Objective To explore the expression levels of CD33⁺ myeloid-derived suppressor cell (MDSC)-mediated T lymphocyte function and related inflammatory factors secreted by T lymphocyte subsets in patients with cervical cancer, and to analyze their correlation with the treatment efficacy of ¹²⁵I particle implantation combined with arterial chemoembolization, as well as predictive value for treatment outcomes and interaction effects. Methods From January 1st, 2021 to January 1st, 2024, our hospital admitted 152 patients with advanced cervical cancer, who were confirmed by pathological examination. All patients received uterine artery chemoembolization combined with ¹²⁵I particle implantation. The predictive value of CD33⁺MDSC levels for clinical treatment response in cervical cancer was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was performed to evaluate both multiplicative and additive interactions between CD33⁺MDSC and T lymphocytes in predicting clinical treatment failure of cervical cancer. Kaplan Meier method was used to analyze the survival differences between cervical cancer patients with high and low CD33⁺MDSC expression levels. Results Compared with the effective group, patients in the ineffective group had decreased expression levels of CD3⁺ T lymphocyte, CD4⁺ T lymphocyte, interleukin 2 (IL-2) and interferon γ (IFN-γ), while showing increased expression levels of CD33⁺MDSC, CD8⁺ T lymphocyte, IL-4 and IL-6, along with increased tumor necrosis factor α (TNF-α) levels, larger maximum tumor diameters, and a higher incidence of lymph node metastasis. The expression levels of CD33⁺MDSCs demonstrated good predictive performance for treatment efficacy in cervical cancer patients. The high CD33⁺MDSC expression group had a significantly shorter overall survival (OS) than the low CD33⁺MDSC expression group (6.0±1.0 months vs. 12.0±1.2 months; t=33.280). The interaction analysis revealed that CD33⁺MDSCs and CD8⁺ T lymphocytes were highly expressed, while CD3⁺ and CD4⁺ T lymphocytes were lowly expressed, which was associated with an increased risk of clinical treatment failure in cervical cancer patients. Conclusion CD33⁺MDSCs can inhibit CD3⁺ and CD4⁺ T lymphocytes. It can upregulate the expression of CD8⁺ T lymphocytes, form an immunosuppressive microenvironment, and reduce the treatment response rate of ¹²⁵I particle implantation combined with arterial chemoembolization. CD33⁺MDSCs may serve as an independent biomarker for predicting the therapeutic efficacy and poor prognosis.
Humans ; Female ; Uterine Cervical Neoplasms/immunology* ; Middle Aged ; Chemoembolization, Therapeutic/methods* ; Sialic Acid Binding Ig-like Lectin 3/immunology* ; Adult ; T-Lymphocytes/immunology* ; Aged ; Treatment Outcome

OBJECTIVE: To investigate the expressions of CD33 and CD13 in newly diagnosed multiple myeloma (MM) patients and its relationship with prognosis. METHODS: It was retrospectively observed that the expression of CD33 and CD13 in 121 MM patients who were newly diagnosed from January 2014 to January 2020, and the relationship between the expressions of CD33 and CD13 and patients prognosis was analyzed. RESULTS: Among the 121 newly diagnosed MM patients, there were 30 patients (24.8%) in the CD33⁺ group and 12 patients (9.9%) in the CD13⁺ group. Kaplan-Meier analysis showed that, compared with the CD33^- group, the progression-free survival (PFS) time and overall survival (OS) time were significantly shortened in MM patients in CD33⁺ group (PFS 17.5 vs 23 months, P=0.000; OS 18.5 vs 25 months, P=0.000); and the PFS time and OS time of MM patients in the CD13⁺ group were also significantly shortened than those in CD13^- group (PFS 21 vs 22 months, P=0.012; OS 25 vs 26 months, P=0.006). Cox regression analysis showed that CD33 and CD13 were independent adverse prognostic factors in MM patients (CD33: P=0.000;CD13: P=0.003). CONCLUSION CD33 and CD13 are prognostic risk factors in patients with MM.
CD13 Antigens ; Cell Count ; Humans ; Kaplan-Meier Estimate ; Multiple Myeloma ; Prognosis ; Retrospective Studies ; Sialic Acid Binding Ig-like Lectin 3

