Search

Gene editing is a growing gene engineering technique that allows accurate editing of a broad spectrum of gene‐regulated diseases to achieve curative treatment and also has the potential to be used as an adjunct to the conventional treatment of diseases. Gene editing technology, mainly based on clustered regularly interspaced palindromic repeats (CRISPR)–CRISPR‐associated protein systems, which is capable of generating genetic modifications in somatic cells, provides a promising new strategy for gene therapy for a wide range of human diseases. Currently, gene editing technology shows great application prospects in a variety of human diseases, not only in therapeutic potential but also in the construction of animal models of human diseases. This paper describes the application of gene editing technology in hematological diseases, solid tumors, immune disorders, ophthalmological diseases, and metabolic diseases; focuses on the therapeutic strategies of gene editing technology in sickle cell disease; provides an overview of the role of gene editing technology in the construction of animal models of human diseases; and discusses the limitations of gene editing technology in the treatment of diseases, which is intended to provide an important reference for the applications of gene editing technology in the human disease. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) impairs the wound healing process, seriously threatening the health of the diabetic population. To date, few effective approaches have been developed for the treatment of diabetic wounds. Krill oil (KO) contains bioactive components that have potent anti-inflammatory and anti-oxidative activities. As prolonged inflammation is a crucial contributor to DM-impaired wound healing, we speculated that the local application of KO would accelerate diabetic wound healing. Therefore, KO was applied to artificially created wounds of type 2 diabetic mice induced by streptozotocin and high-fat diet. The diabetic mice had a delayed wound healing process compared with the non-diabetic control mice, with excessive inflammation, impaired collagen deposition, and depressed neovascularization in the wound area. These effects were dramatically reversed by KO. In vitro, KO blocked the TNF-α-induced macrophage inflammation, fibroblast dysfunction, and endothelial angiogenic impairment. The present study in mice suggests that KO local application could be a viable approach in the management of diabetic wounds. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a serious health problem and may lead to advanced liver cirrhosis and hepatocellular carcinoma if left untreated. In this study, a mouse liver fibrosis model was established by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and tanshinone IIA. Salvia miltiorrhiza Bunge extract, shown to play a regulatory role in liver fibrosis, was administered to study its effect on the expression of COL1A1. Mice were divided into 3 groups, control (Con), model (DDC), and drug administration (DDC-Tan) groups, and were subjected to the respective treatment for 2 months. Following treatment, the degree of liver fibrosis in mice in each group was determined. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and albumin levels in mice were determined using enzyme-linked immunosorbent assay (ELISA). Mouse liver tissues were used for hematoxylin-eosin and immunohistochemical staining. ELISA results showed that treatment with tanshinone IIA inhibited the expression of ALT, AST, and bilirubin in the DDC-Tan group compared with the DDC group. Hematoxylin-eosin, Sirius red, and α-SMA staining showed that liver injury was delayed in the DDC-Tan group. Immunohistochemistry, quantitative polymerase chain reaction, and Western blot results showed that COL1A1 expression was reduced after tanshinone IIA treatment. Moreover, the bioinformatic analysis indicated that let-7a targets COL1A1, and H19 regulates let-7a expression. The quantitative polymerase chain reaction and Western blot results confirmed that the H19/let-7a axis regulates COL1A1 expression. Thus, tanshinone IIA inhibited liver fibrosis by regulating COL1A1 expression through the H19/let-7a axis in mice. [ABSTRACT FROM AUTHOR]

Flavonoids are present in a wide range of plants. They have been used in the treatment of cancer, but the mechanism underlying this activity is unclear. In recent years, microRNA (miRNA) and long non-coding RNA (lncRNA) levels have been observed to differ between normal tissues and cancer cells, and both types of RNA have been shown to have a role in tumor treatment. In addition, flavonoids have been proven to regulate miRNAs and LncRNAs in the treatment of cancer. The competing endogenous RNA (ceRNA) network is a complex post-transcriptional regulatory mechanism in cells, in which coding and non-coding RNAs competitively bind miRNAs to regulate messenger RNAs (mRNAs). This review focused on the role of the ceRNA network in the treatment of cancer by flavonoids. [ABSTRACT FROM AUTHOR]

