Exploring the landscape of stem cell extracellular vesicle research for angiogenesis: A bibliometric analysis from 2003 to 2023.

BACKGROUND: Exosomes and other secretory membrane vesicles are collectively referred to as extracellular vesicles (EVs). Relevant data indicate that stem cell-derived extracellular vesicles (SC-EVs) play a critical role in angiogenesis by transmitting crucial information such as proteins, second messengers, and genetic material between cells. Therefore, this study aimed to map current trends on SC-EVs for angiogenesis and provide directions for future research to advance this important field. METHODS: We conducted a thorough search for relevant studies on SC-EVs for angiogenesis from 2003 to 2023 using the Web of Science database. Subsequently, we used VOSviewer and CiteSpace to analyze the collected data. RESULTS: A total of 2359 relevant publications, which included original articles and reviews, related to the role of SC-EVs in angiogenesis were screened in this study based on the search strategy. China and the United States were leading in this field, with China having a higher output in terms of publications and citations (1172, 43681). Also, the top five universities were located in China, with Shanghai Jiao Tong University having the highest output. Stem Cell Research & Therapy and International Journal of Molecular Sciences, are prominent platforms for researchers in this field to share their findings and advancements, and they had most of published studies on SC-EVs for angiogenesis. The results derived from the cluster analysis suggested that future investigations should predominantly prioritize studying the involvement of SC-EVs in angiogenesis across various diseases, with a specific emphasis on skin wound healing. CONCLUSION: In this comprehensive review, global trends in SC-EVs for angiogenesis were analyzed. The analysis of journals, institutions, references, and keywords could assist researchers in deciding on the direction of research. The role of SC-EVs in promoting angiogenesis during wound healing and repair represents an emerging research focus.

Bioinspired engineering ADSC nanovesicles thermosensitive hydrogel enhance autophagy of dermal papilla cells for androgenetic alopecia treatment.

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.

Long-Term Retrogradation Properties and In Vitro Digestibility of Waxy Rice Starch Modified with Pectin.

In recent years, the blending of hydrocolloids and natural starch to improve the properties of natural starch has become a research hotspot. In this study, the effects of pectin (PEC) on the retrogradation properties and in vitro digestibility of waxy rice starch (WRS) were investigated. The results showed that PEC could significantly (p < 0.05) reduce the retrogradation enthalpy and reduce the hardness of WRS gel. X-ray diffraction results indicated that PEC could reduce the relative crystallinity of the composite system, and the higher the PEC content, the lower the relative crystallinity. When the PEC content was 10%, the relative crystallinity of the composite system was only 10.6% after 21 d of cold storage. Fourier transform infrared spectroscopy results proved that the interaction between PEC and WRS was mainly a hydrogen bond interaction. Furthermore, after 21 d of cold storage, the T23 free water signal appeared in the natural WRS paste, while only a small free water signal appeared in the compound system with 2% PEC addition. Moreover, addition of PEC could reduce the starch digestion rate and digestibility. When the content of PEC increased from 0% to 10%, the digestibility decreased from 82.31% to 71.84%. This study provides a theoretical basis for the further application of hydrocolloids in starch-based foods.

Dietary docosahexaenoic acid plays an opposed role in ferroptotic and non-ferroptotic acute kidney injury.

Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary intake of PUFA for people susceptible to AKI. Clinically, however, in addition to ferroptosis, other mechanisms also contribute to different types of AKI such as inflammation associated necroptosis and pyroptosis. Therefore, the role of PUFA, especially ω3 PUFA which is a common food supplement, in various AKIs deserves further evaluation. In this study, rhabdomyolysis- and folic acid-induced AKI (Rha-AKI and FA-AKI) were established in mice fed with different fatty acids Histology of kidney, blood urea nitrogen and creatinine, lipid peroxidation, and inflammatory factors were examined. Results showed that these two types of AKIs had diametrically different pathogenesis indicated by that ferrostatin-1 (Fer-1), a lipid antioxidant, can attenuate FA-AKI rather than Rha-AKI. Further, dietary DHA (provided by fish oil) reduced tubular injury and renal lesion by inhibiting peroxidation and inflammation in mice with Rha-AKI while increasing cell death, tissue damage, peroxidation and inflammation in mice with FA-AKI. In human renal tubular epithelial cell line HK-2, MTT assay and DHE staining showed that both myoglobin and ferroptosis inducers can cause cell death and oxidative stress. Ferroptosis inducer-induced cell death was promoted by DHA, while such result was not observed in myoglobin-induced cell death when adding DHA. This study illustrates that the mechanisms of AKI might be either ferroptosis dependent or -independent and the deterioration effect of dietary DHA depends on whether ferroptosis is involved.

