Neutralizing antibody responses to the Delta variant of SARS-CoV-2 following vaccination with Ad5-nCoV (CanSino) in the Mexican population.

During the COVID-19 pandemic, the Ad5-nCoV vaccine was applied to the Mexican population before the WHO approved it. In a transversal study, we compare the CanSino vaccine efficacy and a natural SARS-CoV-2 infection in eliciting neutralizing antibodies against the SARS-CoV-2 Delta variant in Guadalajara, Mexico. Participants between 30-60 years were included in the study and classified into three groups: 1) Natural immunity (unvaccinated), 2) Vaccine-induced immunity (vaccinated individuals without a COVID-19 history), and 3) Natural immunity + vaccine-induced immunity. These groups were matched by age and gender. We assessed the ability of individuals' serum to neutralize the Delta variant and compared the results of the different groups using a neutralization test followed by plaque-forming units. Results showed that 39% of individuals' serum with a history of COVID-19 (natural immunity, Group 1) could not neutralize the Delta variant, compared to 33% in vaccinated individuals without COVID-19 (vaccine immunity, Group 2). In contrast, only 7% of vaccinated individuals with a history of COVID-19 (natural + vaccine immunities) could not neutralize the Delta variant. We concluded that the effectiveness of the Ad5-nCoV vaccine to induce neutralizing antibodies against the Delta variant is comparable to that of natural infection (61% vs. 67%). However, in individuals with both forms of immunity (Group 3), it increased to 93%. Based on these results, despite the Ad5-nCoV vaccine originally being designed as a single-dose regimen, it could be recommended that even those who have recovered from COVID-19 should consider vaccination to boost their immunity against this variant.

Nanomedicine-mediated drug delivery for potential treatment of inflammatory bowel disease: a narrative review.

Background & aims: Inflammatory bowel disease (IBD) is a condition characterized by chronic inflammation of the gastrointestinal tract, manifesting as either Crohn's disease (CrD) or ulcerative colitis (UC). Current treatment options for CrD and UC primarily focus on symptom management. In recent years, advancements in nanotechnology have increased the clinical applicability of nanoparticles (NPs) in treating IBD. This review explores the current research on NP-mediated drug-delivery systems for IBD treatment and assesses its advantages and limitations. Results: The authors examine diverse nanomedicine applications for IBD and address the current challenges and prospects in the field to advance nanomediated therapies in the future. Conclusion: Innovative NP-based treatment strategies promise a reliable and effective approach to IBD management.

Influence of feeding practices in the composition and functionality of infant gut microbiota and its relationship with health.

Establishing the infant's gut microbiota has long-term implications on health and immunity. Breastfeeding is recognized as the best practice of infant nutrition in comparison with formula feeding. We evaluated the effects of the primary feeding practices by analyzing the infant growth and the potential association with gut diseases. A cross-sectional and observational study was designed. This study included 55 mothers with infants, who were divided according to their feeding practices in breastfeeding (BF), formula feeding (FF), and combined breast and formula feeding (CF). Anthropometric measurements of the participants were recorded. Additionally, non-invasive fecal samples from the infants were collected to analyze the microbiota by sequencing, immunoglobulin A (IgA) concentration (ELISA), and volatile organic compounds (gas chromatography with an electronic nose). Results showed that the microbiota diversity in the BF group was the highest compared to the other two groups. The IgA levels in the BF group were twice as high as those in the FF group. Moreover, the child´s growth in the BF group showed the best infant development when the data were compared at birth to the recollection time, as noted by the correlation with a decreased concentration of toxic volatile organic compounds. Interestingly, the CF group showed a significant difference in health status when the data were compared with the FF group. We conclude that early health practices influence children's growth, which is relevant to further research about how those infants' health evolved.

Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review.

The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.

In vitro assessment of antibacterial and antiviral activity of three copper products after 200 rounds of simulated use.

