Application of cuminaldehyde and ciprofloxacin for the effective control of biofilm assembly of Pseudomonas aeruginosa: A combinatorial study.

Pseudomonas aeruginosa is widely associated with biofilm-mediated antibiotic resistant chronic and acute infections which constitute a persistent healthcare challenges. Addressing this threat requires exploration of novel therapeutic strategies involving the combination of natural compounds and conventional antibiotics. Hence, our study has focused on two compounds; cuminaldehyde and ciprofloxacin, which were strategically combined to target the biofilm challenge of P. aeruginosa. The minimum inhibitory concentration (MIC) of cuminaldehyde and ciprofloxacin was found to be 400 µg/mL and 0.4 µg/mL, respectively. Moreover, the fractional inhibitory concentration index (FICI = 0.62) indicated an additive interaction prevailed between cuminaldehyde and ciprofloxacin. Subsequently, sub-MIC doses of cuminaldehyde (25 µg/mL) and ciprofloxacin (0.05 µg/mL) were selected for an array of antibiofilm assays which confirmed their biofilm inhibitory potential without exhibiting any antimicrobial activity. Furthermore, selected doses of the mentioned compounds could manage biofilm on catheter surface by inhibiting and disintegrating existing biofilm. Additionally, the test combination of the mentioned compounds reduced virulence factors secretion, accumulated reactive oxygen species and increased cell-membrane permeability. Thus, the combination of cuminaldehyde and ciprofloxacin demonstrates potential in combating biofilm-associated Pseudomonal threats.

Cuminaldehyde and Tobramycin Forestall the Biofilm Threats of Staphylococcus aureus: A Combinatorial Strategy to Evade the Biofilm Challenges.

Staphylococcus aureus, an opportunistic Gram-positive pathogen, is known for causing various infections in humans, primarily by forming biofilms. The biofilm-induced antibiotic resistance has been considered a significant medical threat. Combinatorial therapy has been considered a reliable approach to combat antibiotic resistance by using multiple antimicrobial agents simultaneously, targeting bacteria through different mechanisms of action. To this end, we examined the effects of two molecules, cuminaldehyde (a natural compound) and tobramycin (an antibiotic), individually and in combination, against staphylococcal biofilm. Our experimental observations demonstrated that cuminaldehyde (20 µg/mL) in combination with tobramycin (0.05 µg/mL) exhibited efficient reduction in biofilm formation compared to their individual treatments (p < 0.01). Additionally, the combination showed an additive interaction (fractional inhibitory concentration value 0.66) against S. aureus. Further analysis revealed that the effective combination accelerated the buildup of reactive oxygen species (ROS) and increased the membrane permeability of the bacteria. Our findings also specified that the cuminaldehyde in combination with tobramycin efficiently reduced biofilm-associated pathogenicity factors of S. aureus, including fibrinogen clumping ability, hemolysis property, and staphyloxanthin production. The selected concentrations of tobramycin and cuminaldehyde demonstrated promising activity against the biofilm development of S. aureus on catheter models without exerting antimicrobial effects. In conclusion, the combination of tobramycin and cuminaldehyde presented a successful strategy for combating staphylococcal biofilm-related healthcare threats. This combinatorial approach holds the potential for controlling biofilm-associated infections caused by S. aureus.

Piperine, a phytochemical prevents the biofilm city of methicillin-resistant Staphylococcus aureus: A biochemical approach to understand the underlying mechanism.

