Density Functional Theory Study of the Interaction of Arginine-Glycine-Aspartic Acid with Graphene, Defective Graphene, and Graphene Oxide

This study investigated the interaction between carbon nanostructures, including pristine graphene, defective graphene with monovacancy, graphene oxide (GO), and tripeptide arginine-glycine-aspartic acid (RGD), by density functional theory. The results from the adsorption energy analysis show that the strongest adsorption is observed when RGD is parallel to graphene surfaces, in which graphene interacts with all three functional groups of RGD, including NH₃⁺, COO^–, and guanidine. The interaction of NH₃⁺···π was stronger than that of guanidine–NH₂···π and COO^–···π. The vacancy improves the ability of graphene to attract RGD because of active dangling C atoms. GO has a stronger interaction with RGD than the pristine and defective graphene because of O-containing groups. The comparison of the GO model with the OH, epoxy, and mixed OH/epoxy groups reveals that various O-containing groups have distinguishing binding abilities with RGD. Water molecules strengthen the interactions between graphene and RGD, whereas they weaken the interaction between GO and RGD. The results provide useful guidance in designing optimal carbon nanomaterial surfaces with specific characteristics that could satisfy the demand for diverse applications of carbon nanomaterials in biomedical fields

High-Strength, Biomimetic Functional Chitosan-Based Hydrogels for Full-Thickness Osteochondral Defect Repair

Fabrication of a hydrogel scaffold for full-thickness osteochondral defect repair remains a grand challenge. Developing layered and multiphasic hydrogels to mimic the intrinsic hierarchical structure of the osteochondral unit is a promising strategy. Chitosan-based hydrogels are widely applied for biomedical applications. However, insufficient mechanical strength and lack of biological cues to restore damaged cartilage and subchondral tissue significantly hinder their application in osteochondral tissue engineering. In this study, a strong and tough, osteochondral-mimicking functional chitosan-based hydrogel (bilayer-gel) with an in situ mineralized, osteoconductive lower layer and a basic fibroblast growth factor (bFGF)-incorporated, chondrogenic inducing upper layer was developed. The obtained bilayer-gel showed a depth-dependent gradient pore structure and composition. The strong double crosslinked hydrogel network and the homogeneous deposition of hydroxyapatite nanoparticles (HAp) at the lower layer provided a compressive strength of up to 2.5 MPa and a compressive strain of up to 40%. In vitro study showed that the bilayer-gel facilitates both chondrogenic differentiation in the upper layer and osteogenic differentiation in the lower layer. In vivo implantation revealed that the bilayer-gel could simultaneously promote hyaline cartilage and subchondral bone formation, thus resulting in an improved osteochondral reconstruction outcome. The present bilayer-gel thus shows great potential for full-thickness osteochondral defect repair

Polydopamine Nanoparticles Modulating Stimuli-Responsive PNIPAM Hydrogels with Cell/Tissue Adhesiveness

Stimuli-responsive hydrogels can respond to stimuli by phase transformation or volume change and exhibit specific functions. Near-infrared (NIR)-responsive hydrogel is a type of stimuli-responsive hydrogel, which can be precisely controlled by altering the radiation intensity, exposure time of the light source, and irradiation sites. Here, polydopamine nanoparticles (PDA-NPs) were introduced into a poly­(<i>N</i>-isopropylacrylamide) (PNIPAM) network to fabricate a PDA-NPs/PNIPAM hydrogel with NIR responsibility, self-healing ability, and cell/tissue adhesiveness. After incorporation of PDA-NPs into the hydrogel, the PDA-NPs/PNIPAM hydrogel showed phase transitions and volume changes in response to NIR. Thus, the hydrogel can achieve triple response effects, including pulsatile drug release, NIR-driven actuation, and NIR-assisted healing. After coating PDA-NPs onto hydrogel surfaces, the hydrogel showed improved cell affinity, good tissue adhesiveness, and growth factor/protein immobilization ability because of reactive catechol groups on PDA-NPs. The tissue adhesion strength to porcine skin was as high as 90 KPa. <i>In vivo</i> full-skin defect experiments demonstrated that PDA-NPs coating on the hydrogel and an immobilized growth factor had a synergistic effect on accelerating wound healing. In summary, we combined thermosensitive PNIPAM and mussel-inspired PDA-NPs to form a NIR-responsive hydrogel, which may have potential applications for chemical and physical therapies

Effect of a combination of Rhizoma Coptidis alkaloids, Radix et Rhizoma Rhei polysaccharides, and Radix Scutellaria flavones (APF) on renal TGF-β1 and its receptor expression.

