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1.
Res Microbiol ; : 104211, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38734157

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen that produces two types of siderophores, pyoverdine and pyochelin, that play pivotal roles in iron scavenging from the environment and host cells. P. aeruginosa siderophores can serve as virulence factors and perform various functions. Several bacterial and fungal species are likely to interact with P. aeruginosa due to its ubiquity in soil and water as well as its potential to cause infections in plants, animals, and humans. Siderophores produced by P. aeruginosa play critical roles in iron scavenging for prokaryotic species (bacteria) and eukaryotic hosts (fungi, animals, insects, invertebrates, and plants) as well. This review provides a comprehensive discussion of the role of P. aeruginosa siderophores in interaction with prokaryotes and eukaryotes as well as their underlying mechanisms of action. The evolutionary relationship between P. aeruginosa siderophore recognition receptors, such as FpvA, FpvB, and FptA, and those of other bacterial species has also been investigated.

2.
Mar Drugs ; 22(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38667767

ABSTRACT

Chitosan (CH) shows great potential as an immunostimulatory feed additive in aquaculture. This study evaluates the effects of varying dietary CH levels on the growth, immunity, intestinal morphology, and antioxidant status of Nile tilapia (Oreochromis niloticus) reared in a biofloc system. Tilapia fingerlings (mean weight 13.54 ± 0.05 g) were fed diets supplemented with 0 (CH0), 5 (CH5), 10 (CH10), 20 (CH20), and 40 (CH40) mL·kg-1 of CH for 8 weeks. Parameters were assessed after 4 and 8 weeks. Their final weight was not affected by CH supplementation, but CH at 10 mL·kg-1 significantly improved weight gain (WG) and specific growth rate (SGR) compared to the control (p < 0.05) at 8 weeks. Skin mucus lysozyme and peroxidase activities were lower in the chitosan-treated groups at weeks 4 and 8. Intestinal villi length and width were enhanced by 10 and 20 mL·kg-1 CH compared to the control. However, 40 mL·kg-1 CH caused detrimental impacts on the villi and muscular layer. CH supplementation, especially 5-10 mL·kg-1, increased liver and intestinal expressions of interleukin 1 (IL-1), interleukin 8 (IL-8), LPS-binding protein (LBP), glutathione reductase (GSR), glutathione peroxidase (GPX), and glutathione S-transferase (GST-α) compared to the control group. Overall, dietary CH at 10 mL·kg-1 can effectively promote growth, intestinal morphology, innate immunity, and antioxidant capacity in Nile tilapia fingerlings reared in biofloc systems.


Subject(s)
Animal Feed , Aquaculture , Chitosan , Cichlids , Intestines , Animals , Chitosan/pharmacology , Cichlids/growth & development , Cichlids/immunology , Cichlids/metabolism , Intestines/drug effects , Aquaculture/methods , Dietary Supplements , Antioxidants/pharmacology , Antioxidants/metabolism , Gene Expression/drug effects
3.
J Mater Chem B ; 12(18): 4451-4466, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38623740

ABSTRACT

Non-healing chronic diabetic wound treatment remains an unsolved healthcare challenge and still threatens patients' lives. Recently, hydrogel dressings based on natural biomaterials have been widely investigated to accelerate the healing of diabetic wounds. In this study, we introduce a bioactive hydrogel based on fish gelatin (FG) as a candidate for diabetic wound treatments, which is a recently emerged substitute for mammalian derived gelatin. The composite hydrogel simply fabricated with FG and oxidized hyaluronate (OHy) through Schiff base reaction could successfully accelerate wound healing due to their adequate mechanical stability and self-healing ability. In vitro studies showed that the fabricated hydrogels exhibited cytocompatibility and could reduce pro-inflammatory cytokine expression such as NO, IL-1ß, TNF-α, and PGE2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In addition, the production of reactive oxygen species (ROS), a key marker of free radicals producing oxidative stress, was also reduced by fabricated hydrogels. Furthermore, in vivo experiments demonstrated that the hydrogel could promote wound closure, re-epithelialization, collagen deposition, and protein expression of CD31, CD206, and Arg1 in diabetic mice models. Our study highlights the advanced potential of FG as a promising alternative material and indicates that FOHI can be successfully used for diabetic wound healing applications.


