The role of Staphylococcus aureus in cystic fibrosis pathogenesis and clinico-microbiological interactions.

Cystic fibrosis (CF) is a progressive and inherited disease that affects approximately 70000 individuals all over the world annually. A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene serves as its defining feature. Bacterial infections have a significant impact on the occurrence and development of CF. In this manuscript, we discuss the role and virulence factors of Staphylococcus aureus as an important human pathogen with the ability to induce respiratory tract infections. Recent studies have reported S. aureus as the first isolated bacteria in CF patients. Methicillin-resistant Staphylococcus aureus (MRSA) pathogens are approximately resistant to all ß-lactams. CF patients are colonized by MRSA expressing various virulence factors including toxins, and Staphylococcal Cassette Chromosome mec (SCCmec) types, and have the potential for biofilm formation. Therefore, variations in clinical outcomes will be manifested. SCCmec type II has been reported in CF patients more than in other SCCmec types from different countries. The small-colony variants (SCVs) as specific morphologic subtypes of S. aureus with slow growth and unusual properties can also contribute to persistent and difficult-to-treat infections in CF patients. The pathophysiology of SCVs is complicated and not fully understood. Patients with cystic fibrosis should be aware of the intrinsic risk factors for complex S. aureus infections, including recurring infections, physiological issues, or coinfection with P. aeruginosa.

Gut microbiota in neurological diseases: Melatonin plays an important regulatory role.

Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity, circadian rhythm regulator, and immunomodulatory effects. The gut is one of the primary known sources of melatonin. The gut microbiota helps produce melatonin from tryptophan, and melatonin has been shown to have a beneficial effect on gut barrier function and microbial population. Dysbiosis of the intestinal microbiota is associated with bacterial imbalance and decreased beneficial microbial metabolites, including melatonin. In this way, low melatonin levels may be related to several human diseases. Melatonin has shown both preventive and therapeutic effects against various conditions, including neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review was aimed to discuss the role of melatonin in the body, and to describe the possible relationship between gut microbiota and melatonin production, as well as the potential therapeutic effects of melatonin on neurological diseases.

Tuberculosis vaccine developments and efficient delivery systems: A comprehensive appraisal.

Despite the widespread use of the Bacillus Calmette-Guérin (BCG) vaccine, Mycobacterium tuberculosis (MTB) continues to be a global burden. Vaccination has been proposed to prevent and treat tuberculosis (TB) infection, and several of them are in different phases of clinical trials. Though vaccine production is in progress but requires more attention. There are several TB vaccines in the trial phase, most of which are based on a combination of proteins/adjuvants or recombinant viral vectors used for selected MTB antigens. In this review, we attempted to discuss different types of TB vaccines based on the vaccine composition, the immune responses generated, and their clinical trial phases. Furthermore, we have briefly overviewed the effective delivery systems used for the TB vaccine and their effectiveness in different vaccines.

Epidemiological characterization of clinical isolates of meticillin resistant Staphylococcus aureus through multilocus sequence typing and staphylococcal cassette chromosome mec typing in Northwest Iran.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), is considered a potential and aggressive nosocomial pathogen. It accounts for 50% of S. aureus isolates in tertiary hospitals in Iran, however, there is no sufficient evolutionary and epidemiological investigation about this medically important bacterium. We aimed to study the lineage and evolution of MRSA in Northwest Iran during 2021-2022 based on the obtained phenotypic and genotypic characteristics. MATERIALS AND METHODS: Seventy-two non-duplicate MRSA isolates were collected from 3 referral hospitals in Tabriz, Ardebil, and Urmia cities. The antimicrobial susceptibility patterns were determined by disk diffusion test and micro broth dilution methods. Thereafter 4 virulence genes (eta, etb, pvl, tst) and 5 types of staphylococcal cassette chromosome mec (SCCmec) were detected by PCR. In the final step, representative isolates were selected to be studied by Multilocus sequence typing (MLST). RESULTS: The highest resistance was observed to erythromycin and clindamycin at a rate of 76.4%, followed by ciprofloxacin (61.1%), gentamicin (54.2%), rifampin (38.9%), and co-trimoxazole (27.8%). All isolates were susceptible to vancomycin. The virulence genes of etb, pvl, tst, and eta were detected in 50%, 29.2%, 21.8%, and 13.9% of isolates, respectively. SCCmec types III and I were the most prevalent types, followed by types IV, II, and V. MLST analysis revealed 6 sequence types: ST6854, ST5282, ST127, ST7804, ST1607, and ST7784. Two MLST-based clonal complexes (CC8, and CC97) were identified as well. CONCLUSION: The ST numbers were non-repetitive. CC8 as a pandemic clone and an individual lineage and clinically significant clade was reported as the most prevalent clonal complex. It is essential periodic evaluations of antibiotic susceptibility patterns and study the evolutionary characteristics of medical-challenging microorganisms in particular MRSA to effectively treat and restrict the outbreaks.

