Advances in the role and mechanism of fibroblasts in fracture healing.

With the development of social population ageing, bone fracture has become a global public health problem due to its high morbidity, disability and mortality. Fracture healing is a complex phenomenon involving the coordinated participation of immigration, differentiation and proliferation of inflammatory cells, angioblasts, fibroblasts, chondroblasts and osteoblasts which synthesize and release bioactive substances of extracellular matrix components, Mortality caused by age-related bone fractures or osteoporosis is steadily increasing worldwide as the population ages. Fibroblasts play an important role in the process of fracture healing. However, it is not clear how the growth factors and extracellular matrix stiffness of the bone-regeneration microenvironment affects the function of osteoblasts and fibroblasts in healing process. Therefore, this article focuses on the role of fibroblasts in the process of fracture healing and mechanisms of research progress.

Corrigendum: The therapeutic efficacy of adipose tissue-derived mesenchymal stem cell conditioned medium on experimental colitis was improved by the serum from colitis rats.

[This corrects the article DOI: 10.3389/fbioe.2021.694908.].

The intriguing roles of Siglec family members in the tumor microenvironment.

Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.

Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis.

Background: Siglec-15 is expressed in a variety of cancers. However, the role of Siglec-15 in the prognosis of cancer patients remains controversial. Therefore, we conducted a meta-analysis to clarify the potential prognostic value of Siglec-15 in solid tumors. Methods: The PubMed, Web of Science, Embase and CNKI databases were comprehensively searched to identify studies assessing the effect of Siglec-15 on the survival of cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) from individual studies were evaluated. Results: The data from 13 observational studies consisting of 1376 patients were summarized. Elevated baseline Siglec-15 expression was significantly correlated with poor OS (pooled HR = 1.28, 95% CI: 1.05-1.56; P = 0.013). However, high Siglec-15 expression predicted a significantly better DSS (pooled HR = 0.73 (95% CI: 0.57-0.94; P = 0.015) but not PFS (pooled HR = 1.49, 95% CI: 0.46-4.87; P=0.510). In addition, high Siglec-15 expression was not associated with PD-L1 (OR=0.64, 95% CI: 0.42-0.95; P = 0.028). High Siglec-15 expression was associated with male sex (OR = 1.39, 95% CI: 1.05-1.84; P = 0.022), larger tumor size (OR = 1.896, 95% CI: 1.26-2.9; P = 0.002), and advanced tumor-node-metastasis (TNM) stage (OR = 1.84; 95% CI: 1.19-2.84; P =0.006) in solid tumors. Conclusions: This updated study suggested the expression of Siglec-15 is significantly associated with poor outcomes in human solid tumors, but further studies are needed to determine the prognostic value of Siglec-15 in solid tumors.

The Therapeutic Efficacy of Adipose Tissue-Derived Mesenchymal Stem Cell Conditioned Medium on Experimental Colitis Was Improved by the Serum From Colitis Rats.

Adipose derived mesenchymal stem cells (AD-MSCs) have shown therapeutic potential in treatments of inflammatory bowel disease (IBD). Due to the harsh host environment and poor survival of the cells, controversy concerning the homing, proliferation and differentiation of MSCs in lesion tissue still remains. It has been reported that conditioned media from MSCs could improve the colitis, whereas the therapeutic efficiency could be significantly elevated by the stimulation of pro-cytokines. In this study, we pre-treated the adipose derived MSCs with the serum from colitis rats and then the activated conditioned media (CM-AcMSC) were collected. To compare the therapeutic effects of CM-MSC and CM-AcMSC on IBD, we constructed dextran sodium sulphate (DSS)-induced colitis rat models. The colitis was induced in rats by administrating 5% DSS in drinking water for 10 days, and the disease symptoms were recorded daily. The colon histopathological changes were observed by different staining methods (H&E and PAS). The expression levels of MUC2 and tight junctions (TJs) were determined by RT-qPCR. The levels of inflammatory cytokines were analyzed by ELISA and western blot analysis. Our findings suggested that CM-AcMSC was more effective in ameliorating the clinical features and histological damage scores. Treatment with CM-AcMSC significantly increased the expression of MUC2 and TJs and suppressed the production of pro-inflammatory cytokines in colonic tissues of colitis rats. The inhibitory effects of CM-AcMSC on inflammatory responses of colitis rats were mediated by NF-κB signaling pathway. These results suggested that pre-activation of MSCs with serum from colitis rats could promote the production of paracrine factors and improve the therapeutic effects of conditioned medium on colitis rats.

Blood transfusion practices affect CD4+ CD25+ FOXP3+ regulatory T cells/T helper-17 cells and the clinical outcome of geriatric patients with hip fracture.

