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Scientific Reports Sep 2023Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium...
Surface proteins of Propionibacterium freudenreichii MJ2 inhibit RANKL-induced osteoclast differentiation by lipocalin-2 upregulation and lipocalin-2-mediated NFATc1 inhibition.
Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk inhibits osteoclast differentiation and ameliorates collagen-induced arthritis. This study aimed to investigate the inhibitory effect of the surface proteins of MJ2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and explain the underlying mechanism. The murine macrophage cell line RAW 264.7 was used to study the inhibition of osteoclast differentiation. The surface proteins significantly inhibited RANKL-induced osteoclast differentiation in a protein concentration-dependent manner by inhibiting the expression of genes and proteins related to osteoclast differentiation. RNA microarray analysis showed that the surface proteins significantly upregulated lipocalin-2 (lcn2) expression. In addition, they downregulated c-fos and NFATc1 and inhibited the expression of NFATc1-downstream genes Atp6v0d2, Calcr, and Ctsk. siRNA silencing of lcn2 decreased the extent of surface protein inhibition on osteoclast differentiation, suggesting that lcn2 plays an important role in the inhibition of RANKL-induced osteoclast differentiation. In conclusion, surface proteins of MJ2 show inhibitory effects on RANKL-induced osteoclast differentiation by upregulating lcn2 expression, in turn downregulating NFATc1, leading to the inhibition of NFATc1-downstream osteoclastogenesis-related gene expression.
Topics: Animals; Mice; Up-Regulation; Membrane Proteins; Osteoclasts; Propionibacterium freudenreichii; Lipocalin-2; RANK Ligand; Proto-Oncogene Proteins c-fos; Cell Differentiation
PubMed: 37730858
DOI: 10.1038/s41598-023-42944-y -
Scientific Reports Sep 2023This study aimed at investigating the influence of different variants of bacterial starter cultures on the metabolism of the bacteria used, cheese protein digestibility,...
This study aimed at investigating the influence of different variants of bacterial starter cultures on the metabolism of the bacteria used, cheese protein digestibility, and fatty acid profile. The results revealed that lactic acid bacteria had a significant effect on the proportions of fatty acids in cheeses, with saturated fatty acids being predominant in in all cheese variants. Fatty acid proportions are complex and depend on the type of cheese culture and monoculture used. Additionally, the analysis of fatty acid composition showed variations in the proportion of saturated and unsaturated fatty acids, impacting the values of atherogenic and thrombogenic indices. Notably, the atherogenic index was highest in samples of mature cheeses obtained from a typical mesophilic cheese culture, whereas it was lowest in samples of fresh milk and mature cheeses obtained from a mesophilic cheese culture and monocultures of Lacticaseibacillus casei and Propionibacterium. The study also highlighted the influence of lactobacilli on the content of available free lysine, glycine, and methionine in cheese proteins. Mature cheeses obtained with Propionibacterium and L. casei starter cultures exhibited higher free lysine and glycine content compared with fresh cheeses and those obtained solely with the cheese culture. Additionally, mature cheeses obtained with starter cultures of mesophilic cheese culture, Propionibacterium, and L. casei had the highest free methionine content. Based on these findings, it is evident that the choice of cheese making cultures and monocultures can significantly affect the fatty acid composition and amino acid content of cheese and fresh milk, potentially bearing important health implications.
Topics: Lactobacillales; Fatty Acids; Cheese; Lysine; Propionibacterium; Methionine; Fabaceae; Glycine; Racemethionine
PubMed: 37717086
DOI: 10.1038/s41598-023-42633-w -
Frontiers in Bioscience (Landmark... Aug 2023causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive...
BACKGROUND
causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties.
METHODS
In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO's anti-inflammatory actions were investigated using -induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry.
RESULTS
The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37.
CONCLUSIONS
In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.