A bibliometric and visualized research on global trends of immune checkpoint inhibitors related complications in melanoma, 2011-2021.

Background: Melanoma is a malignant tumor that originates from the canceration of melanocytes with a high rate of invasiveness and lethality. Immune escape has been regarded as an important mechanism for tumor development, while the treatment of immune checkpoint inhibitors (ICIs) is beneficial in restoring and enhancing the body's anti-tumor immune response to kill tumor cells. To date, ICIs therapy has achieved remarkable efficacy in treating melanoma patients. Despite the significant clinical benefits of ICIs, multiple complications such as rashes, thyroiditis, and colitis occur in melanoma patients. In this study, we aim to explore the development process and trends in the field of ICIs-related complications in melanoma, analyze current hot topics, and predict future research directions. Methods: We screened the most relevant literatures on ICIs-related complications in melanoma from 2011 to 2021 in the Web of Science Core Collection (WoSCC). Using VOSviewer, CiteSpace and R language packages, we analyzed the research trends in this field. Results: A total of 1,087 articles were screened, and the USA had the highest number of publications (publications = 454, citations = 60,483), followed by Germany (publications = 155, citations = 27,743) and Italy (publications = 139, citations = 27,837). The Memorial Sloan Kettering Cancer Center had the most publications, but the Angeles Clinic and Research Institute had the highest average citation rate. Lancet oncology (IF, 2021 = 54.43) was the most prominent of all journals in terms of average citation rate. Reference and keyword cluster analysis revealed that anti-tumor efficacy, adjuvant treatment, clinical response, clinical outcome, etc. were the hotspots and trends of research in recent years. Conclusions: This study offers a comprehensive summary and analysis of global research trends on ICIs-related complications in melanoma. Over the past decade, there has been a significant increase in the number of publications on this topic. However, the safety and benefits of retreatment after the recovery of ICIs-related complications remain unknown. Therefore,the establishment of related prediction models, as well as the immunotherapy of melanoma with ICIs in combination with other adjuvant therapies, are future research hotspots.

A bibliometric and visualized research on global trends of scar, 2011-2021.

OBJECTIVE: Pathological scars are the results of abnormal wound healing, which not only affect the appearance, but may also be accompanied by significant psychosocial burdens. In this study, we aimed to conduct a bibliometric and visualized analysis on pathological scars and provide directions for future research. METHODS: The articles on scar research from 2011 to 2021 in the Web of Science Core Collection database were collected. The bibliometrics records were retrieved and analyzed with Excel, CiteSpace V and VOSviewer. RESULTS: A total of 944 scar research records published between 2011 and 2021 were collected. Publication output has shown an upward trend as a whole. China ranked first in terms of country contributions (418 publications, 5176 citations), while Germany, with only 22 studies published, had the highest average citation rate (57.18). Shanghai Jiaotong University was the institution with the largest number of related articles published, followed by the fourth military medical university, the University of Alberta and the Second military medical university. Wound repair and regeneration, Burns, Journal of Burn Care & Research, Journal of Cosmetic Dermatology published the most research in this field. Dahai Hu was the most prolific author, while Rei Ogawa was the most cited. The cluster analysis of the reference contributions and keywords indicated that current research hotspots mainly include pathogenesis, treatment strategies, and the safety evaluation of new scar treatment options. CONCLUSION: This study provides a comprehensive summary and analysis of the current status and research trends of pathological scars. International research interest in pathological scars is on the rise, and high-quality studies related to the field have also increased in the last decade. The pathogenesis of pathological scars, treatment strategies, such as fractional ablative CO2 laser and molecular targeted therapy, and the safety evaluation of new treatment options will be the focus of future research.

A bibliometric and visualized study on global trends of breast augmentation complications, 2011-2021.

