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Biotechnologia 2023Plants provide an unlimited source of bioactive compounds, possessing tremendous applications in the pharmaceutical industry. In the search for sources of antioxidants...
Plants provide an unlimited source of bioactive compounds, possessing tremendous applications in the pharmaceutical industry. In the search for sources of antioxidants and antimicrobial agents against human pathogens, ethanol extracts of flowers (CJ flower extract) were evaluated. The highest total phenolic (5.65 μg GAE/ml) and flavonoid (0.43 μg QE/ml) contents were observed in the 100 μg/ml CJ flower extract. To assess antioxidant activity, three antioxidant tests were employed: DPPH radical-scavenging, ABTS radical-scavenging, and hydroxyl radical-scavenging assay. The CJ flower extract demonstrated significant ( < 0.05) antioxidant activity, dependent on the percentage of solvent extraction and the specific assays utilized. The highest antioxidant activity was obtained with 100% ethanol extraction and using the hydroxyl radical-scavenging assay (56.63%). Antimicrobial activity was assessed against six human pathogens, including the fungi and five Gram-positive bacteria (, , , , and ), as well as one Gram-negative bacterium ( ). The CJ flower extract inhibited the growth of both fungal and bacterial pathogens. The cytotoxicity of the CJ flower extract was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the highest concentration of the extract (100 μg/ml) did not affect L929 cell viability. Moreover, the CJ flower extract demonstrated the ability to suppress HO-induced toxicity in L929 cells. Overall, the CJ flower extract has potential as an alternative source for exploring new antioxidants, antimicrobial agents, and cytoprotectants that could prove valuable for biomedical applications.
PubMed: 38213478
DOI: 10.5114/bta.2023.132772 -
Plants (Basel, Switzerland) Dec 2023Griseb. is a Balkan endemic species listed in The Red Data Book of Bulgaria with the conservation status "endangered". Successful micropropagation was achieved on MS...
Griseb. is a Balkan endemic species listed in The Red Data Book of Bulgaria with the conservation status "endangered". Successful micropropagation was achieved on MS medium supplemented with 1.5 mg/L benzyladenine (BA), followed by a subsequent ex vitro adaptation in an experimental field resulting in 92% regenerated plants. Using nuclear magnetic resonance (NMR), phenylethanoid glycosides (verbascoside, leucosceptoside A), phenolic acids (chlorogenic acid), iridoids (allobetonicoside and 8-OAc-harpagide), and alkaloids (trigonelline) were identified, characteristic of plants belonging to the genus . High antioxidant and radical scavenging activities were observed in both in situ and ex vitro acclimated plants, correlating with the reported high concentrations of total phenols and flavonoids in these variants. Ex vitro adapted plants also exhibited a well-defined anti-inflammatory potential, demonstrating high inhibitory activity against the complement system. Employing a disk diffusion method, a 100% inhibition effect was achieved compared to positive antibiotic controls against and , with moderate activity against . The induced in vitro and ex vitro model systems can enable the conservation of in nature and offer future opportunities for the targeted biosynthesis of valuable secondary metabolites, with potential applications in the pharmaceutical and cosmetic industries.
PubMed: 38202340
DOI: 10.3390/plants13010030 -
Microbiology Spectrum Feb 2024Acne vulgaris caused by antibiotic-resistant () infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the...
Acne vulgaris caused by antibiotic-resistant () infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating -induced inflammation in rat models. We found that rats infected with had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with , which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of -induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCE infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating . Bacteriophages are currently proven effective in MDR (multiple drug-resistant) , but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing . However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.
