and MEC values were analyzed according to CLSI M38-A2 document. The isolates were previously identified to the species level using PCR-RFLP on ITS rDNA region. The range of luliconazole and lanoconazole minimum inhibitory concentrations (MICs) was 0.016-0.032 and 0.063-1 µg/ml, respectively for dermatophyte species. Luliconazole and lanoconazole revealed potent activity against all dermatophyte isolates. Anidulafungin, caspofungin, and luliconazole showed the best activity with the lowest geometric mean 0.01, 0.016, and 0.018 µg/ml, respectively, followed by tolnaftate (0.06 µg/ml), terbinafine (0.07 µg/ml), itraconazole (0.183 µg/ml), butenafine (0.188 µg/ml), econazole (0.20 µg/ml), lanoconazole (0.24 µg/ml), griseofulvin (1.28 µg/ml), miconazole (2.34 µg/ml) and fluconazole (15.34 µg/ml). The current study demonstrated luliconazole and lanoconazole displayed excellent activity against all dermatophyte isolates, although the majority of dermatophyte isolates showed low susceptibility to griseofulvin and very low to miconazole, and fluconazole.

Immunometabolism Dysfunction in the Pathophysiology and Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint damage. Systemic complications and progressive disability are burdens that lead to a significant socio-economic costs in patients with RA. Current RA biomarkers used in predicting, diagnosing, and monitoring the treatment of the disease have not been very successful. Moreover, only 60% of patients show a satisfactory response to current biological and conventional therapies. Studies on immunometabolism have suggested that dysregulated enzymes, transcription factors, metabolites, and metabolic pathways could be considered potential therapeutic targets for the treatment of RA. Factors such as the high concentration of various intermediate molecules arising from metabolism, hypoxia, lack of nutrients, and other metabolic alterations affect local immune responses and preserve a state of chronic inflammation in synovial tissues. Fortunately, in vitro and in vivo studies have shown that targeting specific metabolic pathways is associated with a decreased level of inflammation. Specifically, targeting metabolic intermediates, such as succinate or lactate, has shown promising clinical outcomes in RA treatment. These findings open an avenue for the identification of novel biomarkers for diagnosis, prognosis, and determining the success of various treatments in RA patients, as well as the discovery of new therapeutic targets.

In Vitro Effect of a High-Intensity Laser on Candida albicans Colony Count.

Introduction: This study assessed the effect of a high-intensity laser on Candida albicans colony count. Methods: This in vitro, experimental study was conducted on standard-strain C. albicans (ATCC18804). Seventy-two samples with two different concentrations of C. albicans (104 cells/mL and 106 cells/mL) were randomly assigned to three groups of control, laser and nystatin. Each group included 12 samples from each concentration. In the nystatin group, 10 cc of nystatin suspension was added to the samples and mixed for 30-60 seconds. In the laser group, the Ga-Al-Ar diode laser with a 940-nm wavelength and 2-W power was irradiated to the samples with 0.4 mm tip diameter in non-contact mode (1-mm distance) at a speed of 1 mm/s. The suspensions in the three groups were cultured on the Sabouraud dextrose agar culture medium and incubated at 37°C for 24 hours. The number of C. albicans colonies was then counted and reported. The three groups were compared by ANOVA and Tukey's test (alpha=0.05). Results: In both concentrations, the mean colony count in the nystatin group was significantly lower than that in the control (P<0.05) and laser (P<0.05) groups. The mean colony count in the laser group was significantly lower than that in the control group (P<0.05). Conclusion: The high-intensity laser with a 940-nm wavelength and 2-W power in non-contact mode can significantly decrease the C. albicans colony count in vitro, but its effect is lower than that of nystatin.

Eugenol: A novel therapeutic agent for the inhibition of Candida species infection.