Background: Women undergo breast augmentation surgery for a variety of reasons, but surgical complications can seriously affect patient outcomes and quality of life, making it a hot research topic. Although a large body of literature exists in this field, a lack of systemic generalization hinders the ability to guide clinical practice. We aimed to identify the current research hotspots and common surgical approaches of breast augmentation and to predict future research hotspots by analyzing the literature of the past 10 years. Methods: All relevant literature on breast augmentation complications were screened in the Web of Science (WoS) platform from 2011 to 2021. We analyzed the research within this field using the software programs VOSviewer and CiteSpace. Results: In total, 2,798 publications were selected. The United States ranked first in the world (1,173 articles), followed by Italy (243 articles), and the United Kingdom (208 articles). Memorial Sloan Kettering Cancer Center was the institution with the most publications, but the academic achievements of Harvard were the most recognized. Plastic and Reconstructive Surgery was the most prominent of all journals in terms of both the number and quality of the articles published. Albornoz was the hub author in the co-citation network. Keyword cluster analysis showed that capsular contracture, breast cancer, and postoperative nausea, among others, were the hotspots and trends of research in recent years. Conclusions: This study comprehensively summarized and analyzed the research trends of breast augmentation complications worldwide. Capsular contracture and postoperative nausea are current research hotspots. Periareolar incision and the breast crease incision are the most common incision approaches. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a future research hotspot.

Exploration of the roles of microbiota on biogenic amines formation during traditional fermentation of Scomber japonicus.

The influence of microbiota composition and metabolisms on the safety and quality of fermented fish products is attracting increasing attention. In this study, the total viable count (TVC), pH, total volatile base nitrogen (TVB-N) as well as biogenic amines (BAs) of traditional fermented Scomber japonicus (zaoyu) were quantitatively determined. To comprehend microbial community variation and predict their functions during fermentation, 16S rRNA-based high-throughput sequencing (HTS) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were employed, respectively. The fresh samples stored without fermentation were used as controls. TVC and TVB-N values increased rapidly, and the content of BAs exceeded the permissible limit on day 2 in the controls, indicating serious spoilage of the fish. In contrast, a slower increase in TVC and TVB-N was observed and the content of BAs was within the acceptable limit throughout the fermentation of zaoyu. Significant differences in microbiota composition were observed between zaoyu and the controls. The bacterial community composition of zaoyu was relatively simple and Lactobacillus was identified as the dominant microbial group. The accumulation of histamine was inhibited in zaoyu, which was positively correlated with the relative abundance of Vibrio, Enterobacter, Macrococcus, Weissella, et al. based on Redundancy analysis (RDA), while Lactobacillus showed a positive correlation with tyramine, cadaverine, and putrescine. Functional predictions, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, revealed that the relative abundance of metabolic function exhibited a decreasing trend with prolonged fermentation time and the abundance of metabolism-related genes was relatively stable in the later stage of fermentation. Those metabolisms related to the formation of BAs like histidine metabolism and arginine metabolism were inhibited in zaoyu. This study has accompanied microbiota analysis and functional metabolism with the accumulation of BAs to trace their correspondences, clarifying the roles of microorganisms in the inhibition of BAs during fermentation of Scomber japonicus.

A Comprehensive Review of Microneedling as a Potential Treatment Option for Androgenetic Alopecia.

BACKGROUND: Microneedling refers to a minimally invasive technique that uses multiple fine needles targeted skin epidermis for mechanical stimulation to obtain therapeutic or cosmetic effects. It is suitable for the treatment of a variety of dermatological conditions, including androgenetic alopecia (AGA). OBJECTIVE: This article aims to make a comprehensive review of the relevant studies on microneedling for the management of AGA. METHODS: Extensive literature search was performed using PubMed, Web of Science, and EBSCO databases. 4 in vivo studies and 25 clinical trials were included according to the inclusion and exclusion criteria. RESULTS: The effects of microneedling on AGA was investigated in animal experiments. Several clinical trials, including randomized controlled trials, strengthen the validity of the findings. Microneedling therapy showed some encouraging results with minor complications when used alone or in combination with topical products. CONCLUSIONS: Microneedling appears to be a safe and effective therapeutic option for AGA. Larger and more randomized controlled trials regarding the role of microneedling in AGA are strongly recommended to provide more definitive evidence. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effects of microneedling with 5% minoxidil topical solution combination therapy in treatment of androgenetic alopecia.