Topics: Animals; Rats; Bacteriophages; Insulin-Like Growth Factor I; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Keratinocytes; Acne Vulgaris; Propionibacterium acnes; Inflammation; Apoptosis
PubMed: 38197658
DOI: 10.1128/spectrum.02838-23 -
Dermatology and Therapy Jan 2024The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a... (Review)
Review
The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a key factor in acne development, regulating inflammatory and immune pathways. Dysbiosis has been described as the imbalance in skin microbiome homeostasis and may play a role in acne pathogenesis. Microbial interference has been shown to be a contributor to healthy skin homeostasis and staphylococcal strains may exclude acne-associated C. acnes phylotypes. In this review we present an update on the skin microbiome in acne and discuss how current acne treatments such as benzoyl peroxide, orally administered isotretinoin, and antibiotics may affect the skin microbiome homeostasis. We highlight the collateral damage of acne antibiotics on the skin microbiome, including the risk of antimicrobial resistance and the dysregulation of the microbiome equilibrium that may occur even with short-term antibiotic courses. Consequently, the interest is shifting towards new non-antibiotic pharmacological acne treatments. Orally administered spironolactone is an emerging off-label treatment for adult female patients and topical peroxisome proliferator-activated receptor gamma (PPARγ) modulation is being studied for patients with acne. The potential application of topical or oral probiotics, bacteriotherapy, and phage therapy for acne are further promising areas of future research.
PubMed: 38183614
DOI: 10.1007/s13555-023-01079-8 -
Cellular Immunology 2024Pulmonary sarcoidosis is an immune-mediated disorder closely related to Th17/Treg cell imbalance. Dexamethasone has been shown to regulate inflammation and immune...
Pulmonary sarcoidosis is an immune-mediated disorder closely related to Th17/Treg cell imbalance. Dexamethasone has been shown to regulate inflammation and immune responses in sarcoidosis patients. However, the underlying mechanisms of dexamethasone regulating Th17/Treg balance in sarcoidosis remain elusive. Herein, we elucidated the function role of TGF-β/Smad3 signaling in pulmonary sarcoidosis development and explored the underlying mechanism of dexamethasone in treating pulmonary sarcoidosis. We found that the TGF-β/Smad3 pathway was inactivated in pulmonary sarcoidosis patients. Propionibacterium acnes (PA) induced mouse model was generated to investigate the function of TGF-β/Smad3 signaling in vivo. Data indicated that IL17A inhibition with neutralizing antibody and activation of TGF-β/Smad3 signaling with SRI-011381 alleviated granuloma formation in the sarcoidosis mouse model. Moreover, we revealed that the Th17/Treg cell ratio was increased with PA treatment in mouse bronchoalveolar lavage fluid (BALF) and peripheral blood. The concentration of cytokines produced by Th17 cells (IL-17A, IL-23) was up-regulated in the BALF of PA-treated mice, while those produced by Tregs (IL-10, TGF-β1) presented significant reduction. The treatment of IL-17A neutralizing antibody or SRI-011381 was demonstrated to rescue the PA-induced changes in the concentration of IL-17A, IL-23, IL-10, and TGF-β1. Additionally, we demonstrated that dexamethasone treatment activated the TGF-β/Smad3 signaling in the lung tissues of pulmonary sarcoidosis mice. Dexamethasone was also revealed to promote the rebalancing of the Th17/Treg ratio and attenuated the granuloma formation in pulmonary sarcoidosis. In conclusion, dexamethasone activates the TGF-β/Smad3 signaling and induces Th17/Treg rebalance, alleviating pulmonary sarcoidosis, which suggests the potential of dexamethasone in treating pulmonary sarcoidosis.
Topics: Animals; Humans; Mice; Antibodies, Neutralizing; Dexamethasone; Granuloma; Interleukin-10; Interleukin-17; Interleukin-23; Sarcoidosis, Pulmonary; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta; Transforming Growth Factor beta1
PubMed: 38159414
DOI: 10.1016/j.cellimm.2023.104781 -
International Orthopaedics Apr 2024Optimization of medical factors including diabetes and obesity is a cornerstone in the prevention of prosthetic joint infection (PJI). Dyslipidaemia is another component...
PURPOSE
Optimization of medical factors including diabetes and obesity is a cornerstone in the prevention of prosthetic joint infection (PJI). Dyslipidaemia is another component of metabolic syndrome which has not been thoroughly investigated as an individual, modifiable risk factor. This study examined the association of dyslipidaemia with PJI caused by the lipophilic microbe Cutibacterium acnes (C. acnes).