Topics: Humans; Propionibacterium acnes; Schisandra; Calcium; Cathelicidins; Fruit; HaCaT Cells; Reactive Oxygen Species; Inflammation; Antimicrobial Peptides; Dinoprostone
PubMed: 37664918
DOI: 10.31083/j.fbl2808177 -
Frontiers in Cellular and Infection... 2023Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income...
INTRODUCTION
Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income countries. There is no effective treatment and no vaccine. New therapeutics are emerging from drug discovery efforts. It is critical that mode of action studies are performed alongside drug discovery to ensure the best clinical outcomes. Unfortunately, technology to identify and validate drug targets for is severely lacking.
METHODS
We used lysyl-tRNA synthetase (KRS) and DDD01510706 as a target-compound pair to develop both chemical and genetic tools for mode of action studies for . We adapted thermal proteome profiling (TPP) for , an unbiased approach for target identification.
RESULTS
Using TPP we identified the molecular target of DDD01510706 and confirm that it is KRS. Genetic tools confirm that KRS is expressed throughout the life cycle and that this target is essential for parasite survival. Parasites genetically modified to over-express KRS or parasites with a mutation at the compound-binding site are resistant to treatment with DDD01510706. We leveraged these mutations to generate a second drug selection marker for genetic modification of , KRS. This second selection marker is interchangeable with the original selection marker, Neo, and expands the range of reverse genetic approaches available to study parasite biology. Due to the sexual nature of the life cycle, parental strains containing different drug selection markers can be crossed .
DISCUSSION
Selection with both drug markers produces highly efficient genetic crosses (>99% hybrid progeny), paving the way for forward genetics approaches in .
Topics: Child; Humans; Child, Preschool; Cryptosporidium; Cryptosporidiosis; Lysine-tRNA Ligase; Binding Sites; Diarrhea; Propionibacterium acnes
PubMed: 37600947
DOI: 10.3389/fcimb.2023.1236814 -
PloS One 2023We identified a fragment (Domain 3-D3) of the immunodominant sporozoite surface glycoprotein of the zoonotic parasite Cryptosporidium gp900, which is absent C. hominis...
We identified a fragment (Domain 3-D3) of the immunodominant sporozoite surface glycoprotein of the zoonotic parasite Cryptosporidium gp900, which is absent C. hominis and C. parvum anthroponosum. The fragment is highly antigenic and is able to effectively differentiate between zoonotic C. parvum and species/genotypes that infect preferentially humans. D3 detection provides a serological tool to determine whether the source of human cryptosporidiosis is of animal or human origin. We demonstrate this in experimentally challenged piglets, mice, rats, and alpaca. We speculate that the absence of this fragment from the C. hominis and C. parvum anthroponosum gp900 protein may play a key role in their host restriction.
Topics: Humans; Animals; Mice; Rats; Swine; Cryptosporidium parvum; Cryptosporidium; Cryptosporidiosis; Glycoproteins; Membrane Glycoproteins; Camelids, New World; Propionibacterium acnes
PubMed: 37590269
DOI: 10.1371/journal.pone.0287997 -
Italian Journal of Dermatology and... Aug 2023Condylomata are a manifestation of HPV infection of the ano-genital epithelium. Recurrence is frequent after any type of treatment (from 20% up to 50%). We assessed the... (Observational Study)
Observational Study
BACKGROUND
Condylomata are a manifestation of HPV infection of the ano-genital epithelium. Recurrence is frequent after any type of treatment (from 20% up to 50%). We assessed the use of a gel containing panthenol, tocopheryl acetate and Propionibacterium extract in the treatment of anal warts.
METHODS
Enrollment period was from January 15 to June 15, 2018. Main exclusion criteria were immunodepression, extensive condylomatosis and other treatments (topical/ablative) in the previous six months.
