Supported of gold nanoparticles on carboxymethyl lignin modified magnetic nanoparticles as an efficient catalyst for reduction of nitroarenes and treatment of human melanoma.

This article represents the synthesis and characterizations of Au NPs immobilized and carboxymethyl lignin (CML) modified Fe3O4 nanoparticles (Fe3O4@CML/Au NPs) following a bio-inspired protocol without the participation of any toxic and harmful reductant or stabilizers. Following various physicochemical methodologies, such as FT-IR, FE-SEM, TEM, EDX, XRD, VSM, and ICP-OES, the textural characteristics and different structural aspects were evaluated. The Fe3O4@CML/Au NPs nanocomposite was subsequently explored towards the catalytic reduction of diverse aromatic nitro functions using green conditions. An excellent yield were achieved within very short reaction time. Nine recycling runs of the nanocatalyst were completed without a discernible loss of catalytic activity, thanks to its easy magnetic recovery. The DPPH assay was carried out to examine the antioxidant effectiveness. The Fe3O4@CML/Au NPs nanocomposite inhibited half of the DPPH in a 250 µg/mL solution. To measure the anti-human melanoma efficacy of Fe3O4@CML/Au NPs nanocomposite, MTT assay was applied on HT144, MUM2C, IPC-298 and SKMEL24 cell lines. Fe3O4@CML/Au NPs nanocomposite had high anti-human melanoma efficacy on above tumor cells. The best finding of anti-human melanoma properties of Fe3O4@CML/Au NPs nanocomposite was seen in the case of the SKMEL24 cell line. The IC50 of Fe3O4@CML/Au NPs nanocomposite was 137, 145, 185, and 125 µg/mL against HT144, MUM2C, IPC-298 and SKMEL24 cells, respectively. This research exhibited remarkable anti-human melanoma and antioxidant efficacies of Fe3O4@CML/Au NPs nanocomposite in the in vitro condition.

Multicenter effect analysis of one-step acellular dermis combined with autologous ultra-thin split thickness skin composite transplantation in treating burn and traumatic wounds.

To evaluate the efficacy of one-step acellular dermis combined with autologous split thickness skin grafting in the treatment of burn or trauma wounds by a multicenter controlled study. In patients with extensive burns, it is even difficult to repair the wounds due to the shortage of autologous skin. The traditional skin grafting method has the disadvantages of large damage to the donor site, insufficient skin source and unsatisfactory appearance, wear resistance and elasticity of the wound tissue after skin grafting. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft can achieve better healing effect in the treatment of burn and trauma wounds. A total of 1208 patients who underwent single-layer skin grafting and one-step composite skin grafting in the First Affiliated Hospital of Wannan Medical College, Wuhan Third People's Hospital and Lu 'an People's Hospital from 2019 to 2022 were retrospectively analysed. The total hospitalization cost, total operation cost, hospitalization days after surgery, wound healing rate after 1 week of skin grafting and scar follow-up at 6 months after discharge were compared and studied. The total cost of hospitalization and operation in the composite skin grafting group was significantly higher than those in the single-layer autologous skin grafting group. The wound healing rate after 1 week of skin grafting and the VSS score of scar in the follow-up of 6 months after discharge were better than those in the single-layer skin grafting group. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft has high wound healing rate, less scar, smooth appearance and good elasticity in repairing burn and trauma wounds, which can provide an ideal repair method for wounds.

Fabrication of silver nanoparticles immobilized on magnetic lignosulfonate: Evaluation of its catalytic activity in the N-acetylation reactions and investigation of its anti-cutaneous squamous cell carcinoma effects.

