Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Objective:To explore the effects of age and gender on the sagittal spinal-pelvic parameters during the natural aging process of healthy adults.Methods:A total of 647 Chinese healthy adults who underwent health check-ups at the Second Affiliated Hospital of Zhejiang University School of Medicine and Songyang County People's Hospital, from January 2017 to September 2024 were collected. There were 277 males and 370 females, aged 18-93 years. Anteroposterior and lateral X-ray films of the whole spine were taken to evaluate the spinal-pelvic sagittal morphology. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis(LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), global tilt (GT), T 1-pelvic angle (TPA), sagittal vertical axis (SVA), thoracic Cobb angle (T-Cobb), lower end vertebra of thoracic Cobb angle (T-LEV), apex vertebra of thoracic Cobb angle (T-Apex), lumbar Cobb angle (L-Cobb). Compare the differences in spine-pelvis parameters among patients of different genders and age groups (in this study, the subjects were subdivided into the 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years groups according to the age range). Results:The results showed that GT, SVA, TPA, and PT increased with age ( P<0.05). For males aged 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years, PT values were 8.58°±6.47°, 9.60°±5.63°, 12.65°±7.13°, 11.00°±6.99°, 13.01°±8.63°, 15.77°±8.02°, and 18.47°±10.03° respectively; for females in the same age groups, the PT values were 8.44°±6.83°, 9.00°±6.44°, 11.84°±7.35°, 12.07°±7.51°, 15.44°±9.39°, 19.26°±8.28°, and 18.17°±9.43° respectively. For males in these age groups, the global tilt (GT) values were 6.37°±7.20°, 8.77°±6.51°, 10.38°±9.07°, 8.80°±7.49°, 10.80°±8.62°, 16.07°±10.42°, and 21.99°±12.65° respectively; for females, the GT values were 4.46°±8.09°, 5.96°±7.83°, 8.17°±6.88°, 9.41°±8.03°, 9.96°±1.39°, 17.89°±9.39°, and 19.55°±12.34° respectively. The sagittal vertical axis (SVA) values for males in the age groups were -7.94±25.57 mm, -2.98±25.69 mm, -4.63±20.90 mm, -6.43±32.81 mm, 7.85±43.39 mm, 36.49±53.89 mm, and 55.57±51.10 mm respectively; for females, they were -24.12±31.35 mm, -17.49±25.12 mm, -17.88±22.72 mm, -8.25±30.91 mm, 8.80±27.45 mm, 28.67±38.22 mm, and 23.23±35.19 mm respectively. For males, the thoracic pelvic angle (TPA) values across the age groups were 4.46°±5.94°, 6.05°±5.38°, 9.58°±9.35°, 7.52°±7.64°, 11.23°±9.59°, 16.32°±12.38°, and 18.49°±11.70° respectively; for females, the TPA values were 2.72°±6.88°, 3.68°±6.26°, 7.30°±6.11°, 7.44°±6.75°, 12.64°±9.79°, 19.08°±10.39°, and 16.79°±13.19° respectively. T-Cobb, T-LEV, and T-Apex increased slowly with age ( P<0.05). The pelvic incidence (PI) remained relatively constant in males ( P>0.05), while it increased slowly with age in females ( P<0.05). Conclusions:Sagittal anteversion of the spinal-pelvis increases with age. Gender differences are reflected in specific changes in the fluctuation amplitude of certain parameters (such as PI), and the fluctuations of indicators like T-Cobb, T-LEV, and T-Apex are closely related to the natural aging process of the spine.