METHODS
A retrospective chart review examined patients with positive C. acnes culture at hip or knee arthroplasty explantation. A control group with methicillin-sensitive Staphylococcus aureus (MSSA) positive cultures at explantation was matched for age, sex, and surgical site, as well as a second control group with no infection. A total of 80 patients were included, 16 with C. acnes, 32 with MSSA, and 32 with no infection. All patients had a lipid panel performed within one year of surgery. Lipid values and categories were compared using multinomial logistic regressions.
RESULTS
High or borderline triglycerides (TG) (relative risk ratio (RRR) = 0.13; P = 0.013) and low high-density lipoprotein (HDL) (RRR = 0.13; P = 0.025) were significantly associated with C. acnes PJI compared to MSSA-PJI. High or borderline TG (RRR = 0.21; P = 0.041) and low HDL (RRR = 0.17; P = 0.043) were also associated with a greater probability of C. acnes infection compared to no infection.
CONCLUSIONS
The presence of elevated TG and low HDL were both associated at a statistically significant level with C. acnes hip or knee PJI compared to controls with either MSSA PJI or no infection. This may represent a specific risk factor for C. acnes PJI that is modifiable.
Topics: Humans; Retrospective Studies; Arthroplasty, Replacement, Hip; Knee Joint; Arthritis, Infectious; Propionibacterium acnes; Staphylococcal Infections; Staphylococcus aureus; Dyslipidemias; Lipids; Prosthesis-Related Infections
PubMed: 38157039
DOI: 10.1007/s00264-023-06066-4 -
Biomedicine & Pharmacotherapy =... Jan 2024The two major challenges in cancer treatment are reducing the side effects and minimizing the cost of cancer treatment. A better therapy to treat cancer remains to be...
The two major challenges in cancer treatment are reducing the side effects and minimizing the cost of cancer treatment. A better therapy to treat cancer remains to be developed despite the presence of many therapeutic options. Here, we present bacterial therapy for treating cancer using tumor-isolated Cutibacterium acnes, which is safe to use, has minimal side effects compared to chemotherapeutic drugs, and most importantly, targets the tumor microenvironment due to the bacterium's anaerobic nature. It activates the immune system, and the immune cells effectively penetrate through the tumor tissue and form an immunologic hub inside, explicitly targeting the tumor and destroying the cells. This bacterial therapy is a new cost-effective innovative treatment.
Topics: Humans; Neoplasms; Treatment Outcome; Propionibacterium acnes; Tumor Microenvironment
PubMed: 38113626
DOI: 10.1016/j.biopha.2023.116041 -
Transfusion Jan 2024We evaluated the operational and safety impact of implementing anaerobic culture screening of apheresis and pooled platelets at the American Red Cross on the already...
BACKGROUND AND OBJECTIVES
We evaluated the operational and safety impact of implementing anaerobic culture screening of apheresis and pooled platelets at the American Red Cross on the already established use of the aerobic culture screening of each donation performed no sooner than 24 h following collection.
MATERIALS AND METHODS
Platelets were screened for bacterial contamination with the BACT/ALERT 3D® (bioMérieux, Durham, NC) microbial detection testing system. The addition of anaerobic culture to the already existing aerobic culture resulted in sampling an additional 8-10 mL from each donation.
RESULTS
Implementation of anaerobic testing resulted in an approximate 3.5-fold increased rate of False Positive BACT/ALERT alarms. There was a modest increase in the rate of True Positive alarms of 1.4-fold with increased detection of Klebsiella and Propionibacterium species, including Cutibacterium acnes. In addition, there was an approximate 3.5-fold increase rate of False Positives and a 13.5-fold increase rate of Indeterminates, the majority (~57%) were due to Cutibacterium acnes. The combined costs and lost revenue associated with adding anaerobic screening increased by ~$1,000,000/year due to testing cost and product discards.
CONCLUSION
The addition of anaerobic culture to aerobic culture to the original donation (without the introduction of sampling delay) resulted in a significant increase in the rate of alerts. The 40% increased rate of True Positive alarms may have modestly improved platelet safety. However, there was a disproportionate increase in the rate of False Positive and Indeterminate bacterial culture alarms, which added substantial cost and overall loss of platelet products.
