Modulation of immunosuppressive cells and noncoding RNAs as immunotherapy in osteosarcoma.

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.

Corrigendum: Applications of chitosan and its derivatives in skin and soft tissue diseases.

[This corrects the article DOI: 10.3389/fbioe.2022.894667.].

Preparation and Gas Sensing Properties of Hair-Based Carbon Sheets.

Waste human hair was carbonized into carbon sheets by a simple carbonization method, which was studied as gas sensing materials for the first time. The effect of carbonization temperature on the structure and gas sensing properties of hair-based carbon sheet was studied by scanning electron microscope, X-ray diffraction, infrared spectrum, Raman spectrum, and gas-sensitive tester. The results showed that the carbonization temperature had a significant effect on the structure and gas sensing performance of carbon sheets, which were doped with K, N, P, and S elements during carbonization. However, the sensor of the carbon sheet does not show good selectivity among six target gases. Fortunately, the carbon sheets prepared at different temperatures have different responses to the target gases. The sensor array constructed by the carbon sheets prepared at different temperatures can realize the discriminative detection of a variety of target gases. For the optimized carbon sheet, the theoretical limit of detection of hydrogen peroxide is 0.83 ppm. This work provides a reference for the resource utilization of waste protein and the development of gas sensors.

Compounds purified from edible fungi fight against chronic inflammation through oxidative stress regulation.

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.

Astragalus polysaccharide alleviated the inhibition of CSFV C-strain replication caused by PRRSV via the TLRs/NF­κB/TNF-α pathways.

It is a common phenomenon that PRRSV infection can interfere with the protective efficacy of the CSFV vaccine in clinical settings, and no effective treatment is available. In our previous study, we found that PRRSV infection could inhibit the replication of CSFV-C by promoting the high expression of inflammatory cytokines. In order to further investigate whether Chinese medicine could alleviate the inhibition effect, the PAM39 cells model, which was co-infected with PRRSV and CSFV-C, was established. The effects of Chinese medicine on this co-infection model, as well as the effect of astragalus polysaccharide on the TLRs/NF-κB/TNF-α pathways, were investigated. Our results demonstrated that PAM39 cells inoculated with different pathogenic PRRSV significantly inhibited the replication of CSFV-C and up-regulated the major inflammatory mediators, including TNF-α. For the following studies, 50 µM of astragalus polysaccharide was selected from six kinds of representative Chinese medicine based on their cytotoxicity, viral titers, and inflammatory mediators. Further experiments indicated that astragalus polysaccharide could alleviate the inhibition of CSFV-C replication in the co-infection group with no influence on cell viability. In addition, astragalus polysaccharide treatment clearly reduced P65 phosphorylation and down-regulated the expression of TLR7, TLR9, and TNF-α in co-infection group, implying that the TLRs/NF-κB/TNF-α pathways may play an important role in astragalus polysaccharide's anti-inflammatory response. In conclusion, astragalus polysaccharide treatment alleviated PRRSV-mediated inhibition of CSFV-C replication via the TLRs/NF-κB/TNF-α pathways, and the molecular mechanism of PRRSV co-infection leading to the failure of CSFV vaccine immunization was partially elucidated, providing a scientific basis for effective CSF prevention and control in pig farms.

Applications of Chitosan and its Derivatives in Skin and Soft Tissue Diseases.

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.

Wool-Based Carbon Fiber/MoS2 Composite Prepared by Low-Temperature Catalytic Hydrothermal Method and Its Application in the Field of Gas Sensors.

Under the background of the Paris Agreement on reducing greenhouse gases, waste wools were converted into wool carbon fiber (WCF) and WCF-MoS2 composites by low-temperature catalytic hydrothermal carbonization. Their structures and gas-sensing performances were studied for the first time. Due to the existence of heterojunctions, the responses of the WCF-MoS2 composite to the five analytes were 3-400 times those of MoS2 and 2-11 times those of WCF. Interestingly, because of the N, P, and S elements contained in wools, the WCF prepared by the hydrothermal method was realized the doping of N, P, and S, which caused the sensing curves of WCF to have different shapes for different analytes. This characteristic was also well demonstrated by the WCF-MoS2 composite, which inspired us to realize the discriminative detection only by a single WCF-MoS2 sensor and image recognition technology. What's more, the WCF-MoS2 composite also showed a high sensitivity, a high selectivity, and a rapid response to NH3. The response time and the recovery time to 3 ppm NH3 were about 16 and 5 s, respectively. The detection of limit of WCF-MoS2 for NH3 was 19.1 ppb. This work provides a new idea for the development of sensors and the resource utilization of wool waste.

Corrigendum: Compounds purified from edible fungi fight against chronic inflammation through oxidative stress regulation.

[This corrects the article DOI: 10.3389/fphar.2022.974794.].

