Decorin attenuates hypertrophic scar fibrosis via TGFß/Smad signalling.

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.

Somatic hypermutation at A.T pairs: polymerase error versus dUTP incorporation.

Somatic hypermutation of immunoglobulin genes occurs at both C.G pairs and A.T pairs. Mutations at C.G pairs are created by activation-induced deaminase (AID)-catalysed deamination of C residues to U residues. Mutations at A.T pairs are probably produced during patch repair of the AID-generated U.G lesion, but they occur through an unknown mechanism. Here, we compare the popular suggestion of nucleotide mispairing through polymerase error with an alternative possibility, mutation through incorporation of dUTP (or another non-canonical nucleotide).

Ionic Liquid-Based Ultrasonic-Assisted Extraction of Secoisolariciresinol Diglucoside from Flaxseed (Linum usitatissimum L.) with Further Purification by an Aqueous Two-Phase System.

In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated as the extractants, to identify the IL that affords the optimum extraction yield. The extraction conditions such as IL concentration, ultrasonic irradiation time, and liquid-solid ratio were optimized using response surface methodology (RSM). In the IL-ATPS step, ATPS formed by adding kosmotropic salts to the IL extract was used for further separation and purification of SDG. The most influential parameters (type and concentration of salt, temperature, and pH) were investigated to obtain the optimum extraction efficiency. The maximum extraction efficiency was 93.35% under the optimal conditions of 45.86% (w/w) IL and 8.27% (w/w) Na2SO4 at 22 °C and pH 11.0. Thus, the combination of IL-UAE and IL-ATPS makes up a simple and effective methodology for the extraction and purification of SDG. This process is also expected to be highly useful for the extraction and purification of bioactive compounds from other important medicinal plants.

Noninvasive Assessment of Kidney Injury by Combining Structure and Function Using Artificial Intelligence-Based Manganese-Enhanced Magnetic Resonance Imaging.

Contrast-enhanced magnetic resonance imaging (MRI) is seriously limited in kidney injury detection due to the nephrotoxicity of clinically used gadolinium-based contrast agents. Herein, we propose a noninvasive method for the assessment of kidney injury by combining structure and function information based on manganese (Mn)-enhanced MRI for the first time. As a proof of concept, the Mn-melanin nanoprobe with good biocompatibility and excellent T1 relaxivity is applied in MRI of a unilateral ureteral obstruction mice model. The abundant renal structure and function information is obtained through qualitative and quantitative analysis of MR images, and a brand new comprehensive assessment framework is proposed to precisely identify the degree of kidney injury successfully. Our study demonstrates that Mn-enhanced MRI is a promising approach for the highly sensitive and biosafe assessment of kidney injury in vivo.

Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and in vivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient in vivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

A Bibliometric Analysis of Metabolic Reprogramming in the Tumor Microenvironment From 2003 to 2022.

BACKGROUND: Despite considerable progress in cancer immunotherapy, it is not available for many patients. Resistance to immune checkpoint blockers arises from the intricate interactions between cancer and its microenvironment. Metabolic reprogramming in tumor and immune cells in the tumor microenvironment (TME) influences anti-tumor immune responses by remodeling the immune microenvironment. Metabolic reprogramming has emerged as an important hallmark of tumorigenesis. However, few studies have focused on the TME and metabolic reprogramming. Therefore, we aimed to explore the current research status and popular topics in TME-related metabolic reprogramming over a 20 years using a bibliometric approach. METHODS: Studies focusing on metabolic reprogramming and TME were searched using the Web of Science Core Collection database. Bibliometric and visual analyses of the articles and reviews were performed using Bibliometrix, VOSviewer, and CiteSpace. RESULTS: In total, 4726 articles published between 2003 and 2022 were selected. The number of publications and citations has increased annually. Cooperation network analysis indicated that the United States holds the foremost position in metabolic reprogramming and TME research with the highest volume of publications and citations, thus exerting the greatest influence. Among these institutions, Fudan University displayed the highest level of productivity. Frontiers in Immunology showed the highest degree of productivity in this field. Ho Ping-Chih made the most article contributions, and Pearce Edward J. was the most co-cited author. Four clusters were obtained after a cluster analysis of the authors' keywords: TME, metabolic reprogramming, immunometabolism, and immunity. Immunometabolism, glycolysis, immune cells, and tumor-associated macrophages are relatively recent keywords that have attracted increasing attention. CONCLUSIONS: A comprehensive landscape of advancements in metabolic reprogramming and the TME was evaluated, which provided crucial information for scholars to further advance this promising field. Further research should explore new topics related to immunometabolism in the TME using a transdisciplinary approach.

