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This study explores for the first time the impact of chitosan (CS) with varying molecular weights (MW), orange peel extract concentration, and hydroxypropyl methylcellulose (HPMC) content on the formulation of buccal tablets for treating oral infections. Utilizing a statistical design of experiments (DoE), nine different formulations were evaluated for mechanical properties, dissolution behavior, mucoadhesion, and biological activity. A formulation with high CS MW, 60% orange peel extract, and 8% HPMC, emerged as the optimal formulation, demonstrating superior tabletability, compressibility, and compactibility. Dissolution studies indicated that hesperidin release followed the Higuchi model, with higher extract content enhancing this phenomenon. Mucoadhesion improved with increased HPMC and CS concentrations, although higher extract content reduced bioadhesion. Biological assays showed that higher extract levels boosted antioxidant activity, while CS primarily contributed to anti-inflammatory effects. The optimized formulation exhibited broad antimicrobial activity against key oral pathogens, surpassing the effectiveness of the individual components. Principal component analysis (PCA) further confirmed the significant influence of extract content on tablet properties. These findings suggest that the optimized tablet formulation holds promise for effective buccal delivery in the treatment of oral infections, warranting further investigation in clinical settings.

Three new dihydroflavonols, gloverinols A-C ( 1 - 3 ), a new flavon-3-ol, gloverinol D ( 4 ), two new isoflavans, gloveriflavan A ( 5 ) and B ( 6 ), and seven known compounds were isolated from the root bark of Dalbergia gloveri . The structures of the isolates were elucidated by using NMR, ECD, and HRESIMS data analyses. Among the isolated compounds, gloverinol B ( 2 ), gloveriflavan B ( 6 ), and 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl)-1-propanone ( 10 ) were the most active against Staphylococcus aureus , with MIC values of 9.2, 18.4, and 14.2 μM, respectively.

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.

This literature review provides an up-to-date exploration of the multifaceted attributes of maitake mushrooms ( Grifola frondosa ), elucidating their bioactive phytochemicals and diverse health advantages, including their substantial role in supporting human health and potential incorporation into the medicinal industry. Carbohydrates and protein are the major constituents contributing to the dry weight of G. frondosa , taking up around 70-80 % and 13-21 %, respectively, with emerging research linking these constituents to various health benefits. By synthesising current research findings, this review emphasises the substantial role of maitake mushrooms in supporting human health and underscores their potential incorporation into the medicinal industry. To further advance our understanding, future research should delve into the mechanisms underlying their health-promoting effects, with a focus on conducting quantitative studies to elucidate physiological pathways and potential drug interactions. Additionally, exploring their integration into functional foods or nutraceuticals through quantitative assessments of bioavailability and efficacy will be crucial for maximising their therapeutic benefits. This review aims to provide comprehensive insights, catalysing further research and innovation in utilising maitake mushrooms for improved well-being and industry advancement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Marigold flower is a traditionally used plant material topically applied on the skin due to its anti-inflammatory properties and antibacterial activity. This potential of action justifies the implementation of marigold extract in nanofiber scaffolds based on poly-vinylpyrrolidone/hydroxypropyl-β-cyclodextrin (PVP/HPβCD) and polycaprolactone/polyvinylpyrrolidone (PCL/PVP) obtained by electrospinning for wound treatment. Using SEM, the morphology of electrospun scaffolds showed a fiber diameter in the range of 298-527 nm, with a uniform and bead-free appearance. ATR-FTIR spectroscopy confirmed the presence of marigold extracts in nanofibrous scaffolds. The composition of the nanofibers can control the release; in the case of PVP/HPβCD, immediate release of 80% of chlorogenic acid (an analytical and functional marker for marigold extract) was achieved within 30 min, while in the case of PCL/PVP, the controlled release was achieved within 24 h (70% of chlorogenic acid). All systems showed weak antibacterial activity against skin and wound-infecting bacteria Staphylococcus aureus (MIC 100 mg/mL), and Pseudomonas aeruginosa (MIC 200 mg/mL) and yeasts Candida albicans (MIC 100 mg/mL). 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 scratch was closed after 36 h, compared to the 48 h required for PVP/HPβCD. Overall, the study shows that scaffolds of PCL/PVP nanofibers loaded with classic marigold extract have the best potential as wound dressing materials because of their ability to selectively modulate inflammation (via inhibition of hyaluronidase enzyme) and supportive antimicrobial properties, thereby aiding in the early stages of wound healing and repair.

Candida albicans 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 C. albicans . 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 C. albicans . 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- Candida 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%), Scutellaria 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 Candida albicans , 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.

Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has long been found to be dysregulated in human lung adenocarcinomas (LUADs). Nevertheless, the function, mutational profile, epigenetic regulation, co-expression profile, and clinicopathological significance of the GPC3 gene in LUAD progression are not well understood. In this study, we analyzed cancer microarray datasets from publicly available databases using bioinformatics tools to elucidate the above parameters. We observed significant downregulation of GPC3 in LUAD tissues compared to their normal counterparts, and this downregulation was associated with shorter overall survival (OS) and relapse-free survival (RFS). Nevertheless, no significant differences in the methylation pattern of GPC3 were observed between LUAD and normal tissues, although lower promoter methylation was observed in male patients. GPC3 expression was also found to correlate significantly with infiltration of B cells, CD8+, CD4+, macrophages, neutrophils, and dendritic cells in LUAD. In addition, a total of 11 missense mutations were identified in LUAD patients, and ~1.4% to 2.2% of LUAD patients had copy number amplifications in GPC3. Seventeen genes, mainly involved in dopamine receptor-mediated signaling pathways, were frequently co-expressed with GPC3. We also found 11 TFs and 7 miRNAs interacting with GPC3 and contributing to disease progression. Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The inappropriate use of antimicrobials, along with environmental conditions, can lead to the emergence of resistant microorganisms. The use of phytopharmaceuticals and herbal medicines has a positive impact and represents a promising alternative. Psidium guajava extracts have been widely reported to have antimicrobial potential; however, studies reporting their activity against resistant bacterial strains are scarce. Because of the emerging resistance, the aim of this study was to analyze the antimicrobial capacity of the aqueous extract of guava leaves against wild-type and resistant bacterial strains. The aqueous extract obtained from the leaves of P. guajava was evaluated by HPLC for the content of total phenolics and tannins, antioxidant activity, and chemical composition. The antimicrobial activity of the extracts was analyzed by the disk diffusion and broth microdilution methods. The results of the chemical analysis of the extracts showed total phenolics content of 17.02 ± 6.87 mg/g of dry extract, total tannin content of 14.09 ± 1.20 mg of tannic acid equivalents/g of dry extract, and moderate antioxidant capacity with an EC 50 value of 140 µg/mL. Flavonoids are the major compounds (rutin, hesperidin, and quercetin), followed by phenolic acids. Disk diffusion test results showed the presence of inhibition halos for Gram-positive bacteria ( Staphylococcus aureus, sensitive and resistant; Staphylococcus pseudintermedius, sensitive and resistant; and Streptococcus spp., beta-hemolytic), while for Gram-negative bacteria ( Escherichia coli , sensitive and resistant), there was no inhibition in the tested concentration range. The Minimal Inhibitory Concentration was 6.8 mg/mL for all Gram-positive strains evaluated. The present study demonstrated the antimicrobial activity of the aqueous extract of P. guajava against sensitive and resistant Gram-positive bacteria. The better antimicrobial activity found in the present study compared with previously reported activity should be highlighted and may be related to the higher concentration of total phenolics present in the tested extract. Moreover, the content of tannins found suggests a species with high quality that produces tannins. These new findings suggest an innovative profile regarding therapeutic resources that can be adopted to combat resistant microbial strains.

Furofuran lignanes show important biological activities for the treatment of infectious diseases, inflammatory and metabolic pathologies. They have been isolated from leaves and barks of many plants. In Chile the native conifer Araucaria araucana produces eudesmin, matairesinol, secoisolariciresinol and lariciresinol in stemwood, branchwood and knotwood. These compounds were previously isolated by laborious flash chromatography on silica gel. Here we report the easy isolation of eudesmin by soxhlet extraction from milled knots of Araucaria araucana with hexane, followed by cryo-crystallization at -20 °C. Upon bromination of the isolated eudesmin epimerization at one benzylic position occurs, giving epieudesmin and the corresponding mono and di-brominated derivatives. The structures were determined by 1D, 2D NMR and X-ray diffraction. The analysis of products against Candida yeast showed that eudesmin has a moderate activity against different strains of Candida from 62.5 to 500 µg/mL. This activity decreases for epieudesmin, while bromine derivatives are not active.

Hepatitis C virus (HCV) is a dangerous virus that is responsible for a large number of infections and deaths worldwide. In the treatment of HCV, it is important that the drugs are effective and do not have additional hepatotoxic effects. The aim of this study was to test the in silico activity of 1893 terpenes against the HCV NS5B polymerase (PDB-ID: 3FQK). Two drugs, sofosbuvir and dasabuvir, were used as controls. The GOLD software (CCDC) and InstaDock were used for docking. By using the results obtained from PLP.Fitness (GOLD), pKi, and binding free energy (InstaDock), nine terpenes were finally selected based on their scores. The drug-likeness properties were calculated using Lipinski's rule of five. The ADMET values were studied using SwissADME and pkCSM servers. Ultimately, it was shown that nine terpenes have better docking results than sofosbuvir and dasabuvir. These were gniditrin, mulberrofuran G, cochlearine A, ingenol dibenzoate, mulberrofuran G, isogemichalcone C, pawhuskin B, 3-cinnamyl-4-oxoretinoic acid, DTXSID501019279, and mezerein. Each docked complex was submitted to 150 ns-long molecular dynamics simulations to ascertain the binding stability. The results show that mulberrofuran G, cochlearine A, and both stereoisomers of pawhuskin B form very stable interactions with the active site region where the reaction product should form and are, therefore, good candidates for use as effective competitive inhibitors. The other compounds identified in the docking screen either afford extremely weak (or even hardly any) binding (such as ingenol dibenzoate, gniditrin, and mezerein) or must first undergo preliminary movements in the active site before attaining their stable binding conformations, in a process which may take from 60 to 80 ns (for DTXSID501019279, 3-cinnamyl-4-oxoretinoic acid or isogemichalcone C).

