Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review.

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.

Right stellate ganglion block improves learning and memory dysfunction and hippocampal injury in rats with sleep deprivation.

BACKGROUND: Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats. METHODS: Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels. RESULTS: Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1ß and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased. CONCLUSIONS: The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.

Molecular characterization and functional analysis of two phospholipid hydroperoxide isoforms from Larimichthys crocea under Vibrio parahaemolyticus challenge.

Glutathione peroxidases family is a key role in the antioxidant system in oxybiotic organisms for cell redox homeostasis. One of their members, phospholipid hydroperoxide glutathione peroxidase (GPx4) have unique monomeric structure and can directly react with complex lipid and membrane-bound peroxides under the presence of glutathione(GSH). In this paper, two complete GPx4 cDNAs (designated as LcGPx4a and LcGPx4b) from Larimichthys crocea are identified by rapid amplification of cDNA ends. The cDNA of LcGPx4a was consisted of a 5'-untranslated region (UTR) of 258 bp, a 3'-UTR of 330 bp, and an open reading frame (ORF) of 561 bp encoding 186 amino acid (aa) polypeptides. And the full-length sequence of LcGPx4b was 1164 bp with a 5'-UTR of 34 bp, a 3'-UTR of 551 bp and an ORF of 576 bp encoding a polypeptide of 191 aa residues with a predicted signal peptide of 15 aa. The characteristic selenocysteine insertion (SECIS) sequence was detected in the 3'UTR of the two sequences with 78 bp in length. The conserved active site of selenocysteine (Sec) encoded by TGA was also identified and formed a tetrad functional structure with glutamine, tryptophan, and asparagine in LcGPx4a and LcGPx4b. Two signature site motifs ("LRILAFPSNQFGNQEPG" and "LRILGFPCNQFGGQEPG") were both conserved in the deduced amino acid of LcGPx4a and LcGPx4b. The genomic structure analysis revealed that the two sequences both had 7 exons and 6 introns, and the Sec opal codon and SECIS element were located at the third and seventh exons, respectively. LcGPx4a and LcGPx4b both have a wide distribution in 9 tissues with various relative expression levels and a highest expression pattern in the liver. Under Vibrio parahaemolyticus challenge, their relative expression levels were altered in the liver, spleen, kidney, and head kidney but with different magnitudes and response time. LcGPx4a and LcGPx4b showed a significantly up-regulated trend in the spleen during experimental period. Above results suggested that LcGPx4a and LcGPx4b were two conserved immune molecules and might play a role in the immune response of fish with a tissue-depemdent manners.

Cloning and functional characterization of thioredoxin genes from large yellow croaker Larimichthys crocea.

Thioredoxin(Trx)with a redox-active disulfide/dithiol in the active site, is an ubiquitous disulfide reductase majorly responsible for maintaining the balance of reactive oxygen species. In this study, the complete thioredoxin-like protein 1 (designated as LcTrx) was cloned from large yellow croaker Larimichthys crocea through rapid amplification of cDNA ends. The full-length cDNA of LcTrx was 1295 bp in length containing a 131 bp 5' untranslated region (UTR) ,a 3'UTR of 294bp with a poly (A) tail, and an 870 bp open reading frame (ORF) encoding a polypeptide of 289 amino acids. Protein sequence analysis revealed that LcTrx contains the evolutionarily conserved redox motif CRPC (Cys-Arg-Pro-Cys-). Multiple alignments revealed that LcTrx is highly identical to Trx from other organisms, especially in the CRPC motifs. The recombinant LcTrx showed obvious insulin reduction activity in vitro. The LcTrx transcripts were constitutively expressed in all examined tissues with the highest levels found in the muscles and the lowest in the head kidney. Results of Vibrio parahaemolyticus infection experiment showed that the expression levels of LcTrx were tissue and time dependent. In the liver and kidney, LcTrx was down-regulated both at 12 h and 48 h post-infection. In contrast, LcTrx showed induced expression in the spleen and head kidney at same post-infection time points. The different responses to pathogen stimulation indicated the diversified physiological function of LcTrx in the four examined tissues.

