Browsing by Author "Zhan, Jixun"

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Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature
(FRONTIERS MEDIA SA, 2023) Srivastava, Kamal; Cao, Mingzhuo; Fidan, Ozkan; Shi, Yanmei; Yang, Nan; Nowak-Wegrzyn, Anna; Miao, Mingsan; Zhan, Jixun; Sampson, Hugh A.; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE(+)B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE(+) B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. ConclusionsBNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.
Editorial: Microbial production of medicinally important agents
(FRONTIERS MEDIA SA, 2023) Zeng, Jia; Zhan, Jixun; Qiao, Xue; Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
Harnessing microbial systems as bio-factories for the production of medically significant agents presents a thriving avenue in pharmaceutical research. From manufacturing natural products, including potent secondary metabolites, to the sophisticated engineering of recombinant proteins, microbial production’s contributions are manifold (Katz and Baltz, 2016). A salient trend is the rapid evolution of synthetic and molecular biology tools, which substantially enhance our capacity to manipulate microbial metabolism (Keasling, 2012; Ko et al., 2020). Furthermore, refinements in bioprocessing strategies have significantly improved the overall yield of microbial products, emphasizing the cost-effectiveness and efficiency of microbial production (Garcia-Ochoa and Gomez, 2009; Sharma et al., 2020). These advancements, in tandem with predictive technologies such as machine learning for optimal microbial strain selection and fermentation condition prediction, showcase this field’s innovative trajectory.
Engineered Production of Bioactive Natural Products from Medicinal Plants
(WOLTERS KLUWER MEDKNOW, 2022) Fidan, Ozkan; Ren, Jie; Zhan, Jixun; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Özkan, Fidan
Plant natural products have been particularly important due to their use in food, cosmetic, and pharmaceutical industries. In particular, Traditional Chinese Medicine provides a precious potential for the discovery of bioactive natural products and development of novel modern medicines. However, the existing production methods for plant natural products such as chemical synthesis and plant extraction does not meet the current demand. Due to their environmental and economic concerns, engineered production of valuable natural products in microbial hosts has become an attractive alternative platform. This review covers the recent advances in the engineered production of plant natural products in microorganisms. A special focus was placed on the biotechnological production of plant‑derived terpenoids, flavonoids, and alkaloids. Some successful examples of engineered production of plant natural products (or their precursors) such as artemisinin, paclitaxel, naringenin, quercetin, berberine, and noscapine are summarized. This clearly indicates that the engineered production method is a promising approach with various advantages over current methods.
Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation
(FRONTIERS MEDIA SA, 2023) Yang, Nan; Maskey, Anish R.; Srivastava, Kamal; Kim, Monica; Wang, Zixi; Musa, Ibrahim; Shi, Yanmei; Fidan, Ozkan; Wang, Julie; Dunkin, David; Chung, Danna; Zhan, Jixun; Miao, Mingsan; Sampson, Hugh A; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
IntroductionFood allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production. MethodsIgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE(+) plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated. ResultsEBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line. ConclusionsEBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.