A Study of the Relationship between Inflammatory Immune Function and Intestinal Flora in Adolescent Patients with First-Episode Depression.

BACKGROUND: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. METHODS: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. RESULTS: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1ß, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). Bifidobacterium, Escherichia coli, Lactobacillus, and Bacteroides in the observation group were less than those in the control group (p < 0.05). The content of Bifidobacterium was negatively correlated with the level of TNF-α (r = -0.358, p < 0.001), positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = 0.490, 0.169, 0.165, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.154, p < 0.05). The level of Escherichia coli content was negatively correlated with the levels of IL-6, CD3+, CD4+, CD4+/CD8+ (r = -0.483, -0.548, -0.317, -0.328, p < 0.001), and positively correlated with the levels of CD8+ (r = 0.325, p < 0.001). The content of Lactobacillus was positively correlated with the levels of CD3+, CD4+, CD4+/CD8+ (r = 0.552, 0.188, 0.194, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.186, p < 0.05). The content of Bacteroides was positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = -0.570, -0.183, -0.193, p < 0.05), and negatively correlated with the level of CD8+ levels were positively correlated (r = 0.187, p < 0.05). CONCLUSIONS: The intestinal flora is related to the level of inflammatory factors and immune function. Further study on the relationship between intestinal flora, inflammatory immune function, and depression could offer novel insights for the prevention and treatment of depressive disorders.

A Study of the Relationship between Inflammatory Immune Function and Intestinal Flora in Adolescent Patients with First-Episode Depression

Background: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. Methods: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. Results: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1β, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). ... (AU)

Wnt3a knockdown promotes collagen type II expression in rat chondrocytes.

Osteoarthritis (OA) is a chronic condition caused by cartilage degradation, and there are currently no effective methods for preventing the progression of this disease; gene therapy is a relatively novel method for treating arthritis. Decreased collagen type II (Col2) expression within the cartilage matrix is an important factor for the development of OA, and Wnt3a serves a significant role in cartilage homeostasis. The present study assessed whether Wnt3a knockdown promoted Col2 expression in chondrocytes. Lentivirus-introduced small interfering RNA was used to knock down the expression of Wnt3a in primary rat chondrocytes, and then IL-1ß treatment was used to establish an OA chondrocyte model. The expression of target genes (Wnt3a, Col2, MMP-13 and ß-catenin) was analyzed using reverse transcription-quantitative PCR, western blotting and immunocytochemistry. There was significantly less MMP-13 and ß-catenin expression in the Wnt3a knockdown cells compared with the other controls. Col2 expression was significantly higher in the Wnt3a-knockdown cells compared with the control cells, indicating that knockdown of Wnt3a may promote Col2 expression. Consequently, Wnt3a was indicated to be an important factor in cartilage homeostasis, and Wnt3a knockdown may serve as a novel method for OA therapy.

Silencing of Wnt5a prevents interleukin-1ß-induced collagen type II degradation in rat chondrocytes.

Osteoarthritis (OA) is a joint disease, and few treatments to date have been able to delay OA progression. The degradation of collagen type II (COL2) in the cartilage matrix is an important initiating factor for OA progression; the upregulation of Wnt5a protein activates COL2 degradation. In the present study, small interfering RNA of Wnt-5a was delivered by a lentiviral vector (LV-Wnt5a-RNAi) to silence Wnt-5a mRNA and prevent COL2 degradation. To determine the function of LV-Wnt5a-RNAi, the OA chondrocyte model (OA-like chondrocytes) were constructed using interleukin (IL)-1ß. Detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Wnt-5a mRNA in the OA-like chondrocytes were upregulated in a time-dependent manner, indicating that OA-like chondrocytes were successfully constructed. The bioactivity of OA-like chondrocytes was determined using Live-Dead staining, and the result illustrated that the OA-like chondrocytes stimulated with IL-1ß for 6 h remained viable, and these were used in Wnt5a silencing. The OA-like chondrocytes were divided into three groups: Group I, cultivated with common medium; group II, cultivated with common medium supplemented with empty lentiviral vector; group III, cultivated with common medium supplemented with LV-Wnt5a-RNAi. The efficiency of LV-Wnt5a-RNAi transfection was determined using fluorescence microscopy, the result of which indicated that LV-Wnt5a-RNAi could efficiently be transfected into the OA-like chondrocytes. The LV-Wnt5a-RNAi efficiency for the Wnt5a mRNA silencing was determined using RT-qPCR. The result illustrated that the mRNA of Wnt5a in group III was significantly lower in group I compared with that in group II (P<0.05), indicating that the LV-Wnt5a-RNAi could successfully silence Wnt5a mRNA. To further verify whether the silencing of Wnt5a mRNA could prevent COL2 degradation, western blotting and immunohistochemical analyses were performed. The results demonstrated that COL2 in group III was significantly higher compared with that in groups I and II (P<0.05), which illustrated that the silencing of Wnt5a mRNA could prevent COL2 degradation. In conclusion, LV-Wnt5a-RNAi was formed successfully and could efficiently silence Wnt5a mRNA expressed by OA-like chondrocytes. In addition, the silencing of Wnt5a mRNA could prevent the degradation of COL2 in OA-like chondrocytes, confirming that LV-Wnt5a-RNAi may be used as a novel tool for OA treatment.