Identification and characterization of two selenium-dependent glutathione peroxidase 1 isoforms from Larimichthys crocea.

Glutathione peroxidases, a vital family of antioxidant enzymes in oxybiotic organisms, are involved in anti-pathogen immune response. In this study, two complete selenium-dependent glutathione peroxidase 1 cDNAs (designated as LcGPx1a and LcGPx1b) were obtained from the large yellow croaker Larimichthys crocea by rapid amplification of cDNA ends. The full-length sequence of LcGPx1a was 917 bp with a 5'-untranslated region (UTR) of 52 bp, a 3'-UTR of 289 bp, and an open reading frame of 576 bp encoding 191 amino acid (aa) polypeptides. The cDNA of LcGPx1b was composed of 884 bp with a 5'-UTR of 59 bp, a 3'-UTR of 258 bp, and an open reading frame of 567 bp encoding 188 aa polypeptides. The conserved selenocysteine insertion sequence was detected in the 3'-UTR of both isoforms, which can classify types I and II. Protein sequence analysis revealed that both isoforms included a selenocysteine encoded by an opal codon (TGA) and formed the functioning tetrad site with glutamine, tryptophan, and asparagine. Three conservative motifs, including one active site motif ("GKVVLIENVASLUGTT") and two signature site motifs ("LVILGVPCNQFGHQENC" and "V(A/S)WNFEKFLI"), were conserved both in sequence and location. Multiple alignments revealed that they exhibited a high level of identities with GPx1 from other organisms, especially in the abovementioned conserved amino acid sequence motifs. Tissue expression analysis indicated that LcGPx1a and LcGPx1b had a wide distribution in nine tissues with various abundances. The transcript level of LcGPx1a was not significantly different among the nine tissues, whereas that of LcGPx1b was higher in the kidney and head kidney than in the other tissues. After Vibrio parahaemolyticus stimulation, the expression levels of LcGPx1a and LcGPx1b were unanimously altered in the liver, spleen, kidney, and head kidney but with different magnitudes and response time. LcGPx1a and LcGPx1b showed distinct expression trends in the liver, where LcGPx1b was induced and LcGPx1a was depressed in response to pathogen infection. These results indicate that LcGPx1a and LcGPx1b display functional diversities and play crucial roles in mediating the immune response of fish.

Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Identification and Characterization of Three Novel Solemo-like Viruses in the White-Backed Planthopper, Sogatella furcifera.

Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; Sogatella furcifera, Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family Solemoviridae and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Circadian clock genes as promising therapeutic targets for bone loss.

The circadian clock regulates many key physiological processes such as the sleep-wake cycle, hormone release, cardiovascular health, glucose metabolism and body temperature. Recent evidence has suggested a critical role of the circadian system in controlling bone metabolism. Here we review the connection between bone metabolism and the biological clock, and the roles of these mechanisms in bone loss. We also analyze the regulatory effects of clock-related genes on signaling pathways and transcription factors in osteoblasts and osteoclasts. Additionally, osteocytes and endothelial cells (ECs) regulated by the circadian clock are also discussed in our review. Furthermore, we also summarize the regulation of circadian clock genes by some novel modulators, which provides us with a new insight into a potential strategy to prevent and treat bone diseases such as osteoporosis by targeting circadian genes.

Physiological functions of podosomes: From structure and function to therapy implications in osteoclast biology of bone resorption.

With increasing age, bone tissue undergoes significant alterations in composition, architecture, and metabolic functions, probably causing senile osteoporosis. Osteoporosis possess the vast majority of bone disease and associates with a reduction in bone mass and increased fracture risk. Bone loss is on account of the disorder in osteoblast-induced bone formation and osteoclast-induced bone resorption. As a unique bone resorptive cell type, mature bone-resorbing osteoclasts exhibit dynamic actin-based cytoskeletal structures called podosomes that participate in cell-matrix adhesions specialized in the degradation of mineralized bone matrix. Podosomes share many of the same molecular constitutions as focal adhesions, but they have a unique structural organization, with a central core abundant in F-actin and encircled by scaffolding proteins, kinases and integrins. Here, we conclude recent advancements in our knowledge of the architecture and the functions of podosomes. We also discuss the regulatory pathways in osteoclast podosomes, providing a reference for future research on the podosomes of osteoclasts and considering podosomes as a therapeutic target for inhibiting bone resorption.