<p>(a-e) Immunohistochemistry of TGF-β1; (f) Quantitative analysis of immunohistochemical staining of TGF-β1; (g-h) Western blot analysis of TGF-β1 and α-SMA protein levels; (i-j) Real-time RCR analysis of TGF-β1 and TβRⅡmRNA levels. a: db/m, b: db/db, c: APF 300mg/kg, d: 600 mg/kg, e: metformin. Data are expressed as mean ±S.D., n = 3 for Western blot, and n = 5 for Immunohistochemistry and Real-time PCR, *p<0.05, **p<0.01 as compared with db/db group.</p

Effect of a combination of Rhizoma Coptidis alkaloids, Radix et Rhizoma Rhei polysaccharides, and Radix Scutellaria flavones (APF) on renal histopathology and ultrastructural pathology.

<p>(a-e) hematoxylin and eosin (HE) stain. (f-j) Periodic Acid Schiff (PAS) stain. Original magnification (a–j) × 400. (k-o) Electron microscopy (EM) analysis, Representative images of glomerular basement membrane thickening and mesangial matrix expansion, scale bars 2 μm, original magnification electron microscopy × 6000. (p) Ratio of the mesangial matrix area to total glomerular area (M/G) in PAS staining. Data are expressed as mean ± S.D., n = 10, **<i>p</i> < 0.01 as compared with db/db group.</p

Effect of a combination of Rhizoma Coptidis alkaloids, Radix et Rhizoma Rhei polysaccharides, and Radix Scutellaria flavones (APF) on renal histopathology and ultrastructural pathology.

<p>(a-e) hematoxylin and eosin (HE) stain. (f-j) Periodic Acid Schiff (PAS) stain. Original magnification (a–j) × 400. (k-o) Electron microscopy (EM) analysis, Representative images of glomerular basement membrane thickening and mesangial matrix expansion, scale bars 2 μm, original magnification electron microscopy × 6000. (p) Ratio of the mesangial matrix area to total glomerular area (M/G) in PAS staining. Data are expressed as mean ± S.D., n = 10, **<i>p</i> < 0.01 as compared with db/db group.</p

Effect of a combination of Rhizoma Coptidis alkaloids, Radix et Rhizoma Rhei polysaccharides, and Radix Scutellaria flavones (APF) on renal fibrosis.

<p>(a-e) Masson’s modified trichrome histological (Masson); (p) Ratio of area with collagen accumulation to total glomerular area; (f-j) Immunohistochemistry of collagen I; (k-o) Immunohistochemistry of collagen IV. Original magnification (a–o) × 400; (q) Quantitative analysis of immunohistochemical staining of collagen I (Col I); (r) glomerular of collagen IV (Col IV); (s) interstitial of collagen IV (Col IV); (t-u) Real-time RCR analysis of collagen I and collagen IV mRNA levels. Data are expressed as mean ±S.D., n = 5, **p<0.01 as compared with db/db group.</p

Combination of Active Components of Xiexin Decoction Ameliorates Renal Fibrosis Through the Inhibition of NF-κB and TGF-β1/Smad Pathways in db/db Diabetic Mice

<div><p>Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A), Radix et Rhizoma Rhei polysaccharides (P), and Radix Scutellaria flavones (F). Our previous studies have shown that a combination of A, P, and F (APF) exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively) once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB). APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1), and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate that treatment with multi-component herbal therapeutic formulations may be a useful approach for the treatment of diabetic nephropathy.</p></div

Effect of a combination of Rhizoma Coptidis alkaloids, Radix et Rhizoma Rhei polysaccharides, and Radix Scutellaria flavones (APF) on renal inflammation in db/db mice.

<p>(a-b) Western blot analysis of protein levels; (c-d) Real-time RCR analysis of mRNA levels; ICAM-1: intercellular adhesion molecule-1; MCP-1: monocyte chemotactic protein-1; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β. Data are expressed as mean ±S.D., n = 3 for Western blot, and n = 5 for Real-time PCR, *p<0.05, **p<0.01 as compared with db/db group.</p