The function of human milk oligosaccharides and their substitute oligosaccharides as probiotics in gut inflammation.

Gut inflammation seriously affects the healthy life of patients, and has a trend of increasing incidence rate. However, the current methods for treating gut inflammation are limited to surgery and drugs, which can cause irreversible damage to patients, especially infants. As natural oligosaccharides in human breast milk, human milk oligosaccharides (HMOs) function as probiotics in treating and preventing gut inflammation: improving the abundance of the gut microbiota, increasing the gut barrier function, and reducing the gut inflammatory reaction. Meanwhile, due to the complexity and high cost of their synthesis, people are searching for functional oligosaccharides that can replace HMOs as a food additive in infants milk powder and adjuvant therapy for chronic inflammation. The purpose of this review is to summarize the therapeutic and preventive effects of HMOs and their substitute functional oligosaccharides as probiotics in gut inflammation, and to summarize the prospect of their application in infant breast milk replacement in the future.

Successful Liver Transplantation From a Deceased Donor With Congenital Extrahepatic Portosystemic Shunt: A Case Report.

Congenital extrahepatic portosystemic shunt belongs to a family of rare vascular abnormalities. We present a case of congenital extrahepatic portosystemic shunt occurring in a 42-year-old man who died of cerebral hemorrhage and donated his liver. His portal vein angiography revealed that the main portal vein communicated with the left renal vein, suggesting a portosystemic shunt. A liver biopsy showed that the liver tissue structure was normal. His liver was not involved, and the transplantation was carried out smoothly. The recipient recovered smoothly, and the function of the transplanted liver was good.

Transforming Commercial Copper Sulfide into Injectable Hydrogels for Local Photothermal Therapy.

Photothermal therapy (PTT) is a promising local therapy playing an increasingly important role in tumor treatment. To maximize PTT efficacy, various near-infrared photoabsorbers have been developed. Among them, metal sulfides have attracted considerable interest due to the advantages of good stability and high photothermal conversion efficiency. However, the existing synthesis methods of metal-sulfide-based photoabsorbers suffer from the drawbacks of complicated procedures, low raw material utilization, and poor universality. Herein, we proposed a flexible, adjustable strategy capable of transforming commercial metal sulfides into injectable hydrogels for local PTT. We took copper sulfide (CuS) as a typical example, which has intense second-window near-infrared absorption (1064 nm), to systematically investigate its in vitro and in vivo characteristics. CuS hydrogel with good syringeability was synthesized by simply dispersing commercial CuS powders as photoabsorbers in alginate-Ca2+ hydrogel. This synthesis strategy exhibits the unique merits of an ultra-simple synthesizing process, 100% loading efficiency, good biocompatibility, low cost, outstanding photothermal capacity, and good universality. The in vitro experiments indicated that the hydrogel exhibits favorable photothermal heating ability, and it obviously destroyed tumor cells under 1064 nm laser irradiation. After intratumoral administration in vivo, large-sized CuS particles in the hydrogel highly efficiently accumulated in tumor tissues, and robust local PTT was realized under mild laser irradiation (0.3 W/cm2). The developed strategy for the synthesis of CuS hydrogel provides a novel way to utilize commercial metal sulfides for diverse biological applications.

The role of functional oligosaccharides as prebiotics in ulcerative colitis.