Subject(s)
Diabetes Mellitus, Experimental , Gelatin , Hyaluronic Acid , Hydrogels , Wound Healing , Animals , Wound Healing/drug effects , Mice , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Gelatin/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , RAW 264.7 Cells , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/chemically induced , Fishes , Bandages , Oxidation-Reduction , Male , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
4.
Int J Biol Macromol ; 267(Pt 1): 131166, 2024 May.
Article in English | MEDLINE | ID: mdl-38582464

ABSTRACT

Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.


Subject(s)
Caffeic Acids , Carcinoma, Squamous Cell , Polysaccharides, Bacterial , Psyllium , Caffeic Acids/pharmacology , Caffeic Acids/chemistry , Caffeic Acids/administration & dosage , Animals , Humans , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/pharmacology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Mice , Psyllium/chemistry , Psyllium/pharmacology , Cell Line, Tumor , Polysaccharides/chemistry , Polysaccharides/pharmacology , Hydrogels/chemistry , Xenograft Model Antitumor Assays , Drug Delivery Systems
5.
Eur J Pharmacol ; 973: 176610, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38663541

ABSTRACT

Aripiprazole, a third-generation antipsychotic, has been widely used to treat schizophrenia. In this study, we evaluated the effect of aripiprazole on voltage-gated potassium (Kv) channels in rabbit coronary arterial smooth muscle cells using the patch clamp technique. Aripiprazole reduced the Kv current in a concentration-dependent manner with a half-maximal inhibitory concentration of 0.89 ± 0.20 µM and a Hill coefficient of 1.30 ± 0.25. The inhibitory effect of aripiprazole on Kv channels was voltage-dependent, and an additional aripiprazole-induced decrease in the Kv current was observed in the voltage range of full channel activation. The decay rate of Kv channel inactivation was accelerated by aripiprazole. Aripiprazole shifted the steady-state activation curve to the right and the inactivation curve to the left. Application of a repetitive train of pulses (1 and 2 Hz) promoted inhibition of the Kv current by aripiprazole. Furthermore, the recovery time constant from inactivation increased in the presence of aripiprazole. Pretreatment of Kv1.5 subtype inhibitor reduced the inhibitory effect of aripiprazole. However, pretreatment with Kv 7 and Kv2.1 subtype inhibitors did not change the degree of aripiprazole-induced inhibition of the Kv current. We conclude that aripiprazole inhibits Kv channels in a concentration-, voltage-, time-, and use (state)-dependent manner by affecting the gating properties of the channels.


Subject(s)
Aripiprazole , Coronary Vessels , Myocytes, Smooth Muscle , Potassium Channel Blockers , Potassium Channels, Voltage-Gated , Animals , Aripiprazole/pharmacology , Rabbits , Potassium Channels, Voltage-Gated/metabolism , Potassium Channels, Voltage-Gated/antagonists & inhibitors , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Coronary Vessels/drug effects , Coronary Vessels/cytology , Potassium Channel Blockers/pharmacology , Male , Antipsychotic Agents/pharmacology , Dose-Response Relationship, Drug
6.
J Med Food ; 27(4): 359-368, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38526569

ABSTRACT

As the body's largest organ, the skin is located at the internal and external environment interface, serving as a line of defense against various harmful stressors. Recently, marine-derived physiologically active ingredients have attracted considerable attention in the cosmeceutical industry due to their beneficial effects on skin health. Sargassum, a genus of brown macroalgae, has traditionally been consumed as food and medicine in several countries and is rich in bioactive compounds such as meroterpenoids, sulfated polysaccharides, fucoidan, fucoxanthin, flavonoids, and terpenoids. Sargassum spp. have various beneficial effects on skin disorders. They help with atopic dermatitis by improving skin barrier protection and reducing inflammation. Several species show potential in treating acne by inhibiting bacterial growth and reducing inflammation. Some species, such as Sargassum horneri, demonstrate antiallergic effects by modulating mast cell activity. Certain Sargassum species exhibit anticancer activity by inhibiting tumor growth and promoting apoptosis, and some species help with wound healing by promoting angiogenesis and reducing oxidative stress. Overall, Sargassum spp. demonstrate potential for treating and managing various skin conditions. Therefore, the bioactive compounds of Sargassum spp. may be natural ingredients with a wide range of functional properties for preventing and treating skin disorders. The present review focused on the various biological effects of Sargassum extracts and derived compounds on skin disorders.