Hip fracture (HF) is common among older individuals and associated with high mortality, poor vitality and functional impairment. HF patients suffer whole body immunological changes and that lead to severe consequences, including immobilization, physical impairment and a high risk of complications. The objective of this study was to decipher the pattern of dynamic immunological changes, especially in two major T cell subsets, CD4+ CD25+ FOXP3+ regulatory T (Treg) cells and T helper-17 (Th17) cells, and their balance, during the hospital stay and to observe whether blood transfusion could influence these cells and clinical patietns' prognosis. In this study, ninety-eight consecutive HF patients were initially enrolled, and finally fifty-one patients qualified for the study, and correlation analysis of their clinical parameters was carried out to predict the meaning of their distribution in clinical practice. Our results showed that the frequency of Tregs gradually decreased, while the frequency of Th17 cells slowly increased in HF patients who received blood transfusion. The Treg frequency was inversely correlated with the level of hemoglobin (Hb), and Th17 cell frequency was positively related to fluctuations in Hb levels in HF patients after trauma. HF patients with a better prognosis and survival time showed decreased a Treg frequency and a decreased Treg/Th17 ratio. Transfusion helped reverse the imbalance in the frequencies of Tregs and Th17 cells and the Treg/Th17 ratio and especially contributed to a better outcome in HF patients with moderate-to-severe anemia. In conclusion, a higher frequency of peripheral blood Tregs and a higher Treg/Th17 ratio may be associated with unfavorable outcomes in HF patients, and blood transfusion may benefit moderate-to-severe HF patients rebalance their immune response.

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway.

Recurrence and metastasis are important features of osteosarcoma (OS) that cause its poor prognosis. Aberrant expression of Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been reported in various kinds of cancers. However, the expression and function of Siglec-15 in OS remain unclear. In cultured OS cells (143B cells and MNNG/HOS cells) and their xenograft mouse models, we found that downregulation of Siglec-15 could inhibit the proliferation, migration and invasion of by inducing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Conversely, Siglec-15 overexpression promoted the growth, migration and invasion of OS cells in a significant manner. Then, we screened a number of differentially expressed genes (DEGs) between Siglec-15-knockdown group and control group by RNA-Seq assay. Among these DEGs, we found that dual-specificity phosphatase 1 (DUSP1/MKP1) was significantly downregulated after Siglec-15 silencing. We investigated the DUSP1 functions in influencing OS cells' biology, and found that the proliferation, migration and invasion of OS cells were promoted by overexpressing DUSP1 and crucially, the proliferation, migration and invasion of Siglec-15-knockdown OS cells were rescued by overexpressing DUSP1. Mechanically, we further showed that DUSP1-mediated inhibition of p38/MAPK and JNK/MAPK expression was attenuated when Siglec-15 expression was inhibited, suggesting that Siglec-15 promotes the malignant progression of OS cells by suppressing DUSP1-mediated suppression of the MAPK pathway. Moreover, we showed that both Siglec-15 and DUSP1 were highly expressed in human OS tissues by immunohistochemistry. High Siglec-15 expression was associated with OS lung metastasis, and high DUSP1 expression was associated with the high Enneking stage. Kaplan-Meier analysis indicated that high expression of Siglec-15 could predict poor prognosis of OS patients. Altogether, these results showed that Siglec-15 expression promoted OS development and progression by activating DUSP1 and might be a novel target in OS treatment.

The Updated Status and Future Direction of Immunotherapy Targeting B7-H1/PD-1 in Osteosarcoma.

Although the mortality rate of osteosarcoma (OS) patients has improved, there are still many unsolved problems concerning how to reduce recurrence and metastasis. In the tumor microenvironment, immune escape plays a more important role in tumor progression and development. Many costimulatory molecules of the B7 family have been reported to be involved in regulating immunological interactions between OS cells and immune cells. Among these molecules, B7-H1 and its receptor, programmed death-1 (PD-1), have been the focus of the fields of tumor immunology and have been recently applied in clinical trials of therapies for several solid tumors. These therapies, referred to as B7-H1/PD-1 checkpoint blockade therapies, are designed to block the interaction between the two molecules. Although the mechanism has been reported in some malignancies, the specific impact of B7-H1/PD-1 expression on OS has not been well defined. Here, we review the expression, function, and regulatory mechanism of the B7-H1/PD-1 axis in OS and introduce and compare the advantages and disadvantages of B7-H1/PD-1 immunotherapies in OS.

The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC.

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC.

[Culture and Application of Entamoeba invadens Trophozoites from Snake].

The trophozoites of Entamoeba invadens from snake were seeded in liquid medium, incubated at 22 ℃ under constant temperature, and transferred weekly. The liquid medium which contained a large number of trophozoites was used for preparation of samples for microscopic observation. The cultured trophozoites of snake E. invadens displayed similar morphological changes, movement patterns, reproductive cycle and invasiveness with human E. histolytica. Therefore, the snake E. invadens trophozoites can be used as an alternative to the human E. histolytica trophozoites to facilitate students' observation of living amoeba trophozoites.