Objective:To explore the effects of age and gender on the sagittal spinal-pelvic parameters during the natural aging process of healthy adults.Methods:A total of 647 Chinese healthy adults who underwent health check-ups at the Second Affiliated Hospital of Zhejiang University School of Medicine and Songyang County People's Hospital, from January 2017 to September 2024 were collected. There were 277 males and 370 females, aged 18-93 years. Anteroposterior and lateral X-ray films of the whole spine were taken to evaluate the spinal-pelvic sagittal morphology. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis(LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), global tilt (GT), T 1-pelvic angle (TPA), sagittal vertical axis (SVA), thoracic Cobb angle (T-Cobb), lower end vertebra of thoracic Cobb angle (T-LEV), apex vertebra of thoracic Cobb angle (T-Apex), lumbar Cobb angle (L-Cobb). Compare the differences in spine-pelvis parameters among patients of different genders and age groups (in this study, the subjects were subdivided into the 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years groups according to the age range). Results:The results showed that GT, SVA, TPA, and PT increased with age ( P<0.05). For males aged 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years, PT values were 8.58°±6.47°, 9.60°±5.63°, 12.65°±7.13°, 11.00°±6.99°, 13.01°±8.63°, 15.77°±8.02°, and 18.47°±10.03° respectively; for females in the same age groups, the PT values were 8.44°±6.83°, 9.00°±6.44°, 11.84°±7.35°, 12.07°±7.51°, 15.44°±9.39°, 19.26°±8.28°, and 18.17°±9.43° respectively. For males in these age groups, the global tilt (GT) values were 6.37°±7.20°, 8.77°±6.51°, 10.38°±9.07°, 8.80°±7.49°, 10.80°±8.62°, 16.07°±10.42°, and 21.99°±12.65° respectively; for females, the GT values were 4.46°±8.09°, 5.96°±7.83°, 8.17°±6.88°, 9.41°±8.03°, 9.96°±1.39°, 17.89°±9.39°, and 19.55°±12.34° respectively. The sagittal vertical axis (SVA) values for males in the age groups were -7.94±25.57 mm, -2.98±25.69 mm, -4.63±20.90 mm, -6.43±32.81 mm, 7.85±43.39 mm, 36.49±53.89 mm, and 55.57±51.10 mm respectively; for females, they were -24.12±31.35 mm, -17.49±25.12 mm, -17.88±22.72 mm, -8.25±30.91 mm, 8.80±27.45 mm, 28.67±38.22 mm, and 23.23±35.19 mm respectively. For males, the thoracic pelvic angle (TPA) values across the age groups were 4.46°±5.94°, 6.05°±5.38°, 9.58°±9.35°, 7.52°±7.64°, 11.23°±9.59°, 16.32°±12.38°, and 18.49°±11.70° respectively; for females, the TPA values were 2.72°±6.88°, 3.68°±6.26°, 7.30°±6.11°, 7.44°±6.75°, 12.64°±9.79°, 19.08°±10.39°, and 16.79°±13.19° respectively. T-Cobb, T-LEV, and T-Apex increased slowly with age ( P<0.05). The pelvic incidence (PI) remained relatively constant in males ( P>0.05), while it increased slowly with age in females ( P<0.05). Conclusions:Sagittal anteversion of the spinal-pelvis increases with age. Gender differences are reflected in specific changes in the fluctuation amplitude of certain parameters (such as PI), and the fluctuations of indicators like T-Cobb, T-LEV, and T-Apex are closely related to the natural aging process of the spine.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Objective: Dithiothreitol(DTT) and ?-Mercaptoethanol(2-ME) are important reducing agents for SDS-PAGE.This study is to observe the diffusing effect of DTT and 2-ME during electrophoresis,and to find a way of avoiding this effect.Methods: We placed protein samples containing reducing agents and non-reduced protein samples separately in the sample wells at intervals for SDS-PAGE electrophoresis,and determined whether or not the electrophoretic lanes of the non-reduced samples were interfered by the adjacent lanes.Results: DTT and 2-ME diffused to the neighboring lane,so that the non-reduced samples were reduced partially.The spreading effect was positively correlated with the content of the reducing agent.Conclusion: DTT and 2-ME have a diffusing effect during SDS-PAGE electrophoresis.In separating the reduced and non-reduced proteins in the same gel at the same time,at least a blank lane should be set up in between them in order to avoid the diffusing effect.