Due to the non-optimal response of most types of cancer to various treatment methods and their rapid progress, research continues in the field of producing drugs with less toxicity and greater efficiency. There are many nanocomposites with diverse biological activities that include part of anticancer drugs in new pharmacological science. The present investigation describes a green procedure for the in situ support of Ag nanoparticles (NPs) over sodium lignosulfonate (NaLS) modified magnetic nanoparticles (Fe3O4@NaLS/Ag) and its subsequent biological and chemical performance. FT-IR, TEM, FE-SEM, EDS, ICP, VSM and XRD techniques were used to characterize the synthesized Fe3O4@NaLS/Ag. The catalytic efficacy of the desired composite was applied in the N-acetylation of various amines in the presence of Ac2O under solvent-free conditions. The Fe3O4@NaLS/Ag catalyst was recovered by an external magnet and reused for nine runs without a significant decrease in the activity. The cytotoxic and anti-cutaneous squamous cell carcinoma potentials of biologically synthesized Fe3O4@NaLS/Ag nanocomposite against PM1 and MET1 cells were determined. The anti-cutaneous squamous cell carcinoma properties of the Fe3O4@NaLS/Ag nanocomposite could significantly remove PM1 and MET1 cells. The IC50 of Fe3O4@NaLS/Ag nanocomposite was 288 and 270 µg/mL against PM1 and MET1 cells, respectively. Also, Fe3O4@NaLS/Ag nanocomposite presented a high antioxidant potential according to the IC50 value. According to the above results, the recent nanocomposite can be used in treating cutaneous squamous cell carcinoma after doing clinical trial studies.

Ellagic acid inhibits the formation of hypertrophic scars by suppressing TGF-ß/Smad signaling pathway activity.

Hypertrophic scar (HS) is a benign fibroproliferative skin disease, which lacks the ideal treatment and drugs. Ellagic acid (EA) is a natural polyphenol that prevents fibroblasts from proliferating and migrating. This study aimed to determine the role of EA in HS formation and its possible mechanism by in vitro experiments. HS fibroblasts (HSFs) and normal fibroblasts (NFs) were separated from HS tissue and normal skin tissue, respectively. HSFs were treated with 10 and 50 µM EA to assess their effect on HS formation. In particular, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and scratch assay were used to detect the viability and migration ability of HSFs. Quantitative reverse transcriptase real-time polymerase chain reaction was used to measure the mRNA expression level of basic fibroblast growth factor (bFGF), extracellular matrix (ECM)-related gene collagen-I (COL-I), and fibronectin 1 (FN1) in HSFs. Finally, Western blot was utilized to measure the expression level of TGF-ß/Smad signaling pathway-related proteins in HSFs. The viability of HSFs was significantly increased compared with NFs. 10 and 50 µM EA treatment markedly inhibition the cell viability and migration of HSFs. EA treatment upregulated the bFGF expression level and downregulated the COL-I and FN1 expression level in HSFs. In addition, p-Smad2, p-Smad3, and transforming growth factor (TGF)-ß1 expression levels as well as p-Smad2/Smad2 and p-Smad3/Smad3 ratios remarkably decreased in HSFs after EA treatment. EA inhibited the formation of HSs by suppressing the viability and migration of HSFs and ECM deposition as well as by preventing the activation of TGF-ß/Smad signaling.

Biomaterials releasing drug responsively to promote wound healing via regulation of pathological microenvironment.

Wound healing is characterized by complex, orchestrated, spatiotemporal dynamic processes. Recent findings demonstrated suitable local microenvironments were necessities for wound healing. Wound microenvironments include various biological, biochemical and physical factors, which are produced and regulated by endogenous biomediators, exogenous drugs, and external environment. Successful drug delivery to wound is complicated, and need to overcome the destroyed blood supply, persistent inflammation and enzymes, spatiotemporal requirements of special supplements, and easy deactivation of drugs. Triggered by various factors from wound microenvironment itself or external elements, stimuli-responsive biomaterials have tremendous advantages of precise drug delivery and release. Here, we discuss recent advances of stimuli-responsive biomaterials to regulate local microenvironments during wound healing, emphasizing on the design and application of different biomaterials which respond to wound biological/biochemical microenvironments (ROS, pH, enzymes, glucose and glutathione), physical microenvironments (mechanical force, temperature, light, ultrasound, magnetic and electric field), and the combination modes. Moreover, several novel promising drug carriers (microbiota, metal-organic frameworks and microneedles) are also discussed.

