¹³C metabolic flux analysis (¹³C-MFA) enables the precise quantification of intracellular metabolic reaction rates by analyzing the distribution of mass isotopomers of proteinogenic amino acids or intracellular metabolites through ¹³C labeling experiments. ¹³C-MFA has received much attention as it can help systematically understand cellular metabolic characteristics, guide metabolic engineering design and gain mechanistic insights into pathophysiology. This article reviews the advances of ¹³C-MFA in the past 30 years and discusses its potential and future perspective, with a focus on its application in industrial biotechnology and biomedicine.
Amino Acids ; Carbon Isotopes ; Isotope Labeling ; Metabolic Engineering ; Metabolic Flux Analysis ; Models, Biological

OBJECTIVETo investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats.

METHODSThe rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration.

RESULTSCompared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased (P <0.05 or P <0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P <0.05 or P <0.01).

CONCLUSIONThere are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; physiopathology ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Forkhead Transcription Factors ; metabolism ; Lung ; drug effects ; pathology ; physiopathology ; Male ; Rats ; Rats, Wistar ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Transforming Growth Factor beta1 ; metabolism

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUCin 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUCin 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUCratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.