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Objectives: To investigate whether the prophylactic effect of Cyclosorus terminans extract mitigates metabolic impairment and submandibular gland changes, as indicated by increased aquaporin5 expression, decreased fibrosis, oxidative stress and inflammation, improved mitochondrial homeostasis/dynamics, and decreased cell death in the submandibular glands of high-fat diet (HFD)-feeding rats., Methods: Thirty-two male Wistar rats were assigned to either a normal diet (ND) as control rats (n=8) or a HFD (n=24) for 12 weeks. The HFD-treated rats were divided into 3 subgroups to receive either: 1) vehicle (HDV), 2) Cyclosorus terminans at a dose of 100 mg/kg/d (HF100), or 3) Cyclosorus terminans at a dose of 200 mg/kg/d (HF200). At week 13, metabolic parameters, systemic oxidative stress, and submandibular gland parameters were assessed., Results: Twelve weeks of HFD-feeding rats induced obese-insulin resistance and submandibular gland changes. Both HF100- and HF200-treated groups improved metabolic parameters and prevented gland changes by reducing fibrosis (TGF-β and p-38), malondialdehyde levels, inflammation (TNF-α, NF-κB, and Ifng), and cell death markers (Caspase 3, GSDMD, and MLKL). Both treatments supported balanced mitochondrial homeostasis/dynamics, as indicated by regulating related genes (Cpt1b, Ndufb8, Mfn1, Mfn2, Opa1, and Dnm1l). However, only the HF200-treated rats restored aquaporin-5 and antioxidants (SOD2 and GPX4) expression to control levels., Conclusions: Cyclosorus terminans mitigates metabolic disturbances and submandibular gland changes in HFD-feeding rats. The high dose was more effective, improving gland function by increasing aquaporin5 and antioxidants. These results suggest Cyclosorus terminans may be a promising therapeutic for metabolic disturbances and submandibular gland changes in obese-insulin resistant patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

High-fat diet consumption for an extended period causes obesity, systemic metabolic disturbance, and brain insulin resistance, resulting in neuroinflammation. Although the beneficial effect of Cyclosorus terminans extract on obesity-related insulin resistance has been demonstrated, little is known about how it affects neuroinflammation and brain insulin resistance in obese rats. Male Wistar rats were given either a normal diet (ND, n = 6) or a high-fat diet (HFD, n = 24) for a total of 14 weeks. At the beginning of the week, 13 rats in the ND group were given vehicle orally for 2 weeks, while rats on HFD diets were randomized to one of four groups and given either vehicle, 100 mg/kg/day of Cyclosorus terminans extract, 200 mg/kg/day of Cyclosorus terminans extract, or 20 mg/kg/day of pioglitazone orally for 2 weeks. After the experimental period, blood and brain samples were taken to assess metabolic and brain parameters. HFD-fed rats had obesity, systemic and brain insulin resistance, brain inflammation, microglial and astrocyte hyperactivity, and brain necroptosis. Treatment with 200 mg/kg/day of Cyclosorus terminans extract and pioglitazone equally attenuated obesity, insulin resistance, brain insulin dysfunction, and neuroinflammation in insulin resistant rats. Our findings suggest that Cyclosorus terminans extract may hold promise as a therapeutic agent for insulin resistance and neuroinflammation in obese conditions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Human skin is exposed daily to oxidative stress factors such as UV light, chemical pollutants, and invading organisms. Reactive oxygen species (ROS) are intermediate molecules that cause cellular oxidative stress. In order to survive in an oxygen-rich environment, all aerobic organisms, including mammals, have evolved enzymatic and non-enzymatic defence systems. The interruptins from an edible fern Cyclosorus terminans possess antioxidative properties and can scavenge intracellular ROS in adipose-derived stem cells.

Objectives: This study aimed to evaluate the antioxidative efficacy of interruptins A, B, and C in cultured human dermal fibroblasts (HDFs) and epidermal keratinocytes (HEKs). Moreover, the anti-photooxidative activity of interruptins in ultraviolet (UV)-exposed skin cells was investigated.

Methods: The intracellular ROS scavenging capacity of interruptins in skin cells was measured by flow cytometry. Their induction effects on gene expression of the endogenous antioxidant enzymes was monitored using real-time polymerase chain reaction.