The incidence rate of ulcerative colitis (UC) has increased significantly over the past decades and it places an increasing burden on health and social systems. The current studies on UC implicate a strong correlation between host gut microbiota immunity and the pathogenesis of UC. Meanwhile, more and more functional oligosaccharides have been reported as prebiotics to alleviate UC, since many of them can be metabolized by gut microbiota to produce short-chain fatty acids (SCFAs). The present review is focused on the structure, sources and specific applications of various functional oligosaccharides related to the prevention and treatment of UC. The available evidence for the usage of functional oligosaccharides in UC treatment are summarized, including fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), chito-oligosaccharides (COS), alginate-oligosaccharides (AOS), xylooligosaccharides (XOS), stachyose and inulin.

Preventive effect of pectic oligosaccharides on acute colitis model mice: modulating epithelial barrier, gut microbiota and Treg/Th17 balance.

Pectin as a dietary fiber supplement has shown emerging potential in clinical ulcerative colitis (UC) adjuvant therapy. In this study, the preventive and prebiotic effects of enzymatically degraded pectic oligosaccharides (POS) were further explored in dextran sodium sulfate (DSS)-induced colitis mice. The POS supplement (400 mg kg-1) was significantly effective at improving preventive efficacy, promoting colonic epithelial barrier integrity and reducing inflammatory cytokines. Meanwhile, the changes in T regulatory (Treg) cells and T helper 17 (Th17) cells indicated that POS treatment regulated the Treg/Th17 balance. Gut microbiota analysis showed that the POS supplement reshaped the dysfunctional gut microbiota. Further Spearman's correlation coefficient analysis indicated that the changes of the gut microbiota were highly associated with modulating the epithelial barrier, promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. All of these results suggest that enzymatically- degraded POS is a promising therapeutic agent for UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Algal polysaccharides and derivatives as potential therapeutics for obesity and related metabolic diseases.

The worldwide upward trend in obesity has been dramatic, but there is a lack of effective and safe drug treatment. Marine-derived algal polysaccharides, including fucoidan, alginate, polysaccharide of Spirulina platensis (PSP), ulvan, rhamnan sulfate (RS), laminarin, agar, and carrageenan, are widely used in combination with wound healing, drug delivery, and tissue-related biomedical research engineering. Recently, the prebiotic effects of algal polysaccharides and their related derivatives have received more and more attention. In this review, we discuss the potential and challenges of algal polysaccharides and their derivatives as potential therapeutic agents for obesity and its related metabolic diseases. Relevant studies have demonstrated that a variety of algal polysaccharides can play a significant role in weight loss and treatment of obesity-related metabolic diseases by improving the composition of gut microbiota, promoting bile acid formation, and upregulating cholesterol receptors in the liver. Because of their low price, non-toxic properties, and easy availability, algal polysaccharides have the potential to be developed as weight loss products.

Boosted charge transfer in dual Z-scheme BiVO4@ZnIn2S4/Bi2Sn2O7 heterojunctions: Towards superior photocatalytic properties for organic pollutant degradation.

A core-shell structured dual Z-scheme ternary photocatalyst BiVO4@ZnIn2S4/Bi2Sn2O7 was fabricated via hydrothermal and heat-circumfluence strategy. With ZnIn2S4 serving as a bridge to connect BiVO4 and Bi2Sn2O7, the developed ternary catalyst displayed boosted charge transfer and spatial separation capabilities. The effect of mass ratios of BiVO4@ZnIn2S4 and Bi2Sn2O7 on photodegradation efficiency under visible light irradiation was explored. The optimal ternary heterojunction photocatalyst possessed remarkable photocatalytic rate constant for Rhodamine B (RhB) degradation, which was 63 and 12 times higher than that of BiVO4 and Bi2Sn2O7, respectively. In addition, the as-prepared ternary photocatalyst had good universality. Notably, the novel dual Z-scheme photocatalysts could improve the separating/transferring efficiency and reduction/oxidation ability of charge carriers. Meanwhile, the hierarchical structure offered sufficient reaction sites for photodegradation. This work provides a new insight into the rational design of ternary dual Z-scheme photocatalysts.

Enzymatically synthesized α-galactooligosaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with the modulation of gut microbiota.