Background: Candidiasis is a common oral and vaginal infection. Some papers have presented that the essential oils of Lamiaceae plants can have antifungal activity. This study aimed to investigate the activity of 7 essential oils of the Lamiaceae family with known phytochemical compositions against Candida fungi., Methods: Forty-four strains belonging to six species were tested: C. albicans , C. glabrata , C. guilliermondii , C. krusei , C. parapsilosis , and C. tropicalis . During this investigation, the following methods were used: determination of the minimal inhibitory concentrations (MICs), biofilm inhibition studies, and in silico toxicity tests., Results: Essential oils of lemon balm ( Melissa officinalis ) and oregano ( Origanum vulgare ) showed the best anti- Candida activity, with MIC values below 3.125 mg/mL. Lavender ( Lavandula stoechas ), mint ( Mentha × piperita ), rosemary ( Rosmarinus officinalis ), and thyme ( Thymus vulgaris ) essential oils were also very active (0.39 to 6.25 or 12.5 mg/mL). Sage ( Salvia officinalis ) essential oil presented the lowest activity, with MIC values ranging from 3.125 to 100 mg/mL. In an antibiofilm study using MIC values, oregano and thyme essential oils showed the greatest effect, followed by lavender, mint, and rosemary oils. The weakest antibiofilm activity was observed with the lemon balm and sage oils. In silico toxicity research suggests that most of main compounds of Lamiaceae essential oils probably do not exhibit carcinogenicity, mutagenicity, or cytotoxicity., Conclusions: The obtained results showed that Lamiaceae essential oils have anti- Candida and antibiofilm activity. Further research is required to confirm the safety and efficacy of essential oils in the topical treatment of candidiasis., Competing Interests: Given their role as Guest Editors, Tomasz M. Karpiński and Marcin Ożarowski had no involvement in the peer-review of this article and have no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Graham Pawelec. The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: 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., Methods: 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., Results: 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., Conclusions: Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF., (© 2023. The Author(s).)

The Ganoderma genus is known for its diverse use as a functional food and therapeutic agent. This fungus has over 428 species, with Ganoderma lucidum being the most studied. The Ganoderma 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 Ganoderma 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 Ganoderma 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 Ganoderma species and the underlying physiological mechanisms.

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools., Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST., Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events., Competing Interests: Conflict of Interest Authors Dr. Rajeev K. Singla and Shailja Singla have an honorary-based associations with the iGlobal Research and Publishing Foundation (iGRPF), New Delhi, India. Dr. Bernd Fiebich is associated with VivaCell Biotechnology GmbH. RKS, SS and BF along with the remaining authors, declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Given their role as Editor/Associate Editor/ Editorial board members, “Prof. Thomas Efferth”, “Ilkay Erdogan Orhan”, “Milen Georgiev”, “Davide Barreca”, “Maurizio Battino”, “Anupam Bishayee”, “Michael Heinrich”,and“Jianbo Xiao”had no involvement in the peer-review of this article and has no access to information regarding its peer-review., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused by viruses such as severe acute respiratory syndrome coronavirus 2, influenza viruses, the parainfluenza virus and rhinoviruses. One of the main challenges in recent years has been severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19. Recently, an increasing number of studies are focusing on the activity of various propolis preparations against SARS-CoV-2 as an adjuvant treatment for this infection. Propolis has shown a few key mechanisms of anti-SARS-CoV-2 action such as: the inhibition of the interaction of the S1 spike protein and ACE-2 protein; decreasing the replication of viruses by diminishing the synthesis of RNA transcripts in cells; decreasing the particles of coronaviruses. The anti-viral effect is observed not only with extracts but also with the single biologically active compounds found in propolis (e.g., apigenin, caffeic acid, chrysin, kaempferol, quercetin). Moreover, propolis is effective in the treatment of hyperglycemia, which increases the risk of SARS-CoV-2 infections. The aim of the literature review was to summarize recent studies from the PubMed database evaluating the antiviral activity of propolis extracts in terms of prevention and the therapy of respiratory tract diseases (in vitro, in vivo, clinical trials). Based upon this review, it was found that in recent years studies have focused mainly on the assessment of the effectiveness of propolis and its chemical components against COVID-19. Propolis exerts wide-spectrum antimicrobial activities; thus, propolis extracts can be an effective option in the prevention and treatment of co-infections associated with diseases of the respiratory tract.

