Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease featured by insulin resistance (IR) and decreased insulin secretion. Currently, vitamin D deficiency is found in most patients with T2DM, but the relationship between vitamin D and IR in T2DM patients requires further investigation. AIM: To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM. METHODS: Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed. Based on the diagnostic criteria of IR, the patients were divided into a resistance group (n = 100) and a non-resistance group (n = 62). Subsequently, patients in the resistance group were subdivided to a conventional group (n = 44) or a joint group (n = 56) according to the treatment regimens. Logistic regression was carried out to analyze the risk factors of IR in T2DM patients. The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment. RESULTS: Notable differences were observed in age and body mass index (BMI) between the resistance group and the non-resistance group (both P < 0.05). The resistance group exhibited a lower 25-hydroxyvitamin D3 (25(OH)D3) level, as well as notably higher levels of 2-h postprandial blood glucose (2hPG), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) than the non-resistance group (all P < 0.0001). Additionally, the resistance group demonstrated a higher triglyceride (TG) level but a lower high-density lipoprotein-cholesterol (HDL-C) level than the non-resistance group (all P < 0.0001). The BMI, TG, HDL-C, 25(OH)D3, 2hPG, and HbA1c were found to be risk factors of IR. Moreover, the post-treatment changes in levels of 25(OH)D3, 2hPG, FBG and HbA1c, as well as TG, total cholesterol, and HDL-C in the joint group were more significant than those in the conventional group (all P < 0.05). CONCLUSION: Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the non-insulin resistant group. Logistic regression analysis revealed that 25(OH)D3 is an independent risk factor influencing IR. Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

Sodium selenite inhibits proliferation of lung cancer cells by inhibiting NF-κB nuclear translocation and down-regulating PDK1 expression which is a key enzyme in energy metabolism expression.

As a trace element that maintains homeostasis in human body, selenium has significant anti-tumor activity. However, its exact molecular mechanism remains to be elucidated. Sodium selenite (SSe) is the most widely-distributed inorganic selenium in nature. In this study, we selected SSe as the research object to explore its anti-tumor mechanism in lung cancer. In vitro experiment showed that SSe could inhibit the activation of NF-κB signaling pathway, knowing that NF-κB is an important intracellular nuclear transcription factor that regulates the expression of pyruvate dehydrogenase kinase 1 (PDK1), a key energy metabolism switch affecting the survival status of the whole cell.At the same time, Bay11-7082(NF-κB signaling pathway inhibitors) and SSe resulted in phosphorylation of p65 and IκBα, decreased expression of PDK1 and Bcl-2,and increased expression of Bax in lung cancer cells. Our further study demonstrated that the reduction of PDK1 activity inhibited lactate secretion, reduced mitochondrial membrane potential, caused the release of Cytochrome C (Cyto C), activated mitochondrial respiration, and promoted the apoptosis of lung cancer cells. The in vivo experiment revealed that SSe inhibited the activation of NF-κB signaling pathway, decreased the expression of PDK1, and induced lung cancer cell proliferation and apoptosis. All these findings indicated that SSe promoted lung cancer cell apoptosis by inhibiting the activation of NF-κB signaling pathway, down-regulating PDK1 and activating mitochondrial apoptosis pathway.

Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascade in Vitro and in Vivo.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and p < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.

Berberine induces apoptosis in non-small-cell lung cancer cells by upregulating miR-19a targeting tissue factor.

BACKGROUND: Berberine (BBR) from the widely used Chinese herbal medicine Huanglian has an array of pharmacological and biochemical properties, including anti-neoplastic activity. However, the specific mechanisms underlying these properties are unknown. The aim of this study was to explore the anti-tumor mechanisms of BBR in non-small cell lung cancer (NSCLC). METHODS: The effects of BBR on NSCLC tumor development and programmed cell death were investigated both in vivo and in vitro. Luciferase reporter assays were used to determine whether tissue factor (TF) was a target of miR-19a. RESULTS: BBR suppressed NSCLC growth and promoted apoptosis in NSCLC cells by modulating miR-19a and TF expression. Luciferase assays showed that TF was a direct inhibitory target of miR-19a in NSCLC cells. BBR induced apoptosis through the miR-19a/TF/MAPK axis. CONCLUSION: The results suggest that BBR induces apoptosis of NSCLC cells via the miR-19a/TF/MAPK signaling pathway.

Recent updates and future perspectives about amygdalin as a potential anticancer agent: A review.

The overall incidence of cancer is increasing in recent years. Despite advances in various comprehensive treatments, the mortality of advanced malignant tumors remains at a high level. Numerous pharmacological studies have confirmed that many Chinese herbal medicines possess remarkable antitumor activities. Amygdalin, mainly existing in bitter almond, is reported to have antitumor properties in addition to the antioxidative, antibacterial, anti-inflammatory and immunoregulatory activities. This article summarizes the structural characteristics of amygdalin, its antitumor mechanisms, and recent progress and achievement in the research of amygdalin, hoping that it could provide theoretical clues for exploring the clinical value of amygdalin against tumors. Amygdalin is known to have an antitumor effect in solid tumors such as lung cancer, bladder cancer and renal cell carcinoma by affecting cell cycle, inducing apoptosis and cytotoxicity, and regulating immune function. Further research is needed to elucidate the pharmacological mechanisms of amygdalin in terms of the optimal dosage, the feasibility of combined use of amygdalin with other antitumor drugs, and even artificial synthesis of the active components in amygdalin, for the sake of enhancing its antitumor activities and reducing its adverse effects for clinical use.