Subject(s)
Sargassum , Seaweed , Humans , Skin , Inflammation , Terpenes/pharmacology
7.
Sci Rep ; 14(1): 3945, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38365854

ABSTRACT

The phlorotannin-polycaprolactone-coated endotracheal tube (PP tube) has been developed with the aim of preventing tracheal stenosis that can result from endotracheal intubation, a factor that can lead to a serious airway obstruction. Its preventive efficacy has been assessed through both in vitro and in vivo investigations. However, there is a lack of studies concerning its biocompatibility and sub-chronic toxicity in animal models, a crucial factor to ensure the safety of its usage as a functional endotracheal tube. Thus, this study aimed to evaluate the biocompatibility and sub-chronic (13 weeks) toxicity of the PP tube through L929 cell line and diverse in vivo models. The cytotoxicity testing was performed using the extracts of PP tube on L929 cells for 72 h. Furthermore, other tests conducted on animal models, including ICR mice (acute systemic toxicity), New Zealand white rabbit (intradermal reactivity and pyrogen tests), guinea pig (maximization sensitization), and Sprague Dawley rats (sub-chronic toxicity). In both biocompatibility and sub-chronic toxicity analyses, no significant adverse effects are observed in the groups exposed to the PP tube, when compared to control group. Altogether, the findings suggested that the PP tube exhibits relative non-toxic and safety, supporting its suitability for clinical usage. However, extended periods of intubation may produce mild irritant responses, highlighting the clinical caution of limiting intubation duration to less than 13 weeks.


Subject(s)
Intubation, Intratracheal , Polyesters , Trachea , Mice , Rats , Animals , Rabbits , Guinea Pigs , Rats, Sprague-Dawley , Mice, Inbred ICR , Intubation, Intratracheal/adverse effects
8.
Microb Pathog ; 188: 106546, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38278457

ABSTRACT

Nanomaterials derived from seaweed have developed as an alternative option for fighting infections caused by biofilm-forming microbial pathogens. This research aimed to discover potential seaweed-derived nanomaterials with antimicrobial and antibiofilm action against bacterial and fungal pathogens. Among seven algal species, the extract from Eisenia bicyclis inhibited biofilms of Klebsiella pneumoniae, Staphylococcus aureus, and Listeria monocytogenes most effectively at sub-MIC levels. As a result, in the present study, E. bicyclis was chosen as a prospective seaweed for producing E. bicyclis-gold nanoparticles (EB-AuNPs). Furthermore, the mass spectra of E. bicyclis reveal the presence of a number of potentially beneficial chemicals. The polyhedral shape of the synthesized EB-AuNP with a size value of 154.74 ± 33.46 nm was extensively described. The lowest inhibitory concentration of EB-AuNPs against bacterial pathogens (e.g., L.monocytogenes, S. aureus, Pseudomonas aeruginosa, and K. pneumoniae) and fungal pathogens (Candida albicans) ranges from 512 to >2048 µg/mL. Sub-MIC of EB-AuNPs reduces biofilm formation in P. aeruginosa, K. pneumoniae, L. monocytogenes, and S. aureus by 57.22 %, 58.60 %, 33.80 %, and 91.13 %, respectively. EB-AuNPs eliminate the mature biofilm of K. pneumoniae at > MIC, MIC, and sub-MIC concentrations. Furthermore, EB-AuNPs at the sub-MIC level suppress key virulence factors generated by P. aeruginosa, including motility, protease activity, pyoverdine, and pyocyanin, whereas it also suppresses the production of staphyloxanthin virulence factor from S. aureus. The current research reveals that seaweed extracts and a biocompatible seaweed-AuNP have substantial antibacterial, antibiofilm, and antivirulence actions against bacterial and fungal pathogens.


