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Scientific Reports Jan 2024In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 3. The...
In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 3. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.
Topics: Humans; Mice; Animals; Adapalene; Acne Vulgaris; Skin; Polymers; Dermatologic Agents; Treatment Outcome; Gels
PubMed: 38228631
DOI: 10.1038/s41598-024-51392-1 -
ACS Omega Jan 2024Conjugated linoleic acid (CLA) holds significant application prospects due to its anticancer, anti-atherosclerosis, lipid-lowering, weight-loss, and growth-promoting...
Conjugated linoleic acid (CLA) holds significant application prospects due to its anticancer, anti-atherosclerosis, lipid-lowering, weight-loss, and growth-promoting functions. The key to its efficient production lies in optimizing the biocatalytic performance of linoleic acid isomerase (LAI). Here, we constructed a mutant library and screened positive mutants with high linoleate isomerase activity. The proteomics and metabolomics were used to explore the mechanism in the regulation of linoleic acid isomerase activity. High-throughput proteomics revealed 104 differentially expressed proteins unique to positive mutant strains of linoleic acid isomerase of which 57 were upregulated and 47 were downregulated. These differentially expressed proteins were primarily involved in galactose metabolism, the phosphotransferase system, starch metabolism, and sucrose metabolism. Differential metabolic pathways were mainly enriched in amino acid biosynthesis, including glutamate metabolism, the Aminoacyl-tRNA biosynthesis pathway, and the ABC transporter pathway. The upregulated metabolites include dl-valine and Acetyl coA, while the downregulated metabolites include Glutamic acid and Phosphoenolpyruvate. Overall, the activity of linoleic acid isomerase in the mutant strain was increased by the regulation of key proteins involved in galactose metabolism, sucrose metabolism, and the phosphotransferase system. This study provides a theoretical basis for the development of high-yield CLA food.
PubMed: 38222669
DOI: 10.1021/acsomega.3c08243 -
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 -
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 -
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 -
Photodiagnosis and Photodynamic Therapy Feb 2024The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked...
BACKGROUND
The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition.
OBJECTIVE
The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism.
METHODS
Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy.
RESULTS
The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin.
CONCLUSION
The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.
Topics: Humans; Clindamycin; Doxycycline; Curcumin; Minocycline; Microbial Sensitivity Tests; Photosensitizing Agents; Photochemotherapy; Acne Vulgaris; Anti-Bacterial Agents; Erythromycin; Tetracycline; Biofilms; Propionibacterium acnes
PubMed: 38070633
DOI: 10.1016/j.pdpdt.2023.103928 -
Molecules (Basel, Switzerland) Nov 2023Maxim is an annual herb with many potential purposes in agricultural, industrial, and pharmaceutical fields. At present, the extract of the whole plant from has been...
Maxim is an annual herb with many potential purposes in agricultural, industrial, and pharmaceutical fields. At present, the extract of the whole plant from has been proven to demonstrate antifungal, antioxidant, and anti-inflammatory activities. Previous studies focused on the enzyme pretreatment in hydrodistillation from . However, organic solvent or supercritical fluid carbon dioxide extraction (SFE-CO) methods, which are commonly utilized in industry, have seldom been studied and cannot provide multiple evaluations of yield. In this work, we analysed compounds from by HPLC-DAD, discussed -hexane extraction, and conducted further investigations on SFE-CO through the design of response surface methodology (RSM). The sample obtained from pilot-scale SFE-CO was also tested against nine kinds of microorganisms. Single-factor results revealed that the extraction rates from by steam distillation, -hexane extraction, and SFE-CO were 1%, 2.09%, and 3.26%, respectively. RSM results showed a significant improvement in extraction rate through optimising pressure and time, and the interaction of both factors was more important than that of temperature-pressure and temperature-time. A pilot-scale test with an extraction rate of 3.34% indicated that the predicted RSM condition was operable. In addition, samples from the pilot-scale SFE-CO showed antibacterial effects against three previously unreported bacteria (, methicillin-resistant , and ). These results fill the gap in previous research and provide more information for the application and development of in the future.
Topics: Oils, Volatile; Carbon Dioxide; Chromatography, High Pressure Liquid; Methicillin-Resistant Staphylococcus aureus; Lamiaceae; Chromatography, Supercritical Fluid
PubMed: 38067455
DOI: 10.3390/molecules28237724