Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Article Title: CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

doi: 10.1002/jor.26006

Figure Lengend Snippet: FIGURE 1 Macroscopic, histological and micro‐CT analysis of Achilles tendon chondrification/ossification. (A) A mouse Achilles tendon rupture model and administration of CD1530. (B) Macroscopic view of mouse Achilles tendon in Control or CD1530 group at 4 weeks after transection (black line and arrow indicates plantaris tendon, red dot line and arrow indicates Achilles tendon). (C) Histological analysis of chondrification with Saf‐O staining and (E) IHC for Type 2 collagen and evaluated with (D) chondrification scoring system (n = 20) and (F) Type 2 collagen‐positive area (n = 20) quantified by ImageJ. The black line indicates the plantaris tendon, the yellow line indicates a mature tendon, and the red dot line indicates a healing tendon. (G) Micro‐CT 3D imaging and quantitative analysis of the Achilles tendon from Control and CD1530 group mice at post injury 5 weeks (n = 10). The data are represented as mean. Comparisons of mean values were performed using paired t‐test. *p < 0.05, **p < 0.01, and ***p < 0.001 versus Control. Scale bars: 500 and 200 µm.

Article Snippet: After the longitudinal skin incision, a complete transverse incision was made at the midpoint of both Achilles tendons with scissors.18 Twenty microliters of suspension with CD1530 (Tocris, 107430‐66‐0, 10μg) and DMSO/PBS (Control) were injected into the gap between transected tendons starting from day 3 after transection and thereafter injected three times a week for 3 weeks (Figure 1A).

Techniques: Micro-CT, Control, Staining, Imaging

Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Article Title: CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

doi: 10.1002/jor.26006

Figure Lengend Snippet: FIGURE 2 Histological analysis of Achilles tendon healing. (A) H.E staining, (B) MT staining, and (C) Picro‐Sirius Red (PSR) staining on Achilles tendon rupture model. (D) Healing scores were significantly increased in CD1530 treatment group compared with Control group (n = 20). The black line (white line in PSR) indicates plantaris tendon, the yellow line indicates a mature tendon, and the red dot line indicates a healing tendon. The data are represented as mean. Comparisons of mean values were performed using paired t‐test. *p < 0.05, **p < 0.01, and ***p < 0.001 versus Control. Scale bars: 500 and 200 µm.

Article Snippet: After the longitudinal skin incision, a complete transverse incision was made at the midpoint of both Achilles tendons with scissors.18 Twenty microliters of suspension with CD1530 (Tocris, 107430‐66‐0, 10μg) and DMSO/PBS (Control) were injected into the gap between transected tendons starting from day 3 after transection and thereafter injected three times a week for 3 weeks (Figure 1A).

Techniques: Staining, Control

Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Article Title: CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

doi: 10.1002/jor.26006

Figure Lengend Snippet: FIGURE 3 Lineage tracing of Scx+ cells in Achilles tendon rupture model. (A) Pre‐injury labeled ScxCreERT‐tdTomato mouse model. TMX was injected once in 3 different days 1 week before Achilles tendon transection. (B) Labeled tdT+ (Scx+) cells at 4 weeks after transection (n = 5, yellow dot line indicates mature tendon, and white dot line indicates healing tendon). (C) Scx+ (tdTomato+) cells in the chondrification site which is expressed by SOX9 (n = 5, white dot line indicates chondrification area). (D) Post‐injury labeled ScxCreERT2‐tdTomato mouse model. TMX was injected 3 weeks after Achilles tendon transection. (E) Scx+ cells labeled at 3 weeks post‐injury in Control, and CD1530 group at 4 weeks after transection (orange dot line indicates chondrification site and blue dot line indicates healing site). (F) Percentage of SOX9+ cells and tdT+ cells in chondrification sites and healing sites between Control and CD1530 group (n = 5, white arrows indicate chondrification area and the yellow arrow indicates ossification area). The data are represented as mean ± S.E. Comparison of mean values was performed using paired t‐test. ns = not significant, and *p < 0.05 versus Control. Scale bars: 500 and 100 µm.