Topics: Humans; Anaerobiosis; Blood Platelets; Bacteria; Blood Component Removal; Drug Contamination; Bacteriological Techniques
PubMed: 38098310
DOI: 10.1111/trf.17611 -
Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances.Biochemistry and Biophysics Reports Dec 2023Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave... (Review)
Review
BACKGROUND
Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave the sufferer with scars, irritation, and significant psychological effects (including depression). In the current review, we have included various factors for acne and their treatment explained. It also narrated the current medicament and the new investigation dosage forms with clinical phases information provided.
MAIN BODY OF THE ABSTRACT
Acne's pathophysiology involves four important factors: excessive sebum production, hyperkeratinization of pilosebaceous follicles, hyperproliferation of propionibacterium acnes (P. acnes), and inflammation. Identifying both inflammatory (Papule, pustule, nodule, and cyst) and non-inflammatory (black heads, white heads) acne lesions is necessary for diagnosing and treating acne vulgaris.
SHORT CONCLUSION
In this review, traditional therapy approaches such as topical (i.e., retinoids and antibiotics), systemic (i.e., retinoids, antibiotics, and hormonal), and physical therapies are briefly discussed. In addition, we highlight the issues posed by P. acne's resistance to the antibiotics used in commercially available medications and the necessity for novel therapeutic techniques. Finally, we examined a few innovative acne therapies pending clinical trial approval and commercial acne medications.
PubMed: 38076662
DOI: 10.1016/j.bbrep.2023.101578 -
Journal of Shoulder and Elbow Surgery Mar 2024Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been... (Randomized Controlled Trial)
Randomized Controlled Trial
Does hydrogen peroxide application to the dermis following surgical incision affect Cutibacterium acnes cultures in total shoulder arthroplasty in male patients? A randomized controlled trial.
BACKGROUND
Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been shown to persist in the dermis despite use of preoperative antibiotics and standard skin preparations. Studies have shown decreased rates of cultures positive for C acnes with use of preoperative benzoyl peroxide or hydrogen peroxide (HO), but even with this positive deep cultures remain common. We sought to determine whether an additional application of HO directly to the dermis following skin incision would further decrease deep culture positivity rates.
METHODS
We performed a randomized controlled trial comparing tissue culture results in primary TSA in patients who received a standard skin preparation with HO, ethanol, and ChloraPrep (CareFusion, Leawood, KS, USA) vs. an additional application of HO to the dermis immediately after skin incision. Given the sexual dimorphism seen in the shoulder microbiome regarding C acnes colonization rates, only male patients were included. Bivariable and multivariable analyses were performed to compare rates of positive cultures based on demographic and surgical factors.
RESULTS
Dermal cultures were found to be positive for C acnes at similar rates between the experimental and control cohorts for the initial (22% vs. 28%, P = .600) and final (61% vs. 50%, P > .999) dermal swabs. On bivariable analysis, the rate of positive deep cultures for C acnes was lower in the experimental group, but this difference was not statistically significant (28% vs. 44%, P = .130). However, patients who underwent anatomic TSA were found to have a significantly greater rate of deep cultures positive for C acnes (57% vs. 28%, P = .048); when controlling for this on multivariable analysis, the experimental cohort was found to be associated with significantly lower odds of having positive deep cultures (odds ratio, 0.37 [95% confidence interval, 0.16-0.90], P = .023). There were no wound complications in either cohort.
CONCLUSIONS
An additional HO application directly to the dermis following skin incision resulted in a small but statistically significant decrease in the odds of having deep cultures positive for C acnes without any obvious adverse effects on wound healing. Given its cost-effectiveness, use of a post-incisional dermal decontamination protocol may be considered as an adjuvant to preoperative use of benzoyl peroxide or HO to decrease C acnes contamination.
Topics: Humans; Male; Hydrogen Peroxide; Arthroplasty, Replacement, Shoulder; Surgical Wound; Shoulder Joint; Gram-Positive Bacterial Infections; Skin; Benzoyl Peroxide; Shoulder; Propionibacterium acnes; Dermis
PubMed: 38072031
DOI: 10.1016/j.jse.2023.10.019