Methicillin-resistant Staphylococcus aureus (MRSA), a drug-resistant human pathogen causes several nosocomial as well as community-acquired infections involving biofilm machinery. Hence, it has gained a wide interest within the scientific community to impede biofilm-induced MRSA-associated health complications. The current study focuses on the utilization of a natural bioactive compound called piperine to control the biofilm development of MRSA. Quantitative assessments like crystal violet, total protein recovery, and fluorescein-di-acetate (FDA) hydrolysis assays, demonstrated that piperine (8 and 16 µg/mL) could effectively compromise the biofilm formation of MRSA. Light and scanning electron microscopic image analysis confirmed the same. Further investigation revealed that piperine could reduce extracellular polysaccharide production by down-regulating the expression of icaA gene. Besides, piperine could reduce the cell-surface hydrophobicity of MRSA, a crucial factor of biofilm formation. Moreover, the introduction of piperine could interfere with microbial motility indicating the interaction of piperine with the quorum-sensing components. A molecular dynamics study showed a stable binding between piperine and AgrA protein (regulator of quorum sensing) suggesting the possible meddling of piperine in quorum-sensing of MRSA. Additionally, the exposure to piperine led to the accumulation of intracellular reactive oxygen species (ROS) and potentially heightened cell membrane permeability in inhibiting microbial biofilm formation. Besides, piperine could reduce the secretion of diverse virulence factors from MRSA. Further exploration revealed that piperine interacted with extracellular DNA (e-DNA), causing disintegration by weakening the biofilm architecture. Conclusively, this study suggests that piperine could be a potential antibiofilm molecule against MRSA-associated biofilm infections.

Piperine, a Plant Alkaloid, Exhibits Efficient Disintegration of the Pre-existing Biofilm of Staphylococcus aureus: a Step Towards Effective Management of Biofilm Threats.

Staphylococcus aureus causes a range of chronic infections in humans by exploiting its biofilm machinery and drug-tolerance property. Although several strategies have been proposed to eradicate biofilm-linked issues, here, we have explored whether piperine, a bioactive plant alkaloid, can disintegrate an already existing Staphylococcal biofilm. Towards this direction, the cells of S. aureus were allowed to develop biofilm first followed by treatment with the test concentrations (8 and 16 µg/mL) of piperine. In this connection, several assays such as total protein recovery assay, crystal violet assay, extracellular polymeric substances (EPS) measurement assay, fluorescein diacetate hydrolysis assay, and fluorescence microscopic image analysis confirmed the biofilm-disintegrating property of piperine against S. aureus. Piperine reduced the cellular auto-aggregation by decreasing the cell surface hydrophobicity. On further investigation, we observed that piperine could down regulate the dltA gene expression that might reduce the cell surface hydrophobicity of S. aureus. It was also observed that the piperine-induced accumulation of reactive oxygen species (ROS) could enhance biofilm disintegration by decreasing the cell surface hydrophobicity of the test organism. Together, all the observations suggested that piperine could be used as a potential molecule for the effective management of the pre-existing biofilm of S. aureus.

Combinatorial application of cuminaldehyde and gentamicin shows enhanced antimicrobial and antibiofilm action on Pseudomonas aeruginosa.

The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections. Thus, P. aeruginosa has been treated with cuminaldehyde (a naturally occurring phytochemical) and gentamicin (an aminoglycoside antibiotic) in connection to the effective management of the biofilm challenges. It was also observed that the test molecules could show increased antimicrobial activity against P. aeruginosa. A fractional inhibitory concentration index (FICI) of 0.65 suggested an additive interaction between cuminaldehyde and gentamicin. Besides, a series of experiments such as crystal violet assay, estimation of extracellular polymeric substance (EPS), and microscopic images indicated that an enhanced antibiofilm activity was obtained when the selected compounds were applied together on P. aeruginosa. Furthermore, the combination of the selected compounds was found to reduce the secretion of virulence factors from P. aeruginosa. Taken together, this study suggested that the combinatorial application of cuminaldehyde and gentamicin could be considered an effective approach towards the control of biofilm-linked infections caused by P. aeruginosa.

1, 4-naphthoquinone efficiently facilitates the disintegration of pre-existing biofilm of Staphylococcus aureus through eDNA intercalation.