[Program optimization in the stage treatment of periarthritis of shoulder with acupuncture, moxibustion and positive functional exercise].

OBJECTIVE: To optimize the therapeutic programs for periarthritis of shoulder treated with acupuncture, moxibustion and kinetohterapy with orthogonal design method adopted. METHODS: The orthogonal design table of L8 (2(7)) hierarchical principle was used to randomly divide 192 patients of periarthritis of shoulder into 8 groups, 24 cases in each one. Separately, 4 factors and each different 2 levels were adopted in treatment, named acupuncture timing (factor A: A, acute stage, A2 adhesion stage), acupoint combination (factor B: B, local acupoints, B2 local acupoints and distal acupoints along meridians), filiform needling and warm needling therapy (factor C: C1 acupuncture with filiform needle, CZ acupuncture with filiform needle and warm needling therapy) and positive functional exercise (factor D: D1 without positive functional exercise, D2 with positive functional exercise). The treatment was given once a day, 10 treatments made one session and 2 sessions were required totally. The time points of observation were the point after 1 session of treatment and after 2 sessions of treatment. The short-form McGill pain questionnaire (MPQ) and shoulder joint motor disturbance score were adopted for evaluation. RESULTS: In the orthogonal design analysis, taking the hierarchical factors into consideration, the age was considered as the main factor in the evaluation of shoulder pain and shoulder motor disturbance (P<0.01), and the shoulder function grade apparently impacted pain evaluation and the efficacy on shoulder motor disturbance (P<0.01). The best combination of 4 factors and 2 levels were A1B1CzD2 and A2BC2D2. SAS statistical analysis showed that at acute stage and adhesion stage, CZ Dz , meaning acupuncture with fifiform needling and warm needling therapy combined with positive functional exercise, is the main factor of the improvements of shoulder motor function (P<0.05). CONCLUSION: For periarthritis of shoulder at acute stage, the combined therapy of acupuncture at local acupoints, warm needling and positive functional exercise is adopted. At chronic stage, the combined therapy of acupuncture at local acupoints and distal acupoints, acupuncture with filiform needle and warm needling and positive functional exercise is the best program. Additionally, in clinical treatment, the patients' age, sex, shoulder joint function and duration of treatment should be considered comprehensively for the impacts on the efficacy.

[Biological characteristics of calliphoridae and its application in forensic medicine].

Diptera Calliphoridae is the first major kind of flies that appears on the decomposed corpses. In forensic entomology, according to the living characteristics of Calliphoridae flies, we could accurately estimate postmortem interval (PMI) in a murder or unidentified case and could provide useful clues to solve the case. This paper introduces the characteristics of the biology and morphology of Diptera Calliphoridae, and reviews the combined application of forensic entomology, molecular biology, mathematical morphology and toxicology.

Influence of masticatory fatigue on the fracture resistance of the pulpless teeth restored with quartz-fiber post-core and crown.

To investigate whether masticatory fatigue affects the fracture resistance and pattern of lower premolars restored with quartz-fiber post-core and full crown, 44 single rooted lower premolars recently extracted from orthodontic patients were divided into two groups of 22 each. The crowns of all teeth were removed and endodontically treated and then restored with quartz-fiber post-core and full crown. Twenty-two teeth in one group were selected randomly and circularly loaded at 45° to the long axis of the teeth of 127.4 N at a 6 Hz frequency, and the other group was not delivered to cyclic loading and considered as control. Subsequently, all teeth in two groups were continually loaded to fail at 45° to the long axis of the teeth at a crosshead speed of 1 mm⋅min(-1). The mean destructive force values were (733.88±254.99) and (869.14±280.26) N for the experimental and the control group, respectively, and no statistically significant differences were found between two groups (P>0.05). Bevel fracture and horizontal fracture in the neck of root were the major fracture mode of the specimens. Under the circumstances of this study, it seems that cyclic loading does not affect the fracture strength and pattern of the quartz-fiber post-core-crown complex.

[Prevention of hospital-acquired pneumonia with Yupingfeng Powder in patients with acute cerebral vascular diseases: a randomized controlled trial].