Preparation, Physicochemical Characterization, Antimicrobial Effects, Biocompatibility and Cytotoxicity of Co-Loaded Meropenem and Vancomycin in Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNPs) have been reported as an effective system to co-deliver a variety of different agents to enhance efficiency and improve biocompatibility. This study was aimed at the preparation, physicochemical characterization, antimicrobial effects, biocompatibility, and cytotoxicity of vancomycin and meropenem co-loaded in the mesoporous silica nanoparticles (Van/Mrp-MSNPs). The prepared nanoparticles were explored for their physicochemical features, antibacterial and antibiofilm effects, biocompatibility, and cytotoxicity. The minimum inhibitory concentrations (MICs) of the Van/Mrp-MSNPs (0.12-1 µg/mL) against Staphylococcus aureus isolates were observed to be lower than those of the same concentrations of vancomycin and meropenem. The minimum biofilm inhibitory concentration (MBIC) range of the Van/Mrp-MSNPs was 8-64 µg/mL, which was lower than the meropenem and vancomycin MBICs. The bacterial adherence was not significantly decreased upon exposure to levels lower than the MICs of the MSNPs and Van/Mrp-MSNPs. The viability of NIH/3T3 cells treated with serial concentrations of the MSNPs and Van/Mrp-MSNPs were 73-88% and 74-90%, respectively. The Van/Mrp-MSNPs displayed considerable inhibitory effects against MRSA, favorable biocompatibility, and low cytotoxicity. The Van/Mrp-MSNPs could be a potential system for the treatment of infections.

Bile effects on the Pseudomonas aeruginosa pathogenesis in cystic fibrosis patients with gastroesophageal reflux.

Gastroesophageal reflux (GER) occurs in most cystic fibrosis (CF) patients and is the primary source of bile aspiration in the airway tract of CF individuals. Aspirated bile is associated with the severity of lung diseases and chronic inflammation caused by Pseudomonas aeruginosa as the most common pathogen of CF respiratory tract infections. P. aeruginosa is equipped with several mechanisms to facilitate the infection process, including but not limited to the expression of virulence factors, biofilm formation, and antimicrobial resistance, all of which are under the strong regulation of quorum sensing (QS) mechanism. By increasing the expression of lasI, rhlI, and pqsA-E, bile exposure directly impacts the QS network. An increase in psl expression and pyocyanin production can promote biofilm formation. Along with the loss of flagella and reduced swarming motility, GER-derived bile can repress the expression of genes involved in creating an acute infection, such as expression of Type Three Secretion (T3SS), hydrogen cyanide (hcnABC), amidase (amiR), and phenazine (phzA-E). Inversely, to cause persistent infection, bile exposure can increase the Type Six Secretion System (T6SS) and efflux pump expression, which can trigger resistance to antibiotics such as colistin, polymyxin B, and erythromycin. This review will discuss the influence of aspirated bile on the pathogenesis, resistance, and persistence of P. aeruginosa in CF patients.

Caccinia macranthera Brand var. macranthera: Phytochemical analysis, phytotoxicity and antimicrobial investigations of essential oils with concomitant in silico molecular docking based on OPLS force-field.