Copper has well-documented antibacterial effects but few have evaluated it after prolonged use and against bacteria and viruses. Coupons from three copper formulations (solid, thermal coating, and decal applications) and carbon steel controls were subjected to 200 rounds simulated cleaning using a Wiperator™ and either an accelerated hydrogen peroxide, quaternary ammonium, or artificial sweat products. Antibacterial activity against S. aureus and P. aeruginosa was then evaluated using a modified Environmental Protection Agency protocol. Antiviral activity against coronavirus (229E) and norovirus (MNV-1) surrogates was assessed using the TCID50 method. Results were compared to untreated control coupons. One hour after inoculation, S. aureus exhibited a difference in log kill of 1.16 to 4.87 and P. aeruginosa a log kill difference of 3.39-5.23 (dependent upon copper product and disinfectant) compared to carbon steel. MNV-1 demonstrated an 87-99% reduction on each copper surfaces at 1 h and 99% reduction at 2 h compared to carbon steel. Similarly, coronavirus 229E exhibited a 97-99% reduction after 1 h and 90-99% after 2 h. Simulated use with artificial sweat did not hinder the antiviral nor the antibacterial activity of Cu surfaces. Self-sanitizing copper surfaces maintained antibacterial and antiviral activity after 200 rounds of simulated cleaning.

Antimicrobial Activity of Filtered Far-UVC Light (222 nm) against Different Pathogens.

Ultraviolet (UV) light is an effective disinfection technology, able to inactivate a wide range of microorganisms, including bacteria and fungi. A safer UV wavelength of 222 nm, also known as far-UVC, has been proposed to minimize these harmful effects while retaining the light's disinfection capability. This study is aimed at exploring the antimicrobial activity of filtered far-UVC (222 nm) on a panel of pathogens commonly found in nosocomial installations. A panel of Gram-positive and Gram-negative bacteria and yeast pathogens was tested. Microorganisms were deposited on a plastic surface, allowing them to dry before exposure to the far-UVC light at a distance of 50 cm. Results showed that far-UVC light successfully inhibits the growth of the tested pathogens, although at different exposure times. In conclusion, the results of this study provide fundamental information to achieve reliable disinfection performance with far-UVC lamps with potential applications in healthcare facilities like hospitals and long-term care homes.

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

CONTEXT: The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. OBJECTIVE: We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. RESULTS: The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 µg/mL to 8-128 µg/mL, respectively. Formulation at concentrations <64 µg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. CONCLUSIONS: The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

Biological Activities and Chemical Profiles of Kalanchoe fedtschenkoi Extracts.

In this study, the leaves of Kalanchoe fedtschenkoi were consecutively macerated with hexane, chloroform, and methanol. These extracts were used to assess the bioactivities of the plant. The antimicrobial activity was tested against a panel of Gram-positive and -negative pathogenic bacterial and fungal strains using the microdilution method. The cytotoxicity of K. fedtschenkoi extracts was investigated using human-derived macrophage THP-1 cells through the MTT assay. Finally, the anti-inflammatory activity of extracts was studied using the same cell line by measuring the secretion of IL-10 and IL-6. The phytoconstituents of hexane and chloroform extracts were evaluated using gas chromatography-mass spectrometry (GC/MS). In addition, high-performance liquid chromatography (HPLC) was used to study the phytochemical content of methanol extract. The total flavonoid content (TFC) of methanol extract is also reported. The chemical composition of K. fedtschenkoi extracts was evaluated using Fourier-transform infrared spectroscopy (FTIR). Results revealed that the chloroform extract inhibited the growth of Pseudomonas aeruginosa at 150 µg/mL. At the same concentration, methanol extract inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). Regarding their cytotoxicity, the three extracts were highly cytotoxic against the tested cell line at IC50 < 3 µg/mL. In addition, the chloroform extract significantly stimulated the secretion of IL-10 at 50 µg/mL (p < 0.01). GC/MS analyses revealed that hexane and chloroform extracts contain fatty acids, sterols, vitamin E, and triterpenes. The HPLC analysis demonstrated that methanol extract was constituted by quercetin and kaempferol derivatives. This is the first report in which the bioactivities and chemical profiles of K. fedtschenkoi are assessed for non-polar and polar extracts.

Antimicrobial, Cytotoxic, and Anti-Inflammatory Activities of Tigridia vanhouttei Extracts.