The composition and structure of gut microbiota plays an important role in obesity induced by a high-fat diet (HFD) and related metabolic syndrome (MetS). Previous studies have shown that galacto-oligosaccharides (GOSs) have an effective anti-obesity effect. In this study, we aimed to investigate the effect of enzymatically synthesized α-galacto-oligosaccharides (ES-α-GOSs) on MetS and gut microbiota dysbiosis in HFD-fed mice, and to further investigate whether the attenuation of MetS is associated with the modulation of gut microbiota. Our results indicated that ES-α-GOS could notably ameliorate obesity-related MetS, including hyperlipidemia, insulin resistance and mild inflammation. The subsequent analysis of gut microbiota further showed that ES-α-GOS supplements can significantly modulate the overall composition of the gut microbiota and reverse the gut microbiota disorder caused by HFD feeding. Moreover, Spearman correlation analysis showed that 40 key bacteria reversed by ES-α-GOS were highly associated with metabolic parameters. These results suggested that ES-α-GOSs could serve as a potential candidate for preventing obesity-induced MetS in association with the modulation of gut microbiota.

DNA deamination in immunity: AID in the context of its APOBEC relatives.

The activation-induced cytidine deaminase (AID)/apolipoprotein B RNA-editing catalytic component (APOBEC) family is a vertebrate-restricted subgrouping of a superfamily of zinc (Zn)-dependent deaminases that has members distributed throughout the biological world. AID and APOBEC2 are the oldest family members with APOBEC1 and the APOBEC3s being later arrivals restricted to placental mammals. Many AID/APOBEC family members exhibit cytidine deaminase activity on polynucleotides, although in different physiological contexts. Here, we examine the AID/APOBEC proteins in the context of the entire Zn-dependent deaminase superfamily. On the basis of secondary structure predictions, we propose that the cytosine and tRNA deaminases are likely to provide better structural paradigms for the AID/APOBEC family than do the cytidine deaminases, to which they have conventionally been compared. These comparisons yield predictions concerning likely polynucleotide-interacting residues in AID/APOBEC3s, predictions that are supported by mutagenesis studies. We also focus on a specific comparison between AID and the APOBEC3s. Both are DNA deaminases that function in immunity and are responsible for the hypermutation of their target substrates. AID functions in the adaptive immune system to diversify antibodies with targeted DNA deamination being central to this function. APOBEC3s function as part of an innate pathway of immunity to retroviruses with targeted DNA deamination being central to their activity in retroviral hypermutation. However, the mechanism by which the APOBEC3s fulfill their function of retroviral restriction remains unresolved.

Prognositic significance of P-cadherin expression in breast cancer: Protocol for a meta-analysis.

BACKGROUND: P-cadherin is a calcium-dependent cell-cell adhesion glycoprotein. It has been implicated in invasiveness and metastasis. However, the clinical prognostic value of overexpression of P-cadherin in patients with breast cancer (BC) remains unsettled. METHODS: A systematic literature search will be performed in all available databases to quantitatively review eligible studies and identify all relevant data, which could be used to detect the relationship between overexpression of P-cadherin and overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. Hazard ratio and 95% confidence intervals (CIs) or P value will be employed as effect measures to estimate the correlation between P-cadherin and the oncologic outcomes including overall survival (OS), disease-free survival (DFS). Odds ratios (ORs) and the 95% CIs will be evaluated for the pooled analysis of the correlation between P-cadherin expression and clinicopathological features. We will use the Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX) to perform the meta-analysis to calculate the data. RESULTS: The review will provide a high-quality synthesis of current evidence of the prognostic role of P-cadherin in BCs. The results will be published in a peer-reviewed journal. CONCLUSION: We hope that the results of this study will provide significant evidence to assess whether the expression of P-cadherin is associated with poor prognosis in patients with BC. PROSPERO REGISTRATION NUMBER: This meta-analysis protocol has been registered in the PROSPERO network with registration number: CRD42019119880.

Pre-administration of BAX-inhibiting peptides decrease the loss of the nigral dopaminergic neurons in rats.