Subject(s)
Anti-Infective Agents , Edible Seaweeds , Kelp , Metal Nanoparticles , Seaweed , Gold/pharmacology , Gold/chemistry , Staphylococcus aureus , Prospective Studies , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , Biofilms , Seaweed/chemistry , Virulence Factors , Microbial Sensitivity Tests , Pseudomonas aeruginosa
9.
Heliyon ; 10(2): e24216, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38293511

ABSTRACT

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

10.
ACS Omega ; 9(1): 157-165, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38222507

ABSTRACT

A mixture of three distinct cerium precursors (Ce(NO3)3·6H2O, CeCl3·7H2O, and Ce(CH3COO)3·H2O) was used to prepare cerium oxide nanoparticles (CeO2 NPs) in a polyol-mediated synthesis. Different ratios of diethylene glycol (DEG) and H2O were utilized in the synthesis. The properties of the synthesized CeO2 NPs, such as structural and morphological properties, were investigated to observe the effect of the mixed cerium precursors. Crystallite sizes of 7-8 nm were obtained for all samples, and all synthesized samples were confirmed to be in the cubic phase. The average particle sizes of the spherical CeO2 were between 9 and 13 nm. The successful synthesis of CeO2 can also be confirmed via the vibrational band of Ce-O from the FTIR. Antidiabetic properties of the synthesized CeO2 NPs were investigated using α-glucosidase enzyme inhibition assay, and the concentration of the synthesized CeO2 NPs was varied in the study. The biocompatibility properties of the synthesized CeO2 NPs were investigated via cytotoxicity tests, and it was found that all synthesized materials showed no cytotoxic properties at lower concentrations (62.5-125 µg/mL).

11.
Int J Biol Macromol ; 255: 128047, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37956810

ABSTRACT

The design and development of wound dressing with antioxidant and antibacterial properties to accelerate wound healing remain challenging. In this study, we synthesize a chitooligosaccharide-gentisic acid (COS-GSA) conjugate using the free-radical grafting method, and fabricate a poly(vinyl alcohol) (PVA)/chitosan (CH)/COS-GSA (PVA/CH/CG) hydrogel using a freeze-thaw method. We characterize the synthesized COS-GSA conjugates using through polyphenol assay, absorbance, and 1H NMR spectroscopy and evaluate their antioxidant properties. The COS-GSA conjugates are successfully synthesized and exhibit better antioxidant properties than pristine COSs. Subsequently, the fabricated hydrogel is characterized based on its morphological analysis, rheological properties, water contact angle, swelling, degradation, water retention properties, and COS-GSA release profiles. Finally, the biocompatibility of the fabricated hydrogel is evaluated on HDF and HaCaT cells through indirect and direct cytotoxicity. The PVA/CH/CG hydrogel exhibited significantly higher antioxidant properties (DPPH, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydrogen peroxide (H2O2) scavenging activities) and antibacterial activities (Staphylococcus aureus and Pseudomonas aeruginosa) compared to other fabricated hydrogels such as PVA, PVA/CH, and PVA/CH/COS (PVA/CH/C). These results provide evidence that PVA/CH/CG hydrogels with antioxidant, antibacterial, and non-cytotoxic properties have great potential for wound-dressing applications.


Subject(s)
Chitosan , Chitosan/chemistry , Antioxidants/pharmacology , Polyvinyl Alcohol/chemistry , Hydrogels/chemistry , Hydrogen Peroxide , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bandages , Water , Ethanol
12.
Planta Med ; 90(1): 25-37, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37848042

ABSTRACT

This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.


Subject(s)
Lipopolysaccharides , NF-kappa B , Animals , Mice , NF-kappa B/metabolism , RAW 264.7 Cells , Lipopolysaccharides/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , NF-E2-Related Factor 2/metabolism , Anti-Inflammatory Agents/pharmacology , Heme Oxygenase-1/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Cyclooxygenase 2/metabolism
13.
Cell Biochem Funct ; 41(7): 889-897, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37589166

ABSTRACT

Polydeoxyribonucleotide (PDRN) is a DNA-derived drug extracted from the sperm cells of Oncorhynchus mykiss or O. keta. PDRN exhibits wound healing and anti-inflammatory activities by activating adenosine A2A receptor and salvage pathways. However, commercial PDRN products (e.g., Placentex, Rejuvenex, and HiDr) have limitations as they are exclusively extracted O. mykiss and O. keta, which are expensive and can only be used as extraction sources during a specific period when their sperm cells are activated. Therefore, this study aimed to extract PDRN from Porphyra sp. (Ps-PDRN) and investigate whether it has anti-inflammatory activity through a comparative study with commercial product. The results indicated that Ps-PDRN had an anti-inflammatory effect on Escherichia coli lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. It inhibited nitric oxide production and inducible nitric oxygen synthase protein expression by suppressing phosphorylation of p38 and ERK, without cytotoxicity. Furthermore, Ps-PDRN promoted cell proliferation and collagen production in human dermal fibroblast. In conclusion, our study confirms that Ps-PDRN exhibits both anti-inflammatory and cell proliferative effects. These results indicated that Ps-PDRN has the potential as a bioactive drug for tissue engineering.