Article Snippet: After the longitudinal skin incision, a complete transverse incision was made at the midpoint of both Achilles tendons with scissors.18 Twenty microliters of suspension with CD1530 (Tocris, 107430‐66‐0, 10μg) and DMSO/PBS (Control) were injected into the gap between transected tendons starting from day 3 after transection and thereafter injected three times a week for 3 weeks (Figure 1A).

Techniques: Labeling, Injection, Control, Comparison

Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Article Title: CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

doi: 10.1002/jor.26006

Figure Lengend Snippet: FIGURE 5 Cellular response to CD1530 in injured Achilles tendon‐derived tendon fibroblasts (iATF). iAT were treated with CD1530 (10, 100, and 1000 nM). (A) Proliferation of iATF for 48 h (n = 3 each group). (B) Migration capacity of iATF by scratch assay at 24 h (n = 5 each group, scale bars: 500 µm). (C) Expression of Il‐6 and Ccl2 in iATF with CD1530 under inflammatory conditions (10 ng/mL of IL‐1β for 24 h, n = 5 each group). These data are represented as mean ± S.E. Comparison of mean values was performed using repeated measures one‐way ANOVA with Dunnet's multiple comparisons test. *p < 0.05, **p < 0.01, and ***p < 0.001 versus Control.

Article Snippet: After the longitudinal skin incision, a complete transverse incision was made at the midpoint of both Achilles tendons with scissors.18 Twenty microliters of suspension with CD1530 (Tocris, 107430‐66‐0, 10μg) and DMSO/PBS (Control) were injected into the gap between transected tendons starting from day 3 after transection and thereafter injected three times a week for 3 weeks (Figure 1A).

Techniques: Derivative Assay, Migration, Wound Healing Assay, Expressing, Comparison, Control

Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Article Title: CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

doi: 10.1002/jor.26006

Figure Lengend Snippet: FIGURE 6 Effect of CD1530 on chondrogenic differentiation of injured Achilles tendon‐derived tendon fibroblasts (iATF). (A) Macro‐view and Saf‐O staining of pellet (chondrogenic induction of iATF for 3 weeks, scale bars: 500 and 50 µm). (B) Expression of chondrogenic marker genes (n = 5 each group). The data are represented as mean ± S.E. Comparison of mean values was performed using Repeated measures one‐way ANOVA with Dunnet's multiple comparisons test. *p < 0.05, **p < 0.01, and ***p < 0.001 versus Control.

Article Snippet: After the longitudinal skin incision, a complete transverse incision was made at the midpoint of both Achilles tendons with scissors.18 Twenty microliters of suspension with CD1530 (Tocris, 107430‐66‐0, 10μg) and DMSO/PBS (Control) were injected into the gap between transected tendons starting from day 3 after transection and thereafter injected three times a week for 3 weeks (Figure 1A).

Techniques: Derivative Assay, Staining, Expressing, Marker, Comparison, Control

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 1. Fasting blood glucose levels in different experimental rats. 1 week re- presented the day after STZ injection. 4–12weeks represented after different treatment; data are presented as mean ± SD, n = 6/group; *: P < 0.05, for T2DM vs. other four groups, #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Injection

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 2. Double fluorescent labeling of the femur in different experimental rats. (A) Control group; (B) T2DM group; (C) DM-Cinaciguat group; (D) DM-Insulin group and (E) DM-Cinaciguat + Insulin group, n = 3/group.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Labeling, Control

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 3. Concentration of plasma cGMP after 3-month treatment. Data are pre- sented as mean ± SD, n = 6/group; *: P < 0.05, for T2DM vs. other four groups. #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Concentration Assay, Clinical Proteomics

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 4. Results of biomechanical pull-out test after 3-month treatment. Data are presented as mean ± SD, n = 3/group; *: P < 0.05, for T2DM vs. other four groups. #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques:

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 5. Transverse three-dimensional images of femur implants (A) and quantitative analysis of the micro-CT evaluation of (B) BV/TV, (C) %OI and (D) Tb.N. Data are presented as mean ± SD, n = 3/group; *: P < 0.05, for T2DM vs. other four groups, #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Micro-CT