Objective: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. Methods: The CD33-targeted bi-specific T-cell engager (CD33-BiTE) and tri-specific T-cell engager (CD33-TriTE) expression vectors were successfully constructed and expressed through a eukaryotic cell expression system. CD33-BiTE and CD33-TriTE were purified by affinity chromatography. The effects of CD33-BiTE and CD33-TriTE on T cells were analyzed through in vitro experiments. Results: ① CD33-BiTE and CD33-TriTE were successfully constructed and purified and could compete with flow cytometry antibodies for binding to the target cells. ② After 12 days of co-culture with CD33-BiTE and CD33-TriTE, the number of human T cells were expanded to 33.89±19.46 and 81.56±23.62 folds, respectively. CD33-TriTE induced a stronger proliferation of T cells than CD33-BiTE (P<0.05) . ③ Both CD33-BiTE and CD33-TriTE induced specific dose-dependent cytotoxicity on CD33(+) leukemia cells. ④ Compared to CD33-TriTE, leukemia cells were prone to express PD-L1 when co-cultured with T cells and CD33-BiTE. CD33-TriTE induced powerful cytotoxicity on leukemia cells with high PD-L1 expression. Conclusion: CD33-BiTE and CD33-TriTE expression vectors were constructed, and fusion proteins were expressed in eukaryotic cells. Our results support the proliferative and activating effects of BiTE and TriTE on T cells. Compared to that of CD33-BiTE, CD33-TriTE induced a stronger proliferative effect on T cells and a more powerful cytotoxicity on leukemia cells with high PD-L1 expression.
B7-H1 Antigen/pharmacology* ; Humans ; Leukemia, Myeloid, Acute/metabolism* ; Sialic Acid Binding Ig-like Lectin 3/pharmacology* ; T-Lymphocytes

PURPOSE: To compare the improving effects of diabetic erectile dysfunction with two anti-glycemic agents; phlorizin and insulin. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into four groups (n=15 in each group): normal control (C), untreated diabetic rats (D), and diabetic rats treated by phlorizin (P) or insulin (I). Ten weeks after the diabetic induction using an injection of streptozotocin (55 mg/kg), four weeks of diabetic control was conducted. Erectile response, Western blot, and immunohistochemistry were assessed. RESULTS: During the experiment, the C-group showed continuous weight gain, while the other groups suffered from weight loss. After start of diabetic control, the body weight of I-group was increased; whereas, there was no meaningful change in the P-group. Meanwhile, comparable blood glucose levels were achieved in the P- and I-groups. The erectile response was markedly decreased in the D-group, whereas the P- and I-groups were similar as good as the C-group. In addition, D-group showed the significant decrease in the cavernosal smooth muscle content and increased apoptosis. Platelet endothelial cell adhesion molecule-1 protein expression, phosphorylation of endothelial nitric oxide synthase and myosin phosphatase target subunit 1 were significantly distorted in the D-group, while the P- and I-groups were comparable with the C-group. CONCLUSIONS: Phlorizin treatment resulted in the improvement of erectile function as same as insulin despite the lack of anabolic weight gains. These results suggest that control of blood glucose level rather than a type of anti-glycemic agents is more important for the prevention and treatment of diabetic erectile dysfunction
Animals ; Antigens, CD31 ; Apoptosis ; Blood Glucose ; Blotting, Western ; Body Weight ; Diabetes Complications ; Erectile Dysfunction ; Immunohistochemistry ; Insulin ; Male ; Muscle, Smooth ; Myosin-Light-Chain Phosphatase ; Nitric Oxide Synthase Type III ; Phlorhizin ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Weight Gain ; Weight Loss

Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal tract of animals. Although intensive functional studies have been done for other galectin isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic changes on monocytes by altering the expression of various surface molecules, and induced functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. Concomitant with these changes, Gal-4-treated monocytes became adherent and showed elongated morphology with higher expression of macrophage markers. Notably, we found that Gal-4 interacted with CD14 and activated the MAPK signaling cascade. Therefore, these findings suggest that Gal-4 may exert the immunoregulatory functions through the activation and differentiation of monocytes.
Animals ; Antigens, CD14 ; Cell Differentiation ; Galectin 4 ; Galectins ; Gastrointestinal Tract ; Macrophages ; Monocytes ; Protein Isoforms

PURPOSEMacrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration.

METHODSAdult male Sprague-Dawley rats experienced one session of downhill running (16° decline, 16 m/min) for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately.

RESULTSIt was showed that CD68 M1 macrophages mainly infiltrated into muscle necrotic sites at 1-3 d, while CD163 M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Th1-associated transcripts of iNOS and Ccl2 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running (p < 0.01). M2 phenotype marker Arg-1 increased 12 h and 3 d (p < 0.05, p < 0.01) after exercise, and Clec10a and Mrc2 were up-regulated in muscles 12 h following exercise (p < 0.05, p < 0.05).

CONCLUSIONThe data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise-induced skeletal muscle injury and recovery.