14.
Eur J Pharmacol ; 957: 176005, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37611842

ABSTRACT

Lurasidone is a second-generation antipsychotic drug used to treat schizophrenia, mania, and bipolar disorder. The drug is an antagonist of the 5-HT2A and D2 receptors. No effect of lurasidone on the voltage-gated K+ (Kv) channels has yet been identified. Here, we show that lurasidone inhibits the vascular Kv channels of rabbit coronary arterial smooth muscle cells in a dose-dependent manner with an IC50 of 1.88 ± 0.21 µM and a Hill coefficient of 0.98 ± 0.09. Although lurasidone (3 µM) did not affect the activation kinetics, the drug negatively shifted the inactivation curve, suggesting that the drug interacted with the voltage sensors of Kv channels. Application of 1 or 2 Hz train steps in the presence of lurasidone significantly increased Kv current inhibition. The recovery time after channel inactivation increased in the presence of lurasidone. These results suggest that the inhibitory action of lurasidone is use (state)-dependent. Pretreatment with a Kv 1.5 subtype inhibitor effectively reduced the inhibitory effect of lurasidone. However, the inhibitory effect on Kv channels did not markedly change after pretreatment with a Kv 2.1 or a Kv7 subtype inhibitor. In summary, lurasidone inhibits vascular Kv channels (primarily the Kv1.5 subtype) in a concentration- and use (state)-dependent manner by shifting the steady-state inactivation curve.


Subject(s)
Antipsychotic Agents , Potassium Channels, Voltage-Gated , Animals , Rabbits , Lurasidone Hydrochloride/pharmacology , Antipsychotic Agents/pharmacology , Coronary Vessels , Myocytes, Smooth Muscle
15.
J Appl Toxicol ; 43(12): 1926-1933, 2023 12.
Article in English | MEDLINE | ID: mdl-37551856

ABSTRACT

Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage-dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells. Paliperidone reduced Kv channel activity in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50 ) of 16.58 ± 3.03 µM and a Hill coefficient of 0.60 ± 0.04. It did not significantly shift the steady-state activation or inactivation curves, suggesting that the drug did not affect the gating properties of Kv channels. In the presence of paliperidone, the application of 20 repetitive depolarizing pulses at 1 and 2 Hz gradually increased the inhibition of the Kv current. Further, the recovery time constant after Kv channel inactivation was increased by paliperidone, indicating that it inhibited the Kv channel in a use (state)-dependent manner. Its inhibitory effects were reduced by pretreatment with a Kv1.5 subtype inhibitor. However, pretreatment with a Kv2.1 or Kv7 inhibitor did not reduce its inhibitory effect. We conclude that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration- and use (state)-dependent manner without changing channel gating.


Subject(s)
Antipsychotic Agents , Potassium Channels, Voltage-Gated , Animals , Rabbits , Antipsychotic Agents/toxicity , Paliperidone Palmitate/pharmacology , Potassium Channel Blockers/pharmacology , Potassium Channels, Voltage-Gated/pharmacology , Myocytes, Smooth Muscle
16.
Genes (Basel) ; 14(7)2023 07 22.
Article in English | MEDLINE | ID: mdl-37510398