BACKGROUND: Microneedling (MN) therapy is one of minimal invasive operations with needles rolled over skin to puncturing the epidermis, and it is becoming a widely used treatment during various dermatological diseases includes androgenetic alopecia (AGA). OBJECTIVE: The purpose of the current study is to investigate the clinical observation and safety of MN combined with 5% minoxidil on triggering hair growth in AGA patients. MATERIAL AND METHODS: This retrospective study has analyzed 18 AGA patients who were treated by MN in combination with 5% minoxidil topical solution between July 2021 and February 2022. All patients received six sessions of treatment under aseptic condition at an interval of 1 week. Assessment of hair regrowth was done at the baseline and 10 weeks by photography, investigator, and patient assessment global scoring table on clinical improvement, and the patient's final satisfaction was investigated. RESULTS: According to the standardized 7-point scale, mean scores of investigator and participant assessments were 1.44 ± 0.61 and 1.66 ± 0.59, respectively, indicating that the hair appearance was considerably improved by MN combined with 5% minoxidil treatment. Fifteen patients (83.3%) were satisfied with the improvement in hair growth. No severe adverse events were noted in patients during and after the procedure. CONCLUSION: The combination of the length of 1.5 mm MN and 5% minoxidil in the treatment of AGA showed efficacy with high safety, which is worthy of clinical application.

Emerging Approach for Fish Freshness Evaluation: Principle, Application and Challenges.

Affected by micro-organisms and endogenous enzymes, fish are highly perishable during storage, processing and transportation. Efficient evaluation of fish freshness to ensure consumer safety and reduce raw material losses has received an increasing amount of attention. Several of the conventional freshness assessment techniques have plenty of shortcomings, such as being destructive, time-consuming and laborious. Recently, various sensors and spectroscopic techniques have shown great potential due to rapid analysis, low sample preparation and cost-effectiveness, and some methods are especially non-destructive and suitable for online or large-scale operations. Non-destructive techniques typically respond to characteristic substances produced by fish during spoilage without destroying the sample. In this review, we summarize, in detail, the principles and applications of emerging approaches for assessing fish freshness including visual indicators derived from intelligent packaging, active sensors, nuclear magnetic resonance (NMR) and optical spectroscopic techniques. Recent developments in emerging technologies have demonstrated their advantages in detecting fish freshness, but some challenges remain in popularization, optimizing sensor selectivity and sensitivity, and the development of algorithms and chemometrics in spectroscopic techniques.

Cathelicidin-related antimicrobial peptide protects against enteric pathogen-accelerated type 1 diabetes in mice.

Rationale: Gut barrier disruption caused by enteric pathogen infection results in activated diabetogenic T cells and accelerated type 1 diabetes (T1D). Cathelicidin-related antimicrobial peptide (CRAMP) maintains intestinal barrier integrity, regulates the microbiome, and exerts positive immune-modulatory effects on pancreatic diseases. Methods: The model enteric pathogen Citrobacter rodentium (C. rodentium) was adopted to represent clinical colonic infection with gut barrier disruption. The protective role and gut-pancreas pathophysiological mechanism of CRAMP in enteric pathogen-accelerated T1D were investigated in spontaneous non-obese diabetic (NOD) mice and streptozotocin-induced diabetic mice. Results: Colonic CRAMP production was defective in C. rodentium infection-accelerated T1D. C. rodentium infection triggered the recruitment of interferon-gamma (IFN-γ)+ T cells and accelerated T1D. In the C. rodentium-accelerated T1D mice, CRAMP deficiency further aggravated gut barrier disruption, gut dysbiosis, and diabetic phenotype, which could be reversed by CRAMP treatment. The protective effect of CRAMP may be due to CRAMP inhibiting C. rodentium-aggravated gut immune dysregulation, gut dysbiosis, and migration of gut-primed IFN-γ+ T cells to the pancreas, thus contributing to gut barrier protection and pancreatic-intestinal immune homeostasis. Conclusion: CRAMP plays a pivotal role in pancreatic-gut crosstalk during C. rodentium-accelerated T1D by gut barrier-protective, immune- and microbial-modulatory mechanisms. Cathelicidin supplementation to restore a healthy gut barrier may represent a novel therapeutic strategy for T1D.

Regulators CDCA8 as potential targets and biomarkers for the prognosis of human skin cutaneous melanoma.

