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.

Global prevalence of mutation in the mgrB gene among clinical isolates of colistin-resistant Klebsiella pneumoniae: a systematic review and meta-analysis.

Background: Colistin is used as a last resort for managing infections caused by multidrug-resistant bacteria. However, the high emergence of colistin-resistant strains has restricted the clinical use of this antibiotic in the clinical setting. In the present study, we evaluated the global prevalence of the mutation in the mgrB gene, one of the most important mechanisms of colistin resistance in Klebsiella pneumoniae. Methods: Several databases, including Scopus, Medline (via PubMed), and Web of Science, were searched (until August 2023) to identify those studies that address the mgrB mutation in clinical isolates of K. pneumoniae. Using Stata software, the pooled prevalence of mgrB mutation and subgroup analyses for the year of publication, country, continent, mgrB mutation types, and detection methods of mgrB mutation were analyzed. Results: Out of the 115 studies included in the analysis, the prevalence of mgrB mutations in colistin-resistant K. pneumoniae isolates was estimated at 65% of isolates, and mgrB variations with insertional inactivation had the highest prevalence among the five investigated mutations with 69%. The year subgroup analysis indicated an increase in mutated mgrB from 46% in 2014 to 61% in 2022. Europe had the highest prevalence of mutated mgrB at 73%, while Africa had the lowest at 54%. Conclusion: Mutations in the mgrB gene are reported as one of the most common mechanisms of colistin resistance in K. pneumoniae, and the results of the present study showed that 65% of the reported colistin-resistant K. pneumoniae had a mutation in this gene.

Inhibitory effect of natural compounds on quorum sensing system in Pseudomonas aeruginosa: a helpful promise for managing biofilm community.

Pseudomonas aeruginosa biofilm is a community of bacteria that adhere to live or non-living surfaces and are encapsulated by an extracellular polymeric substance. Unlike individual planktonic cells, biofilms possess a notable inherent resistance to sanitizers and antibiotics. Overcoming this resistance is a substantial barrier in the medical and food industries. Hence, while antibiotics are ineffective in eradicating P. aeruginosa biofilm, scientists have explored alternate strategies, including the utilization of natural compounds as a novel treatment option. To this end, curcumin, carvacrol, thymol, eugenol, cinnamaldehyde, coumarin, catechin, terpinene-4-ol, linalool, pinene, linoleic acid, saponin, and geraniol are the major natural compounds extensively utilized for the management of the P. aeruginosa biofilm community. Noteworthy, the exact interaction of natural compounds and the biofilm of this bacterium is not elucidated yet; however, the interference with the quorum sensing system and the inhibition of autoinducer production in P. aeruginosa are the main possible mechanisms. Noteworthy, the use of different drug platforms can overcome some drawbacks of natural compounds, such as insolubility in water, limited oral bioavailability, fast metabolism, and degradation. Additionally, drug platforms can deliver different antibiofilm agents simultaneously, which enhances the antibiofilm potential of natural compounds. This article explores many facets of utilizing natural compounds to inhibit and eradicate P. aeruginosa biofilms. It also examines the techniques and protocols employed to enhance the effectiveness of these compounds.

Solid lipid nanoparticles and their application in the treatment of bacterial infectious diseases.

Nano pharmacology is considered an effective, safe, and applicable approach for drug delivery applications. Solid lipid nanoparticle (SLNs) colloids contain biocompatible lipids which are capable of encapsulating and maintaining hydrophilic or hydrophobic drugs in the solid matrix followed by releasing the drug in a sustained manner in the target site. SLNs have more promising potential than other drug delivery systems for various purposes. Nowadays, the SLNs are used as a carrier for antibiotics, chemotherapeutic drugs, nucleic acids, herbal compounds, etc. The SLNs have been widely applied in biomedicine because of their non-toxicity, biocompatibility, and simple production procedures. In this review, the complications related to the optimization, preparation process, routes of transplantation, uptake and delivery system, and release of the loaded drug along with the advantages of SLNs as therapeutic agents were discussed.

Exploring the interplay between Fusobacterium nucleatum with the expression of microRNA, and inflammatory mediators in colorectal cancer.