Design and synthesis of Ag NPs/chitosan-starch nano-biocomposite as a modern anti-human malignant melanoma drug.

In recent years, the unprecedented increase in various cancers such as melanoma has caused researchers to focus more on the formulation of newer drugs with less side effects. In this study, we herein indicate the biogenic nanoarchitechtonics of Ag NPs template over chitosan/starch mixed hydrogel having notable reducing potential and anti-malignant melanoma effects. The two biopolymers also could stabilize as-synthesized Ag NPs. Physicochemical features of the material were further characterized over a range of advanced methods like X-ray diffraction (XRD), elemental mapping, dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and Fourier transformed infrared spectroscopy (FT-IR). TEM analysis showed the spherical-shaped nanocomposite with the mean diameter in the range of 5-15 nm. Thereafter, the nanocomposite was exploited in the anti-malignant melanoma and cytotoxicity effects studies against various human malignant melanoma cell lines (HT144, RPMI7951, SKMEL2, UACC3074, WM266-4 and MUM2C) in situ. The bio-composite corresponding IC50 values were 193, 102, 227, 250, 301, and 203 µg/mL against MUM2C, WM266-4, UACC3074, SKMEL2, RPMI7951, and HT144 cell lines, respectively. A significantly high IC50 value offered an excellent antioxidant capacity of bio-composite. According to the above results, Ag NPs/CS-Starch nanomaterial can be utilized as an efficient drug to treat malignant melanoma in humans after doing clinical trial studies.

Stability and biosafety of human epidermal stem cell for wound repair: preclinical evaluation.

BACKGROUND: Cell therapy is a key technology to prevent sacrificing normal skin. Although some studies have shown the promise of human epidermal stem cells (EpiSCs), the efficacy, biosafety and quality control of EpiSC therapy have not been systematically reported. METHODS: The biosafety, stemness maintenance and wound repair of EpiSC were systematically verified by in vitro and in vivo experiments. EpiSC were prepared from the foreskin using a collagen type IV rapid adherence method. The EpiSCs were identified by flow cytometry, immunofluorescence staining and cell morphology. The well-growing passage 1 (P1) EpiSCs were used to determine the proliferation curve (counting method). EpiSC clone formation assay was performed by Giemsa staining. Nude mice were used to prepare a full-thickness skin defect wound model to detect the repair effect of EpiSCs. The biosafety of EpiSCs was double tested in vitro and in vivo. RESULTS: The results showed that the expression of specific markers and clone formation efficiency was stable when passage 1 (P1) to P8 cells were cultured, and the stemness rate of P8 cells was close to 85.1%. EpiSCs were expanded in vitro for 25 days, the number of cells reached 2.5 × 108, and the transplantable area was approximately 75% of the total body surface area (TBSA). At 45 days, the total number of cells was approximately 30 billion, and the transplantable area was approximately the size of a volleyball court. A nude mouse wound model indicated that EpiSCs could rapidly close a wound. On postinjury day 7, the wound epithelialization rate in the cell transplantation group was significantly higher than that in the NaCl group (P < 0.05). In vitro, cell senescence increased, and telomerase activity decreased in P1 to P8 EpiSCs. In vivo, there were no solid tumors or metastatic tumors after EpiSC (P8) transplantation. In addition, the quality control of cultured cells met the clinical application criteria for cell therapy. CONCLUSION: This preclinical study showed the stability and biosafety of human EpiSC therapy for wound repair.

Efficacy of Human-Recombinant Epidermal Growth Factor Combined with Povidone-Iodine for Pressure Ulcers and Its Influence on Inflammatory Cytokines.