RESULTS
Seventy-nine patients were included. Median age was 33 years (19-65), 72.2% were males. Median number of partners and symptoms duration were 6 (1-98) and 3 months (1-18), respectively. Almost all cases had perianal disease (97.5%), while endoanal warts were present in 51.9% of cases. After 30 days of treatment, complete regression occurred in 17 (21.5%) patients, while partial or absent response was reported in 36 (45.6%) and 26 (32.9%) cases, respectively. Forty-seven (59.5%) patients underwent a second month of topical therapy. After a 6-month follow-up, complete or partial response was reported in 53 (67.1%) patients, while in 26 (32.9%) cases the disease remained stable or even worsened. Nineteen (24.1%) patients required cryotherapy, 23 (29.1%) surgical excision, while 2 (2.5%) needed both cryotherapy and surgery. Absence of clinical response was associated with a number of partners ≥10 and symptoms duration of 6 months or shorter (P<0.001 and P=0.050).
CONCLUSIONS
In our study, the gel containing P. acnes lysate was a safe topical treatment for perianal and endoanal condylomata and could help to overcome HPV infection. A high number of partners and short symptoms duration appeared to worsen the outcome.
Topics: Male; Humans; Adult; Female; Papillomavirus Infections; Propionibacterium acnes; Treatment Outcome; Condylomata Acuminata; Administration, Topical
PubMed: 37539504
DOI: 10.23736/S2784-8671.23.07598-9 -
Frontiers in Cellular and Infection... 2023, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The...
, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting , which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent , CA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti- targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.
Topics: Humans; Propionates; Skin; Acne Vulgaris; Propionibacterium acnes; Microbiota
PubMed: 37520435
DOI: 10.3389/fcimb.2023.1099314 -
The Journal of Investigative Dermatology Jan 2024Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease...
Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release. Phylotype II K-type strains were more frequent on healthy and nonlesional skin of subjects with acne than those isolated from lesions. Phylotype IA-1 C-type strains were increased on lesional skin compared with those on healthy skin. The capacity to induce cytokines from cultured monocyte-derived dendritic cells was opposite to this action on sebocytes and keratinocytes and did not correlate with the strain types associated with the disease. Whole-genome sequencing revealed a linear plasmid in high-inflammatory isolates within similar strain types that had different proinflammatory responses. Single-cell RNA sequencing of mouse skin after intradermal injection showed that strains containing this plasmid induced a higher inflammatory response in dermal fibroblasts. These findings revealed that C. acnes strain type is insufficient to predict inflammation and that carriage of a plasmid could contribute to disease.
Topics: Animals; Mice; Humans; Skin; Acne Vulgaris; Dermatitis; Propionibacterium acnes; Plasmids; Inflammation; Cytokines
PubMed: 37478901
DOI: 10.1016/j.jid.2023.05.029 -
Microbiology Spectrum Aug 2023Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of ODRI,...
Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of ODRI, but oral rifampin is frequently used in combination with a fluoroquinolone following intravenous antibiotics. We describe the emergence of combined resistance to rifampin and levofloxacin in a strain isolated from a patient with early-onset ODRI treated with debridement, antibiotic treatment, and implant retention (DAIR) using rifampin combined with levofloxacin as the oral treatment. Whole-genome sequencing of isolates before and after antibiotic exposure confirmed strain identity and identified new mutations in and , leading to amino acid substitutions previously reported to be associated with resistance to rifampin (S446P) and fluoroquinolones (S101L), respectively, in other microbial agents, in the posttherapy isolate. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing a DAIR procedure for ODRI and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens. In this study, we report for the first time the emergence of dual resistance to levofloxacin and rifampin in isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.
Topics: Humans; Levofloxacin; Rifampin; Anti-Bacterial Agents; Propionibacteriaceae; Fluoroquinolones; Microbial Sensitivity Tests
PubMed: 37289061
DOI: 10.1128/spectrum.03687-22 -
Internal Medicine (Tokyo, Japan) Jan 2024A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph...
A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.
Topics: Female; Humans; Aged; Streptococcus gordonii; RNA, Ribosomal, 16S; Lymph Nodes; Sarcoidosis; Lymphadenopathy; Propionibacterium acnes; Clone Cells
PubMed: 37258161
DOI: 10.2169/internalmedicine.1887-23