The high occurrence and mortality rates related to candidiasis emphasize the urgent need to introduce new therapeutic approaches to treat this infection. Eugenol, the main phenolic component of Clove and Cinnamomum essential oil, has been used to inhibit growth and different virulence factors of Candida, including strains with decreased susceptibility to antifungals, particularly fluconazole. The results showed that this compound could bind to Candida membrane and decrease ergosterol biosynthesis, consequently leading to cell wall and membrane damage. Additionally, eugenol not only reduced germ tube formation, which reduces nutrient absorption from host tissues, but it also increased the levels of lipid peroxidation and reactive oxygen species, which induces oxidative stress and causes high permeability in the fungal cell membrane. Eugenol inhibited Candida cells' adhesion capacity; additionally, this compound inhibited the formation of biofilms and eliminated established Candida biofilms on a variety of surfaces. Furthermore, by disrupting fungal cell integrity, eugenol could boost the entry of the antifungal drugs into the Candida cell, improving treatment efficacy. Therefore, eugenol could be used in the clinical management of various presentations of candidiasis, especially mucocutaneous presentations such as oral and vulvovaginal infections. However, further investigations, including in vivo and animal studies, toxicology studies and clinical trials, as well as molecular analysis, are needed to improve formulations and develop novel antifungal agents based on eugenol.

Cinnamomum: The New Therapeutic Agents for Inhibition of Bacterial and Fungal Biofilm-Associated Infection.

Due to the potent antibacterial properties of Cinnamomum and its derivatives, particularly cinnamaldehyde, recent studies have used these compounds to inhibit the growth of the most prevalent bacterial and fungal biofilms. By inhibiting flagella protein synthesis and swarming motility, Cinnamomum could suppress bacterial attachment, colonization, and biofilm formation in an early stage. Furthermore, by downregulation of Cyclic di-guanosine monophosphate (c-di-GMP), biofilm-related genes, and quorum sensing, this compound suppresses intercellular adherence and accumulation of bacterial cells in biofilm and inhibits important bacterial virulence factors. In addition, Cinnamomum could lead to preformed biofilm elimination by enhancing membrane permeability and the disruption of membrane integrity. Moreover, this substance suppresses the Candida species adherence to the oral epithelial cells, leading to the cell wall deformities, damage, and leakages of intracellular material that may contribute to the established Candida's biofilm elimination. Therefore, by inhibiting biofilm maturation and destroying the external structure of biofilm, Cinnamomum could boost antibiotic treatment success in combination therapy. However, Cinnamomum has several disadvantages, such as poor solubility in aqueous solution, instability, and volatility; thus, the use of different drug-delivery systems may resolve these limitations and should be further considered in future investigations. Overall, Cinnamomum could be a promising agent for inhibiting microbial biofilm-associated infection and could be used as a catheter and other medical materials surface coatings to suppress biofilm formation. Nonetheless, further in vitro toxicology analysis and animal experiments are required to confirm the reported molecular antibiofilm effect of Cinnamomum and its derivative components against microbial biofilm.

Clinical presentations, diagnosis, management, and outcomes of renal mucormycosis: An overview of case reports.

Background: Renal mucormycosis (RM) is a rare presentation of invasive mucormycosis with a high mortality rate. There is no single systematic review of the literature that indicates the different clinical aspects of RM. Methods: A systematic search of PubMed/Medline was performed to collect individual case reports of RM in patients of all ages published between 2010 and April 2022. Results: Seventy-one individual cases were detected through PubMed bibliographic database searches, with a final assessment performed on 60 patients with RM. India and Asia had the largest number of reported cases, with 30 (50%) and 42 (70%) reports, respectively. Also, 74 and 26% of the patients with a mean age of 33 years were male and female, respectively. RM showed 44% mortality rate in the analyzed cases. Immunosuppressive agent therapy followed by tissue transplantation (kidney and liver) and diabetes were the most remarkable risk factors in patients. Nevertheless, 22% of the patients were immunocompetent with no apparent underlying condition. COVID-19 positivity was detected in eight adult patients with an 87% mortality rate. The most common signs of infection were fever, flank pain, and oliguria; additionally, isolated RM was reported in 57% of the cases. In 55% of the patients, histopathologic examination alone was sufficient to diagnose RM, whereas molecular methods and culture were used in only 18 and 35% of patients, respectively. Surgery alone, surgery plus anti-infection therapy, and anti-infection therapy alone were used in 12, 60, and 13% of patients, respectively. Furthermore, 15% of the patients died before any treatment. Conclusion: The early diagnosis of RM is necessary. In this regard, the use of molecular-based diagnostic assays can help identify the fungus at the genus and species levels and use an appropriate treatment in the shortest possible amount of time. Because of the increase in antibiotic resistance in recent years, determining microbial susceptibility tests can lead to the better infection management. Additionally, withdrawal of immunosuppressant, appropriate surgical intervention, and antifungal therapy are the main factors associated with a successful outcome in RM.