1, 4-naphthoquinone, a plant-based quinone derivative, has gained much attention for its effectiveness against several biofilm-linked diseases. The biofilm inhibitory effect of 1, 4-naphthoquinone against Staphylococcus aureus has already been reported in our previous study. We observed that the extracellular DNA (eDNA) could play an important role in holding the structural integrity of the biofilm. Hence, in this study, efforts have been directed to examine the possible interactions between 1, 4-naphthoquinone and DNA. An in silico analysis indicated that 1, 4-naphthoquinone could interact with DNA through intercalation. To validate the same, UV-Vis spectrophotometric analysis was performed in which a hypochromic shift was observed when the said molecule was titrated with calf-thymus DNA (CT-DNA). Thermal denaturation studies revealed a change of 8℃ in the melting temperature (Tm) of CT-DNA when complexed with 1, 4-naphthoquinone. The isothermal calorimetric titration (ITC) assay revealed a spontaneous intercalation between CT-DNA and 1, 4-naphthoquinone with a binding constant of 0.95 ± 0.12 × 108. Furthermore, DNA was run through an agarose gel electrophoresis with a fixed concentration of ethidium bromide and increasing concentrations of 1, 4-naphthoquinone. The result showed that the intensity of ethidium bromide-stained DNA got reduced concomitantly with the gradual increase of 1, 4-naphthoquinone suggesting its intercalating nature. To gain further confidence, the pre-existing biofilm was challenged with ethidium bromide wherein we observed that it could also show biofilm disintegration. Therefore, the results suggested that 1, 4-naphthoquinone could exhibit disintegration of the pre-existing biofilm of Staphylococcus aureus through eDNA intercalation.

The combinatorial applications of 1,4-naphthoquinone and tryptophan inhibit the biofilm formation of Staphylococcus aureus.

Microorganisms embedded within an extracellular polymeric matrix are known as biofilm. The extensive use of antibiotics to overcome the biofilm-linked challenges has led to the emergence of multidrug-resistant strains. Staphylococcus aureus is one such nosocomial pathogen that is known to cause biofilm-linked infections. Thus, novel strategies have been adopted in this study to inhibit the biofilm formation of S. aureus. Two natural compounds, namely, 1,4-naphthoquinone (a quinone derivative) and tryptophan (aromatic amino acid), have been chosen as they could independently show efficient antibiofilm activity. To enhance the antibiofilm potential, the two compounds were combined and tested against the same organism. Several experiments like crystal violet (CV) assay, protein estimation, extracellular polymeric substance (EPS) extraction, and estimation of metabolic activity confirmed that the combination of the two compounds could significantly inhibit the biofilm formation of S. aureus. To comprehend the underlying mechanism, efforts were further directed to understand whether the two compounds could inhibit biofilm formation by compromising the cell surface hydrophobicity of the bacteria. The results revealed that the cell surface hydrophobicity got reduced by ~ 49% when the compounds were applied together. Thus, the combinations could show enhanced antibiofilm activity by attenuating cell surface hydrophobicity. Further studies revealed that the selected concentrations of the compounds could disintegrate (~ 70%) the pre-existing biofilm of the test bacteria without showing any antimicrobial activity. Hence, the combined application of tryptophan and 1,4-naphthoquinone could be used to inhibit the biofilm threats of S. aureus.

Effect of vasodilator and immunosuppressive therapy on the endothelial dysfunction in patients with systemic sclerosis.

A comparative analysis of flow-mediated vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated systemic sclerosis (SSc) patients is an unmet need. (1)To assess the FMD and different pathogenic mediators in SSc patients about endothelial dysfunction. (2) To assess the proportion of circulating endothelial cells (CECs) in treatment-naïve patients. SSc patients were grouped into treatment-naïve (Group-I, n = 24) on vasodilator (Group-II, n = 10), on vasodilator + immunosuppressive (Group-III, n = 22)]. Age-sex matched healthy controls (n = 20) were included. Endothelial dysfunction (ED) was measured radiologically using FMD. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGF, IL-6, and VEGF, as well as gene expressions of eNOS, iNOS, ET-1, and TGF, were measured to assess the status of ED in various study groups. CEC was measured in Group-I and HC. CEC was used as a marker to identify a key regulator of ED in SSc. FMD was significantly decreased in all SSc patients through receiving treatment. Upregulation of serum NO and ET concentrations was noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r = 0.6) and negatively with TGFß (r = - 0.5). ET-1 showed a negative correlation with TGFß (r = - 0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r = - 0.7, p = 0.0001) and NO/ET1 (r = - 0.6, p = 0.007). Persistent ED was observed in all SSc patients irrespective of treatment. Dysbalance in NO/ET1 ratio might be the considering factor for the underlying progression of ED. Based on our findings, it may be hypothesized that reduced NO may be a contributing factor in the pathogenesis of endothelial dysfunction in SSc.