Capacity of endometrial thickness measurement to diagnose endometrial carcinoma in asymptomatic postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: Endometrial thickness (ET) is closely related to many gynecological symptoms. The measurement of ET is also an important tool for evaluating adverse symptoms such as bleeding in postmenopausal women. However, the significance of ET in asymptomatic women is still unclear. The purpose of this study was to determine the correlation between ET and the incidence of endometrial lesions in asymptomatic women after menopause, and to statistically analyze the correlation with a 5 mm cutoff value. METHODS: A systematic literature search was conducted in May 2021 to screen out articles that reported that ET measurement was used to diagnose endometrial carcinoma (EC), endometrial hyperplasia (EH), and endometrial polyps (EP) in asymptomatic postmenopausal women who did not use hormone replacement therapy (HRT). The endometrial membrane was set at 5 mm as the cut-off, and using 5 mm as the cut-off of the ET, the relationship between the thickness of the endometrium and the prevalence of EC, EH, and EP was evaluated. Relative risk (RR) and standardized mean difference (SMD) were extrapolated with 95% confidence interval (CI). RESULTS: After screening, 9 studies reported a total of 3,620 cases of asymptomatic postmenopausal women whose ET was measured. Among them, there were 1,758 cases of ET <5 mm, the probability of EC, EH, and EP were 0.284% (5/1,758), 0.398% (7/1,758), and 0.626% (11/1,758), respectively. In another 1,862 cases with ET ≥5 mm, the probabilities of EC, EH, and EP were 1.128% (21/1,862), 1.128% (21/1,862), and 1.557% (29/1,862), respectively. The results showed that ET can be used as a risk factor for predicting EC and other pathological changes. DISCUSSION: The results of this meta-analysis show that when the ET is greater than 5 mm, the incidence of EC, EH, and EP increases significantly. It is reasonable to use ET as a screening test for EC and EH in asymptomatic postmenopausal women.

Efficacy of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: There is a close relationship between cardiovascular risk factors and polycystic ovary syndrome (PCOS), and omega-3 fatty acids may have a key role in improving cardiovascular risk factors. We conducted the current systematic review and meta-analysis to evaluate the effect of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with PCOS. METHODS: We searched 4 databases including PubMed (MEDLINE), Cochrane Library, Embase, and Web of Science from inception to February 2021. We included randomized controlled trials (RCTs) that reported the effects of omega-3 fatty acid treatment for PCOS. According to the Cochrane system evaluation guide manual, 2 researchers independently assessed the methodological quality of the included studies. We pooled results using either a fixed effect model or random effect model. RESULTS: We identified 314 articles, of which 10 met the criteria for inclusion, involving 778 participants. The pooled results suggested an association between the supplementation of omega-3 fatty acids and a reduction in serum insulin [-2.58 pmol/L, 95% confidence interval (CI): -3.34 to -1.82 pmol/L, P<0.00001, I2=0], homeostatic model assessment of insulin resistance (HOMA-IR) (-0.57, 95% CI: -0.75 to -0.40 L, P<0.00001, I2=2%), serum total cholesterol (TC) (-6.87 mg/dL, 95% CI: -10.28 to -3.47 mg/dL, P<0.0001, I2=95%), serum triglyceride (-4.03 mg/dL, 95% CI: -5.53 to -2.52 mg/dL, P<0.00001, I2=97%), serum low-density lipoprotein cholesterol (LDL-C) (-6.64 mg/dL, 95% CI: -11.58 to -1.70 mg/dL, P=0.008, I2=99%), serum very low-density lipoprotein cholesterol (VLDL-C) (-3.29 mg/L, 95% CI: -6.54 to -0.05 mg/L, P=0.05, I2=72%), serum high-sensitivity C-reactive protein (hs-CRP) (-8.97mg/dL, 95% CI: -17.66 to -0.28 mg/dL, P=0.04, I2=99%), an improvement in serum high-density lipoprotein cholesterol (HDL-C) (2.94 mg/dL, 95% CI: 0.63 to 5.26 mg/dL, P=0.01, I2=87%), but no effect on serum glucose (-0.76 mg/dL, 95% CI: -1.71 to 0.19 mg/dL, P=0.12, I2=73%) was found. DISCUSSION: The current meta-analysis demonstrated that omega-3 fatty acid supplementation for women with PCOS resulted in a statistical improvement in insulin, HOMA-IR, TC, triglyceride, LDL-C, VLDL-C, and HDL-C, but did not affect serum glucose. The limitation of this paper is due to the lack of included research literature.

Chrysin Induced Cell Apoptosis and Inhibited Invasion Through Regulation of TET1 Expression in Gastric Cancer Cells.

OBJECTIVE: Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells. MATERIALS AND METHODS: Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo. RESULTS: qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo. CONCLUSION: This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.