AIMS: In this study, we investigated the effects of Bax-inhibiting peptide (Bip)-V5, an anti-apoptosis membrane-permeable peptide, on the 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model rats. MATERIALS AND METHODS: Rats were randomly divided into five groups: Control, 6-OHDA only, Vehicle+6-OHDA, zVAD+6-OHDA, and V5+6-OHDA, that rats were preadministrated with different reagents before 6-OHDA administration. KEY FINDINGS: The result showed that intrastriatal preadministration of Bip-V5 significantly decreased the amphetamine-induced rotation of the 6-OHDA model rats and the loss of the nigral dopaminergic (DA) neurons. Moreover, Bip-V5 intrastriatal preadministration not only significantly decreased the expression of activated caspase 9 and activated caspase 3 but also decreased the enhanced expression of AIF and its nuclear translocation in the SNpc. The results in our study provide the first experimental evidence that both caspase-dependent and AIF-dependent apoptosis pathways are involved in the loss of the nigral DA neurons caused by intrastriatal administration of 6-OHDA, and intrastriatal preadministration of Bip-V5 can inhibit the above two apoptosis pathways to protect the nigral DA neurons. SIGNIFICANCE: Our results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD.

Extraction of Oil from Flaxseed (Linum usitatissimum L.) Using Enzyme-Assisted Three-Phase Partitioning.

In this study, enzyme-assisted three-phase partitioning (EATPP) was used to extract oil from flaxseed. The whole procedure is composed of two parts: the enzymolysis procedure in which the flaxseed was hydrolyzed using an enzyme solution (the influencing parameters such as the type and concentration of enzyme, temperature, and pH were optimized) and three-phase partitioning (TPP), which was conducted by adding salt and t-butanol to the crude flaxseed slurry, resulting in the extraction of flaxseed oil into alcohol-rich upper phase. The concentration of t-butanol, concentration of salt, and the temperature were optimized to maximize the extraction yield. Under optimized conditions of a 49.29 % t-butanol concentration, 30.43 % ammonium sulfate concentration, and 35 °C extraction temperature, a maximum extraction yield of 71.68 % was obtained. This simple and effective EATPP can be used to achieve high extraction yields and oil quality, and thus, it is potential for large-scale oil production.

Update on therapeutic mechanism for bone marrow stromal cells in ischemic stroke.

Cerebral ischemia is a major cause of morbidity and mortality in the aged population, as well as a tremendous burden on the healthcare system. Despite timely treatment with thrombolysis and percutaneous intravascular interventions, many patients are often left with irreversible neurological deficits. Bone marrow stromal cells (BMSCs), also referred to as mesenchymal stem cells (MSCs), are a type of nonhematopoietic stem cells which exists in bone marrow mesh, with the potential to self-renew. Unlike cells in the central nervous system, BMSCs differentiate not only into mesodermal cells, but also endodermal and ectodermal cells. Moreover, it has been reported that BMSCs develop into cells with neural and vascular markers and play a role in recovery from ischemic stroke. These findings have fuelled excitement in regenerative medicine for neurological diseases, especially for ischemic stroke. There is now preclinical evidence to suggest that BMSCs grafted into the brain of ischemic models abrogate neurological deficits. Based on the overwhelming evidence from animal studies as well as in clinical trials, BMSC transplantation is considered a promising strategy for treatment of ischemic stroke. The goal of this review is to present an integrated consideration of molecular mechanisms in a chronological fashion and discuss an optimal BMSC delivery route for ischemic stroke.

Bone marrow stromal cells as a therapeutic treatment for ischemic stroke.

Cerebral ischemia remains the most frequent cause of death and quality-of-life impairments due to neurological deficits, and accounts for the majority of total healthcare costs. However, treatments for cerebral ischemia are limited. Over the last decade, bone marrow stromal cell (BMSC) therapy has emerged as a particularly appealing option, as it is possible to help patients even when initiated days or even weeks after the ischemic insult. BMSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Therapeutic effects of BMSC treatment for ischemic stroke, including sensory and motor recovery, have been reported in pre-clinical studies and clinical trials. In this article, we review the recent progress in BMSC-based therapy for ischemic stroke, focusing on the route of delivery and pre-processing of BMSCs. Selecting an optimal delivery route is of particular importance. The ideal approach, as well as the least risky, for translational applications still requires further identification. Appropriate preprocessing of BMSCs or combination therapy has the benefit of achieving the maximum possible restoration. Further pre-clinical studies are required to determine the time-window for transplantation and the appropriate dosage of cells.