Background: Fusobacterium nucleatum has been recognized as an important key bacterium in the cause and spread of colorectal carcinogenesis. Nevertheless, the clinical relevance of F. nucleatum in colorectal cancer (CRC) and its effect on immune factors and the tumor microenvironment have not been fully elucidated. Materials and methods: The frequency of F. nucleatum was measured in 100 paired tumor and normal tissue specimens by TaqMan quantification Real-Time Polymerase Chain Reaction (qPCR). The mRNA expression levels of cytokines (IL-6, IL-10, IL-12ß, IL-17, TNF-α, TLR-2, and TLR-4), and miRNAs (miR-21, miR-31) were examined. Eventually, any potential correlations between the molecular and clinicopathological features of the neoplastic samples and the abundance of F. nucleatum were analyzed. Results: The relative frequency of F. nucleatum was significantly increased in cancerous tissue compared to adjacent non-tumor tissues. Furthermore, the high level of F. nucleatum was significantly associated with histological grade III and IV CRC tissues (P = 0.027 and P = 0.022, respectively) and perineural invasion-positive patients (P = 0.037). In addition, the expression levels of IL-6, IL-17, TNF-α,IL-12ß, TLR-2, and TLR-4 as well as miR-21 and miR-31 showed a significant increase in the cancer group. A notable correlation was also observed between the high status of F. nucleatum and the expression of IL-6, TNF-α and miR-21. Conclusion: Our results emphasize the importance of F. nucleatum and changes in the expression of genes involved in CRC. Studying the microbial profile and gene expression changes in CRC patients may be a promising approach to improve screening methods and provide therapeutic strategies.

Association of Lactobacillus, Firmicutes, Bifidobacterium, Clostridium, and Enterococcus with colorectal cancer in Iranian patients.

Background: Colorectal cancer (CRC) is one of the primary causes of cancer-associated deaths worldwide, and growing evidence shows that alteration in the gut microbiota may be a contributing factor to the development and progression of the disease. This study investigates the correlation between CRC and specific intestinal microbiota abundance, including Firmicutes, Lactobacillus, Enterococcus, Clostridium, and Bifidobacterium. Material and methods: In this study, 100 CRC samples and adjacent normal tissues were obtained from Iranian patients. Afterward, we assessed the abundance of the mentioned bacteria in matched tumor and normal tissue samples from 100 CRC patients, by TaqMan quantitative real-time polymerase chain reaction (qPCR). Results: Most of the patients (55 %) had grade II cancer (moderately differentiated), followed by grade III (poorly Differentiated) in 19 %, and the distribution of the tumor location was 65 % in the colon and 35 % in the rectum. Our research showed a substantial difference in the relative abundance of specific bacteria in tumors and healthy tissues. To this end, four genera of bacteria, including Bifidobacterium, Lactobacillus, Clostridium, and Firmicutes, exhibited statistically significant reductions in tumor tissues compared to adjacent normal tissue (p < 0.05). Conversely, Enterococcus demonstrated a statistically significant increase in tumor tissue samples (p < 0.05). Noteworthy, statistical analysis revealed a significant relationship between Enterococcus and prior cancer (p < 0.05). Conclusions: These findings provide significant insight into the complex association between the gut microbiota and CRC and may pave the way for future research on novel screening methods, preventive measures, and therapeutic strategies targeting the gut microbiota in CRC patients.

A decreased level of high-density lipoprotein is a possible risk factor for type 2 diabetes mellitus: A review.

Introduction: Type 2 diabetes mellitus (T2DM) is characterized primarily by dyslipidemia and hyperglycemia due to insulin resistance. High-density lipoprotein (HDL) play a significant role in preventing the incidence of dyslipidemia and its complications. HDL has different protective functions, such as reducing oxidation, vascular inflammation, and thrombosis; additionally, its anti-diabetic role is one of the most significant recent discoveries about HDL and some of its constituent lipoproteins. Methods: This research reviews ongoing studies and preliminary investigations into the assessment of relation between decreased level of HDL and T2DM. Results: The levels of HDL and its functions contribute to glucose hemostasis and the development of T2DM through four possible mechanisms, including insulin secretion by beta cells, peripheral insulin sensitivity, non-insulin-dependent glucose uptake, and adipose tissue metabolic activity. Additionally, the anti-oxidant properties of HDL protect beta cells from apoptosis caused by oxidative stress and inflammation induced by low-density lipoprotein, which facilitate insulin secretion. Conclusion: Therefore, HDL and its compositions, especially Apo A-I, play an important role in regulating glucose metabolism, and decreased levels of HDL can be considered a risk factor for DM. Different factors, such as hypoalphalipoproteinemia that manifests as a consequence of genetic factors, such as Apo A-I deficiency, as well as secondary causes arising from lifestyle choices and underlying medical conditions that decrease the level of HDL, could be associated with DM. Moreover, intricate connections between HDL and diabetic complications extend beyond glucose metabolism to encompass complications like cardiovascular disease and kidney disease. Therefore, the exact interactions between HDL level and DM should be evaluated in future studies.