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 6. ESEM images of the bone ultramicro structure on the implant surface in (A, F) Control group; (B, G) T2DM group; (C, H) DM-Cinaciguat group; (D, I) DM- Insulin group; (E, J) DM-Cinaciguat + Insulin group; The magnifications of upper and lower images are x500 and x1000 respectively; IM represented an implant.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Control

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 7. Hard tissue slicing analysis of implant osseointegration. The methylene blue-acid fuchsin staining images (A) displayed bone microarchitecture at bone- implant interface: the upper column showed images through the longitudinal section of implants, and the lower column exhibited images through the cross section of implants; BIC ratio (B) was demonstrated in the right histogram. Data are presented as mean ± SD, n = 3 /group; *: P < 0.05, for T2DM vs. other four groups, #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups. IM represented an implant.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Staining

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 8. The photomicrograph of HE (upper) and modified Masson (lower) staining in (A, F) Control group; (B, G) T2DM group; (C, H) DM-Cinaciguat group; (D, I) DM-Insulin group; (E, J) DM-Cinaciguat + Insulin group; IM represented an implant.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Staining, Control

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

doi: 10.1016/j.biopha.2019.109216

Figure Lengend Snippet: Fig. 9. Expression of PKG II and PDE5 protein in the peri-implant bone area after 3-month treatment. Immunohistochemical images for PKG II (A) and PDE5 (C): the magnifications of upper and lower images are x20 and x40 respectively; Quantitative analysis of mean integral optical density (IOD) for PKG II (B) and PDE5 (D). Data are presented as mean ± SD, n = 3 /group; *: P < 0.05, for T2DM vs. other four groups, #: P < 0.05, for DM-Cinaciguat + Insulin vs. other four groups. IM represented an implant.

Article Snippet: Three days after surgery, the DM-Insulin rats were treated daily with Neutral Protamine Harguerdon insulin (12 IU/kg, Novolin, Denmark) subcutaneously [24] and DM-Cinaciguat rats received intraperitoneal injection with cinaciguat (MedChemExpress, USA, the purity is 99.40%), which were dissolved in dimethyl sulfoxide (DMSO) and diluted in 0.9% NaCl to a final concentration of 0.1% DMSO, at a dose of 7 μg/kg six days per week during the whole experiment.

Techniques: Expressing, Immunohistochemical staining

Journal: Cellular and Molecular Immunology

Article Title: Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming

doi: 10.1038/s41423-025-01268-9

Figure Lengend Snippet: The FDA-approved drug bexarotene inhibits M1 macrophage polarization and alleviates arthritis in CIA model mice. A Workflow of the molecular docking and virtual screening analyses. B Molecular docking of bexarotene to Pim2 and the bonds between bexarotene and Pim2. C Pim2 (2IWI or 4X7Q) interacting with bexarotene at the beginning and end of 40-ns molecular dynamics simulations. D , E The RMSD and potential energy plot indicating the interaction between Pim2 and bexarotene (PDB 2IWI). F , G The RMSD and potential energy plot indicating the interaction between Pim2 and bexarotene (PDB ID: 4X7Q). H , I MFIs of HLA-DR and CD206 in CD68+ hMDMs treated with or without bexarotene (200 or 400 nM) after M1/M2 induction, as detected by flow cytometry ( n = 3). J Schematic of CIA model mice treated orally with bexarotene (25 or 50 mg/kg). K CIA scores and hind paw thickness of the mice in each group ( n = 6). L Macroscopic images, micro-CT, H&E, and safranin O staining of the ankles from the mice in each group ( n = 6). M The expression of TNF-α, IL-1β, IL-6 and IL-10 in mice from each group after CIA induction, as detected by IHC. N The expression of iNOS and Arg-1 in the synovial macrophages of the mice in each group, as detected by immunofluorescence staining (F4/80, green; iNOS, red; Arg-1, red)

Article Snippet: For the treatment of CIA, DBA/1 mice were treated orally with either 1 mg/mL HJ-PI01 (MCE, #HY-129163), formulated with 0.5% methylcellulose in water, or 1 mg/mL bexarotene (Selleck, #S2098), which contains 0.5% methylcellulose in water.

Techniques: Flow Cytometry, Micro-CT, Staining, Expressing, Immunofluorescence