In this work, bulb extracts of Tigridia vanhouttei were obtained by maceration with solvents of increasing polarity. The extracts were evaluated against a panel of pathogenic bacterial and fungal strains using the minimal inhibitory concentration (MIC) assay. The cytotoxicity of the extracts was tested against two cell lines (THP-1 and A549) using the MTT assay. The anti-inflammatory activity of the extracts was evaluated in THP-1 cells by measuring the secretion of pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines by ELISA. The chemical composition of the extracts was recorded by FTIR spectroscopy, and their chemical profiles were evaluated using GC-MS. The results revealed that only hexane extract inhibited the growth of the clinical isolate of Pseudomonas aeruginosa at 200 µg/mL. Against THP-1 cells, hexane and chloroform extracts were moderately cytotoxic, as they exhibited LC50 values of 90.16, and 46.42 µg/mL, respectively. Treatment with methanol extract was weakly cytotoxic at LC50 443.12 µg/mL against the same cell line. Against the A549 cell line, hexane, chloroform, and methanol extracts were weakly cytotoxic because of their LC50 values: 294.77, 1472.37, and 843.12 µg/mL. The FTIR analysis suggested the presence of natural products were confirmed by carboxylic acids, ketones, hydroxyl groups, or esters. The GC-MS profile of extracts revealed the presence of phytosterols, tetracyclic triterpenes, multiple fatty acids, and sugars. This report confirms the antimicrobial, cytotoxic, and anti-inflammatory activities of T. vanhouttei.

Targeting SARS-CoV-2 Non-Structural Proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped respiratory ß coronavirus that causes coronavirus disease (COVID-19), leading to a deadly pandemic that has claimed millions of lives worldwide. Like other coronaviruses, the SARS-CoV-2 genome also codes for non-structural proteins (NSPs). These NSPs are found within open reading frame 1a (ORF1a) and open reading frame 1ab (ORF1ab) of the SARS-CoV-2 genome and encode NSP1 to NSP11 and NSP12 to NSP16, respectively. This study aimed to collect the available literature regarding NSP inhibitors. In addition, we searched the natural product database looking for similar structures. The results showed that similar structures could be tested as potential inhibitors of the NSPs.

The Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. Among these cells, CD8+ T cells are particularly important in controlling tumor growth by recognizing and killing cancer cells. However, the TIME of ccRCC is also characterized by an immunosuppressive environment that hinders the function of immune cells. Several mechanisms contribute to the immunosuppressive nature of the ccRCC TIME. For instance, ccRCC cells produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), which suppress immune cell activation and promote the differentiation of regulatory T cells (Tregs). Tregs, in turn, dampen the activity of effector T cells and promote tumor growth. In addition, ccRCC cells can express programmed death-ligand 1 (PD-L1), which interacts with the programmed cell death protein 1 (PD-1) receptor on T cells to inhibit their function. In addition, other immune checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3), also contribute to the immunosuppressive milieu of the ccRCC TIME. Finally, the hypoxic and nutrient-poor microenvironment of ccRCC can stimulate the production of immunosuppressive metabolites, such as adenosine and kynurenine, which further impair the function of immune cells. Understanding the complex interplay between tumor cells and the immune system in the ccRCC TIME is crucial for developing effective immunotherapies to treat this disease.

Antimicrobial activity of the Flo peptide produced in Scenedesmus acutus and Nannochloropsis oculata.

The continuous increase of bacterial pathogen resistance to conventional antibiotics has challenged the research community to develop new antimicrobial strategies. Antimicrobial peptides (AMP) are a promising alternative to combat multidrug-resistant strains compared to conventional antibiotics because of their biocompatibility. In the present study, the Flo peptide, an AMP from the Moringa oleifera tree, was expressed in the chloroplast of the microalgae Nannochloropsis oculata and Scenedesmus acutus. The transgene insertion was verified by PCR amplification, and the homoplasmy was corroborated in spectinomycin-resistant lines. The identification and quantification of the peptide were performed using ELISA. The antimicrobial activity was studied against the Gram-negative Escherichia coli (ATCC 25,922) and Klebsiella pneumoniae (ATCC 700,603). The inflammatory response of the total soluble proteins of transplastomic N. oculata was assessed by measuring secretion of the cytokines IL-6, IL-10, and alpha-tumor necrosis (TNF-α), and cytotoxicity was assessed. These results provide a potential strategy to produce the Flo peptide in microalgae with antibacterial activities.

A systematic review of the protein composition of whole saliva in subjects with healthy periodontium compared with chronic periodontitis.