Ginkgo biloba extract (GBE) has antitumor and antioxidant properties, which play a role in regulating gene and protein expression. The ten-eleven translocation (TET) proteins have the ability to regulate epigenetic modifications. However, the abnormal expression of TET2 protein has also been demonstrated in cancer development. In the present study, we analyzed the effects of GBE administration on TET2 expression in human colorectal cancer (CRC). The Cancer Genome Atlas database suggested that the expression of TET2 was lost in CRC. To investigate the expression profiles of TET2, GBE was used to treat CRC cells. The results showed that GBE could increase the expression of TET2 and 5-hydroxymethylcytosine (5hmC). In addition, GBE inhibited cell growth and invasion in SW480 cells. Moreover, to confirm whether TET2 expression affected cell proliferation, apoptosis, migration, and invasion, TET2 was knocked down and a TET2-overexpressing vector was constructed in human CRC cells. The results showed that overexpression of TET2 induced cell proliferation and invasion. Bioinformatic analyses showed that TET2 is a target gene of microRNA-29a (miR-29a). Moreover, reduced expression of miR-29a and increased TET2 expression in CRC cells. GBE was also used to treat a tumor model in nude mice. Compared to the control group, tumor growth was inhibited, and there was increased expression of TET2 in the GBE-treatment group in vivo. In conclusion, these results indicated that GBE inhibited cell proliferation and invasion through TET2 protein expression regulated by miR-29a in the development of CRC. [ABSTRACT FROM AUTHOR]

Background: Chrysin is a natural flavone that is present in honey and has exhibited anti-tumor properties. It has been widely studied as a therapeutic agent for the treatment of various types of cancers. The objectives of this present study were to elucidate how chrysin regulates non-coding RNA expression to exert anti-tumor effects in gastric cancer cells. Methods: Through the use of RNA sequencing, we investigated the differential expression of mRNAs in gastric cancer cells treated with chrysin. Furthermore, COPB2, H19 and let-7a overexpression and knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion, were also analyzed. Knockout of the COPB2 gene was generated using the CRISPR/Cas9 system for tumor growth analysis in vivo. Results: Our results identified COPB2 as a differentially expressed mRNA that is down-regulated following treatment with chrysin. Moreover, the results showed that chrysin can induce cellular apoptosis and inhibit cell migration and invasion. To further determine the underlying mechanism of COPB2 expression, we investigated the expression of the long non-coding RNA (lncRNA) H19 and microRNA let-7a. Our results showed that treatment with chrysin significantly increased let-7a expression and reduced the expression of H19 and COPB2. In addition, our results demonstrated that reduced expression of COPB2 markedly promotes cell apoptosis. Finally, in vivo data suggested that COPB2 expression is related to tumor growth. Conclusions: This study suggests that chrysin exhibited anti-tumor effects through a H19 /let-7a/ COPB2 axis. [ABSTRACT FROM AUTHOR]

Metacarpals are unique bones that support the finger to aid hand function. Metacarpals are also the commonest bones to get fractured in the hand. Historically, most metacarpal fractures were managed conservatively. Due to increased patient expectations as well as advancements in diagnosis and osteosynthesis, various surgical options are now available for metacarpal fractures. The goal of operative management of metacarpal management is no longer limited to achieving clinical or radiological union. To restore hand function to a preinjury level, the surgeon must achieve adequate anatomical reduction and stable fixation with minimal soft tissue damage. Similar to tendon repair, to start early active motion should be the goal after metacarpal fracture fixation. Intraoperative consideration should also include minimizing soft tissue damage and avoiding tendon, ligament or capsular entrapment. The aim of this article is to explain the principles of surgical management, the different options available for metacarpal fractures, the techniques, pearls, advantages and disadvantages of each technique, so the surgeon can choose the ideal option to achieve the best result. [ABSTRACT FROM AUTHOR]

Macrovascular complications develop in over a half of the diabetic individuals, resulting in high morbidity and mortality. This poses a severe threat to public health and a heavy burden to social economy. It is therefore important to develop effective approaches to prevent or slow down the pathogenesis and progression of macrovascular complications of diabetes (MCD). Oxidative stress is a major contributor to MCD. Nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) governs cellular antioxidant defence system by activating the transcription of various antioxidant genes, combating diabetes‐induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch‐like ECH‐associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of the Nfe2l2 gene transcription, decreasing KEAP1 protein level by microRNA‐induced degradation of Keap1 mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in prevention of MCD. This review provides a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review. [ABSTRACT FROM AUTHOR]