The destruction of mucosal barriers, epithelial remodeling, and impaired mucociliary clearance: possible pathogenic mechanisms of Pseudomonas aeruginosa and Staphylococcus aureus in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a pathological condition characterized by persistent inflammation in the upper respiratory tract and paranasal sinuses. The epithelium serves as the first line of defense against potential threats and protects the nasal mucosa. The fundamental mechanical barrier is formed by the cell-cell contact and mucociliary clearance (MCC) systems. The physical-mechanical barrier is comprised of many cellular structures, including adhesion junctions and tight junctions (TJs). To this end, different factors, such as the dysfunction of MCC, destruction of epithelial barriers, and tissue remodeling, are related to the onset and development of CRS. Recently published studies reported the critical role of different microorganisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, in the induction of the mentioned factors. Bacteria could result in diminished ciliary stimulation capacity, and enhance the chance of CRS by reducing basal ciliary beat frequency. Additionally, bacterial exoproteins have been demonstrated to disrupt the epithelial barrier and induce downregulation of transmembrane proteins such as occludin, claudin, and tricellulin. Moreover, bacteria exert an influence on TJ proteins, leading to an increase in the permeability of polarized epithelial cells. Noteworthy, it is evident that the activation of TLR2 by staphylococcal enterotoxin can potentially undermine the structural integrity of TJs and the epithelial barrier through the induction of pro-inflammatory cytokines. The purpose of this article is an attempt to investigate the possible role of the most important microorganisms associated with CRS and their pathogenic mechanisms against mucosal surfaces and epithelial barriers in the paranasal sinuses. Video Abstract.

Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/ß-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. MATERIALS AND METHODS: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. RESULTS: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. CONCLUSION: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.

Fatal vanishing bile duct syndrome in Iranian patient with Hodgkin's lymphoma.

Vanishing bile duct syndrome (VBDS) has been postulated that may be related to Hodgkin's lymphoma (HL). In the present study, we present a 75-year-old male patient with HL who received chemotherapy but has not received any radiotherapy. The patient's condition worsened in further days, and he died with the diagnosis of cirrhosis and hepatic failure.

Bacteriophages: The promising therapeutic approach for enhancing ciprofloxacin efficacy against bacterial infection.

BACKGROUND: The emergence of ciprofloxacin-resistant bacteria is a serious challenge worldwide, bringing the need to find new approaches to manage this bacterium. Bacteriophages (phages) have been shown inhibitory effects against ciprofloxacin-resistance bacteria; thus, ciprofloxacin resistance or tolerance may not affect the phage's infection ability. Additionally, researchers used phage-ciprofloxacin combination therapy for the inhibition of multidrug-resistant bacteria. RESULTS: The sublethal concentrations of ciprofloxacin could lead to an increase in progeny production. Antibiotic treatments could enhance the release of progeny phages by shortening the lytic cycle and latent period. Thus, sublethal concentrations of antibiotics combined with phages can be used for the management of bacterial infections with high antibiotic resistance. In addition, combination therapy exerts various selection pressures that can mutually decrease phage and antibiotic resistance. Moreover, phage ciprofloxacin could significantly reduce bacterial counts in the biofilm community. Immediate usage of phages after the attachment of bacteria to the surface of the flow cells, before the development of micro-colonies, could lead to the best effect of phage therapy against bacterial biofilm. Noteworthy, phage should be used before antibiotics usage because this condition may have allowed phage replication to occur first before ciprofloxacin interrupted the bacterial DNA replication process, thereby interfering with the activity of the phages. Furthermore, the phage-ciprofloxacin combination showed a promising result for the management of Pseudomonas aeruginosa infections in mouse models. Nevertheless, low data are existing about the interaction between phages and ciprofloxacin in combination therapies, especially regarding the emergence of phage-resistant mutants. Additionally, there is a challenging and important question of how the combined ciprofloxacin with phages can increase antibacterial functions. Therefore, more examinations are required to support the clinical usage of phage-ciprofloxacin combination therapy.

The potential role of telemedicine in the infectious disease pandemic with an emphasis on COVID-19: A narrative review.