This study was conducted to extract the essential oils (EOs) of Caccinia macranthera identify their phytochemicals, evaluate their phytotoxicity, antimicrobial activity and enzyme inhibition effects using in silico molecular docking technique. EOs of aerial parts, seeds, and roots of C. macranthera were extracted and analyzed via Gas chromatography-Mass Spectrometry. The antibacterial activity of EOs were determined on nine microorganisms via disk diffusion and microbroth dilution assays. In addition, the allelopathic properties of EOs were investigated by calculating the IC50s for inhibition of germination, seedling length and seedling weight growth of Cuscuta campestris seeds. In order to assess the possible inhibitory effect of major components of C. macranthera EOs on enzymes inhibiting germination and plant growth, molecular docking was employed against the glutamine synthetase (GS), acetohydroxyacid synthetase (AHAS), and 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzymes. The main compounds of EOs from aerial parts, seeds, and roots EOs were dihydrocarveol (29.5%), Trimethyl-2-Pentadecanone (13.6%), and Palmitic acid (16.8%), respectively. The maximum antibacterial effect was related to the aerial parts EO against Staphylococcus epidermidis. Phytotoxicity analysis exhibited a concentration-dependent increase (p ≤ 0.05) activity. The aerial parts EO demonstrated a substantial allelopathy effect, with IC50 values of 0.22 ± 0.026, 0.39 ± 0.021, and 0.20 ± 0.025 mg/mL, respectively, on inhibitory germination, seedling length and seedling weight growth of Cuscuta campestris seeds. Molecular docking analyzes showed that Oleic acid was suitable for dynamic stabilization of HPPD (-6.552 kJ/mol) and GS (-7.265 kJ/mol) and Eupatoriochromene had the inhibitory potential against AHAS, with docking score of -4.189 kJ/mol. The current research demonstrated that C. macranthera EOs from its aerial parts have an acceptable phytotoxic activity against Cuscuta campestris weed. The major components of EOs, Oleic acid and Eupatoriochromene, presented the strongest binding with HPPD, GS, and AHAS active sites causing disturbance in germination, photosynthesis and weed growth suggesting it as a natural herbicide for controlling the weeds.

Short-chain fatty acids profile in patients with SARS-CoV-2: A case-control study.

Background and Aims: SARS-CoV-2, as a new pandemic disease, affected the world. Short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids are the main metabolites of human gut microbiota. The positive effects of SCFAs have been shown in infections caused by respiratory syncytial virus, adenovirus, influenza, and rhinovirus. Therefore, this study aimed to evaluate the concentration of SCFAs in patients with SARS-CoV-2 compared with the healthy group. Methods: This research was designed based on a case and control study. Twenty healthy individuals as the control group and 20 persons admitted to the hospital with a positive test of coronavirus disease (COVID-19) real-time polymerase chain reaction were included in the study as the patient group from September 2021 to October 2021, in Tabriz, Iran. Stool specimens were collected from volunteers, and analysis of SCFAs was carried out by a high-performance liquid chromatography system. Results: The amount of acetic acid in the healthy group was 67.88 ± 23.09 µmol/g, while in the group of patients with COVID-19 was 37.04 ± 13.29 µmol/g. Therefore, the concentration of acetic acid in the patient group was significantly (p < 0.001) lower than in the healthy group. Propionic and butyric acid were present in a higher amount in the control group compared with the case group; however, this value was not statistically significant (p > 0.05). Conclusion: This study showed that the concentration of acetic acid as the metabolite caused by gut microbiota is significantly disturbed in patients with COVID-19. Therefore, therapeutic interventions based on gut microbiota metabolites in future research may be effective against COVID-19.

Collateral sensitivity: An evolutionary trade-off between antibiotic resistance mechanisms, attractive for dealing with drug-resistance crisis.

Background: The discovery and development of antimicrobial drugs were one of the most significant advances in medicine, but the evolution of microbial resistance limited the efficiency of these drugs. Aim: This paper reviews the collateral sensitivity in bacteria and its potential and limitation as a new target for treating infections. Results and Discussion: Knowledge mechanisms of resistance to antimicrobial agents are useful to trace a practical approach to treat and control of resistant pathogens. The effect of a resistance mechanism to certain antibiotics on the susceptibility or resistance to other drugs is a key point that may be helpful for applying a strategy to control resistance challenges. In an evolutionary trade-off known as collateral sensitivity, the resistance mechanism to a certain drug may be mediated by the hypersensitivity to other drugs. Collateral sensitivity has been described for different drugs in various bacteria, but the molecular mechanisms affecting susceptibility are not well demonstrated. Collateral sensitivity could be studied to detect its potential in the battle against resistance crisis as well as in the treatment of pathogens adapting to antibiotics. Collateral sensitivity-based antimicrobial therapy may have the potential to limit the emergence of antibiotic resistance.