Results: Interruptins A and B, but not interruptin C, were highly effective in ROS scavenging, particularly in HDFs. Interruptins A and B upregulated gene expression of superoxide dismutase (SOD)1, SOD2, catalase (CAT), and glutathione peroxidase (GPx) in HEKs, but they only induced SOD1, SOD2, and GPx gene expression in HDFs. Additionally, interruptins A and B efficiently suppressed UVA- and UVB-induced ROS generation in both HEKs and HDFs.

Conclusion: The results suggest that these naturally occurring interruptins A and B are potent natural antioxidants and therefore may have the potential in the future of inclusion in antiaging cosmeceutical products.

Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes ( Slc2a2, Slc2a4, Irs1 and Irs2 ) along with diminished expression of inflammatory genes ( Il6 and Tnf ). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn , together with an increase in fatty acid oxidation genes, Ppara and Cpt2 , in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.

Metabolic extremes provide opportunities to understand enzymatic and metabolic plasticity and biotechnological tools for novel biomaterial production. We discovered that seed oils of many Thunbergia species contain up to 92% of the unusual monounsaturated petroselinic acid (18:1Δ6), one of the highest reported levels for a single fatty acid in plants. Supporting the biosynthetic origin of petroselinic acid, we identified a Δ6-stearoyl-acyl carrier protein (18:0-ACP) desaturase from Thunbergia laurifolia , closely related to a previously identified Δ6-palmitoyl-ACP desaturase that produces sapienic acid (16:1Δ6)-rich oils in Thunbergia alata seeds. Guided by a T. laurifolia desaturase crystal structure obtained in this study, enzyme mutagenesis identified key amino acids for functional divergence of Δ6 desaturases from the archetypal Δ9-18:0-ACP desaturase and mutations that result in nonnative enzyme regiospecificity. Furthermore, we demonstrate the utility of the T. laurifolia desaturase for the production of unusual monounsaturated fatty acids in engineered plant and bacterial hosts. Through stepwise metabolic engineering, we provide evidence that divergent evolution of extreme petroselinic acid and sapienic acid production arises from biosynthetic and metabolic functional specialization and enhanced expression of specific enzymes to accommodate metabolism of atypical substrates.

Radiotherapy is a common method to treat cancers, with the goal of maximizing the dose to tumors while minimizing the dose to normal tissues. Radioprotectors can reduce the toxicity to normal tissues during radiotherapy. Several plant-derived compounds can function as radioprotectors by scavenging free radicals. We investigated the radioprotective activity of interruptin C from the fern Cyclosorus terminans . The molecular mechanism of interruptin C's activity in X-ray-irradiated cells was evaluated. Superoxide dismutase activity was examined to investigate the antioxidant enzyme activity. Clonogenic cell survival was also investigated following radiation exposure. DNA damage and cell cycle progression were detected using micronuclei formation assays. DNA repair after irradiation was analyzed in a γH2AX assay. The levels of the proteins related to the radioprotective responses were analyzed by Western blotting. Interruptin C increased the antioxidant enzyme activity and significantly decreased the DNA damage by reducing the γH2AX foci and micronucleus formation in irradiated MCF-10A normal breast and HaCaT human keratinocyte cells. The apoptotic protein levels decreased, whereas the antiapoptotic protein levels increased. Interruptin C pretreatment increased the survival rate of irradiated MCF-10A and HaCaT cells. Moreover, the compound did not promote the survival of MDA-MB-231 and Hs578T breast cancer cells. Therefore, interruptin C may exert radioprotective activity without enhancing cancer cell proliferation.