Background: In the case of COVID-19 patients, it has been observed that the immune system of the infected person exhibits an extreme inflammatory response known as cytokine release syndrome (CRS) where the inflammatory cytokines are swiftly produced in quite large amounts in response to infective stimuli. Numerous case studies of COVID-19 patients with severe symptoms have documented the presence of higher plasma concentrations of human interleukin-6 (IL-6), which suggests that IL-6 is a crucial factor in the pathophysiology of the disease. In order to prevent CRS in COVID-19 patients, the drugs that can exhibit binding interactions with IL-6 and block the signaling pathways to decrease the IL-6 activity may be repurposed., Methods: This research work focused on molecular docking-based screening of the drugs celecoxib (CXB) and dexamethasone (DME) to explore their potential to interact with the binding sites of IL-6 protein and reduce the hyper-activation of IL-6 in the infected personnel., Results: Both of the drugs were observed to bind with the IL-6 (IL-6 receptor alpha chain) and IL-6Rα receptor with the respective affinities of -7.3 kcal/mol and -6.3 kcal/mol, respectively, for CXB and DME. Moreover, various types of binding interactions of the drugs with the target proteins were also observed in the docking studies. The dynamic behaviors of IL-6/IL-6Rα in complex with the drugs were also explored through molecular dynamics simulation analysis. The results indicated significant stabilities of the acquired drug-protein complexes up to 100 ns., Conclusion: The findings of this study have suggested the potential of the drugs studied to be utilized as antagonists for countering CRS in COVID-19 ailment. This study presents the studied drugs as promising candidates both for the clinical and pre-clinical treatment of COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Despite decades of research, cancer continues to be a major global health concern. In recent years, the role played by microorganisms in the development and progression of cancer has come under increased scrutiny. The aim of the present review is to highlight the main associations between members of the human oral microbiota and various cancers. The PubMed database was searched for available literature to outline the current state of understanding regarding the role of the oral microbiota and a variety of human cancers. Oral squamous cell carcinoma (OSCC) is associated with carriage of a number of oral bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.), certain viruses (e.g., human papilloma virus, human herpes virus 8, herpes simplex virus 1 and Epstein-Barr virus) and yeast (Candida albicans). Moreover, members of the oral microbiota are associated with cancers of the esophagus, stomach, pancreas, colon/rectum and lung. Furthermore, the present review outlines a number of the carcinogenic mechanisms underlying the presented microbial associations with cancer. Such information may one day help clinicians to diagnose neoplastic diseases at earlier stages and prescribe treatments that take into account the possible microbial nature of carcinogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hassan, Samanta, Dash, Karpiński, Habibi, Sadiq, Ahmadi and Bunagu.)

Background: Bovine leukemia virus (BLV) is an oncogenic delta-retrovirus causing bovine leucosis. Studies on BLV have shown the association with human breast cancer. However, the exact molecular mechanism is neither known nor their appropriate preventative measure to halt the disease initiation and progression. In this study, we designed a multi-epitope vaccine against BLV using a computational analyses., Methods: Following a rigorous assessment, the vaccine was constructed using the T-cell epitopes from each BLV-derived protein with suitable adjuvant and linkers. Both physicochemistry and immunogenic potency as well as the safeness of the vaccine candidate were assessed. Population coverage was done to evaluate the vaccine probable efficiency in eliciting the immune response worldwide. After homology modeling, the three-dimensional structure was refined and validated to determine the quality of the designed vaccine. The vaccine protein was then subjected to molecular docking with Toll-like receptor 3 (TLR3) to evaluate the binding efficiency followed by dynamic simulation for stable interaction., Results: Our vaccine construct has the potential immune response and good physicochemical properties. The vaccine is antigenic and immunogenic, and has no allergenic or toxic effect on the human body. This novel vaccine contains a significant interactions and binding affinity with the TLR3 receptor., Conclusions: The proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat BLV infections. However, experimental evaluations are essential to validate the exact safety and immunogenic profiling of this vaccine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (-1424.9 kcal/mol) and GPCR (-1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis.

Analysis of sensorimotor behavioral responses to stimuli such as light can provide an enhanced relevance during rapid prioritisation of chemical risk. Due to technical limitations, there have been, however, only minimal studies on using invertebrate phototactic behaviors in aquatic ecotoxicity testing. In this work, we demonstrate an innovative, purpose-built analytical system for a high-throughput phototactic biotest with nauplii of euryhaline brine shrimp Artemia franciscana . We also, for the first time, present a novel and dedicated bioinformatic approach that facilitates high-throughput analysis of phototactic behaviors at scale with great fidelity. The nauplii exhibited consistent light-seeking behaviors upon extinguishing a brief programmable light stimulus (5500K, 400 lux) without habituation. A proof-of-concept validation involving the short-term exposure of eggs (24 h) and instar I larval stages (6 h) to sub-lethal concentrations of insecticides organophosphate chlorpyrifos (10 µg/L) and neonicotinoid imidacloprid (50 µg/L) showed perturbation in light seeking behaviors in the absence of or minimal alteration in general mobility. Our preliminary data further support the notion that phototactic bioassays can represent an attractive new avenue in behavioral ecotoxicology because of their potential sensitivity, responsiveness, and low cost.