Background: Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive. Methods: Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used. Results: Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin‐treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA‐seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19. Conclusion: Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)‐treated endothelial cells (ECs) were subjected to pifithrin‐α (PFT‐α)—a specific inhibitor of P53, or P53‐small interfering RNA (siRNA), both of which attenuated the HG‐induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT‐α or P53‐siRNA prohibited P53 acetylation, decreased microRNA‐34a (miR‐34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR‐34a inhibitor (miR‐34a‐I) and PFT‐α increased SIRT1 protein level and alleviated the HG‐induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT‐α were completely abrogated by the miR‐34a mimic. In addition, SIRT1 inhibition by EX‐527 or Sirt1‐siRNA completely abolished miR‐34a‐I's protection against HG‐induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin‐induced diabetic mice, both PFT‐α and miR‐34a‐I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycaemia. Hence, the present study has uncovered a P53/miR‐34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR‐34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the leading cause of end stage renal disease, posing a severe threat to public health. Previous studies reported the protective role of sirtuin 1 (SIRT1) in DN, encouraging the investigation of more potent and specific SIRT1 activators. SRT2104 is a novel, first-in-class, highly selective small-molecule activator of SIRT1, with its effect and mechanism unknown on DN. To this end, streptozotocin-induced C57BL/6 wild-type (WT) diabetic mice were treated with SRT2104, for 24 weeks. To determine whether SRT2104 acted through inhibition of P53 – a substrate of SIRT1, the P53 activator nutlin3a was administered to the WT diabetic mice in the presence of SRT2104. In order to test whether nuclear factor erythroid 2-related factor 2 (NRF2) – the master of cellular antioxidants – mediated SIRT1 and P53's actions, WT and Nrf2 gene knockout (KO) diabetic mice were treated with SRT2104 or the P53 inhibitor pifithrin-α (PFT-α). In the WT mice, SRT2104 enhanced renal SIRT1 expression and activity, deacetylated P53, and activated NRF2 antioxidant signaling, providing remarkable protection against the DM-induced renal oxidative stress, inflammation, fibrosis, glomerular remodeling and albuminuria. These effects were completely abolished in the presence of nutlin3a. Deletion of the Nrf2 gene completely abrogated the efficacies of SRT2104 and PFT-α in elevating antioxidants and ameliorating DN, despite their abilities to activate SIRT1 and inhibit P53 in the Nrf2 KO mice. The present study reports the beneficial effects of SRT2104 on DN, uncovering a SIRT1/P53/NRF2 pathway that modulates the pathogenesis of DN. Unlabelled Image • The novel SIRT1 activator SRT2104 improved diabetic nephropathy. • Activation of P53 abolished SRT2104's protective effects on diabetic nephropathy. • Activation of SIRT1 and inhibition of P53 activated NRF2 antioxidant signaling. • SIRT1/P53's actions in diabetic nephropathy were mediated by NRF2. • A SIRT1/P53/NRF2 pathway controlled renal antioxidant activity under diabetes. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to analyze the differences in perioperative complications for pedicled island flaps in the reconstruction of extremities and to identify the factors contributing to pedicled island flap necrosis. Furthermore, the flap indications based on these outcomes are summarized. Methods Based on the inclusion criteria, 228 skin flaps were included in this study. Univariate and multivariate analyses were used to identify the risk factors for pedicled island flap necrosis. Differences in perioperative complications between upper and lower extremities were analyzed using the chi-square test or Fisher's exact test. Results The average age of the patients was 38 years. The overall complication rate was 21.93%, including partial flap necrosis (10.09%) and total flap necrosis (5.70%). The overall complication rate and flap necrosis rate in upper extremity reconstruction were significantly lower than the rates in lower extremity reconstruction. Flap area and postoperative wound infection were statistically significant risk factors for pedicled island flap necrosis in extremity reconstruction. Preoperative contamination of the wound bed was a statistically significant risk factor for postoperative wound infection. Conclusions The flap area and postoperative wound infection were both independent risk factors for pedicled island flap necrosis in extremity reconstruction. The causes contributing to the differences in perioperative complications between upper and lower extremities reconstruction included preoperative contamination of the wound bed, postoperative wound infection, and the flap area but were also related to anatomical factors of the skin flap. Pedicled island flaps are more suitable for small- and medium-sized soft tissue defects. [ABSTRACT FROM AUTHOR]

Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Sun, Zhuo, Jiang, Li, Lin, Jin, Gao and Wang.)

Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Jiang, Li, Xue, Lin, Deng, Jin and Sun.)

The most common bone cancer is osteosarcoma (OS), which mostly affects children and teenagers. Early surgical resection combined with chemotherapy significantly improves the prognosis of patients with OS. Existing chemotherapies have poor efficacy in individuals with distant metastases or inoperable resection, and these patients may respond better to novel immunotherapies. Immune escape, which is mediated by immunosuppressive cells in the tumour microenvironment (TME), is a major cause of poor OS prognosis and a primary target of immunotherapy. Myeloid-derived suppressor cells, regulatory T cells, and tumour-associated macrophages are the main immunosuppressor cells, which can regulate tumorigenesis and growth on a variety of levels through the interaction in the TME. The proliferation, migration, invasion, and epithelial-mesenchymal transition of OS cells can all be impacted by the expression of non-coding RNAs (ncRNAs), which can also influence how immunosuppressive cells work and support immune suppression in TME. Interferon, checkpoint inhibitors, cancer vaccines, and engineered chimeric antigen receptor (CAR-T) T cells for OS have all been developed using information from studies on the metabolic properties of immunosuppressive cells in TME and ncRNAs in OS cells. This review summarizes the regulatory effect of ncRNAs on OS cells as well as the metabolic heterogeneity of immunosuppressive cells in the context of OS immunotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Wang, Piao, Chen, Wang, Jiang and Liu.)

Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells' growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhang, Hao, Wang, Jiang, Sun, Gao, Jin, Lei and Zhuo.)

Chronic inflammation is associated with various chronic diseases, including cardiovascular disease, neurodegenerative disease, and cancer, which severely affect the health and quality of life of people. Oxidative stress induced by unbalanced production and elimination of reactive oxygen species (ROS) is one of the essential risk factors for chronic inflammation. Recent studies, including the studies of mushrooms, which have received considerable attention, report that the antioxidant effects of natural compounds have more advantages than synthetic antioxidants. Mushrooms have been consumed by humans as precious nourishment for 3,000 years, and so far, more than 350 types have been identified in China. Mushrooms are rich in polysaccharides, peptides, polyphenols, alkaloids, and terpenoids and are associated with several healthy biological functions, especially antioxidant properties. As such, the extracts purified from mushrooms could activate the expression of antioxidant enzymes through the Keap1/Nrf2/ARE pathway to neutralize excessive ROS and inhibit ROS-induced chronic inflammation through the NF-κB pathway. Recently, the antioxidant properties of mushrooms have been successfully applied to treating cardiovascular disease (CAD), neurodegenerative diseases, diabetes mellitus, and cancer. The present review summarizes the antioxidant properties and the mechanism of compounds purified from mushrooms, emphasizing the oxidative stress regulation of mushrooms to fight against chronic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Wang, Li, Chen, Wang, Jiang and Liu.)

More than 10% of the world's population already suffers from varying degrees of diabetes mellitus (DM), but there is still no cure for the disease. Cardiovascular disease (CVD) is one of the most common and dangerous of the many health complications that can be brought on by DM, and has become the leading cause of death in people with diabetes. While research on DM and associated CVD is advancing, the specific mechanisms of their development are still unclear. Given the threat of DM and CVD to humans, the search for new predictive markers and therapeutic ideas is imminent. Non-coding RNAs (ncRNAs) have been a popular subject of research in recent years. Although they do not encode proteins, they play an important role in living organisms, and they can cause disease when their expression is abnormal. Numerous studies have observed aberrant ncRNAs in patients with DM complications, suggesting that they may play an important role in the development of DM and CVD and could potentially act as biomarkers for diagnosis. There is additional evidence that treatment with existing drugs for DM, such as metformin, alters ncRNA expression levels, suggesting that regulation of ncRNA expression may be a key mechanism in future DM treatment. In this review, we assess the role of ncRNAs in the development of DM and CVD, as well as the evidence for ncRNAs as potential therapeutic targets, and make use of bioinformatics to analyze differential ncRNAs with potential functions in DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Jiang, Gao, Sun, Li, Chen, Lin and Liu.)