Background: Curcumin is claimed as a potent protectant against Gastric Ulcer (GU) induced by strong necrotizing agents, including NSAIDs through its antioxidant, anti-inflammatory and gastroprotective activities. However, it was found to exert opposite effects to either delay ulcer healing or exacerbate ulcer inflammation through some curative mechanisms differently modified by curcumin dosage. Its ability to inhibit the expression of COX-2 may also delay the healing of NSAIDs-induced GU. Recently, a topical chitosan-curcumin solution has been found to be a safe and potential alternative agent in treating oral ulcer. Therefore, an oral chitosan-curcumin mixture was developed and determined for its efficacy in treating NSAIDs-induced GU in the rat., Methods: A chitosan (150 mg)-curcumin (20 mg) mixture with optimal gastric pH was developed. Indomethacin (30 mg/kg) was given orally to the rat and test preparations were administered orally at 5 h later and then every 24 h for two consecutive days. The sum of all gastric ulcerated areas (mm2) for each stomach was used as ulcer index. Gastric pro-inflammatory mediators and cytoprotective factors were determined., Results: An oral administration of a chitosan-curcumin mixture exerted a superior efficacy than curcumin, chitosan or lansoprazole (a standard antiulcer agent) in healing indomethacin-induced GU. It was revealed that the mixture exhibited the highest anti-oxidant, anti-inflammatory and gastric mucus producing activities including the high potency in down-regulating pro-inflammatory COX-2 and iNOS expression but up-regulating cytoprotective COX-1, nNOS and eNOS expression., Conclusion: The present findings indicated the benefit of a chitosan-curcumin mixture as a potential alternative agent in treating NSAIDs-induced gastric ulcers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Used lubricating oil (ULO) is a widespread contaminant, particularly throughout tropical regions, and may be a candidate for bioremediation. However, little is known about the biodegradation potential or basic microbial ecology of ULO-contaminated soils. This study aims to determine the effects of used ULO on bacterial community structure and diversity. Using a combination of culture-based (agar plate counts) and molecular techniques (16S rRNA gene sequencing and DGGE), we investigated changes in soil bacterial communities from three different ULO-contaminated soils collected from motorcycle mechanical workshops (soil A, B, and C). We further explored the relationship between bacterial community structure, physiochemical soil parameters, and ULO composition in three ULO-contaminated soils. Results indicated that the three investigated soils had different community structures, which may be a result of the different ULO characteristics and physiochemical soil parameters of each site. Soil C had the highest ULO concentration and also the greatest diversity and richness of bacteria, which may be a result of higher nutrient retention, organic matter and cation exchange capacity, as well as freshness of oil compared to the other soils. In soils A and B, Proteobacteria (esp. Gammaproteobacteria) dominated the bacterial community, and in soil C, Actinobacteria and Firmicutes dominated. The genus Enterobacter, a member of the class Gammaproteobacteria, is known to include ULO-degraders, and this genus was the only one found in all three soils, suggesting that it could play a key role in the in situ degradation of ULO-contaminated tropical Thai soils. This study provides insights into our understanding of soil microbial richness, diversity, composition, and structure in tropical ULO-contaminated soils, and may be useful for the development of strategies to improve bioremediation.

Lactococcus lactis KTH0-1S isolated from Thai traditional fermented shrimp (Kung-som) is able to produce heat-stable bacteriocin and inhibits food spoilage bacteria and food-borne pathogens. The inhibitory effect of bacteriocin remained intact after treatment with different pHs and after heating, but was sensitive to some proteolytic enzymes. Addition of bacteriocin KTH0-1S to Staphylococcus aureus cultures decreased viable cell counts by 2.8 log CFU/ml, demonstrating a bactericidal mode of action. Furthermore, the growth of S. aureus decreased significantly after 12-h co-cultivation with bacteriocinogenic strain. The molecular mass of bacteriocin KTH0-1S was found to be 3.346 kDa after ammonium sulfate precipitation, reversed phase (C 8 Sep-Pak), cation-exchange chromatography, RP-HPLC on C 8 column and mass spectrometry (MS/MS) analysis. Bacteriocin KTH0-1S was identified as nisin Z using PCR amplification and sequencing. The majority of tested virulence factors were absent, confirming the safety. Evidenced inhibitory effect of this strain, the absence of virulence factors creates the possibility for its application as protective culture to inhibit pathogenic bacteria in the several fermented seafood products.

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose‑derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose‑dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator‑activated receptor (PPAR)‑α and PPAR‑γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)‑1 and cyclooxygenase (COX)‑2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)‑1 and GLUT‑4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR‑α and PPAR‑γ (K(D) values of 5.32 and 0.10 µm, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR‑α and PPAR‑γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes.