Background and Aims: Due of its low cost, rapid speed, data record, and vast communication coverage, information and communication technology might be useful for health-related fields in times of crisis. By providing medical or hygienic services to a patient who lives elsewhere using communication methods like email, fax, cellphones, applications, and wireless gadgets, telemedicine can aid in the better management of diseases. Reviewing the potential role of telemedicine in the pandemic of infectious diseases with a focus on the Coronavirus disease 2019 (COVID-19) epidemic was the main goal of this study. Methods: "Google Scholar," "PubMed," "Science Direct," and "Scopus" databases were searched to collect the papers that identify the advantages and disadvantages of telemedicine in the disease pandemic. Searched keywords include: telepharmacy, telemedicine, remote communication, pandemic(s), epidemic, distant care, distant communication, phone consulation, video conference communication and patient education. Results: Information and communication technology are crucial, especially when dealing with pandemics of infectious diseases like COVID-19. Less "in-person" patient visits to hospitals as a result of telemedicine eventually means less labor for the medical staff, less viral exposure for patients, and ultimately less disease spread. By establishing a bidirectional reciprocal relationship between patients and healthcare providers although they are in separate geographical areas, it can improve patient health status. Conclusion: Governments are currently facing a significant budgetary burden because to the COVID-19 pandemic. Since patients are not sent to medical facilities in person, which could be a source of infection, telemedicine reduces disease spread while saving money.

Graphene-Based Materials for Inhibition of Wound Infection and Accelerating Wound Healing.

Bacterial infection of the wound could potentially cause serious complications and an enormous medical and financial cost to the rapid emergence of drug-resistant bacteria. Nanomaterials are an emerging technology, that has been researched as possible antimicrobial nanomaterials for the inhibition of wound infection and enhancement of wound healing. Graphene is 2-dimensional (2D) sheet of sp2 carbon atoms in a honeycomb structure. It has superior properties, strength, conductivity, antimicrobial, and molecular carrier abilities. Graphene and its derivatives, Graphene oxide (GO) and reduced GO (rGO), have antibacterial activity and could damage bacterial morphology and lead to the leakage of intracellular substances. Besides, for wound infection management, Graphene-platforms could be functionalized by different antibacterial agents such as metal-nanoparticles, natural compounds, and antibiotics. The Graphene structure can absorb near-infrared wavelengths, allowing it to be used as antimicrobial photodynamic therapy. Therefore, Graphene-based material could be used to inhibit pathogens that cause serious skin infections and destroy their biofilm community, which is one of the biggest challenges in treating wound infection. Due to its agglomerated structure, GO hydrogel could entrap and stack the bacteria; thus, it prevents their initial attachment and biofilm formation. The sharp edges of GO could destroy the extracellular polymeric substance surrounding the biofilm and ruin the biofilm biomass structure. As well as, Chitosan and different natural and synthetic polymers such as collagen and polyvinyl alcohol (PVA) also have attracted a great deal of attention for use with GO as wound dressing material. To this end, multi-functional polymers based on Graphene and blends of synthetic and natural polymers can be considered valid non-antibiotic compounds useful against wound infection and improvement of wound healing. Finally, the global wound care market size was valued at USD 20.8 billion in 2022 and is expected to expand at a compound annual growth rate (CAGR) of 5.4% from 2022 to 2027 (USD 27.2 billion). This will encourage academic as well as pharmaceutical and medical device industries to investigate any new materials such as graphene and its derivatives for the treatment of wound healing.

The significant role of Carbapenems-resistant Acinetobacter Baumannii in mortality rate of patients with COVID-19.

Background: Infections caused by Acinetobacter baumannii, especially carbapenem-resistant (CR) strains, pose important challenges in patients with COVID-19 infection. Therefore, in the present study, we investigated co-infection and antimicrobial resistance patterns, as well as the role of A. baumannii in the outcome of patients with COVID-19. Materials and methods: Between February 2019 and January 2021, 141 patients with A. baumannii infections were detected from seven different hospitals (A to G) in Arak, Iran, and the antibacterial susceptibility pattern of these isolates was evaluated using disk diffusion and E-test methods. Forty-seven of these patients were co-infected with COVID-19. During the study, the data about the clinical course, demographic data, and the role of A. baumannii infections in the mortality rate of COVID-19 patients were collected. Results: Hospitals A and B reported the most patients, with 53 (38%) and 47 (33%), respectively. Additionally, most cases (105 cases, 75%) were reported from surgical and general ICUs. Mechanical ventilators were detected as predisposing factors in 95 (67%) patients, and infection was detected in 20% of patients on the 10th day after intubation. All of the A. baumannii isolates were resistant to different classes of antibiotics, such as carbapenems. Notably, 33% (47 patients) were also positive for COVID-19, and 68% (32 patients) died due to the infection. Statistical analysis showed a significant role of A. baumannii co-infection in the mortality rate of COVID-19 patients (p-value 0.05). Conclusion: co-infection with A. baumannii is one of the most important challenges in COVID-19 patients. Our results showed that all isolated bacteria were CR and significantly increased mortality rates in COVID-19 patients.