Chitosan and its derivatives are bioactive molecules that have recently been used in various fields, especially in the medical field. The antibacterial, antitumor, and immunomodulatory properties of chitosan have been extensively studied. Chitosan can be used as a drug-delivery carrier in the form of hydrogels, sponges, microspheres, nanoparticles, and thin films to treat diseases, especially those of the skin and soft tissue such as injuries and lesions of the skin, muscles, blood vessels, and nerves. Chitosan can prevent and also treat soft tissue diseases by exerting diverse biological effects such as antibacterial, antitumor, antioxidant, and tissue regeneration effects. Owing to its antitumor properties, chitosan can be used as a targeted therapy to treat soft tissue tumors. Moreover, owing to its antibacterial and antioxidant properties, chitosan can be used in the prevention and treatment of soft tissue infections. Chitosan can stop the bleeding of open wounds by promoting platelet agglutination. It can also promote the regeneration of soft tissues such as the skin, muscles, and nerves. Drug-delivery carriers containing chitosan can be used as wound dressings to promote wound healing. This review summarizes the structure and biological characteristics of chitosan and its derivatives. The recent breakthroughs and future trends of chitosan and its derivatives in therapeutic effects and drug delivery functions including anti-infection, promotion of wound healing, tissue regeneration and anticancer on soft tissue diseases are elaborated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Wang, Liu, Su, Jin, Wang, Han, Jiang and Liu.)

Precise prediction on brain age is urgently needed by many biomedical areas including mental rehabilitation prognosis as well as various medicine or treatment trials. People began to realize that contrasting physical (real) age and predicted brain age can help to highlight brain issues and evaluate if patients' brains are healthy or not. Such age prediction is often challenging for single model-based prediction, while the conditions of brains vary drastically over age. In this work, we present an age-adaptive ensemble model that is based on the combination of four different machine learning algorithms, including a support vector machine (SVR), a convolutional neural network (CNN) model, and the popular GoogLeNet and ResNet deep networks. The ensemble model proposed here is nonlinearly adaptive, where age is taken as a key factor in the nonlinear combination of various single-algorithm-based independent models. In our age-adaptive ensemble method, the weights of each model are learned automatically as nonlinear functions over age instead of fixed values, while brain age estimation is based on such an age-adaptive integration of various single models. The quality of the model is quantified by the mean absolute errors (MAE) and spearman correlation between the predicted age and the actual age, with the least MAE and the highest Spearman correlation representing the highest accuracy in age prediction. By testing on the Predictive Analysis Challenge 2019 (PAC 2019) dataset, our novel ensemble model has achieved a MAE down to 3.19, which is a significantly increased accuracy in this brain age competition. If deployed in the real world, our novel ensemble model having an improved accuracy could potentially help doctors to identify the risk of brain diseases more accurately and quickly, thus helping pharmaceutical companies develop drugs or treatments precisely, and potential offer a new powerful tool for researchers in the field of brain science.

N6-methyl-adenosine (m6A) methylation is one of the most common and abundant modifications of RNA molecules in eukaryotes. Although various biological roles of m6A methylation have been elucidated, its role in embryonic development is still unclear. In this review, we focused on the function and expression patterns of m6A-related genes in mammalian embryonic development and the role of m6A modification in the embryonic epigenetic reprogramming process. The modification of m6A is regulated by the combined activities of methyltransferases, demethylases, and m6A-binding proteins. m6A-related genes act synergistically to form a dynamic, reversible m6A pattern, which exists in several physiological processes in various stages of embryonic development. The lack of one of these enzymes affects embryonic m6A levels, leading to abnormal embryonic development and even death. Moreover, m6A is a positive regulator of reprogramming to pluripotency and can affect embryo reprogramming by affecting activation of the maternal-to-zygotic transition. In conclusion, m6A is involved in the regulation of gene expression during embryonic development and the metabolic processes of RNA and plays an important role in the epigenetic modification of embryos.