Piperine Exhibits Potential Antibiofilm Activity Against Pseudomonas aeruginosa by Accumulating Reactive Oxygen Species, Affecting Cell Surface Hydrophobicity and Quorum Sensing.

Gram-positive and Gram-negative bacteria often develop biofilm through different mechanisms in promoting pathogenicity. Hence, the antibiofilm molecule needs to be examined separately on both organisms to manage the biofilm threat. Since the antibiofilm activity of piperine against Staphylococcus aureus was already reported; here, we aimed to examine the antibiofilm activity of it against Pseudomonas aeruginosa. P. aeruginosa is an opportunistic Gram-negative pathogen that can cause several healthcare-associated infections by exploiting biofilm. Several experiments like crystal violet assay, estimation of total protein, measurement of extracellular polymeric substance, and microscopic analysis confirmed that lower concentrations (8 and 16 µg/mL) of piperine could inhibit the microbial biofilm formation considerably. Besides, it could also reduce the secretion of virulence factors from P. aeruginosa. Further investigation showed that the cell surface hydrophobicity and microbial motility of the test organism got reduced under the influence of piperine. Piperine exposure was found to increase the accumulation of reactive oxygen species (ROS) that resulted in the inhibition of biofilm formation. Furthermore, the molecular simulation studies suggested that piperine could affect the quorum sensing network of P. aeruginosa. Towards this direction, we noticed that piperine treatment could decrease the expression of the quorum sensing gene (lasI) that resulted in the inhibition of biofilm formation. Besides biofilm inhibition, piperine was also found to disintegrate the pre-existing biofilm of P. aeruginosa without showing any antimicrobial property to the test organism. Thus, piperine could be used for the sustainable protection of public-healthcare by compromising the biofilm assembly of P. aeruginosa.

Synergistic interaction of cuminaldehyde and tobramycin: a potential strategy for the efficient management of biofilm caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic pathogen, has been found to cause several chronic and acute infections in human. Moreover, it often shows drug-tolerance and poses a severe threat to public healthcare through biofilm formation. In this scenario, two molecules, namely, cuminaldehyde and tobramycin, were used separately and in combination for the efficient management of biofilm challenge. The minimum inhibitory concentration (MIC) of cuminaldehyde and tobramycin was found to be 150 µg/mL and 1 µg/mL, respectively, against Pseudomonas aeruginosa. The checkerboard assay revealed that the fractional inhibitory concentration (FIC) index of cuminaldehyde and tobramycin was 0.36 suggesting a synergistic association between them. The sub-MIC dose of cuminaldehyde (60 µg/mL) or tobramycin (0.06 µg/mL) individually did not show any effect on the microbial growth curve. However, the same combinations could affect microbial growth curve of Pseudomonas aeruginosa efficiently. In connection to biofilm management, it was observed that the synergistic interaction between cuminaldehyde and tobramycin could inhibit biofilm formation more efficiently than their single use (p < 0.01). Further investigation revealed that the combinations of cuminaldehyde and tobramycin could generate reactive oxygen species (ROS) that resulted in the increase of membrane permeability of bacterial cells leading to the efficient inhibition of microbial biofilm formation. Besides, the synergistic interaction between cuminaldehyde (20 µg/mL) and tobramycin (0.03 µg/mL) also showed significant biofilm dispersal of the test microorganism (p < 0.01). Hence, the results suggested that synergistic action of cuminaldehyde and tobramycin could be applied for the efficient management of microbial biofilm.