Immunologic biomarkers for bacterial meningitis.

Meningitis is defined as the inflammation of the meninges that is most often caused by various bacterial and viral pathogens, and is associated with high rates of mortality and morbidity. Early detection of bacterial meningitis is essential to appropriate antibiotic therapy. Alterations in immunologic biomarkers levels have been considered the diagnostic approach in medical laboratories for the identifying of infections. The early increasing immunologic mediators such as cytokines and acute phase proteins (APPs) during bacterial meningitis have made they significant indicators for laboratory diagnosis. Immunology biomarkers showed wide variable sensitivity and specificity values that influenced by different reference values, selected a certain cutoff point, methods of detection, patient characterization and inclusion criteria, as well as etiology of meningitis and time of CSF or blood specimens' collection. This study provides an overview of different immunologic biomarkers as diagnostic markers for the identification of bacterial meningitis and their efficiencies in the differentiating of bacterial from viral meningitis.

The Antibacterial Effect of Ciprofloxacin Loaded Calcium Carbonate (CaCO3) Nanoparticles Against the Common Bacterial Agents of Osteomyelitis.

The present study aimed to investigate the biocompatibility, antibacterial/anti-biofilm effects of ciprofloxacin-loaded calcium carbonate (Cip- loaded CaCO3) nanoparticles against the common organisms responsible for osteomyelitis. The antibacterial and biofilm inhibitory activities were studied by determination of minimum inhibitory concentrations (MICs) and minimum biofilm inhibitory concentrations (MBICs), respectively. Hemolytic effects were determined for studying hemocompatibility. The SDS-PAGE method was used to study the interaction of Cip- loaded CaCO3 with plasma proteins. The effects of Cip- loaded CaCO3 on the cell viability of human bone marrow mesenchymal stem cells (hBM-MSCs) was detected. The Cip- loaded CaCO3 nanoparticles were shown a significant antimicrobial effect at lower concentrations than free ciprofloxacin. No significant hemolytic effect was observed. The Cip- loaded CaCO3 nanoparticles have shown interaction with apolipoprotein A1 (28 kDa) and albumin (66.5 kDa). The viability of hBM-MSCs treated with Cip- loaded CaCO3 was more than 96%. Our results indicated that Cip-loaded CaCO3 nanoparticles had favorable in vitro compatibility with human red blood cells, antimicrobial effects, and low cytotoxicity.

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.

Antibacterial and biofilm-inhibitory effects of vancomycin-loaded mesoporous silica nanoparticles on methicillin-resistant staphylococcus aureus and gram-negative bacteria.

The present study aimed to prepare and characterize vancomycin-loaded mesoporous silica nanoparticles (Van-MSNs) to detect inhibitory effects on the planktonic and biofilm forms of methicillin-resistant Staphylococcus aureus (MRSA) isolates, and study the biocompatibility and toxicity of Van-MSNs in vitro as well as antibacterial activity of Van-MSNs against Gram-negative bacteria. The inhibitory effects of Van-MSNs were investigated on MRSA using the determination of minimum inhibitory (MIC) and minimum biofilm-inhibitory concentrations (MBIC) as well as the effect on bacterial attachment. Biocompatibility was studied by examining the effect of Van-MSNs on the lysis and sedimentation rate of red blood cells (RBC). The interaction of Van-MSNs with human blood plasma was detected by the SDS-PAGE approach. The cytotoxic effect of the Van-MSNs on human bone marrow mesenchymal stem cells (hBM-MSCs) was evaluated by the MTT assay. The antibacterial effects of vancomycin and Van-MSNs on Gram-negative bacteria were also investigated using MIC determination using the broth microdilution method. Furthermore, bacteria outer membrane (OM) permeabilization was determined. Van-MSNs showed inhibitory effects on planktonic and biofilm forms of bacteria on all isolates at levels lower than MICs and MBICs of free vancomycin, but the antibiofilm effect of Van-MSNs was not significant. However, Van-MSNs did not affect bacterial attachment to surfaces. Van-loaded MSNs did not show a considerable effect on the lysis and sedimentation of RBC. A low interaction of Van-MSNs was detected with albumin (66.5 kDa). The hBM-MSCs viability in exposure to different levels of Van-MSNs was 91-100%. MICs of ≥ 128 µg/mL were observed for vancomycin against all Gram-negative bacteria. In contrast, Van-MSNs exhibited modest antibacterial activity inhibiting the tested Gram-negative bacterial strains, at concentrations of ≤ 16 µg/mL. Van-MSNs increased the OM permeability of bacteria that can increase the antimicrobial effect of vancomycin. According to our findings, Van-loaded MSNs have low cytotoxicity, desirable biocompatibility, and antibacterial effects and can be an option for the battle against planktonic MRSA.