Methylation of the adenine base at the nitrogen 6 position (m6A) is the most common post-transcriptional epigenetic modification of RNA, and it plays a very important role in regulating gene expression. To investigate the role of m6A methylation in the expression of non-coding RNA and miRNA, we used a system of adenine base editors (ABEs). Here, we mutated regions up- and downstream of miRNA 675 m6A modification sites in the H19 locus using HEK293T, L02, MHCC97L, MHCC97H, A549, and SGC-7901 cells. Our results showed that a T-A base transversion had occurred in all cell lines. Moreover, mutation of the regions upstream of the miRNA 675 m6A modification site led to reduced expression of H19 and the induction of cell apoptosis in HEK293T cells. To further confirm our results, L02 and MHCC97L cells were detected using ABEs system. The results indicated increased cell apoptosis and reduced expression of miR675 as well as H19. To confirm the relationship between H19 and miR675 expression, overexpression and knockdown studies were performed. The results showed that reduced HI9 expression induced cell apoptosis through miR675. Taken together, these results indicate that m6A modification can regulate the expression of H19 and miR675 which induce cell apoptosis., (© 2020 The Author(s).)

Over a half of the diabetic individuals develop macrovascular complications that cause high mortality. Oxidative stress (OS) promotes endothelial dysfunction (ED) which is a critical early step toward diabetic macrovascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system and combats diabetes-induced OS. Previously, we found that impaired NRF2 antioxidant signaling contributed to diabetes-induced endothelial OS and dysfunction in mice. The present study has investigated the effect of microRNA-200a (miR-200a) on NRF2 signaling and diabetic ED. In aortic endothelial cells (ECs) isolated from C57BL/6 wild-type (WT) mice, high glucose (HG) reduced miR-200a levels and increased the expression of kelch-like ECH-associated protein 1 (Keap1) - a target of miR-200a and a negative regulator of NRF2. This led to the inactivation of NRF2 signaling and exacerbation of OS and inflammation. miR-200a mimic (miR-200a-M) or inhibitor modulated KEAP1/NRF2 antioxidant signaling and manipulated OS and inflammation under HG conditions. These effects were completely abolished by knockdown of Keap1, indicating that Keap1 mRNA is a major target of miR-200a. Moreover, the protective effect of miR-200a-M was completely abrogated in aortic ECs isolated from C57BL/6 Nrf2 knockout (KO) mice, demonstrating that NRF2 is required for miR-200a's actions. In vivo, miR-200a-M inhibited aortic Keap1 expression, activated NRF2 signaling, and attenuated hyperglycemia-induced OS, inflammation and ED in the WT, but not Nrf2 KO, mice. Therefore, the present study has uncovered miR-200a/KEAP1/NRF2 signaling that controls aortic endothelial antioxidant capacity, which protects against diabetic ED.

Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) - a master of cellular antioxidants scavenging excessive DM-induced free radicals - in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation, and accelerated wound closure in the diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG), or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) - inducible in DM - in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage, and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing.

This study aimed to compare the long-term efficacy of Kirschner wires and Herbert screw internal fixation in scaphoid fracture. A retrospective chart with radiographic review and functional follow-up was conducted for patients with the scaphoid fracture. 65 patients (40 for K-wire fixation and 25 for Herbert screw) were enrolled. The nonunion rate for K-wire fixation and screw method were indifferent comprehensively and for iliac graft subgroup. Less bone necrosis was found with K-wire fixation (2.5% vs 16%, P=0.049). There's no difference between groups in Mayo scores, post-operation pain and grid strength. Patients with K-wire fixation have larger range of motion on radial/ulnar deviation (35.25±11.32 vs 28.00±8.66, P=0.007). The results support the use of Kirschner wires in the treatment of scaphoid fractures. Advantages such as high union rates and good function recovery of wrist could be expected from minimal invasion, multi-axial stable fixation.