Animals ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Macrophages ; physiology ; Male ; Muscle, Skeletal ; injuries ; pathology ; Myoglobin ; blood ; Phenotype ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; analysis

The expression of stage-specific embryonic antigens (SSEAs) was determined in several types of canine cancer cells. Flow cytometry showed SSEA-1 expression in glioblastoma, melanoma, and mammary cancer cells, although none expressed SSEA-3 or SSEA-4. Expression of SSEA-1 was not detected in lymphoma, osteosarcoma, or hemangiosarcoma cell lines. Relatively stable SSEA-1 expression was observed between 24 and 72 h of culture. After 8 days in culture, sorted SSEA-1⁻ and SSEA-1⁺ cells re-established SSEA-1 expression to levels comparable to those observed in unsorted cells. Our results document, for the first time, the expression of SSEA-1 in several canine cancer cell lines.
Antigens, CD15 ; Breast Neoplasms* ; Cell Line ; Flow Cytometry ; Glioblastoma* ; Hemangiosarcoma ; Lymphoma ; Melanoma* ; Osteosarcoma ; Stage-Specific Embryonic Antigens*

BACKGROUND: Application of competent cells such as mesenchymal stem cells (MSCs) for treatment of musculoskeletal disorders in equine athletes is increasingly needed. Moreover, similarities of horse and human in size, load and types of joint injuries, make horse as a good model for MSCs therapy studies. This study was designed to isolate and characterize stemness signature of equine bone marrow-derived mesenchymal stem cells (BM-MSCs). METHODS: BM of three mares was aspirated and the mononuclear cells (MNCs) were isolated using density gradient. The primary MNCs were cultured and analyzed after tree passages (P3) for growth characteristics, differentiation potentials, and the expression of genes including CD29, CD34, CD44, CD90, CD105, MHC-I, MHC-II and pluripotency related genes (Nanog, Oct-4, Sox-2, SSEA-1, -3, -4) using RT-PCR or immunocytochemistry techniques. RESULTS: The isolated cells in P3 were adherent and fibroblast-like in shape with doubling times of 78.15 h. Their clonogenic capacity was 8.67±4% and they were able to differentiate to osteogenic, adipogenic and chondrogenic lineages. Cells showed expression of CD29, CD44, CD90, MHC-I and Sox-2 while no expression for CD34, MHC-II, CD105, and pluripotency stemness markers was detected. CONCLUSIONS: In conclusion, data showed that isolated cells have the basic and minimal criteria for MSCs, however, expressing only one pluripotency gene (sox-2).
Antigens, CD15 ; Athletes ; Bone Marrow ; Horses ; Humans ; Immunohistochemistry ; Joints ; Mesenchymal Stromal Cells* ; Trees

PURPOSE: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. MATERIALS AND METHODS: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. RESULTS: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05). CONCLUSIONS: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.
Animals* ; Antigens, CD31 ; Atrophy ; Blotting, Western ; Diabetes Mellitus ; Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Erectile Dysfunction* ; Genetic Therapy ; Guanosine Monophosphate ; Immunohistochemistry ; Magnets ; Male ; Models, Animal* ; Muscle, Smooth ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type III ; Rats ; Regeneration ; Stem Cells ; Vascular Endothelial Growth Factor A

OBJECTIVETo investigate the relationship between atrial fibrillation (AF) and serum soluble CD163.

METHODSA total of 336 patients with heart valve disease were included in this study, including 167 with AF and 169 with sinus rhythm. The clinical data were compared between the two grops, and Logistic regression analysis was used to identify the risk factors associated with AF.

RESULTSThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor (TNF), interleukin-6 (IL - 6), high-sensitivity C-reactive protein (hs-CRP) and left atrial diameter (LAD) all differed significantly between the two groups (P<0.05). Serum soluble CD163 levels in AF patients were significantly higher than those in patients with sinus rhythm (P<0.05). Serum soluble CD163 was positively correlated with TNF (r=0.244, P=0.244), IL-6 (r=0.186, P=0.186), hs-CRP (r=0.183, P=0.183) and LAD (r=0.194, P=0.194) in patients with AF. Logistic regression analysis showed that LAD, IL-6, TNF, hs-CRP and CD163 were all associated with AF. ROC curve analysis showed that the area under curve of serum soluble CD163 was 0.861 in patients with AF (CI 95%: 0.820-0.901, P<0.01) with a sensitivity and a specificity of 80.8 and 76.9%, respectively.

CONCLUSIONSerum soluble CD163 level may be a risk factor for AF, and an increased soluble CD163 level may indicate active inflammation in AF patients.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Atrial Fibrillation ; blood ; C-Reactive Protein ; analysis ; Heart Atria ; pathology ; Humans ; Inflammation ; blood ; Interleukin-6 ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Receptors, Cell Surface ; blood ; Risk Factors ; Tumor Necrosis Factor-alpha ; blood