Anomalous Hall effect in topological Weyl and nodal-line semimetal Heusler compound Co2VAl.

Magnetic topological semimetals (TSMs) with broken time-reversal symmetry are very rare and have drawn significant attention in condensed matter physics due to their numerous intriguing topological properties. Among these various magnetic TSMs, Co2-based full Heusler compounds are of current interest, since a few of these materials exhibit Weyl and nodal fermions in their topological band structure. In this work, we report a comprehensive study of anomalous Hall effect (AHE) in the ferromagnetic full Heusler compound Co2VAl. Recent studies indicate that the intrinsic AHE is closely related to the Berry curvature of the occupied electronic Bloch states. The present study of Co2VAl attempts to understand and explore the possibility of topology-induced AHE. The anomalous Hall resistivityρxyAis observed to scale quadratically with the longitudinal resistivityρxx. Our experimental results also reveal that the anomalous Hall conductivity (AHC) is ∼85 cm-1at 2 K with an intrinsic contribution of ∼75.6 S cm-1, and is nearly insensitive to temperature. The first principle calculations note that the Berry curvature originated from a gapped nodal line and symmetry-protected Weyl nodes near the Fermi level (EF) is the main source of AHE in this compound. Thus, this investigation on Co2VAl discloses that it is a ferromagnetic Weyl and nodal-line TSM. The theoretically calculated AHC is in well agreement with the experimentally obtained AHC.

Piperine exhibits promising antibiofilm activity against Staphylococcus aureus by accumulating reactive oxygen species (ROS).

Staphylococcus aureus causes numerous community-acquired and nosocomial infections in humans by exploiting biofilm. In this context, this study aims to impede the formation of Staphylococcus aureus biofilm by exposing the cells to a plant-based alkaloid, piperine. Our study revealed that piperine exhibited considerable antimicrobial activity against the test organism. However, we had tested the lower concentrations (up to 32 µg/mL) of piperine to observe whether they could show any antibiofilm activity against the same organism. Several experiments, like crystal violet (CV) assay, estimation of total biofilm protein, and fluorescence microscopic observations, established that lower concentrations (up to 16 µg/mL) of piperine showed efficient antibiofilm activity against Staphylococcus aureus. In this connection, we also noticed that the lower concentrations (8 and 16 µg/mL) of piperine showed a considerable reduction in microbial metabolic activity. Besides, it was also observed that the mentioned concentrations of piperine did not compromise the microbial growth of the target organism while exhibiting antibiofilm activity. To understand the underlying mechanism of microbial biofilm inhibition under the influence of piperine, we observed that the compound was found to accumulate reactive oxygen species in the bacterial cells that could play an important role in the inhibition of biofilm formation. Furthermore, the tested concentrations (8 and 16 µg/mL) of piperine were able to inhibit the motility of the test organism that might compromise the development of biofilm. Thus, piperine could be considered as a potential agent for the effective management of biofilm threat caused by Staphylococcus aureus.

Cuminaldehyde exhibits potential antibiofilm activity against Pseudomonas aeruginosa involving reactive oxygen species (ROS) accumulation: a way forward towards sustainable biofilm management.

Pseudomonas aeruginosa often causes various acute and chronic infections in humans exploiting biofilm. Molecules interfering with microbial biofilm formation could be explored for the sustainable management of infections linked to biofilm. Towards this direction, the antimicrobial and antibiofilm activity of cuminaldehyde, an active ingredient of the essential oil of Cuminum cyminum was tested against Pseudomonas aeruginosa. In this regard, the minimum inhibitory concentration (MIC) of cuminaldehyde was found to be 150 µg/mL against the test organism. Experiments such as crystal violet assay, estimation of total biofilm protein, fluorescence microscopy and measurement of extracellular polymeric substances (EPS) indicated that the sub-MIC doses (up to 60 µg/mL) of cuminaldehyde demonstrated considerable antibiofilm activity without showing any antimicrobial activity to the test organism. Moreover, cuminaldehyde treatment resulted in substantial accumulation of cellular reactive oxygen species (ROS) that led to the inhibition of microbial biofilm formation. To this end, the exposure of ascorbic acid was found to restore the biofilm-forming ability of the cuminaldehyde-treated cells. Besides, a noticeable reduction in proteolytic activity was also observed when the organism was treated with cuminaldehyde. Taken together, the results demonstrated that cuminaldehyde could be used as a promising molecule to inhibit the biofilm formation of Pseudomonas aeruginosa.

Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.

BACKGROUND: Imbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible for their abnormal proliferation in rheumatoid arthritis (RA). Methotrexate (MTX) demonstrated limited efficacy in amending this imbalance in fluid-derived (fd)-FLS. The active compound of black tea Theaflavin 3,3'-digallate (TF3) may be effective in restoring apoptosis-autophagy imbalance in (fd)-FLS. The combined effect of MTX + TF3 upon the same is yet to be elucidated. OBJECTIVE: To evaluate the effect of MTX + TF3 on fd-FLS to induce apoptosis and inhibit autophagy through Endoplasmic Reticulum (ER) stress-mediated pathways. METHODS: FLS from synovial fluid of 11 RA and 10 osteoarthritis patients were cultured after treatment with MTX/TF3 or a combination of MTX (125 nM) and TF3(10 µM) and the following parameters were evaluated. C-reactive protein, cytokines (TNF-α, IL-6), angiogenic markers were quantified by ELISA. fd-FLS viability was determined by MTT assay and apoptosis by flow cytometry. ER stress markers were estimated by RT-PCR (IRE1A, spliced-XBP-1) and immunoblotting (Grp78, Hsp70, CHOP, HIF-1α). Immunoblot studies were done to evaluate apoptotic (Bcl-2, Bax, Caspases) and autophagic (Beclin1, LC3b, p62) proteins. RESULTS: MTX (IC25) and TF3 (IC50) both in single doses could down-regulate the levels of pro-inflammatory and angiogenic markers. Combinatorial treatment modulated autophagosomal proteins in fd-FLS and induced apoptosis by regulating ER stress response. CONCLUSION: Disruption in homeostasis between apoptosis and autophagy in fd-FLS might be an underlying phenomenon in the progression of pathophysiology in RA. Co-administration of MTX + TF3 successfully restored the homeostasis by inducing apoptosis.

1,4-Naphthoquinone disintegrates the pre-existing biofilm of Staphylococcus aureus by accumulating reactive oxygen species.

Staphylococcus aureus causes several nosocomial and community-acquired infections in human host involving biofilm. Thus, strategies need to be explored to curb biofilm threats by either inhibiting the formation of biofilm or disintegrating the pre-existing biofilm. Towards this direction, we had already revealed the biofilm inhibiting properties of 1,4-naphthoquinone against S. aureus. In this study, we have investigated whether this compound can act on pre-existing biofilm. Hence, biofilm of S. aureus was developed first and challenged further with 1,4-naphthoquinone. Experiments such as crystal violet assay, fluorescence microscopy, and estimation of total biofilm protein were performed to confirm the biofilm disintegration properties of 1,4-naphthoquinone. The disintegration of pre-existing biofilm could be attributed to the generation of reactive oxygen species (ROS). To investigate further, we observed that extracellular DNA (eDNA) was found to play an important role in holding the biofilm network as DNaseI treatment could cause an efficient disintegration of the same. To examine the effect of ROS on the eDNA, we exposed pre-existing biofilm to either 1,4-naphthoquinone or a combination of both 1,4-naphthoquinone and ascorbic acid for different length of time. Post-incubation, ROS generation and the amount of eDNA associated with the biofilm were determined wherein an inversely proportional relationship was observed between them. The result indicated that with the increase of ROS generation, the amount of eDNA associated with biofilm got decreased substantially. Thus, the results indicated that the generation of ROS could degrade the eDNA thereby compromising the integrity of biofilm which lead to the disintegration of pre-existing biofilm.