BACKGROUND: An increase in the incidence rate of hospital-acquired pneumonia (HAP) has a direct influence on prognosis and survival of patients with acute cerebral vascular diseases (ACVD), and how to prevent HAP is a growing concern to clinicians. OBJECTIVE: To study the efficacy of Yupingfeng Powder, a compound traditional Chinese herbal medicine, in preventing HAP in patients with ACVD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty ACVD patients with lung qi deficiency syndrome without concurrent infections were randomly divided into prevention group (28 cases) and control group (32 cases). The 60 cases were all from Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Tough measures were taken to prevent cross-infection based on treatment of the primary diseases, well nutrition and support therapy. Yupingfeng Powder was used in the prevention group to prevent HAP. The patients were treated for 10 days. MAIN OUTCOME MEASURES: The clinical symptoms, physical signs, body temperature, and chest X-ray were observed. The changes of blood immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and interleukin-6 (IL-6) were detected before and after treatment. RESULTS: The total response rate in the prevention group was higher than that in the control group (P<0.05), and the total response rates were 78.57% (22/28) and 31.25% (10/32) respectively. The incidence rate of HAP in the prevention group was lower than that in the control group. There were no significant differences in white blood cell count, neutrophilic granulocyte count, and the levels of IgA, IgG, IgM and IL-6 between the two groups before treatment. The white blood cell count and neutrophilic granulocyte count in the control group increased after treatment, and there was a significant difference between the two groups (P<0.05). There was no significant difference in IgA level in the two groups after treatment, and the IgM levels in the two groups were higher than those before treatment (P<0.05), however there was no significant difference in IgM level between the two groups. In the prevention group, there were significant differences in values of IgG and IL-6 between before and after treatment (P<0.01), and after treatment there were differences in values of IgG and IL-6 between the two groups (P<0.05). CONCLUSION: Yupingfeng Powder has a good clinical effect in prevention of HAP in patients with ACVD, and it can improve the immunological function and relieve the lung qi deficiency symptoms. So the prevention effect of Yupingfeng Powder on HAP is worth being further investigated.

Curcumin suppresses PPARdelta expression and related genes in HT-29 cells.

AIM: To investigate the effects of curcumin on the expression of peroxisome proliferator-activated receptordelta (PPARdelta) and related genes in HT-29 cells. METHODS: HT-29 cells were treated with curcumin (0-80 micromol/L) for 24 h. The effects of curcumin on the morphology of HT-29 cells were studied by Hoechst 33342 staining. The activity of caspase-3 was determined using DEVD-pNA as substrate. The levels of peroxisome PPARdelta, 14-3-3epsilon and vascular endothelial growth factor (VEGF) in HT-29 cells were determined by Western blotting analysis and their mRNA expression was determined by real-time quantitative RT-PCR. RESULTS: Treatment with 10-80 micromol/L curcumin induced typical features of apoptosis and activated the caspase-3 in HT-29 cells. The expression of PPARdelta, 14-3-3epsilon and VEGF was reduced and the activity of beta-catenin/Tcf-4 signaling was inhibited by curcumin treatment. CONCLUSION: Curcumin can induce apoptosis of HT-29 cells and down-regulate the expression of PPARdelta, 14-3-3epsilon and VEGF in HT-29.

Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells.

OBJECTIVE: To investigate the effects of curcumin on release of cytochrome c and expressions of Bcl-2, Bax, Bad, Bcl-xL, caspase-3, poly ADP-ribose polymerase (PARP), and survivin of HT-29 cells. METHODS: HT-29 cells were treated with curcumin (0 approximately 80 micromol/L) for 24 h. The release of cytochrome c from the mitochondria and the apoptosis-related proteins Bax, Bcl-2, Bcl-xL, Bad, caspase-3, PARP, and survivin were determined by Western blot analysis and their mRNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Curcumin significantly induced the growth inhibition and apoptosis of HT-29 cells. A decrease in expressions of Bcl-2, Bcl-xL and survivin was observed after exposure to 10 approximately 80 micromol/L curcumin, while the levels of Bax and Bad increased in the curcumin-treated cells. Curcumin also induced the release of cytochrome c, the activation of caspase-3, and the cleavage of PARP in a dose-dependent manner. CONCLUSION: These data suggest that curcumin induced the HT-29 cell apoptosis possibly via the mitochondria-mediated pathway.

The organization and rate of evolution of wheat genomes are correlated with recombination rates along chromosome arms.

Genes detected by wheat expressed sequence tags (ESTs) were mapped into chromosome bins delineated by breakpoints of 159 overlapping deletions. These data were used to assess the organizational and evolutionary aspects of wheat genomes. Relative gene density and recombination rate increased with the relative distance of a bin from the centromere. Single-gene loci present once in the wheat genomes were found predominantly in the proximal, low-recombination regions, while multigene loci tended to be more frequent in distal, high-recombination regions. One-quarter of all gene motifs within wheat genomes were represented by two or more duplicated loci (paralogous sets). For 40 such sets, ancestral loci and loci derived from them by duplication were identified. Loci derived by duplication were most frequently located in distal, high-recombination chromosome regions whereas ancestral loci were most frequently located proximal to them. It is suggested that recombination has played a central role in the evolution of wheat genome structure and that gradients of recombination rates along chromosome arms promote more rapid rates of genome evolution in distal, high-recombination regions than in proximal, low-recombination regions.