Targeted point mutations of the m6A modification in miR675 using RNA-guided base editing induce cell apoptosis.

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.

microRNA-670 modulates Igf2bp1 expression to regulate RNA methylation in parthenogenetic mouse embryonic development.

Aberrant epigenetic modification, including N6-methylation of adenosine (m6A), has been frequently reported in embryos derived from parthenogenetic activation (PA). However, the role of Igf2bp1 expression pattern in m6A modification and the mechanism through which Igf2bp1 function is regulated in PA embryos remains elusive. Therefore, in this study, using si-Igf2bp1 and betaine (N,N,N-trimethylglycine, a major methyl donor), we investigated the effect of Igf2bp1 expression in m6A modification on the development of PA embryos. The results indicated that the down-regulation of Igf2bp1 reduced the cleavage and blastula rates of PA embryos. Moreover, m6A expression level was markedly down-regulated following microinjection with si-Igf2bp1. However, the treatment with betaine could significantly restore the m6A level. Further bioinformatics analysis revealed Igf2bp1 as the putative target of microRNA 670 (miR-670). Thus, to confirm this finding, mimics and inhibitor of miR-670 were microinjected into PA embryos. The results demonstrated that miR-670 inhibitor augmented the expression of Igf2bp1 and rescued cleavage and blastula rates. In addition, the miR-670 inhibitor promoted the m6A expression level. TUNEL assay revealed a loss of expression of Igf2bp1 induced cell apoptosis in PA embryos. Taken together, these results demonstrated that miR-670-3p functions as the regulator of Igf2bp1 expression and plays a crucial role in PA development through m6A modification.

Survey of Traveler's Diarrhea: Epidemiology and Testing Reveal the Source.

OBJECTIVE: To understand the causes and transmission routes of, as well as risk factors, for a Salmonella outbreak in a tour group. METHOD: A retrospective cohort design was used to conduct an epidemiological field investigation. Real-time fluorescent quantitative PCR, bacterial culture, and serological identification methods were used for pathogen detection and identification. RESULT: There were 7 cases of illness, and the attack rate was 46.67%. The onset date was concentrated on May 9 and 10. All cases were found in the tour group, and no cases occurred in the nontour group. The results of this retrospective cohort study showed that the consumption of boiled eggs for breakfast on May 9 was a common factor (R 2 = 6.67, P=0.023). Salmonella enteritidis was identified from the patients' stool and vomit. CONCLUSION: The food poisoning epidemic was caused by Salmonella enteritidis. In the summer and autumn, attention should be paid to preservation, processing, and cooking of food to avoid bacterial contamination. To prevent sickness, travelers should know the disease prevalence at their destinations in advance.

Dominant serotype distribution and antimicrobial resistance profile of Shigella spp. in Xinjiang, China.

Shigella represents one of the major diarrhea-inducing pathogens threatening public health, but its prevalence and antimicrobial resistance profile in Xinjiang Uygur Autonomous region, China, remains unclear. We conducted comprehensive investigation of Shigella serotype distribution and antimicrobial resistance pattern in Xinjiang, identifying 458 Shigella isolates between 2008 to 2014. Shigella flexneri was identified as predominant species, and several S. flexneri serotypes were isolated, including atypical serotypes 1c, 2c, and 4s. Dominant S. flexneri serotypes were 2a, 1b, 2b, and Xv, different from those generally dominant in China. A hybrid serotype pattern was observed, which included the major Chinese serotypes (2a, Xv) and those predominant in Pakistan (1b, 2b). Shigella sonnei was shown to have a lower frequency compared with that generally observed in China, but an increasing trend of infections associated with this pathogen was observed. Furthermore, a high frequency of drug resistance and different Shigella antimicrobial resistance patterns were demonstrated as well, including very severe resistance phenotypes, such as multidrug resistance and resistance to frontline antibiotics. Seventy-five cephalosporin-resistant Shigella isolates were frequently identified with the resistance determinants that can undergo horizontal transfer, such as blaOXA, blaTEM, blaCTX-M, and integrons, facilitating the development of cephalosporin resistance among Shigella subtypes. Additionally, genetic analyses demonstrated that all 86 quinolone-resistant S. flexneri isolates possess 3-4 mutation sites in quinolone resistance-determining regions, primarily contributing to their resistance to quinolone. However, S. sonnei isolates were not shown to be quinolone resistant. Co-resistance to cephalosporins and quinolones was detected in 17 S. flexneri isolates, and these isolates were additionally multidrug resistant and carried ß-lactamase genes and quinolone-resistance determinants. As is demonstrated in this study, dominant serotypes of Shigella were distributed in unique trend with dangerous drug resistance patterns. Novel strategies are urgently required to prevent the development of drug resistance among diarrhea-inducing pathogens.