Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes.

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.

Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury.

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

Screening and staging for non-small cell lung cancer by serum laser Raman spectroscopy.

OBJECTIVE: Lung cancer is the leading cause of cancer-related death worldwide. Current clinical screening methods to detect lung cancer are expensive and associated with many complications. Raman spectroscopy is a spectroscopic technique that offers a convenient method to gain molecular information about biological samples. In this study, we measured the serum Raman spectral intensity of healthy volunteers and patients with different stages of non-small cell lung cancer. The purpose of this study was to evaluate the application of serum laser Raman spectroscopy as a low cost alternative method in the screening and staging of non-small cell lung cancer (NSCLC). METHODS: The Raman spectra of the sera of peripheral venous blood were measured with a LabRAM HR 800 confocal Micro Raman spectrometer for individuals from five groups including 14 healthy volunteers (control group), 23 patients with stage I NSCLC (stage I group), 24 patients with stage II NSCLC (stage II group), 19 patients with stage III NSCLC (stage III group), 11 patients with stage IV NSCLC (stage IV group). Each serum sample was measured 3 times at different spots and the average spectra represented the signal of Raman spectra in each case. The Raman spectrum signal data of the five groups were statistically analyzed by analysis of variance (ANOVA), principal component analysis (PCA), linear discriminant analysis (LDA), and cross-validation. RESULTS: Raman spectral intensity was sequentially reduced in serum samples from control group, stage I group, stage II group and stage III/IV group. The strongest peak intensity was observed in the control group, and the weakest one was found in the stage III/IV group at bands of 848 cm-1, 999 cm-1, 1152 cm-1, 1446 cm-1 and 1658 cm-1 (P < 0.05). Linear discriminant analysis showed that the sensitivity to identify healthy people, stage I, stage II, and stage III/IV NSCLC was 86%, 65%, 75%, and 87%, respectively; the specificity was 95%, 94%, 88%, and 93%, respectively; and the overall accuracy rate was 92% (71/77). CONCLUSION: The laser Raman spectroscopy can effectively identify patients with stage I, stage II or stage III/IV Non-Small Cell Lung cancer using patient serum samples.

Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced Acute Lung Injury Mice Model.

Acute lung injury (ALI) is a life-threatening syndrome which causes a high mortality rate worldwide. In traditional medicine, lots of aromatic plants-such as some Thymus species-are used for treatment of various lung diseases including pertussis, bronchitis, and asthma. Thymol, one of the primary active constituent derived from Thymus vulgaris (thyme), has been reported to exhibit potent anti-microbial, anti-oxidant, and anti-inflammatory activities in vivo and in vitro. The present study aims to investigate the protective effects of thymol in lipopolysaccharide (LPS)-induced lung injury mice model. In LPS-challenged mice, treatment with thymol (100 mg/kg) before or after LPS challenge significantly improved pathological changes in lung tissues. Thymol also inhibited the LPS-induced inflammatory cells influx, TNF-α and IL-6 releases, and protein concentration in bronchoalveolar lavage fluid (BALF). Additionally, thymol markedly inhibited LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that thymol effectively inhibited the NF-κB activation in the lung. Taken together, these results suggested that thymol might be useful in the therapy of acute lung injury.

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice.

CONTEXT: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). MATERIALS AND METHODS: Male BALB/c mice were treated with standardized myrtol for 1.5 h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively. RESULTS: In LPS-challenged mice, standardized myrtol at a dose of 1200 mg/kg significantly inhibited the neutrophile counts (from 820.97 ± 142.44 to 280.42 ± 65.45, 103/mL), protein concentration (from 0.331 ± 0.02 to 0.183 ± 0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70 ± 748.40 to 2317.70 ± 500.14, ng/mL; IL-6: from 1184.85 ± 143.58 to 509.57 ± 133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82 ± 0.04 to 0.48 ± 0.06, U/g) and pathological changes (lung injury score: from 11.67 ± 0.33 to 7.83 ± 0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues. DISCUSSION AND CONCLUSION: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.

Knockdown of NogoA prevents MPP+­induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway.

NogoA is a myelin­associated protein, which is important in the inhibition of axonal fiber growth and in regeneration following injury of the mammalian central nervous system. A previous study suggested that NogoA may be key in the process of Parkinson's disease (PD), which is the second most common chronic neurodegenerative disorder worldwide. The regulatory mechanism underlying the effect of NogoA on the process of PD remains to be fully elucidated. The present study aimed to investigate the effect and underlying mechanism of NogoA on cellular viability, apoptosis and autophagy induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells, a commonly used in vitro PD model. PC12 cells were treated with 1 mM MPP+ for 24 h and the cells were harvested for western blotting. The results demonstrated that the protien expression levels of NogoA were increased in the PC12 cells treated with MPP+. Subsequently, NogoA small interfering RNA was synthesized and transfected into PC12 cells to silence the expression of NogoA. NogoA knockdown significantly reduced the MPP+­induced decrease in cell viability and apoptosis, detected using a cell counting kit­8 and flow cytometric analysis, respectively. Interference in the expression of NogoA increased the MPP+­induced decrease in mitochondrial membrane potential, determined quantitatively by flow cytometry using JC-1 dye, and the protein levels of Beclin­1. In addition, MPP+ treatment activated the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Knockdown of NogoA significantly inhibited the expression levels of mTOR and STAT3. Furthermore, overexpression of NogoA had similar neurotoxic effects on the PC12 cells as MPP+ treatment. Treatment with rapamycin, an inhibitor of the mTOR/STAT3 signaling pathway had a similar effect to that of NogoA knockdown in the MPP+­treated PC12 cells. Taken together, the results from the present study demonstrated that NogoA may regulate MPP+­induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway and provided an explanation regarding the regulatory mechanism of NogoA on the process of PD.