Purpose: To determine the clinical efficacy of recombinant human epidermal growth factor (rh-EGF) combined with povidone-iodine (PVI) on patients with pressure ulcers (PUs). Methods: One hundred and five PU patients treated between January 2018 and January 2021 were enrolled and retrospectively analyzed. Of them, 50 patients who received conventional treatment were assigned to the control group (Con group), while 55 patients treated with rh-EGF combined with PVI were assigned to the observation group (Obs group). The two groups were compared in clinical efficacy, PU alleviation (total area reduction rate, total depth reduction rate, and total volume reduction rate), healing time, pain degree (Visual Analog Scale [VAS] score), inflammatory indexes (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitive C reactive protein [hs-CRP]), and hydroxyproline content in the wound. Results: The Obs group yielded a higher total effective rate than the Con group (P < 0.05). The Obs group also experienced statistically shorter healing time and milder pain, with better PU alleviation and lower levels of inflammation indexes compared with the Con group (all P < 0.05). In addition, a higher hydroxyproline content in the wound was found in the Obs group. Conclusions: All in all, rh-EGF combined with PVI has a definite curative effect on patients with PUs. It can promote PU alleviation and hydroxyproline secretion in the wound and inhibit pain and inflammatory reactions, which is worthy of clinical promotion.

High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation.

High-salt diets are associated with an elevated risk of autoimmune diseases, and immune dysregulation plays a key role in cancer development. However, the correlation between high-salt diets (HSD) and cancer development remains unclear. Here, we report that HSD increases the local concentration of sodium chloride in tumour tissue, inducing high osmotic stress that decreases both the production of cytokines required for myeloid-derived suppressor cells (MDSCs) expansion and MDSCs accumulation in the blood, spleen, and tumour. Consequently, the two major types of MDSCs change their phenotypes: monocytic-MDSCs differentiate into antitumour macrophages, and granulocytic-MDSCs adopt pro-inflammatory functions, thereby reactivating the antitumour actions of T cells. In addition, the expression of p38 mitogen-activated protein kinase-dependent nuclear factor of activated T cells 5 is enhanced in HSD-induced M-MDSC differentiation. Collectively, our study indicates that high-salt intake inhibits tumour growth in mice by activating antitumour immune surveillance through modulating the activities of MDSCs.

Accelerated wound healing in diabetes by reprogramming the macrophages with particle-induced clustering of the mannose receptors.

The rate-limiting step in cutaneous wound healing, namely, the transition from inflammation to cell proliferation, depends on the high plasticity of macrophages to prevent inflammation in the wound tissues in a timely manner. Thus, strategies that reprogram inflammatory macrophages may improve the healing of poor wounds, particularly in the aged skin of individuals with diabetes or other chronic diseases. As shown in our previous study, KGM-modified SiO2 nanoparticles (KSiNPs) effectively activate macrophages to differentiate into the M2-type phenotype by inducing mannose receptor (MR) clustering on the cell surface. Here, we assess whether KSiNPs accelerate wound healing following acute or chronic skin injury. Using a full-thickness excision model in either diabetic mice or healthy mice, the wounds treated with KSiNPs displayed a dramatically increased closure rate and collagen production, along with decreased inflammation and increased angiogenesis in the regenerating tissues. Furthermore, KSiNPs induced the formation of M2-like macrophages by clustering MR on the cells. Accordingly, the cytokines produced by the KSiNP-treated macrophages were capable of inducing fibroblast proliferation and subsequent secretion of extracellular matrix (ECM). Based on these results, KSiNPs display great potential as an effective therapeutic approach for cutaneous wounds by effectively suppressing excessive or persistent inflammation and fibrosis.

Screening and preliminary validation of T lymphocyte immunoregulation­associated long non­coding RNAs in diabetic foot ulcers.