Review of Applications and Future Prospects of Stimuli-Responsive Hydrogel Based on Thermo-Responsive Biopolymers in Drug Delivery Systems.

Some of thermo-responsive polysaccharides, namely, cellulose, xyloglucan, and chitosan, and protein-like gelatin or elastin-like polypeptides can exhibit temperature dependent sol-gel transitions. Due to their biodegradability, biocompatibility, and non-toxicity, such biomaterials are becoming popular for drug delivery and tissue engineering applications. This paper aims to review the properties of sol-gel transition, mechanical strength, drug release (bioavailability of drugs), and cytotoxicity of stimuli-responsive hydrogel made of thermo-responsive biopolymers in drug delivery systems. One of the major applications of such thermos-responsive biopolymers is on textile-based transdermal therapy where the formulation, mechanical, and drug release properties and the cytotoxicity of thermo-responsive hydrogel in drug delivery systems of traditional Chinese medicine have been fully reviewed. Textile-based transdermal therapy, a non-invasive method to treat skin-related disease, can overcome the poor bioavailability of drugs from conventional non-invasive administration. This study also discusses the future prospects of stimuli-responsive hydrogels made of thermo-responsive biopolymers for non-invasive treatment of skin-related disease via textile-based transdermal therapy.

Phenotypic characterization of circulating endothelial cells induced by inflammation and oxidative stress in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic auto-immune disease, affecting the spine, sacroiliac, and sometimes peripheral joints. It is also involved with cardio-vascular risk factors due to accelerated atherosclerosis. Oxidative burst, systemic inflammation coupled with endothelial dysfunction (ED), resulting in reduced bioavailability of the vasodilator nitric oxide (NO) and an increased number of circulating endothelial cells (CECs) may correlate with disease activity and its sustenance. Hence, the study was aimed to detect and quantify CECs and assess the oxidative stress and inflammatory status in AS patients vis-à-vis healthy controls, as well as relate these parameters with AS disease activity and atherosclerotic markers in patients. Our study showed an increased frequency of endothelial cells in peripheral blood of AS patients in pro-inflammatory conditions. In AS patient population, they showed significant reduction of flow-mediated dilatation (%FMD) (p < 0.05), and increased soluble adhesion molecules such as sICAM-1 (p < 0.01) and sVCAM-1 (p < 0.05) compared to healthy controls. A marked increase in pro-inflammatory markers such as TNF-α (p < 0.01) and IL-1ß (p < 0.001) and reactive free radicals (p < 0.05) along with reduced serum nitrite in AS, provided a strong pro-inflammatory milieu which positively correlated with Bath ankylosing spondylitis disease activity and functional indices (BASDAI and BASFI). The observed significant upregulation in CECs (CD45-/CD31+/CD105+/CD144+) in patients compared to healthy controls positively correlated with disease activity and duration as well as with markers of oxidative stress. Thus, chronic inflammation and oxidative burst induce loss of NO bioavailability, leading to ED. This may cause the derangement of CECs that may be considered as a prognostic biomarker for ED.

Slow Magnetic Relaxation in a Co2 Dy Trimer and a Co2 Dy2 Tetramer.

The combination of Co(III) and Dy(III) with a compartmental Schiff base ligand (H3 L=3-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-propane-1,2-diol), presenting three different coordinating pockets, has allowed the synthesis of two novel Co(III)-Dy(III) complexes: [Co2 Dy(HL)4 ]NO3 ⋅ 2CH3 CN (1), a rare example of trinuclear linear CoIII 2 DyIII complex (and the first with slow relaxation of magnetization in absence of a DC field) and [Co2 Dy2 (µ3 -OH)2 (HL)2 (OAc)6 ] ⋅ 4.6H2 O (2), the first tetranuclear CoIII 2 DyIII 2 cluster with a rhomb-like structure where the Co(III) ions are connected along the short diagonal of the rhomb. 1 presents two different relaxation processes: a fast relaxation dominated by Quantum tunnelling (QT) and a slow relaxation with an energy barrier of 40 K. 2 shows two close relaxation processes without applied DC fields that follow QT and Orbach mechanisms whereas for HDC =500 Oe, the QT is cancelled and a direct term appears. Here we present the synthesis, X-ray structure and magnetic characterization of these two Co(III)-Dy(III) single-ion/molecule magnets.