Effects of Nogo-A Silencing on TNF-α and IL-6 Secretion and TH Downregulation in Lipopolysaccharide-Stimulated PC12 Cells.

Parkinson's disease (PD) is a common degenerative disease that lacks efficient treatment. Myelin-associated neurite outgrowth inhibitor A (Nogo-A) is relevant with inhibition of nerve regeneration and may play vital role in pathogenesis of PD. The study aimed to establish the shRNA expression plasmids of Nogo-A gene and explore the regulatory effects of Nogo-A silencing on the expression of inflammation factor tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as tyrosine hydroxylase (TH) in lipopolysaccharide- (LPS-) stimulated rat PC12 cells. The results showed that both mRNA and protein levels of Nogo-A in pGenesil-nogoA-shRNA group were downregulated. The viabilities of PC12 cells decreased with increase of LPS concentrations. LPS significantly increased the supernatant TNF-alpha and IL-6 concentrations and reduced TH protein expression in PC12 cells, while silencing Nogo-A could block these effects. These results suggested that LPS can activate PC12 cells to secrete inflammatory cytokines and lower the TH expression, which can be regulated by Nogo-A gene silencing. Nogo-A silencing might provide new ideas for PD treatment in the future.

Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic. AIM OF THIS STUDY: The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: Lung injury was induced by intranasal instillation with 10 µg LPS. Mice were randomly divided into four groups: Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot. RESULTS: In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues. CONCLUSION: DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.

Sodium tanshinone IIA sulfonate inhibits canonical transient receptor potential expression in pulmonary arterial smooth muscle from pulmonary hypertensive rats.

Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca(2+) concentration ([Ca(2+)](i)) and store-operated Ca(2+) entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn(2+) quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O(2), 21 d) was increased by 59%, and basal [Ca(2+)](i) was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca(2+)](i) were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 µM) dose-dependently inhibited hypoxia-induced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca(2+)](i), SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca(2+)](i) and attenuated proliferation and migration of PASMCs.

[Cigarette smoke exposure induced pulmonary artery pressure increase through inhibiting Kv1.5 and Kv2.1 mRNA expression in rat pulmonary artery smooth muscles].

OBJECTIVE: To investigate the effect of cigarette smoke exposure on Kv1.5 and Kv2.1 mRNA expression in rat pulmonary arterial smooth muscle cells (PASMCs), and further to clarify the possible mechanism of cigarette smoking induced pulmonary arterial hypertension. METHODS: Primary cell culture and animal experiments were used in this study. Rat distal PASMCs were isolated and cultured by collagenase digestion. PASMCs were treated by nicotine 100 nmol/L. After 48 h, Kv1.5 and Kv2.1 mRNA expression were detected by real-time quantitative PCR and compared with the control group. Rat model of chronic exposure to cigarette smoke was established. Thirty-six male SD rats were randomly divided equally into 6 groups: (1) 1 month control group; (2) 1 month cigarette exposure group; (3) 3 month control group; (4) 3 month cigarette exposure group; (5) 6 month control group; (6) 6 month cigarette exposure group. Direct right heart manometry, HE staining and real-time quantitative PCR were used to detect the effect of smoke exposure on rat right ventricular systolic pressure (RVSP), mean pressure (mPAP), right ventricular hypertrophy index [RV/(LV + S)] as well as Kv1.5 and Kv2.1 mRNA expression on pulmonary artery smooth muscle at different time points (1 month, 3 months and 6 months). RESULTS: The mPAP and RVSP in cigarette smoke exposure 6 month group were (13.08 ± 0.64) mm Hg and (29.73 ± 0.83) mm Hg, slightly higher than those in the control 6 month group [(10.16 ± 0.44) mm Hg and (22.56 ± 0.64) mm Hg] (P < 0.01). The ratio of Kv1.5 mRNA expression in distal pulmonary arteries in 1 month, 3 month, 6 month cigarette exposure group to that in control groups was (52 ± 11)%, (64 ± 19)% and (75 ± 11)% (P < 0.05). The ratio of Kv2.1 mRNA expression in distal pulmonary arteries in 1 month, 3 month, 6 month cigarette exposure groups to that in control groups was (51.0 ± 18.6)%, (78.7 ± 10.1)% and (71.4 ± 2.3)% (P < 0.01); Chronic exposure to cigarette smoke significantly decreased Kv1.5 and Kv2.1 mRNA expression in rat pulmonary arterial smooth muscle at each time point. The ratio of Kv1.5 and Kv2.1 mRNA expression in rat distal PASMCs treated with nicotine (100 nmol/L, 48 h) to control group were (62 ± 14)% (P < 0.05) and (72 ± 15)% (P < 0.01), respectively. Nicotine inhibited Kv1.5 and Kv2.1 mRNA expression in rat distal PASMCs. CONCLUSION: Cigarette smoke exposure may be involved in pulmonary hypertension by downregulating potassium channels Kv1.5 and Kv2.1 mRNA expression in rat pulmonary artery smooth muscles.