Pomegranate peel extract is known for its potent antibacterial, antiviral, antioxidant, anti-inflammatory, wound healing, and probiotic properties, leading to its use in treating oral infections. In ...the first stage of this work, for the first time, using the Design of Experiment (DoE) approach, pomegranate peel extract (70% methanol, temperature 70 °C, and three cycles per 90 min) was optimized and obtained, which showed optimal antioxidant and anti-inflammatory properties. The optimized extract showed antibacterial activity against oral pathogenic bacteria. The second part of this study focused on optimizing an electrospinning process for a combination of polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) nanofibers loaded with the optimized pomegranate peel extract. The characterization of the nanofibers was confirmed by using SEM pictures, XRPD diffractograms, and IR-ATR spectra. The composition of the nanofibers can control the release; in the case of PVP–based nanofibers, immediate release was achieved within 30 min, while in the case of PCL/PVP, controlled release was completed within 24 h. Analysis of the effect of different scaffold compositions of the obtained electrofibers showed that those based on PCL/PVP had better wound healing potential. The proposed strategy to produce electrospun nanofibers with pomegranate peel extract is the first and innovative approach to better use the synergy of biological action of active compounds present in extracts in a patient-friendly pharmaceutical form, beneficial for treating oral infections.
Pancreatic cancer (PC) remains a global health concern with high mortality and is expected to increase as a proportion of overall cancer cases in the coming years. Most patients are diagnosed at a ...late stage of disease progression, which contributes to the extremely low 5-year survival rates. Presently, screening for PC remains costly and time consuming, precluding the use of widespread testing. Biomarkers have been explored as an option by which to ameliorate this situation. The authors conducted a search of available literature on PubMed to present the current state of understanding as it pertains to the use of microbial biomarkers and their associations with PC. Carriage of certain bacteria in the oral cavity (e.g., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus sp.), gut (e.g., Helicobacter pylori, Synergistetes, Proteobacteria), and pancreas (e.g., Fusobacterium sp., Enterobacteriaceae, Pseudomonadaceae) has been associated with an increased risk of developing PC. Additionally, the fungal genus Malassezia has likewise been associated with PC development. This review further outlines potential oncogenic mechanisms involved in the microbial-associated development of PC.
Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons' blood, organs, or ...other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches.
The glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine immunodominant T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus.
After rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans.
Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Wan Mohd Kamaluddin et al. Probiotic inhibits oral carcinogenesis: A systematic review and meta-analysis. Arch Oral Biol. 2020 Oct;118:104,855. Doi: 10.1016/j.archoralbio.2020.104855. Epub 2020 Aug ...2.
The study was funded by International Islamic University Malaysia (P-RIGS18–036–0036).
Systematic review with meta-analysis
The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics. In this prospect, liposomal delivery systems ...have been employed in improving the efficacy of the antibacterial agents. The liposome-based antibiotics enhance the therapeutic potential of the new or existing antibiotics and reduce their adverse effects. The current study describes the development of sulfonium-based antibacterial lipids that demonstrate the delivery of existing antibiotics. The presence of cationic sulfonium moieties and inherent membrane targeting abilities of the lipids could help reduce the antibiotic resistance abilities of the bacteria and deliver the antibiotics to remove the infectious pathogens electively. The transmission electron microscopic images and dynamic light scattering analyses revealed the liposome formation abilities of the sulfonium-based amphiphilic compounds in the aqueous medium. The effectiveness of the compounds was tested against the Gram-negative and Gram-positive bacterial strains. The viability of the bacterial cells was remarkably reduced in the presence of the compounds. The sulfonium-based compounds with pyridinium moiety and long hydrocarbon chains showed the most potent antibacterial activities among the tested compounds. Mechanistic studies revealed the membrane-targeted bactericidal activities of the compounds. The potent compound also showed tetracycline and amoxicillin encapsulation and sustained release profiles in the physiologically relevant medium. The tetracycline and amoxicillin-encapsulated lipid showed much higher antibacterial activities than the free antibiotics at similar concentrations, emphasizing the usefulness of the synergistic effect of sulfonium-based lipid and the antibiotics, signifying that the sulfonium lipid penetrated the bacterial membrane and increased the cellular uptake of the antibiotics. The potent lipid also showed therapeutic potential, as it is less toxic to mammalian cells (like HeLa and HaCaT cells) at concentrations higher than their minimum inhibitory concentration values against
S. aureus
,
E. coli
, and MRSA. Hence, the sulfonium-based lipid exemplifies a promising framework for assimilating various warheads, and provides a potent antibacterial material.