The Sustained-released Polylactic Co-glycolic Acid Nanoparticles Loaded with Chlorhexidine as Antibacterial Agents Inside the Dental Implant Fixture.

INTRODUCTION: Titanium-based implants are widely used due to their good biocompatibility and high corrosion resistance. Infections after implant placement are the main reason for the failure of implant treatment. Some recent studies have also shown that microbial contamination can occur at the implant-abutment level in implants with healthy or diseased surrounding tissue. The purpose of this study is to investigate the antibacterial effect of slow-release nanoparticles of polylactic co-glycolic acid (PLGA) loaded with chlorhexidine (CHX) inside the implant fixture. MATERIALS AND METHODS: Thirty-six implants in three groups were examined in the bacterial culture environment. In the first group, PLGA/CHX nanoparticles; in the second group, the negative control group (distilled water) and in the third group, the positive control groups (chlorhexidine) were used. The bacterial suspensions, including Escherichia coli ATCC: 25922, Staphylococcus aureus ATCC: 6538 and Enterococcus faecalis ATCC: 29212 were used to investigate the antimicrobial effect of the prepared nanoparticles. RESULTS: The results showed that the use of PLGA/CHX nanoparticles significantly inhibited the growth of all three bacteria. Nanoparticles loaded with chlorhexidine had a significant decrease in the growth rate of all three bacteria compared to chlorhexidine and water. The lowest bacterial growth rate was observed in the Enterococcus faecalis/PLGA nanoparticles group, and the highest bacterial growth rate was observed in the Staphylococcus aureus/H2O group. CONCLUSION: The current study showed that the use of PLGA/CHX nanoparticles could significantly inhibit the growth of all three bacteria. Of course, the current study was conducted in vitro, and to obtain clinical results, we need to conduct a study on human samples. In addition, the results of this study showed that the chemical antimicrobial materials could be used in low concentrations and in a sustained- released manner in cases of dealing with bacterial infections, which can lead to better and targeted performance as well as reduce possible side effects.

Promising Antimicrobial Action of Sustained Released Curcumin-Loaded Silica Nanoparticles against Clinically Isolated Porphyromonas gingivalis.