Electrocatalytic Water Oxidation by a Phosphorus-Nitrogen O═PN3-Pincer Cobalt Complex.

Water oxidation is a primary step in natural as well as artificial photosynthesis to convert renewable solar energy into chemical energy/fuels. Electrocatalytic water oxidation to evolve O2, utilizing suitable low-cost catalysts and renewable electricity, is of fundamental importance considering contemporary energy and environmental issues, yet it is kinetically challenging owing to the complex multiproton/electron transfer processes. Herein, we report the first cobalt-based pincer catalyst for catalytic water oxidation at neutral pH with high efficiency under electrochemical conditions. Most importantly, ligand (pseudo)aromaticity is identified to play an important role during electrocatalysis. A significant potential jump (∼300 mV) was achieved toward a lower positive value when the aromatized cobalt complex was transformed into a (pseudo)dearomatized cobalt species. The dearomatized species catalyzes the water oxidation reaction to evolve oxygen at a much lower overpotential (∼340 mV) on the basis of the onset potential (at a current density of 0.5 mA/cm2) of catalysis at pH 10.5, outperforming other Co-based molecular catalysts reported to date. These observations may provide a new strategy for the judicious design of earth-abundant transition-metal-based water oxidation catalysts.

Influence of pH-responsive compounds synthesized from chitosan and hyaluronic acid on dual-responsive (pH/temperature) hydrogel drug delivery systems of Cortex Moutan.

The polysaccharide-based pH-responsive compounds, namely, N,N,N-trimethyl chitosan (TMC), polyethylene glycolated hyaluronic acid (PEG-HA), and polysaccharide-based nano-conjugate of hyaluronic acid, chitosan oligosaccharide and alanine [HA-Ala-Chito(oligo)] were chemically synthesized using biopolymers chitosan and hyaluronic acid, and applied here to observe the changes in morphology, pH-stability, mechanical and drug-release behavior, and cytotoxicity of thermo-responsive polymer: Poloxamer 407 (PF127)-based drug delivery systems for traditional Chinese medicine Cortex Moutan (CM). The thermo-responsive hydrogel of PF127 loaded with CM (GelC) was used as control. The dual-responsive (pH/temperature) hydrogels: PF127/TMC/PEG-HA (Gel1) and PF127/HA-Ala-Chito(oligo) (Gel2) showed improved mechanical behavior as obtained by rheology and mechanical agitation study, and pH-stability under various external pH conditions, and those improvements occurred due to the addition of polysaccharide-based pH-responsive compounds in the systems. Both, Gel1 and Gel2 showed better morphology than GelC as obtained by SEM or TEM suggesting that interaction of polysaccharide-based pH-responsive compounds with PF127 in either gel or sol state gave better porous network structure in the hydrogels or more dispersed micellar arrangements in sol-state, respectively. Gel1 showed the highest cumulative drug release (86.5%) after 5 days under mild acidic condition (pH 6.4) suggesting that release behavior of a hydrogel drug carrier was dependent on morphology, mechanical behavior, and pH-stability. The transdermal release (ex-vivo) results indicated that gallic acid, the active marker of CM passed through porcine ear skin and all the formulations showed more or less similar transdermal release properties. The hydrogels loaded with CM showed no cytotoxicity (cell viability >90.0%) on human HaCaT keratinocytes within concentration range of 0.0-20.0 µg/ml as obtained by MTT assay, and cell viability was more than 100% at a concentration of 20.0 µg/ml for Gel2. The formulations without loaded drug namely, Gel1-CM and Gel2-CM exhibited strong anti-bacterial action against gram positive bacteria Staphylococcus aureus.