Cutaneous melanoma (CM) is considered as the most malignant skin tumor with high distant metastasis and poor prognosis. Cell division cycle-associated protein (CDCA) family has a role in regulating cell proliferation and modulating immune cell and tumor cell proliferation in the tumor microenvironment to regulate tumor oncogenesis, development and affect patient outcomes. However, the differential expression pattern and prognostic value of CDCA factors (CDCAs) have not been clarified. In this study, the role of CDCAs in CM was analyzed by using bioinformatics and found that the transcriptional expressions of CDCA1/2/3/5/6/8 were upregulating in CM samples than in normal compares. CM patients with downregulated of CDCA1/3/4/5/6/8 and high transcriptional levels of CDCA7 suggest a significantly better prognosis. Furthermore, the significant correlations among the expression of CDCAs and the infiltration of immune cells. In terms of the protein level, we found CDCA8 was upregulated in CM patients. In conclusion, CDCA8 is a powerful prognostic biomarker for CM and can be a novel target for immunotherapy.

Comprehensive Analysis of LncRNA AC010789.1 Delays Androgenic Alopecia Progression by Targeting MicroRNA-21 and the Wnt/ß-Catenin Signaling Pathway in Hair Follicle Stem Cells.

Background: Androgen alopecia (AGA), the most common type of alopecia worldwide, has become an important medical and social issue. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the progression of various human diseases, including AGA. However, the potential roles of lncRNAs in hair follicle stem cells (HFSCs) and their subsequent relevance for AGA have not been fully elucidated. The current study aimed to explore the function and molecular mechanism of the lncRNA AC010789.1 in AGA progression. Methods: We investigated the expression levels of AC010789.1 in AGA scalp tissues compared with that in normal tissues and explored the underlying mechanisms using bioinformatics. HFSCs were then isolated from hair follicles of patients with AGA, and an AC010789.1-overexpressing HFSC line was produced and verified. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to verify the molecular mechanisms involved. Results: AC010789.1 overexpression promoted the proliferation and differentiation of HFSCs. Mechanistically, we demonstrated that AC010789.1 overexpression promotes the biological function of HFSCs by downregulating miR-21-5p and TGF-ß1 expression but upregulating the Wnt/ß-catenin signaling pathway. Conclusion: These results reveal that overexpression of AC010789.1 suppresses AGA progression via downregulation of hsa-miR-21-5p and TGF-ß1 and promotion of the Wnt/ß-catenin signaling pathway, highlighting a potentially promising strategy for AGA treatment.

The tooth-specific basic helix-loop-helix factor AmeloD promotes differentiation of ameloblasts.

Tissue-specific basic helix-loop-helix (bHLH) transcription factors play an important role in cellular differentiation. We recently identified AmeloD as a tooth-specific bHLH transcription factor. However, the role of AmeloD in cellular differentiation has not been investigated. The aim of this study was to elucidate the role of AmeloD in dental epithelial cell differentiation. We found that AmeloD-knockout (AmeloD-KO) mice developed an abnormal structure and altered ion composition of enamel in molars, suggesting that AmeloD-KO mice developed enamel hypoplasia. In molars of AmeloD-KO mice, the transcription factor Sox21 encoding SRY-Box transcription factor 21 and ameloblast differentiation marker genes were significantly downregulated. Furthermore, overexpression of AmeloD in the dental epithelial cell line M3H1 upregulated Sox21 and ameloblast differentiation marker genes, indicating that AmeloD is critical for ameloblast differentiation. Our study demonstrated that AmeloD is an important transcription factor in amelogenesis for promoting ameloblast differentiation. This study provides new insights into the mechanisms of amelogenesis.

Chondrogenic Characteristics of Auricular Chondrocytes Cocultured With Adipose-Derived Stem Cells are Superior to Stromal Vascular Fraction of Adipose Tissue.