ABSTRACT

The Indian highland shrew, Suncus niger (Horsfield, 1851), is the least studied soricid species from its original range distribution in Southern India, with several systematics conundrums. Following its discovery in 1851, the species was synonymized with Suncus montanus (Kelaart, 1850) (endemic to Sri Lanka) and subsequently identified as a separate Indian population. However, the systematic status of S. niger from topotype specimens in Southern India has yet to be determined through an integrated approach. Both taxonomy and mitochondrial genetic data (Cytochrome b and 16S ribosomal RNA) were used to re-examine the systematics of S. niger. The mtCytb gene clearly distinguished topotypic S. niger from other Suncus species, with high genetic divergences varying from 8.49% to 26.29%. Further, the Bayesian and maximum likelihood topologies clearly segregated S. niger from other congeners and corroborated the sister relationship with S. stoliczkanus with expected divergence in the late Pliocene (2.62 MYA). The TimeTree analysis also exhibits a strong matrilineal affinity of S. dayi (endemic to India) toward the African species. The current study hypothesizes that the ancestor of the soricids evolved in Africa and that genetic lineages were subsequently shifted by plate tectonic events that subsequently colonized different continents as distinct species during the late Miocene (Tortonian) to the Holocene era. In addition to the new range expansion and elevation records of S. niger in the Central Western Ghats, we propose that additional sampling across its distribution, as well as the use of multiple genetic markers, may be useful in determining the genetic diversity and population structure of this endemic species. The present study also recommends that more molecular data on the Soricomorphs lineages, and estimates of their divergence times, will shed light on the evolution of these small mammals on Earth.


Subject(s)
Eulipotyphla , Shrews , Animals , Shrews/genetics , Phylogeny , Niger , Bayes Theorem , Biodiversity , India
17.
Int J Mol Sci ; 24(14)2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37511225

ABSTRACT

Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body's largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there has been growing evidence that macrophages, immune cells essential for tissue homeostasis and injury response, also contribute to the development of skeletal muscle insulin resistance. This review aims to summarize the current understanding of the role of macrophages in skeletal muscle insulin resistance. Firstly, it provides an overview of the different macrophage populations present in skeletal muscle and their specific functions in the development of insulin resistance. Secondly, it examines the underlying mechanisms by which macrophages promote or alleviate insulin resistance in skeletal muscle, including inflammation, oxidative stress, and altered metabolism. Lastly, the review discusses potential therapeutic strategies targeting macrophages to improve skeletal muscle insulin sensitivity and metabolic health.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Insulin , Humans , Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Insulin Resistance/physiology , Macrophages/metabolism , Muscle, Skeletal/metabolism
18.
Int J Mol Sci ; 24(14)2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37511323

ABSTRACT

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.


Subject(s)
Photochemotherapy , Uterine Cervical Neoplasms , Female , Humans , Caspase 9/metabolism , Caspase 8/metabolism , Uterine Cervical Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , HeLa Cells , Photochemotherapy/methods , Apoptosis , Photosensitizing Agents/chemistry , Oxidative Stress
19.
Int J Biol Macromol ; 245: 125484, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37348579

ABSTRACT

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.


Subject(s)
Gelatin , Hydrogels , Mice , Animals , Hydrogels/chemistry , Gelatin/chemistry , Alginates/chemistry , Mice, Inbred ICR , Wound Healing , Anti-Bacterial Agents
20.
RSC Adv ; 13(23): 15421-15436, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37223416

ABSTRACT

Cerium oxide (CeO2) nanoparticles (NPs) were synthesized using a modified conventional polyol method. The ratio of diethylene glycol (DEG) and water in the synthesis was varied, and three different cerium precursor salts (Ce(NO3)3, CeCl3, and Ce(CH3COO)3) were used. The structure, size, and morphology of the synthesized CeO2 NPs were studied. An average crystallite size of 13 to 33 nm was obtained from the XRD analysis. Spherical and elongated morphologies of the synthesized CeO2 NPs were acquired. Average particle sizes in the range of 16-36 nm were obtained by varying different ratios of DEG and water. The presence of DEG molecules on the surface of CeO2 NPs was confirmed using FTIR. Synthesized CeO2 NPs were used to study the antidiabetic and cell viability (cell cytotoxicity) properties. Antidiabetic studies were carried out using α-glucosidase enzymes inhibition activity. CeO2 synthesized using Ce(NO3)3 and CeCl3 precursors showed approximately 40.0% α-glucosidase enzyme inhibition activity, while CeO2 synthesized using Ce(CH3COO)3 showed the lowest α-glucosidase enzyme inhibition activity. Cell viability properties of CeO2 NPs were investigated using an in vitro cytotoxicity test. CeO2 NPs prepared using Ce(NO3)3 and CeCl3 were non-toxic at lower concentrations, while CeO2 NPs prepared using Ce(CH3COO)3 were non-toxic at all concentrations. Therefore, polyol-mediated synthesized CeO2 NPs showed quite good α-glucosidase inhibition activity and biocompatibility.

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