Two Δ(12)-desaturases associated with the primary steps of long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis were successfully cloned from Physcomitrella patens and their functions identified. The open reading frames (ORFs) of PpFAD2-1 and PpFAD2-2 consisted of 1,128 bp and code for 375 amino acids. Their deduced polypeptides showed 62-64 % identity to microsomal Δ(12)-desaturases from other higher plants, and each contained the three histidine clusters typical of the catalytic domains of such enzymes. Yeast cells transformed with plasmid constructs containing PpFAD2-1 or PpFAD2-2 produced an appreciable amount of hexadecadienoic (16:2 Δ(9,12)) and linoleic acids (18:2 Δ(9,12)), not normally present in wild-type yeast cells, indicating that the genes encoded functional Δ(12)-desaturase enzymes. In addition, reduction of the growth temperature from 30 to 15 °C resulted in increased accumulation of unsaturated fatty acid products.

The lower plant Physcomitrella patens synthesizes several long-chain polyunsaturated fatty acids (LC-PUFAs) by a series of desaturation and elongation reactions. In the present study, the full-length cDNAs for two novel fatty acid elongases designated PpELO1 and PpELO2 were isolated from P. patens using a PCR-based cloning strategy. These cDNAs encoding proteins of 335 and 280 amino acids with predicted molecular masses of 38.7 and 32.9 kDa, respectively, are predicted to contain seven transmembrane domains with a possible localization in the subcellular endoplasmic reticulum. Sequence comparisons and phylogenetic analysis revealed that they are closely related to other LC-PUFA elongases of the lower eukaryotes such as the Δ(5)- and Δ(6)-elongases of Marchantia polymorpha as well as the Δ(6)-elongase of P. patens. Heterologous expression of the PpELO1 in Saccharomyces cerevisiae led to the elongation of Δ(9)-, Δ(6)-C18, and Δ(5)-C20 LC-PUFAs, whereas only Δ(9)- and Δ(6)-C18 LC-PUFA substrates were used by PpELO2. Chimeric proteins were constructed to identify the amino acid regions most likely to be involved in the determination of the fatty acid substrate specificity. The expression of eight chimeric proteins in yeast revealed that substitution of the C-terminal 50 amino acids from PpELO1 into PpELO2 resulted in a high specificity for C20 fatty acid substrates. As a result, we suggest that the C-terminal region of PpELO1 is sufficient for C20 substrate elongation. Overall, these results provide important insights into the structural basis for substrate specificity of PUFA-generating ELO enzymes.

Panax ginseng is considered as one of the most valuable medicinal herbs in traditional medicine, and ginsenoside Rd is one of the main active ingredients in P. ginseng leaf. Although there is significant number of evidences implicated on the beneficial effects of the ginsenosides with diverse associated mechanisms, reports on the skin regeneration by the ginsenoside Rd are not sufficient. Therefore, we examined the mitogenic and protective effects of the ginsenoside Rd in the keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (HDFs). Furthermore, the signaling pathways involved in the activation of KPCs and HDFs were investigated, and wound-healing effect is evaluated in vivo through animal wound models. We found that the ginsenoside Rd significantly increased the proliferation and migration level of KPCs and HDFs in a dose-dependent manner. Additionally, the cell survival was significantly increased in H2O2 treated KPCs. Moreover, the ginsenoside Rd effectively induced collagen type 1 and down-regulated matrix metalloprotinase-1 (MMP-1) in a dose-dependent manner. All of these beneficial effects are associated with an induction of intracellular cAMP levels and phosphorylated cAMP response element-binding protein expression in nucleus, which both attenuated by adenine 9-β-d-arabinofuranoside, an adenylate cyclase inhibitor. Application of the ginsenoside Rd to an excision wound in mice showed an effective healing process. As skin regeneration is mainly associated with the activation of HDFs and KPCs, P. ginseng leaf, an alternative source of the ginsenoside Rd, can be used as a natural source for skin regeneration., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: A stem cell (SC) niche is defined as the microenvironment in which the adult SC resides and includes surrounding cells, low oxygen content and growth factor gradients. Crosstalk between SCs and their niche provides signals that keep SCs quiescent, or modulates their activation., Areas Covered: This review discusses the characterization of niche conditions in the adipose-derived stem cell (ASC) in vivo environment, and introduces key signalling pathways and autocrine/paracrine regulators of ASCs., Expert Opinion: Control of in vivo niche factors (such as low oxygen content, generation of reactive oxygen species and activation of platelet-derived growth factor receptor signalling) should increase ASC yields synergistically and reduce production costs. Additionally, the preconditioning of ASCs with these niche factors prior to transplantation might enhance their regenerative potential. ASC niche is complex, and there are components of the niche that we may not yet understand. Therefore, future research needs to focus on identifying the key regulatory factors of the ASC niche in vivo, and developing a novel method to mimic these niche factors for in vitro manipulation.