The present study aimed to investigate the existence of immunoregulation­associated long non­coding (lnc)RNAs mediated by T lymphocytes in the wound surfaces of diabetic foot ulcers (DFUs). The wound skin tissues of patients receiving debridement for trauma or DFUs associated with infection were obtained. Dermatological histological changes were observed by pathological staining, and T lymphocyte subsets and inflammation­associated cytokines were identified. Gene chip technology was used to screen for lncRNAs regulated by immune cells. The wound skin structure in the control group was revealed to be complete, and the inflammatory response was not marked. However, the wound skin structure in the ulcer group was disordered and exhibited a notable inflammatory response. Compared with the control group, expression levels of cluster of differentiation (CD)3 and CD8 in the wound surface tissues of the ulcer group were significantly increased, while the expression levels of interleukin (IL)­1ß, IL­2, IL­10, interferon­Î³ and tumor necrosis factor­α were significantly upregulated. A target regulatory association was identified between downregulated lncRNA­ENST00000411554 and upregulated mitogen­activated protein kinase (MAPK)1 in DFU tissues, and a negative correlation was detected between this RNA and protein. The present results suggested that an immune functional disorder of T lymphocytes may be closely associated with the development of DFUs. Furthermore, activation of the MAPK signal transduction pathway mediated by the lncRNA­ENST00000411554/MAPK1 axis may affect the DFU immune regulatory imbalance.

Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death.

BACKGROUND: Melanoma is a leading cause of cancer death worldwide, and SMI-4a and G-Rh2 exert anti-tumor activity in multiple cancer. However, SMI-4a as well as a synergistic relationship between SMI-4a and G-Rh2 in anti-melanoma capacity are still unknown. Therefore, we investigated the effects of SMI-4a and combined SMI-4a with G-Rh2 on the viability, apoptosis and autophagy of melanoma, and to preliminarily explore the underlying mechanism of SMI-4a and combined SMI-4a with G-Rh2 in inhibiting tumor growth. METHODS: Cell viability was examined with cell counting Kit 8 assay and colony formation assay; Apoptosis was evaluated by flow cytometry and Caspase 3/7 activity assay; Western blotting was used to test proteins related to autophagy and the AKT/mammalian target of rapamycin (mTOR) signaling pathway; Tumor xenograft model in BALB/c nude mice was performed to evaluate the effects of SMI-4a and combined SMI-4a with G-Rh2 in anti-melanoma in vivo. RESULTS: SMI-4a, a pharmacological inhibitor of PIM-1, could decrease cell viability, induce apoptosis, and promote Caspase 3/7 activity in both A375 and G361 melanoma cells, and SMI-4a inhibited tumor growth by inducing autophagy via down-regulating AKT/mTOR axis in melanoma cells. Furthermore, G-Rh2 amplified the anti-tumor activity of SMI-4a in melanoma cells via strengthening autophagy. CONCLUSIONS: Our results suggested that SMI-4a could enhance autophagy-inducing apoptosis by inhibiting AKT/mTOR signaling pathway in melanoma cells, and G-Rh2 could enhance the effects of SMI-4a against melanoma cancer via amplifying autophagy induction. This study demonstrates that combined SMI-4a and G-Rh2 might be a novel alternative strategy for melanoma treatment.

[The change of cholesterol level and Na+ -K+ -ATPase activity of erythrocyte membrane in early stage of severe burn patients].

AIM: To study the relationship between erythrocyte filtration index (EFI) and cholesterol and Na+ -K+ -ATPase activity of erythrocyte membrane in early stage of severe burns. METHODS: The EFI was measured by means of percolation, the erythrocyte membrane cholesterol level was measured by means of chemically modified electrode, and the membrane Na+ -K+ -ATPase activity by means of detection of Pi. RESULTS: In early stage of severe burns, the cholesterol level and Na+ -K -ATPase activity of erythrocyte membrane were always higher than those of control group (P < 0.01), but the EFI was lower than that of control group (P < 0.01). The cholesterol level and Na+ -K+ -ATPase activity of the erythrocyte membrane were negative correlation with EFI (r cho= -0.871, r ATPase = -0.801, P < 0.01) nospectively. CONCLUSION: The cholesterol level and Na+ -K+ -ATPase activity of erythrocyte membrane play a key role in the change of EFI.