BACKGROUND: Porphyromonas gingivalis (P. gingivalis) has always been one of the leading causes of periodontal disease, and antibiotics are commonly used to control it. Numerous side effects of synthetic drugs, as well as the spread of drug resistance, have led to a tendency toward using natural antimicrobials, such as curcumin. The present study aimed to prepare and physicochemically characterize curcumin-loaded silica nanoparticles and to detect their antimicrobial effects on P. gingivalis. METHODS: Curcumin-loaded silica nanoparticles were prepared using the chemical precipitation method and then were characterized using conventional methods (properties such as the particle size, drug loading percentage, and release pattern). P. gingivalis was isolated from one patient with chronic periodontal diseases. The patient's gingival crevice fluid was sampled using sterile filter paper and was transferred to the microbiology laboratory in less than 30 min. The disk diffusion method was used to determine the sensitivity of clinically isolated P. gingivalis to curcumin-loaded silica nanoparticles. SPSS software, version 20, was used to compare the data between groups with a p value of <0.05 as the level of significance. Then, one-way ANOVA testing was utilized to compare the groups. RESULTS: The curcumin-loaded silica nanoparticles showed a nanometric size and a drug loading percentage of 68% for curcumin. The nanoparticles had a mesoporous structure and rod-shaped morphology. They showed a relatively rapid release pattern in the first 5 days. The release of the drug from the nanoparticles continued slowly until the 45th day. The results of in vitro antimicrobial tests showed that P. gingivalis was sensitive to the curcumin-loaded silica nanoparticles at concentrations of 50, 25, 12.5, and 6.25 µg/mL. One-way ANOVA showed that there was a significant difference between the mean growth inhibition zone, and the concentration of 50 µg/mL showed the highest inhibition zone (p ≤ 0.05). CONCLUSION: Based on the obtained results, it can be concluded that the local nanocurcumin application for periodontal disease and implant-related infections can be considered a promising method for the near future in dentistry.

Molecular Detection and Characterization of the Staphylococcus epidermidis and Staphylococcus haemolyticus Isolated from Hospitalized Patients and Healthcare Workers in Iran.

Background: The present study is aimed at surveying the antibiotics resistance profile, biofilm formation ability, staphylococcal cassette chromosome mec (SCCmec) types, and molecular epidemiology of Staphylococcus epidermidis and Staphylococcus haemolyticus isolated from hospitalized patients and healthcare workers in four teaching hospitals in Iran. Methods: In total, 43 Staphylococcus epidermidis and 12 Staphylococcus haemolyticus were isolated from hospitalized patients, and 19 Staphylococcus epidermidis and 7 Staphylococcus haemolyticus isolated from healthcare workers were included in the present study. The antimicrobial resistance profile of isolates was determined using the disk diffusion method. Moreover, the resistance of isolates to methicillin was identified using the cefoxitin disk diffusion test. The microtiter-plate test was used for quantifying biofilm formation. Moreover, the frequency of icaA and icaD genes was determined using PCR assay. The molecular epidemiology of methicillin-resistant isolates was determined using SCCmec typing and pulsed-field gel electrophoresis methods. Results: Among all coagulase-negative staphylococci isolates, the highest resistance rate (81.5%) was seen for cefoxitin and cotrimoxazole. All of the isolates were susceptible to linezolid. Out of the 66 mecA-positive isolates, the most common SCCmec type was the type I (n = 23; 34.8%) followed by type IV (n = 13; 19.7%). Using pulsed-field gel electrophoresis (PFGE) assay, 27 PFGE types including 14 common types and 13 singletons were obtained among 51 methicillin-resistant S. epidermidis (MRSE) isolates. Moreover, among 12 methicillin-resistant S. haemolyticus (MRSH) isolates, 8 PFGE types were detected, of which 5 PFGE types were singletons. Conclusion: The high rate of resistance to antibiotics as well as the possibility of cross-infection shows the importance of a pattern shift in the management and controlling programs of coagulase-negative staphylococci, especially in healthcare centers. Clinical trial registration. The present study is not a clinical trial study. Thus, a registration number is not required.

The Antibacterial Effect of Tetracycline-loaded Mesoporous Silica Nanoparticles in the Gingival Fluid at Implant-abutment Junction: A Randomized Clinical Trial Study.

INTRODUCTION: Dental implant failure due to periodontal disease caused by anaerobic pathogens occurs, especially in the first year of implant placement. The aim of this clinical trial study was to compare the antibacterial effect of tetracycline gel and gel containing tetracyclineloaded mesoporous silica nanoparticles (MSNs) in the gingival crevice fluid of the implantabutment junction as a randomized clinical trial study. MATERIALS AND METHODS: Fourteen patients applying for implants in the posterior mandibular region were included in the study. During the uncovering session, tetracycline gel and gel containing tetracycline-loaded MSNs were placed in two implants and no substance was placed in the control group. Then, in three sessions, including molding, prosthesis delivery, and one month after delivery, the patient's gingival fluid was sampled and the number of bacteria in the gingival fluid was measured by colony-forming units (CFU/mL). RESULTS: The results of this study showed that in all three stages of sampling, the use of tetracycline gel and gel containing MSNs loaded with tetracycline significantly reduced the CFU/mL of gingival crevice fluid compared to the control group. Tetracycline-loaded MSNs gel showed significantly lower CFU/mL than tetracycline gel. The release of tetracycline from nanoparticles keep continue for a longer time compared to tetracycline gel. CONCLUSION: The use of nano-based delivery systems containing antibiotics inside the implant fixture can reduce the bacterial count of the implant-abutment junction and then improve implant stability.