ABSTRACT: Reconstruction of craniofacial cartilage defects is among the most challenging operations in facial plastic surgery. The co-culture system of partial replacement of chondrocytes by stem cells has been confirmed effective in the repair of cartilaginous defects. The aim of this study is to compare chondrogenic properties of expanded adipose-derived stem cells (ADSCs) and stromal vascular fraction (SVF), including ADSCs/SVF monoculture and coculture with rabbit auricular chondrocytes (ACs). Analysis of morphology, histology, real-time polymerase chain reaction and glycosaminoglycans (GAG) quantification were performed to characterize the chondrogenesis of pellets. The triple differentiation potential of ADSCs had been confirmed. Further, using flow cytometry, the authors demonstrated that ADSCs and SVF have different characteristics in cell surface markers, and ADSCs are more enriched in cells from the mesenchymal lineage than SVF. GAG production of ADSCs is significantly higher than that of SVF in pellet monoculture, and pellet coculture of ADSCs and ACs are better in depositing cartilage matrix than the mixture of SVF and ACs. Our study suggests that ADSCs may be more suitable seed cells for craniofacial cartilage defect or deformity repair.

Protective effects of pretreatment with Fe2+, Cu2+, and Rb+ on phoxim poisoning in silkworm, Bombyx mori.

BACKGROUND: Phoxim is a widely used organophosphorus pesticide in agriculture. People are paying more and more attention to its toxicity. At present, there is no appropriate way to solve the phoxim poisoning of silkworm, which severely affected the development of sericulture. Fe2+, Cu2+, Rb+ exerted their biological effects through various forms in vivo. METHODS: To evaluate the effect of Fe2+/Cu2+/Rb+ on phoxim poisoning in silkworm, Bombyx mori were treated with fresh mulberry leaves soaked in 2.5 mg/L phoxim for 2 min with 50 mg/L FeCl2, 150 mg/L CuCl2, or 0.5 mg/L RbCl from 5 days of the fifth-instar silkworm. RESULTS: Fe2+, Cu2+, and Rb+ pretreatments significantly inhibited the phoxim-induced reduction of survival rate and alleviated the phoxim-induced poisoning symptoms. The protective effects of Fe2+, Cu2+, and Rb+ on phoxim poisoning might be due to their enhancement of superoxide dismutase (SOD), catalase (CAT), and carboxylesterase (CarE) in the hemolymph and fat body of silkworm. This enhancement might reduce reactive oxygen species (ROS) accumulation and oxidative stress (OS) caused by phoxim poisoning. Thereby it reduced the damage to silkworm tissues and cells. CONCLUSIONS: These results showed that Fe2+, Cu2+, and Rb+ treatments protected the silkworm from phoxim poisoning by directly enhancing the activity of SOD, CAT, and CarE enzymes and reducing oxidative stress, but not dependent on the high expression of CYP genes. The use of Fe2+, Cu2+, and Rb+ to enhance the activity of SOD, CAT, and CarE enzymes may be an underlying effective way to solve phoxim poisoning in the silkworm industry.

Prostaglandin E3 attenuates macrophage-associated inflammation and prostate tumour growth by modulating polarization.

Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E3 (PGE3 ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE3 played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE3 had no direct effect on the growth of prostate cancer cells in vitro, PGE3 could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE3 significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE3 inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer.

Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development.

The epithelial-mesenchymal interactions are essential for the initiation and regulation of the development of teeth. Following the initiation of tooth development, numerous growth factors are secreted by the dental epithelium and mesenchyme that play critical roles in cellular differentiation. During tooth morphogenesis, the dental epithelial stem cells differentiate into several cell types, including inner enamel epithelial cells, which then differentiate into enamel matrix-secreting ameloblasts. Recently, we reported that the novel basic-helix-loop-helix transcription factor, AmeloD, is actively engaged in the development of teeth as a regulator of dental epithelial cell motility. However, the gene regulation mechanism of AmeloD is still unknown. In this study, we aimed to uncover the mechanisms regulating AmeloD expression during tooth development. By screening growth factors that are important in the early stages of tooth formation, we found that TGF-ß1 induced AmeloD expression and ameloblast differentiation in the dental epithelial cell line, SF2. TGF-ß1 phosphorylated ERK1/2 and Smad2/3 to induce AmeloD expression, whereas treatment with the MEK inhibitor, U0126, inhibited AmeloD induction. Promoter analysis of AmeloD revealed that the proximal promoter of AmeloD showed high activity in dental epithelial cell lines, which was enhanced following TGF-ß1 stimulation. These results suggested that TGF-ß1 activates AmeloD transcription via ERK1/2 phosphorylation. Our findings provide new insights into the mechanisms that govern tooth development.

[Annual progress in critical care medicine in 2020].

The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.