The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics.
is the most critical fungus causing oral mycosis. Many mouthwashes contain antimicrobial substances, including antifungal agents. This study aimed to investigate the in vitro activity of 15 ...commercial mouthwashes against 12 strains of
. The minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), and anti-biofilm activity were studied. MICs were determined by the micro-dilution method using 96-well plates, and MFCs were determined by culturing MIC suspensions on Sabouraud dextrose agar. Anti-biofilm activity was evaluated using the crystal violet method. The mouthwashes containing octenidine dihydrochloride (OCT; mean MICs 0.09-0.1%), chlorhexidine digluconate (CHX; MIC 0.12%), and CHX with cetylpyridinium chloride (CPC; MIC 0.13%) exhibited the best activity against
. The active compound antifungal concentrations were 0.5-0.9 µg/mL for OCT products and 1.1-2.4 µg/mL for CHX rinses. For mouthwashes with CHX + CPC, concentrations were 1.56 µg/mL and 0.65 µg/mL, respectively. Products with polyaminopropyl biguanide (polyhexanide, PHMB; MIC 1.89%) or benzalkonium chloride (BAC; MIC 6.38%) also showed good anti-
action. In biofilm reduction studies, mouthwashes with OCT demonstrated the most substantial effect (47-51.1%). Products with CHX (32.1-41.7%), PHMB (38.6%), BAC (35.7%),
extract (35.6%), and fluorides + essential oils (33.2%) exhibited moderate antibiofilm activity. The paper also provides an overview of the side effects of CHX, CPC, and OCT. Considering the in vitro activity against
, it can be inferred that, clinically, mouthwashes containing OCT are likely to offer the highest effectiveness. Meanwhile, products containing CHX, PHMB, or BAC can be considered as promising alternatives.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The main risk factors for CRC are family history of colon or rectal cancer, familial polyposis syndrome or hereditary ...nonpolyposis, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease). Recent studies show that the gastrointestinal microbiota play a significant role in colorectal carcinogenesis. In this review we present the microorganisms, whose influence on the development of CRC has been proven: Bacteroides fragilis, Clostridioides and Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Helicobacter pylori, Peptostreptococcus anaerobius, Streptococcus bovis group, and sulfate-reducing bacteria. Moreover, the carcinogenic mechanisms of action mediated by the above bacteria are laid out.
Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. ...Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (−7.5, −7.1, −7.1, and −7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.
•Natural inhibitors against SARS-CoV-2 have been identified by targeting Spike protein recognizer receptor ACE2.•Initially, a structure-based pharmacophore model has been generated and used for virtual screening.•Four potential natural inhibitors have been identified through the virtual screening process.•MD simulations and MM/GBSA confirmed the structural stability of the selected compounds to the targeted protein.
In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, ...virB7, virB8, virB9, virB10, virB11, virD4) and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains), multifocal atrophic gastritis-MAG (group 2) and gastric adenocarcinoma-GC (group 3). Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1) high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains). In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The
genus is known for its diverse use as a functional food and therapeutic agent. This fungus has over 428 species, with
being the most studied. The
species produce several secondary metabolites and ...bioactive compounds like polysaccharides, phenols, and triterpenes, which are largely responsible for their therapeutic properties. Throughout this review, several extracts obtained from
species have been studied to delve into their therapeutic characteristics and mechanisms. Such properties like immunomodulation, antiaging, antimicrobial, and anticancer activities have been demonstrated by several
species and are supported by a large body of evidence. Although its phytochemicals play a vital role in its therapeutic properties, identifying the therapeutic potentials of fungal-secreted metabolites for human health-promoting benefits is a challenging task. Identification of novel compounds with distinct chemical scaffolds and their mechanism of action could help suppress the spread of rising pathogens. Thus, this review provides an updated and comprehensive overview of the bioactive components in different
species and the underlying physiological mechanisms.