OBJECTIVETo explore permeability of artificial blood-brain barrier (aBBB) by oxygen-glucose deprivation combined (OGD)-induced using tetramethylpyrazine combined with puerarin in vitro.

METHODRats were divided into normal control group, model group, tetramethylpyrazine group, puerarin group, tetramethylpyrazine-puerarin group and nimodipine group. Culture rat brain microvascular endothelial cells and astrocytes in vitro and build the OGD-induced aBBB damage model. Evaluate aBBB damage characteristics by TEER, gamma-GT, AKP and LDH. Determine contents of tetramethylpyrazine, puerarin, nimodipine and calculate drug permeating concentration of OGD-induced aBBB model by HPLC.

RESULTCompared with the model, the level of TEER was lower than the control group with significant difference (P < 0.01). The levels of gamma-GT, AKP in tetramethylpyrazine group, tetramethylpyrazine-puerarin group and nimodipine group were higher than the model group, the differences were significant (P < 0.01). Compared with tetramethylpyrazine group or puerarin group, the level of AKP of tetramethylpyrazine-puerarin group increased significantly (P < 0.01). The differences of levels of TEER, gamma-GT, AKP and LDH between tetramethylpyrazine-puerarin group and nimodipinthe group were significant (P < 0.05). Tetramethylpyrazine-puerarin group has a synergistic effect of increasing TEER, gamma-GT, AKP and reducing LDH. The permeating rate in tetramethylpyrazine-puerarin group was higher than tetramethylpyrazine group and puerarin group.

CONCLUSIONTetramethylpyrazine-puerarin can permeate aBBB more easily and protect aBBB. The cause may relate to reducing the permeability of the OGD-induced aBBB.

Animals ; Blood-Brain Barrier ; drug effects ; Drug Combinations ; Glucose ; physiology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Oxygen ; physiology ; Permeability ; Pyrazines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

Adolescents are in a transition period from children to adults, during which they are prone to a variety of emotional disorders, with anxiety and depression being the most common disorders. Anxiety and depressive symptoms are highly correlated and the comorbidity of anxiety and depression is common. At the same time, the most prominent behavioral changes in adolescence are the emergence of getting up late and sleeping late, and the circadian rhythm begins to delay. Previous studies have shown that circadian rhythm is closely related to anxiety and depression, but the association between circadian rhythm disorder and comorbidity of anxiety and depression remains unclear. This article reviews the prevalence, association and potential biological mechanism of circadian rhythm disorder and comorbidity of anxiety and depression in adolescents, so as to provide a possible reference for the prevention and control of comorbidity of anxiety and depression in adolescents.
Adult ; Child ; Adolescent ; Humans ; Depression/epidemiology* ; Anxiety/epidemiology* ; Comorbidity ; Chronobiology Disorders ; Sleep

Adolescents are in a transition period from children to adults, during which they are prone to a variety of emotional disorders, with anxiety and depression being the most common disorders. Anxiety and depressive symptoms are highly correlated and the comorbidity of anxiety and depression is common. At the same time, the most prominent behavioral changes in adolescence are the emergence of getting up late and sleeping late, and the circadian rhythm begins to delay. Previous studies have shown that circadian rhythm is closely related to anxiety and depression, but the association between circadian rhythm disorder and comorbidity of anxiety and depression remains unclear. This article reviews the prevalence, association and potential biological mechanism of circadian rhythm disorder and comorbidity of anxiety and depression in adolescents, so as to provide a possible reference for the prevention and control of comorbidity of anxiety and depression in adolescents.
Adult ; Child ; Adolescent ; Humans ; Depression/epidemiology* ; Anxiety/epidemiology* ; Comorbidity ; Chronobiology Disorders ; Sleep

OBJECTIVE: To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells. METHODS: Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot. RESULTS: KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01). CONCLUSION KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G₁ phase arrest in gastric cancer cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/pharmacology* ; Humans ; Interleukin-6/metabolism* ; RNA, Messenger/metabolism* ; STAT3 Transcription Factor/metabolism* ; Stomach Neoplasms/genetics*