Background: Appropriate levels of cholesterol are necessary for the mother and developing fetus, but theirexcess may cause preeclampsia. The ABCA1 transporter mediates the secretion of cholesterol and is highly regulated at the transcriptional level via the nuclear liver X receptors (LXRs)., Methods: Sixteen preeclamptic and 39 normotensives healthy women with uncomplicated pregnancies were involved in the case-control study. The placental levels of ABCA1, LXRA and LXRB mRNA were quantified by real-time quantitative PCR. The concentrations of ABCA1, LXRA and LXRB proteins from the placenta were determined using an enzyme-linked immunosorbent assay Results: We found in the logistic regression model significantly lower placental expression of LXRB mRNA (crude OR = 0.26, 95% CI: 0.07-0.94, p = 0.040) and LXRA protein level (crude OR = 0.19, 95% CI: 0.05-0.69, p = 0.012) in late-onset preeclamptic women compared to healthy pregnant women. The values remained statistically significant after adjustment for possible confounders., Conclusions: Our results suggest that high placenta LXRA mRNA and LXRA protein expression levels decrease the risk of late-onset preeclampsia. These nuclear receptors could play a role in the development of preeclampsia through disturbances of lipid metabolism., Competing Interests: The authors declare no conflict of interest.

Introduction: Some evidence indicates that the improper trophoblast invasion of maternal spiral arteries could be caused by an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to preeclampsia (PE) development. This study aimed to assess the potential role of MMP1, MMP9, TIMP1 and TIMP2 gene polymorphisms in the pathogenesis of PE. Materials and methods: A total of 308 Polish women, 115 preeclamptic (55 with early-onset preeclampsia [EOPE], 60 with late-onset preeclampsia [LOPE]) and 193 healthy pregnant women, all of Caucasian origin, were recruited to the study. PE was diagnosed following the ACOG criteria. The polymorphic variants of the MMP-TIMP pathway (MMP1 rs1799750, MMP9 rs17576, MMP9 rs17577, TIMP1 rs4898, TIMP2 rs2277698, TIMP2 rs55743137) were genotyped by polymerase chain reaction and restriction fragment length polymorphism. Results: Analyzing all SNPs in the MMP-TIMP pathway, no significant differences in allele frequencies between preeclamptic women and controls were observed. However, comparing the EOPE and LOPE groups with each other, we observed a statistically significant difference between them for the TIMP1 rs4898 variant. In the whole group of 308 women, the mean placenta weight was the lowest in carriers of the rs4898 CC genotype. Post hoc analysis revealed significant differences between CC-CT (p = 0.0209) and CC-TT (p = 0.0469). Additionally, during allele analysis, a statistically significant difference in the mean placenta weight (for C allele 529.32 ± 157.11 g, for T allele 560.24 ± 162.24 g, p = 0.021) was also observed. Conclusion: Our findings suggest a relationship between TIMP1 rs4898 (372T > C) polymorphism and increased risk of early-onset preeclampsia in a population of pregnant Polish women. Our data suggest that the TIMP1 rs4898 C allele might be associated with increased risk for early-onset, but not for late-onset preeclampsia. To evaluate the role of the TIMP1 polymorphic variants in the etiopathology of preeclampsia, further studies with a larger sample size are needed.

Loss of tubulin is associated with neurodegeneration and brain aging. Turmeric (Curcuma longa L.) has frequently been employed as a spice in curry and traditional medications in the Indian subcontinent to attain longevity and better cognitive performance. We aimed to evaluate the unelucidated mechanism of how turmeric protects the brain to be an anti-aging agent. D. melanogaster was cultured on a regular diet and turmeric-supplemented diet. β-tubulin level and physiological traits including survivability, locomotor activity, fertility, tolerance to oxidative stress, and eye health were analyzed. Turmeric showed a hormetic effect, and 0.5% turmeric was the optimal dose in preventing aging. β-tubulin protein level was decreased in the brain of D. melanogaster upon aging, while a 0.5% turmeric-supplemented diet predominantly prevented this aging-induced loss of β-tubulin and degeneration of physiological traits as well as improved β-tubulin synthesis in the brain of D. melanogaster early to mid-age. The higher concentration (≥ 1%) of turmeric-supplemented diet decreased the β-tubulin level and degenerated many of the physiological traits of D. melanogaster. The turmeric concentration-dependent increase and decrease of β-tubulin level were consistent with the increment and decrement data obtained from the evaluated physiological traits. This correlation demonstrated that turmeric targets β-tubulin and has both beneficial and detrimental effects that depend on the concentration of turmeric. The findings of this study concluded that an optimal dosage of turmeric could maintain a healthy neuron and thus healthy aging, by preventing the loss and increasing the level of β-tubulin in the brain., (© 2022. The Author(s).)

Long-term fungal infections that are difficult to treat require new substances for their prevention, treatment, or as adjuvants during antibiotic therapy. Propolis is a very promising source of natural substances that show a wide range of pharmacological properties, including antifungal activity against various fungal strains. The purpose of the literature review was to summarize recent studies (PubMed, Scopus) on progress in evaluating the antifungal activity of chemically defined propolis extracts. During the selection of studies, only those with results of antifungal activity expressed as minimal inhibitory concentration (MIC) and/or minimal fungicidal concentration (MFC) were analyzed. Moreover, plant, animal and environmental factors influencing the chemical composition of propolis are discussed. Mechanisms of antifungal activity of propolis extracts and research trends in the aspect of developing new therapies and the assessment of drug interactions are indicated. The review of the research results shows that there is great progress in the definition of propolis extracts. After comparing the MIC/MFC values, it was assessed that propolis extracts offer a wide range of activity not only against pathogenic Candida strains but also against risky molds; however, the strength of this activity is varied.