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis.

Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP.

Establishment of ultrasound-guided stellate ganglion block in rats.

Background: A novel protocol for accurate stellate ganglion block under ultrasound guidance was designed in rats. This technique raises the success rate of stellate ganglion block and reduces the incidence of brachial plexus and vagus nerve block. Methods: Fifty-six Sprague-Dawley were randomly divided into an ultrasound-guided group (n = 28) and a blind technique group (n = 28). The rats in the blind technique group were injected with 1.5% lidocaine mixed with methylene blue after signs of brachial plexus stimulation were elicited. The lateral side of the cephalic brachial vein was located under the first rib, where lidocaine was injected into the rats in the ultrasound-guided group. The up-and-down sequential method of Dixon was used to determine the minimum effective volume for stellate ganglion block in rats. Furthermore, we calculated the required operative duration of the two methods and observed the difference in the lidocaine diffusion range between the two groups. Results: The minimum effective volume for stellate ganglion block in the ultrasound-guided group was 0.040 ml, and the 95% CI was 0.026-0.052 ml. In the blind technique group, the minimum effective volume was 0.639 ml, and the 95% CI was 0.490-0.733 ml. Within the 95% CI of the lowest effective volume, the incidence of brachial plexus block as a complication of stellate ganglion block under ultrasound guidance was 10.00%. Conclusion: Stellate ganglion block under ultrasound guidance is more accurate than blind detection, which the incidence of complications of stellate ganglion block under ultrasound guidance was significantly lower than under blind detection; the rate of methylene blue staining in the vagus nerve was significantly lower under ultrasound guidance.

Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a disease with high incidence rate in kidney related surgery. Micro RNA (miRNA) and transcription factors (TFs) are widely involved in the process of renal IRI through regulation of their target genes. However, the regulatory relationships and functional roles of TFs, miRNAs and mRNAs in the progression of renal IRI are insufficiently understood. The present study aimed to clarify the underlying mechanism of regulatory relationships in renal IRI. METHODS: Six gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) and differently expressed miRNAs (DEMs) were identified through RRA integrated analysis of mRNA datasets (GSE39548, GSE87025, GSE52004, GSE71647, and GSE131288) and miRNA datasets (GSE29495). miRDB and TransmiR v2.0 database were applied to predict target genes of miRNA and TFs, respectively. DEGs were applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, followed with construction of protein-protein interaction (PPI) network. Then, the TF-miRNA-mRNA network was constructed. Correlation coefficient and ROC analysis were used to verify regulatory relationship between genes and their diagnostic value in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 and in vitro, the expression of hub genes and genes from the network were observed and correlation coefficient and ROC analysis were validated. RESULTS: A total of 21 DEMs and 187 DEGs were identified in renal IRI group compared to control group. The results of PPI analysis showed 15 hub genes. The TF-miRNA-mRNA regulatory network was constructed and several important pathways were identified and further verified, including Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd. Four regulatory loops were identified, including Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25. The hub genes and genes in the network showed good diagnostic value in mice and human. CONCLUSIONS: In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI. Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd were the most important pathways, while Spp1, Fos, Timp1, Tnc, Fosl2 and Junb were the most important hub genes. Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25 might be the negative feedback loops in renal IRI.

Visible-Light-Initiated One-Pot, Three-Component Synthesis of 2-Amino-4H-pyran-3,5-dicarbonitrile Derivatives.

A novel approach for the visible-light-initiated synthesis of 2-amino-4H-pyran-3,5-dicarbonitrile derivatives via a one-pot, three-component reaction of aldehydes or isatins, malononitrile, and α-cyano ketones has been developed. The reaction was carried out at room temperature in ethanol/water to give the corresponding products with a wide range of functional groups in high yields. This process did not require any additives or chromatographic separation and could be applied for gram-scale synthesis.