CONTEXT: Periodontitis is a chronic multifactorial inflammatory disease linked to oral microbiota dysbiosis. This disease progresses to infection that stimulates a host immune/inflammatory response, with progressive destruction of the tooth-supporting structures. OBJECTIVE: This systematic review aims to present a robust critical evaluation of the evidence of salivary protein profiles for identifying oral diseases using proteomic approaches and summarize the use of these approaches to diagnose chronic periodontitis. DATA SOURCES: A systematic literature search was conducted from January 1st, 2010, to December 1st, 2022, based on PICO criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching the three databases Science Direct, Scopus, and Springer Link. STUDY SELECTION: According to the inclusion criteria, eight studies were identified to analyze the proteins identified by proteomics. RESULTS: The protein family S100 was identified as the most abundant in patients with chronic periodontitis. In this family, an increased abundance of S100A8 and S100A9 from individuals with the active disease was observed, which strongly relates to the inflammatory response. Moreover, the ratio S100A8/S100A9 and the metalloproteinase-8 in saliva could differentiate distinct periodontitis groups. The changes in protein profile after non-surgical periodontal therapy improved the health of the buccal area. The results of this systematic review identified a set of proteins that could be used as a complementary tool for periodontitis diagnosis using salivary proteins. CONCLUSION: Biomarkers in saliva can be used to monitor an early stage of periodontitis and the progression of the disease following therapy.

Use of niosomes for the treatment of intracellular pathogens infecting the lungs.

The delivery of drugs in an encapsulated environment is designed to precisely target specific tissues, avoiding a systemic circulation of the drug. Lungs are organs exposed to the environment with multiple defense barriers. However, many pathogens can still colonize and infect the airways bypassing the hostile environment of the lungs. In more complicated situations, some pathogens have developed strategies to multiply and survive within macrophages, one of the first immune cell responses to clearing infections in mammals. Niosomes are artificial vesicles that can be loaded with drugs, offering an alternative strategy to treat intracellular pathogens as nanocarriers. Members of the mycobacteria genus are intracellular pathogens that have evolved to escape the immunological response, specifically in macrophages, the white cells responsible for the clearance of pathogens. This review analyzed the state-of-the-art niosome synthesis aimed at tackling the problem of intracellular pathogen therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Use of a Cellulase from Trichoderma reesei as an Adjuvant for Enterococcus faecalis Biofilm Disruption in Combination with Antibiotics as an Alternative Treatment in Secondary Endodontic Infection.

Apical periodontitis is an inflammation leading to the injury and destruction of periradicular tissues. It is a sequence of events that starts from root canal infection, endodontic treatment, caries, or other dental interventions. Enterococcus faecalis is a ubiquitous oral pathogen that is challenging to eradicate because of biofilm formation during tooth infection. This study evaluated a hydrolase (CEL) from the fungus Trichoderma reesei combined with amoxicillin/clavulanic acid as a treatment against a clinical E. faecalis strain. Electron microscopy was used to visualize the structure modification of the extracellular polymeric substances. Biofilms were developed on human dental apices using standardized bioreactors to evaluate the antibiofilm activity of the treatment. Calcein and ethidium homodimer assays were used to evaluate the cytotoxic activity in human fibroblasts. In contrast, the human-derived monocytic cell line (THP-1) was used to evaluate the immunological response of CEL. In addition, the secretion of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 were measured by ELISA. The results demonstrated that CEL did not induce the secretion of IL-6 and TNF-α when compared with lipopolysaccharide used as a positive control. Furthermore, the treatment combining CEL with amoxicillin/clavulanic acid showed excellent antibiofilm activity, with a 91.4% reduction in CFU on apical biofilms and a 97.6% reduction in the microcolonies. The results of this study could be used to develop a treatment to help eradicate persistent E. faecalis in apical periodontitis.

Osteoregeneration of Critical-Size Defects Using Hydroxyapatite-Chitosan and Silver-Chitosan Nanocomposites.

Bone is a natural nanocomposite composed of proteins and minerals that can regenerate itself. However, there are conditions in which this process is impaired, such as extensive bone defects and infections of the bone or surrounding tissue. This study evaluates the osteoregenerative capacity of bone grafting materials in animals with induced bone defects. Colloidal chitosan dispersion nanocomposites, nanohydroxyapatite−chitosan (NHAP-Q) and nanosilver−chitosan (AgNP-Q), were synthesized and characterized. Non-critical-size defects in Wistar rats were used to evaluate the material's biocompatibility, and critical-size defects in the calvarias of guinea pigs were used to evaluate the regenerative capacity of the bones. Moreover, the toxicity of the nanocomposites was evaluated in the heart, liver, spleen, kidneys, and skin. Histological, radiographic, and electron microscopy tests were also performed. The results showed that neither material produced pathological changes. Radiographic examination showed a significant reduction in defects (75.1% for NHAP-Q and 79.3% for AgNP-Q), angiogenesis, and trabecular formation. A toxicological assessment of all the organs did not show changes in the ultrastructure of tissues, and the distribution of silver was different for different organs (spleen > skin > heart > kidney > liver). The results suggest that both materials are highly biocompatible, and AgNP-Q achieved similar bone regeneration to that reported with autologous bone. The main research outcome of the present study was the combination of two types of NPs to enhance antimicrobial and osteoregeneration activities. These colloidal chitosan dispersions show promise as future biomaterials in the medical field for applications in fast-healing fractures, including broken bones in the oral cavity and hip replacement infections.