Background: Edible and medicinal plants are still an interesting source of promising biologically active substances for drug discovery and development. At a time of increasing cancer incidence in the world, alleviating the bothersome side effects of radiotherapy in debilitated cancer patients is becoming an important challenge., Objective: The aim of the study was to overview the literature data concerning the radioprotective activity of extracts, essential oils, and some chemical compounds obtained from 12 species belonging to the Lamiaceae family, gathering of numerous spice and medicinal plants rich in valuable phytochemicals., Results: The analysis of available publications showed radioprotective effectiveness of essential oils and complex extracts containing phenolic acids and flavonoids in various in vitro and in vivo models. Relatively welldocumented preventive properties exhibited the following species: Mentha × piperita, Ocimum tenuiflorum, Origanum vulgare, and Rosmarinus officinalis. However, few plants such as Lavandula angustifolia, Mentha arvensis, M. spicata, Plectranthus amboinicus, Salvia miltiorrhiza, S. officinalis, Scutellaria baicalensis, and Zataria multiflora should be more investigated in the future. Among the mechanisms of radioprotective effects of well-studied extracts and phytochemicals, it can be mentioned mainly the protection against chromosomal damage, scavenging free radicals, decreasing of lipid peroxidation and elevating of glutathione, superoxide dismutase, catalase, and alkaline phosphatase enzyme levels as well as the reduction of the cell death. The plant substances protected the gastrointestinal tract, bone marrow and lung fibroblasts., Conclusion: The studied species of Lamiaceae family and their active chemical compounds are potent in alleviating the side effects of radiotherapy and should be considered as a complementary therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200-4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10-250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100 nm) can be used to treat cancer due to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nanoformulations have created brand new perspectives for cancer treatment. However, most of the research is limited to in vivo and in vitro studies, and the number of approved nanodrugs has not much amplified over the years. This review discusses numerous types of nanoparticles, targeting mechanisms, and approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation., (© 2021. The Author(s).)

Issues arising in wound healing are very common, and chronic wound infections affect approximately 1.5% of the population. The main substances used in wound washing, cleansing and treatment are antiseptics. Today, there are many compounds with a known antiseptic activity. Older antiseptics (e.g., boric acid, ethacridine lactate, potassium permanganate, hydrogen peroxide, iodoform, iodine and dyes) are not recommended for wound treatment due to a number of disadvantages. According to the newest guidelines of the Polish Society for Wound Treatment and the German Consensus on Wound Antisepsis, only the following antiseptics should be taken into account for wound treatment: octenidine (OCT), polihexanide (PHMB), povidone-iodine (PVP-I), sodium hypochlorite (NaOCl) and nanosilver. This article provides an overview of the five antiseptics mentioned above, their chemical properties, wound applications, side effects and safety.

Article Title and Bibliographic Information: 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., Source of Funding: The study was funded by International Islamic University Malaysia (P-RIGS18-036-0036)., Type of Study/design: Systematic review with meta-analysis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Continuous monitoring and early warning of potential water contamination with toxic chemicals is of paramount importance for human health and sustainable food production. During the last few decades there have been noteworthy advances in technologies for the automated sensing of physicochemical parameters of water. These do not translate well into online monitoring of chemical pollutants since most of them are either incapable of real-time detection or unable to detect impacts on biological organisms. As a result, biological early warning systems have been proposed to supplement conventional water quality test strategies. Such systems can continuously evaluate physiological parameters of suitable aquatic species and alert the user to the presence of toxicants. In this regard, single cellular organisms, such as bacteria, cyanobacteria, micro-algae and vertebrate cell lines, offer promising avenues for development of water biosensors. Historically, only a handful of systems utilising single-cell organisms have been deployed as established online water biomonitoring tools. Recent advances in recombinant microorganisms, cell immobilisation techniques, live-cell microarrays and microfluidic Lab-on-a-Chip technologies open new avenues to develop miniaturised systems capable of detecting a broad range of water contaminants. In experimental settings, they have been shown as sensitive and rapid biosensors with capabilities to detect traces of contaminants. In this work, we critically review the recent advances and practical prospects of biological early warning systems based on live-cell biosensors. We demonstrate historical deployment successes, technological innovations, as well as current challenges for the broader deployment of live-cell biosensors in the monitoring of water quality.

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.