Antecedentes: Las infecciones causadas por Acinetobacter baumannii, especialmente las cepas resistentes a carbapenem (CR), plantean desafíos importantes en pacientes con infección por COVID-19. Por lo tanto, en el presente estudio investigamos los patrones de coinfección y resistencia a los antimicrobianos, así como el papel de A. baumannii en el desenlace de los pacientes con COVID-19.Materiales y métodos: entre febrero de 2019 y enero de 2021, se detectaron 141 pacientes con infecciones por A. baumannii de siete hospitales diferentes (A a G) en Arak, Irán, y se evaluó el patrón de susceptibilidad antibacteriana de estos aislamientos mediante difusión en disco y E- métodos de prueba. Cuarenta y siete de estos pacientes estaban coinfectados con COVID-19. Durante el estudio, se recopilaron datos sobre datos demográficos, curso clínico y el papel de las infecciones por A. baumannii en la tasa de mortalidad de los pacientes con COVID-19.Resultados: Los hospitales A y B reportaron mayor número de pacientes con 53 (38%) y 47 (44%), respectivamente. Además, la mayoría de los casos (105 casos, 75%) se informaron desde la UCI quirúrgica y general. Los ventiladores mecánicos se detectaron como factores predisponentes en 95 (67%) pacientes y la infección se detectó en el 20% de los pacientes al décimo día después de la intubación. Todos los aislamientos de A. baumannii fueron resistentes a diferentes clases de antibióticos, como los carbapenémicos. El 33,6% (47 pacientes) también dieron positivo a COVID-19, y el 68% (32 pacientes) fallecieron a causa de la infección. El análisis estadístico mostró un papel significativo de la coinfección por A. baumannii en la tasa de mortalidad de los pacientes con COVID-19 (valor de p 0,05).Conclusión: la coinfección con A. baumannii es uno de los desafíos más importantes en pacientes positivos para COVID-19. Nuestros resultados mostraron que todas las bacterias aisladas eran CR y aumentaron significativamente las tasas de mortalidad en pacientes con COVID-19.

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.

Viral vector and nucleic acid vaccines against COVID-19: A narrative review.

After about 2 years since the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Wuhan, China, in December 2019 that resulted in a worldwide pandemic, 6.2 million deaths have been recorded. As a result, there is an urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19). Endeavors for the production of effective vaccines inexhaustibly are continuing. At present according to the World Health Organization (WHO) COVID-19 vaccine tracker and landscape, 153 vaccine candidates are developing in the clinical phase all over the world. Some new and exciting platforms are nucleic acid-based vaccines such as Pfizer Biontech and Moderna vaccines consisting of a messenger RNA (mRNA) encoding a viral spike protein in host cells. Another novel vaccine platform is viral vector vaccine candidates that could be replicating or nonreplicating. These types of vaccines that have a harmless viral vector like adenovirus contain a genome encoding the spike protein of SARS-CoV-2, which induces significant immune responses. This technology of vaccine manufacturing has previously been used in many human clinical trials conducted for adenoviral vector-based vaccines against different infectious agents, including Ebola virus, Zika virus, HIV, and malaria. In this paper, we have a review of nucleic acid-based vaccines that are passing their phase 3 and 4 clinical trials and discuss their efficiency and adverse effects.

The effect of bacterial composition shifts in the oral microbiota on Alzheimer's disease.

Alzheimer's disease (AD), a neurological disorder, despite significant advances in medical science, has not yet been definitively cured, and the exact causes of the disease remain unclear. Due to the importance of AD in the clinic, large expenses are spent annually to deal with this neurological disorder, and neurologists warn of an alarm to increase this disease in the elderly people in the near future. It has been believed that microbiota dysbiosis lead to Alzheimer's as a multi-step disease. In this regard, the presence of footprints of perturbations in the oral microbiome and the predominance of pathogenic bacteria and their effect on the nervous system especially AD is a very interesting topic that has been considered by researchers in the last decade. Some studies have looked at the mechanisms by which oral microbiota cause AD. However, many aspects of this interaction are still unclear as to how oral microbiota composition can contribute to this disease. Understanding this interaction requires extensive collaboration by interdisciplinary researchers to explore all aspects of the issue. So, in this review has attempted to give the mechanisms of shift of oral microbiota in AD in order to reveals the link between microbiota composition and this disease with the help of researchers from different fields.

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.

Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species.

The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms' resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, ß-pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.