Application of Silver Nanoparticles to Improve the Antibacterial Activity of Orthodontic Adhesives: An In Vitro Study.

There is a significant change in the bacterial plaque populations in the oral cavity during and after orthodontic treatment. Numerous studies have demonstrated that 2−96% of patients could increase the risk of white spot lesions. Streptococcus mutans and Lactobacilli ssp. are responsible for these white spot lesions. In this work, silver nanoparticles (AgNPs) with a diameter of 11 nm and dispersed in water were impregnated onto three different commercial orthodontic adhesives at 535 µg/mL. The shear bond strength (SBS) was assessed on 180 human premolars and metallic brackets. The premolars were divided into six groups (three groups for the commercial adhesives and three groups for the adhesives with AgNPs). All the groups were tested for their bactericidal properties, and their MIC, MBC, and agar template diffusion assays were measured. After adding AgNPs, the SBS was not significantly modified for any adhesive (p > 0.05), and the forces measured during the SBS did not exceed the threshold of 6 to 8 MPa for clinical acceptability in all groups. An increase in the bactericidal properties against both S. mutans and L. acidophilus was measured when the adhesives were supplemented with AgNPs. It was concluded that AgNPs can be supplement commercial orthodontic adhesives without modifying their mechanical properties with improved bactericidal activity.

Mechanisms of Antifungal Properties of Metal Nanoparticles.

The appearance of resistant species of fungi to the existent antimycotics is challenging for the scientific community. One emergent technology is the application of nanotechnology to develop novel antifungal agents. Metal nanoparticles (NPs) have shown promising results as an alternative to classical antimycotics. This review summarizes and discusses the antifungal mechanisms of metal NPs, including combinations with other antimycotics, covering the period from 2005 to 2022. These mechanisms include but are not limited to the generation of toxic oxygen species and their cellular target, the effect of the cell wall damage and the hyphae and spores, and the mechanisms of defense implied by the fungal cell. Lastly, a description of the impact of NPs on the transcriptomic and proteomic profiles is discussed.

Whole blood RNA-seq demonstrates an increased host immune response in individuals with cystic fibrosis who develop nontuberculous mycobacterial pulmonary disease.

BACKGROUND: Individuals with cystic fibrosis have an elevated lifetime risk of colonization, infection, and disease caused by nontuberculous mycobacteria. A prior study involving non-cystic fibrosis individuals reported a gene expression signature associated with susceptibility to nontuberculous mycobacteria pulmonary disease (NTM-PD). In this study, we determined whether people living with cystic fibrosis who progress to NTM-PD have a gene expression pattern similar to the one seen in the non-cystic fibrosis population. METHODS: We evaluated whole blood transcriptomics using bulk RNA-seq in a cohort of cystic fibrosis patients with samples collected closest in timing to the first isolation of nontuberculous mycobacteria. The study population included patients who did (n = 12) and did not (n = 30) develop NTM-PD following the first mycobacterial growth. Progression to NTM-PD was defined by a consensus of two expert clinicians based on reviewing clinical, microbiological, and radiological information. Differential gene expression was determined by DESeq2. RESULTS: No differences in demographics or composition of white blood cell populations between groups were identified at baseline. Out of 213 genes associated with NTM-PD in the non-CF population, only two were significantly different in our cystic fibrosis NTM-PD cohort. Gene set enrichment analysis of the differential expression results showed that CF individuals who developed NTM-PD had higher expression levels of genes involved in the interferon (α and γ), tumor necrosis factor, and IL6-STAT3-JAK pathways. CONCLUSION: In contrast to the non-cystic fibrosis population, the gene expression signature of patients with cystic fibrosis who develop NTM-PD is characterized by increased innate immune responses.