For the first time in the Polish population, we aimed to investigate associations between the VDR gene single-nucleotide polymorphisms (SNPs) BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) and the development of preeclampsia (PE). A case-control study surveyed 122 preeclamptic and 184 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal VDR FokI , BsmI , TaqI , and ApaI polymorphisms. The VDR BsmI AA homozygous genotype was statistically significantly more frequent in preeclamptic women compared to the control group ( p = 0.0263), which was also associated with a 2-fold increased risk of PE (OR = 2.06, p = 0.012). A correlation between the VDR BsmI polymorphism with systolic and diastolic blood hypertension was noted. Furthermore, 3-marker haplotype CTA ( TaqI/ApaI/BsmI ) was associated with significantly higher systolic ( p = 0.0075) and diastolic ( p = 0.0072) blood pressure. Association and haplotype analysis indicated that the VDR BsmI A allele could play a significant role in the PE pathomechanism and hence could be a risk factor for PE development in pregnant Polish women. These results indicate the importance of the VDR BsmI polymorphism and reveal that this variant is closely associated with a higher predisposition to hypertension.

Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. KEY MESSAGES: • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types., (© 2021. The Author(s).)

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.

Tantalum (Ta) and its application in biomaterials has been attracting more and more attention recently. It can be considered as a material for hard tissue implants. This study focuses on antimicrobial and surface characterization of micro-arc oxidized (MAO) nanocrystalline Ta compared with its microcrystalline equivalent. For the purposes of the investigation, x-ray diffractometry (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), wetting analysis, optical profilometry, corrosion resistance measurement, and antimicrobial tests were performed. Nanocrystalline Ta was fabricated using high-energy ball milling (HEBM) and pulse plasma sintering (PPS). The MAO process done at 250 V results in the formation of a porous oxide surface. An XRD analysis confirmed the presence of a Ta 2 O 5 oxide layer. Based on the SEM pictures, the obtained oxide layer was approximately 3-4 μm thick for nanocrystalline Ta substrate. For microcrystalline Ta, the oxide layer was thinner, in the range of 0.3-0.6 μm. The analysis of polarization curves showed a significant improvement of corrosion resistance for MAO nanocrystalline Ta (2.62 × 10 -8 A/cm 2 ) versus not oxidized nanocrystalline Ta (1.20 × 10 -5 A/cm 2 ). The surface roughness of MAO nanocrystalline Ta proved to be several times higher than that of unoxidized Ta. Wetting analysis showed that the oxide layer on the nanocrystalline substrate is hydrophilic. This research provides detailed information about MAO microcrystalline and MAO nanocrystalline Ta antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. A significant decrease of S. aureus for MAO nanocrystalline Ta (control 10,435 ± 981 vs. sample 3,453 ± 130) was noticed. No significant difference was noticed for MAO microcrystalline and nanocrystalline Ta tested for P. aeruginosa., (© 2020 Wiley Periodicals LLC.)

Background/aim: Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system to each other. The TLRs are activated through binding to damage/danger-associated molecular patterns (DAMPs), microbial/microbe-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). The immunogenetic molecules of TLRs have their own functions, structures, coreceptors, and ligands which make them unique. These properties of TLRs give us an opportunity to find out how we can employ this knowledge for ligand-drug discovery strategies to control TLRs functions and contribution, signaling pathways, and indirect activities. Hence, the authors of this paper have a deep observation on the molecular and structural biology of human TLRs (hTLRs)., Methods and Materials: To prepare this paper and fulfill our goals, different search engines (e.g., GOOGLE SCHOLAR), Databases (e.g., MEDLINE), and websites (e.g., SCOPUS) were recruited to search and find effective papers and investigations. To reach this purpose, we tried with papers published in the English language with no limitation in time. The iCite bibliometrics was exploited to check the quality of the collected publications., Results: Each TLR molecule has its own molecular and structural biology, coreceptor(s), and abilities which make them unique or a complementary portion of the others. These immunogenetic molecules have remarkable roles and are much more important in different sections of immune and nonimmune systems rather than that we understand to date., Conclusion: TLRs are suitable targets for ligand-drug discovery strategies to establish new therapeutics in the fields of infectious and autoimmune diseases, cancers, and other inflammatory diseases and disorders., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Payam Behzadi et al.)

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., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris , which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045-0.07 mg/L), Satureja macrosiphon (0.06-8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica , Lawsonia inermis , and Thymus vulgaris . Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida . Given this, they may be a promising alternative to antifungal drugs.

As the major nonpsychotropic constituent of Cannabis sativa , cannabidiol (CBD) is regarded as one of the most promising therapeutic agents due to its proven effectiveness in clinical trials for many human diseases. Due to the urgent need for more efficient pharmacological treatments for several chronic diseases, in this review, we discuss the potential beneficial effects of CBD for Alzheimer's disease, epilepsy, multiple sclerosis, and neurological cancers. Due to its wide range of pharmacological activities (e.g., antioxidant, anti-inflammatory, and neuroprotective properties), CBD is considered a multimodal drug for the treatment of a range of neurodegenerative disorders, and various cancer types, including neoplasms of the neural system. The different mechanisms of action of CBD are here disclosed, together with recent progress in the use of this cannabis-derived constituent as a new therapeutic approach.