Objective: The posterior thigh region has been neglected as a donor site for free perforator flaps, likely due to difficulties in positioning the patient during surgery. This study describes the clinical application of the posterior thigh perforator flap based on the third perforating artery of the profunda femoris artery (PFA)., Methods: The free posterior thigh perforator flap based on the third perforating artery of the PFA was used for reconstruction of soft tissue defects in nine patients between February 2010 and May 2014., Results: Flap sizes ranged from 12 × 7 cm to 20 × 13 cm. The length of the vascular pedicle averaged 10.28 cm, and the mean diameters of the third perforating artery and venae comitantes were 1.68 and 1.14 mm, respectively. All of the perforators originated from the PFA. Of the 9 free flaps used in 9 patients, 7 flaps survived completely. There were no early complications in these flaps. During the follow-up period, no patient experienced cold intolerance, scar contracture, or scar pain. There were no functional impairments at the donor or recipient sites., Conclusions: The posterior thigh flap based on the third perforating artery of the PFA is an excellent option for reconstructing soft tissue defects. The anatomical location of the third perforating artery is relatively consistent. The vascular pedicle is relatively longer and has large caliber vessels. The scar at the donor site can be well concealed with low morbidity. The skin color and texture of this flap show satisfactory results.

Objective: To study the functional changes of median nerve after removing a certain bundle of it and to explore the functional reserve of median nerves., Methods: 220 three-month old SD rats were randomly divided into experimental groups and sham groups. And the experimental group was further divided as 1/8 group, 1/4 group, 1/3 group, 1/2 group, and 2/3 group according to ratio of the resection portion, with 22 rats in each group. The section of the lowest level on median nerve trunks were exposed, and a certain portion of it were separated and resected in experimental group, while in sham groups, the nerve was only separated without resection. The general state of health of all rats were observed, and the α motor neurons in cornu anterior medullae spinalis were studied 1 week, 2 weeks and 2 months postoperatively. Neuro-electrophysiology and function of dominated muscles were studied 2 weeks, 2 months, 3 months, and 4 months postoperatively., Results: All rats survived without infection and obvious ulcer. The number of the α motor neurons in cornuanterior medullae spinalis didn't change (P>0.05), and obvious superstructure changes were observed in early stage in 1/2 and 2/3 group, but restored after 2 months. There was no significant changes in latencies of motor neuron evoked potentials between experimental groups and sham group (P>0.05), however, there is significant difference if the 2 week group was compared with 2 month, 3 month and 4 month group (P<0.05). Moreover, there is also significant difference in terms of the wave amplitude of evoked potential of motor neurons, the maximum wave amplitude and the persistence time of its innervated muscle if the 2 week group was compared with those in 2 month, 3 month and 4 month group (P<0.05), and there is significant difference between different proportion resection groups (P<0.05)., Conclusions: Median nerve has a certain amount of functional reserve, and the quantity of the functional reserve of median nerve without compromise is the 1/3 of the whole trunk.

We have studied the application of direct aperture optimization (DAO) as an inverse planning tool for breast IMRT. Additionally, we have analysed the impact of respiratory motion on the quality of the delivered dose distribution. From this analysis, we have developed guidelines for balancing the desire for a high-quality optimized plan with the need to create a plan that will not degrade significantly in the presence of respiratory motion. For a DAO optimized breast IMRT plan, the tangential fields incorporate a flash field to cover the range of respiratory motion. The inverse planning algorithm then optimizes the shapes and weights of additional segments that are delivered in combination with the open fields. IMRT plans were generated using DAO with the relative weights of the open segments varied from 0% to 95%. To assess the impact of breathing motion, the dose distribution for the optimized IMRT plan was recalculated with the isocentre sampled from a predefined distribution in a Monte Carlo convolution/superposition dose engine with the breast simulated as a rigid object. The motion amplitudes applied in this study ranged from 0.5 to 2.0 cm. For a range of weighting levels assigned to the open field, comparisons were made between the static plans and the plans recalculated with motion. For the static plans, we found that uniform dose distributions could be generated with relative weights for the open segments equal to and below 80% and unacceptable levels of underdosage were observed with the weights larger than 80%. When simulated breathing motion was incorporated into the dose calculation, we observed a loss in dose uniformity as the weight of the open field was decreased to below 65%. More quantitatively, for each 1% decrease in the weight, the per cent volume of the target covered by at least 95% of the prescribed dose decreased by approximately 0.10% and 0.16% for motion amplitudes equal to 1.5 cm and 2.0 cm, respectively. When taking into account the motion effects, the most uniform and conformal dose distributions were achieved when the open segment weights were in the range of 65-80%. Within this range, high-quality IMRT plans were produced for each case. The study demonstrates that DAO with tangential fields provides a robust and efficient technique for breast IMRT planning and delivery when the open segment weight is selected between 65% and 80%.