Importance of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs) in cancer cells.

Background: In most regions, cancer ranks the second most frequent cause of death following cardiovascular disorders. Aim: In this article, we review the various aspects of glycolysis with a focus on types of MCTs and the importance of lactate in cancer cells. Results and Discussion: Metabolic changes are one of the first and most important alterations in cancer cells. Cancer cells use different pathways to survive, energy generation, growth, and proliferation compared to normal cells. The increase in glycolysis, which produces substances such as lactate and pyruvate, has an important role in metastases and invasion of cancer cells. Two important cellular proteins that play a role in the production and transport of lactate include lactate dehydrogenase and monocarboxylate transporters (MCTs). These molecules by their various isoforms and different tissue distribution help to escape the immune system and expansion of cancer cells under different conditions.

The metabolic, protective, and immune functions of Akkermansia muciniphila.

Numerous studies have almost proven the beneficial effects of gut microbiota in various aspects of human health, and even the gut microbiota is known as a new and forgotten organ. Akkermansia muciniphila, as a member of the gut microbiota, is considered a bacterium with probiotic properties; consequently, it has a remarkable position in microbiome research. This bacterium accounts for about 1-4 % of the total fecal microbiota population and is also considered a health marker. The accumulated evidence has shown a significant association between A. muciniphila and several disorders and diseases, such as obesity, fatty liver disease, diabetes, and even behavioral disorders. On the other hand, the beneficial effects of A. muciniphila in different studies have shown, such as protective role against pathogenic agents, antitumor properties, tight junctions' improvement, reduction of inflammation, gut permeability, and boosting adaptive immune responses. In this review, based on the available evidence and the latest research, we comprehensively evaluated the impact of A. muciniphila on host health from three points of view: metabolic, protective, and immune functions, as well as the possible mechanisms of each process.

Preparation of rutin-loaded mesoporous silica nanoparticles and evaluation of its physicochemical, anticancer, and antibacterial properties.

BACKGROUND: The studies have shown that rutin has great potential as an anticancer and antimicrobial plant base agent; nevertheless, poor bioavailability and low aqueous solubility of rutin limit its application. One of the beneficial routes to increase the solubility and bioavailability of rutin is the development of nanoparticulate material. This study aimed to assess the anticancer and antibacterial effects of rutin-loaded mesoporous silica nanoparticles (RUT-MSNs). METHODS: RUT-MSNs were prepared and physicochemically characterized. The cytotoxicity of RUT-MSNs on the HN5 cells as head and neck cancer cells was evaluated. The expression level of apoptosis-related genes such as Bcl-2 and Bax genes were evaluated. In addition, ROS production of RUT-MSNs treated cells was assessed. In addition, minimum inhibitory concentration (MIC), biofilm, and attachment inhibitory effects of RUT-MSNs compared with free rutin were assessed against different bacterial strains. RESULTS: Transmission electron microscopy (TEM) showed mesoporous rod-shaped nanoparticles with an average particle size of less than 100 nm. RUT-MSNs displayed the cytotoxic effect with IC50 of 20.23 µM in 48 h of incubation time (p < 0.05). The elevation in the ratio of Bax/Bcl-2 was displayed within the IC50 concentration of RUT-MSNs in 48 h (p < 0.05). The antibacterial action of rutin was improved by loading rutin in MSNs to the nano-sized range in the MIC test. CONCLUSION: The anticancer and antibacterial effects of RUT-MSNs were considerably more than rutin. RUT-MSNs inhibited the growth of HN5 cells by inducing apoptosis and producing ROS. These results suggest that RUT-MSNs may be useful in the treatment of cancers and infections.