The current health requirements set the direction in pharmacological research, especially as regards diseases that require improvement of existing therapeutic regimens. Such diseases include preeclampsia, which is a hypertensive disorder of pregnancy during which there occurs progressive increasing activation of the immune system through elevation of pro-inflammatory cytokines and antiangiogenic factors, which is dangerous for the mother and fetus. A promising field of research for new drugs to treat this disease is the study of natural phenolic compounds of plant origin and herbal extracts, which are complex matrices of chemical compounds with broad biological activities. Many plant substances with anti‑inflammatory and anti‑hypertensive properties are known, but studies in animal models of preeclampsia and clinical trials concerning this disease constitute a new and developing research trend of significant medical importance. The aim of our research review was to identify and analyze the results of already available studies on baicalin, curcumin, epigallocatechin gallate, punicalagin, quercetin, resveratrol, salvianolic acid A (danshensu), silibinin, and vitexin, as well as plant extracts from Brassica oleracea L., Euterpe oleracea Mart., Moringa oleifera Lam., Punica granatum L., Silybum marianum (L.) Gaertner, Thymus schimperi Ronniger, Uncaria rhynchophylla (Miq.) Miq. ex Havil., and Vitis vinifera L., which are potential and promising candidates for further research and for potential new therapies.

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1β; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor β-TGF-β; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1β, IL-6, HIF-1α, TGF-β, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.

A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.

The global outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a requirement for two pronged clinical interventions such as development of effective vaccines and acute therapeutic options for medium-to-severe stages of "coronavirus disease 2019" (COVID-19). Effective vaccines, if successfully developed, have been emphasized to become the most effective strategy in the global fight against the COVID-19 pandemic. Basic research advances in biotechnology and genetic engineering have already provided excellent progress and groundbreaking new discoveries in the field of the coronavirus biology and its epidemiology. In particular, for the vaccine development the advances in characterization of a capsid structure and identification of its antigens that can become targets for new vaccines. The development of the experimental vaccines requires a plethora of molecular techniques as well as strict compliance with safety procedures. The research and clinical data integrity, cross-validation of the results, and appropriated studies from the perspective of efficacy and potently side effects have recently become a hotly discussed topic. In this review, we present an update on latest advances and progress in an ongoing race to develop 52 different vaccines against SARS-CoV-2. Our analysis is focused on registered clinical trials (current as of November 04, 2020) that fulfill the international safety and efficacy criteria in the vaccine development. The requirements as well as benefits and risks of diverse types of SARS-CoV-2 vaccines are discussed including those containing whole-virus and live-attenuated vaccines, subunit vaccines, mRNA vaccines, DNA vaccines, live vector vaccines, and also plant-based vaccine formulation containing coronavirus-like particle (VLP). The challenges associated with the vaccine development as well as its distribution, safety and long-term effectiveness have also been highlighted and discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

There is increasing interest in evaluating anti-inflammatory activities of plant substances such as extracts and flavonoid rich fractions. A promising source of new medicinal drugs may be species from the Passifloraceae family. The most interesting group of principal chemical substances in Passiflora species are polyphenolic compounds, including flavonoids (quercetin, rutin, apigenin, luteolin, chrysin, and C-glycosylflavones i.e., vitexin, isovitexin, orientin, isoorientin), due to their antioxidant activity demonstrated in various studies. However, each extract from Passiflora spp. as multi-component mixtures should be estimated for chemical composition (in the standardization process) and its activity using in vitro and in vivo tests. The current standard for drug discovery and development from plants indicates that only collective assessment allows estimating plant substances by definition of the origin of raw materials and their quality, methods of extractions, and metabolite profiles. Increasingly, due to complex phytochemical procedures to obtain extracts, individual flavonoid compounds are also tested for anti-inflammatory action. However, it should be emphasized that various sources of potential new drugs from plant origin are not mutually exclusive, but are complementary. A review of bibliographic data includes the following information about Passiflora species, such as distribution, classification, phytochemical compounds, the anti-inflammatory activity of the extracts, the anti-inflammatory activity of flavonoids, and antioxidant potential. The review concluded that extracts and flavonoids (mainly quercetin, apigenin, and vitexin) from Passiflora spp. can be a valuable source of anti-inflammatory and anti-oxidative medications for the prevention and treatment of many diseases, which occur with complex inflammatory processes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Halitosis is a common ailment concerning 15% to 60% of the human population. Halitosis can be divided into extra-oral halitosis (EOH) and intra-oral halitosis (IOH). The IOH is formed by volatile compounds, which are produced mainly by anaerobic bacteria. To these odorous substances belong volatile sulfur compounds (VSCs), aromatic compounds, amines, short-chain fatty or organic acids, alcohols, aliphatic compounds, aldehydes, and ketones. The most important VSCs are hydrogen sulfide, dimethyl sulfide, dimethyl disulfide, and methyl mercaptan. VSCs can be toxic for human cells even at low concentrations. The oral bacteria most related to halitosis are Actinomyces spp., Bacteroides spp., Dialister spp., Eubacterium spp., Fusobacterium spp., Leptotrichia spp., Peptostreptococcus spp., Porphyromonas spp., Prevotella spp., Selenomonas spp., Solobacterium spp., Tannerella forsythia , and Veillonella spp. Most bacteria that cause halitosis are responsible for periodontitis, but they can also affect the development of oral and digestive tract cancers. Malodorous agents responsible for carcinogenesis are hydrogen sulfide and acetaldehyde.