Pachastrissa nux has two distinctive growth forms in one colony, i.e., the protruding gorgonian-shaped capitum and the substratum-attached irregular-shaped base. The sponge has the ability to allocate specifically its major secondary metabolites to the two parts in different levels. Using two cytotoxic trisoxazole macrolides, kabiramides C (2) and G (3), as chemical markers, it was found that the capitum accumulated higher contents of either or both compounds than did the base. However, there were neither inductive nor suppressive correlations among the allocation profiles of either compound in either part of the sponge. The allocation of kabiramides was a trade-off with the structural materials involved in reinforcing the strength of the sponge. To date, this is the second report that provides evidence of the specific allocation of bioactive metabolites in two distinctively different organ-like structures in a single sponge colony., (Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.)

Adrenic acid (ADA), an omega-6 polyunsaturated fatty acid (PUFA), has attracted much interest due to its pharmaceutical potential. Exploiting the wealth of information currently available on in planta oil biosynthesis, and coupling this information with the tool of genetic engineering, it is now feasible to deliberately alter fatty acid biosynthetic pathways to generate unique oils in commodity crops. In this study, a Delta(5)-elongase gene from the algae Pavlova sp. related to the biosynthesis of C(22) PUFAs was targeted to enable production of ADA in the moss Physcomitrella patens. Heterologous expression of this gene was under the control of a tandemly duplicate 35S promoter. It was established that ADA (0.42mg/l) was synthesized in P. patens from endogenous arachidonic acid (ARA) via the expressed Pavlova sp. Delta(5)-elongase in the moss. In an attempt to maximize ADA production, medium optimization was effected by the response surface methodology (RSM), resulting in a significant elevation of ADA (4.51mg/l) production under optimum conditions. To the best of our knowledge, this is the first study describing the expression of a PUFA synthesizing enzyme in non-seed lower plant without supplying the exogenous fatty acid., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The moss Physcomitrella patens contains high levels of arachidonic acid and lesser amounts of eicosapentaenoic acid. Here we report the identification and characterization of a delta5-desaturase from P. patens that is associated with the synthesis of these fatty acids. A full-length cDNA for this desaturase was identified by data base searches based on homology to sequences of known delta5-desaturase cDNAs from fungal and algal species. The resulting P. patens cDNA encodes a 480-amino acid polypeptide that contains a predicted N-terminal cytochrome b5-like domain as well as three histidine-rich domains. Expression of the enzyme in Saccharomyces cerevisiae resulted in the production of the delta5-containing fatty acid arachidonic acid in cells that were provided di-homo-gamma-linolenic acid. In addition, the expressed enzyme generated delta5-desaturation products with the C20 substrates omega-6 eicosadienoic and omega-3 eicosatrienoic acids, but no products were detected with the C18 fatty acid linoleic and alpha-linolenic acids or with the C22 fatty acid adrenic and docosapentaenoic acids. When the corresponding P. patens genomic sequence was disrupted by replacement through homologous recombination, a dramatic alteration in the fatty acid composition was observed, i.e. an increase in di-homo-gamma-linolenic and eicosatetraenoic acids accompanied by a concomitant disappearance of the delta5-fatty acid arachidonic and eicosapentaenoic acids. In addition, overexpression of the P. patens cDNA in protoplasts isolated from a disrupted line resulted in the restoration of arachidonic acid synthesis.