Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

Objective:To explore the effect of the treatment of tendinous mallet finger deformity by the minimally invasive percutaneous quantitative suture technique eight times.Methods:A retrospective analysis was performed on patients with fresh tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from April 2021 to April 2022. During the procedure, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method" according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Removal of the Kirschner wire 8 weeks, the brace was used to fix the affected finger in the dorsal extension. The flexion and extension of the affected finger were gradually strengthened. The function of the affected finger was evaluated according to the Crawford standard after operation and follow-up: the active flexion and extension range of motion of each joint of the affected finger and the contralateral healthy finger was measured, and the total active ranges of motion of the finger were recorded. Finger function was evaluated according to the total active range of motion (TAM) system of the American Association of Hand Surgeons.Results:A total of 10 patients (10 digits) were enrolled, including 7 males and 3 females, and the age ranged from 20 to 52 years old, with an average age of 36.5 years old. The distance of tendon break was ≤10 mm. The operation time of the patients was 20-30 min, with an average of 24.5 min. The intraoperative blood loss was minimal. All 10 cases were followed up and the follow-up period was 6 to 12 months, with an average of 7 months. Mallet finger deformities were all corrected postoperatively, dorsal skin of fingers without a scar, there were no knot exposure, skin necrosis and other complications. At the last follow-up, the mean active range of motion of the distal interphalangeal joint was 84.4° and the mean TAM of the injured finger was 265.6°. According to TAM system assessment criteria: 8 cases were excellent, and 2 cases were good.Conclusions:Satisfactory therapeutic outcome for the treatment of tendinous mallet finger deformity can be achieved by the minimally invasive percutaneous quantitative suture technique eight times. It is a simple, safe, and effective method with minimal invasion.

Objective:To explore the effect of the treatment of tendinous mallet finger deformity by the minimally invasive percutaneous quantitative suture technique eight times.Methods:A retrospective analysis was performed on patients with fresh tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from April 2021 to April 2022. During the procedure, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method" according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Removal of the Kirschner wire 8 weeks, the brace was used to fix the affected finger in the dorsal extension. The flexion and extension of the affected finger were gradually strengthened. The function of the affected finger was evaluated according to the Crawford standard after operation and follow-up: the active flexion and extension range of motion of each joint of the affected finger and the contralateral healthy finger was measured, and the total active ranges of motion of the finger were recorded. Finger function was evaluated according to the total active range of motion (TAM) system of the American Association of Hand Surgeons.Results:A total of 10 patients (10 digits) were enrolled, including 7 males and 3 females, and the age ranged from 20 to 52 years old, with an average age of 36.5 years old. The distance of tendon break was ≤10 mm. The operation time of the patients was 20-30 min, with an average of 24.5 min. The intraoperative blood loss was minimal. All 10 cases were followed up and the follow-up period was 6 to 12 months, with an average of 7 months. Mallet finger deformities were all corrected postoperatively, dorsal skin of fingers without a scar, there were no knot exposure, skin necrosis and other complications. At the last follow-up, the mean active range of motion of the distal interphalangeal joint was 84.4° and the mean TAM of the injured finger was 265.6°. According to TAM system assessment criteria: 8 cases were excellent, and 2 cases were good.Conclusions:Satisfactory therapeutic outcome for the treatment of tendinous mallet finger deformity can be achieved by the minimally invasive percutaneous quantitative suture technique eight times. It is a simple, safe, and effective method with minimal invasion.

This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting. The viability of the PC12 cells treated with different medicines was examined by MTT assay. The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA. The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP(+)-induced oxidative injury. Moreover, β-PGG induced Nrf2 nuclear translocation, which was found to be upstream of β-PGG-induced HO-1 expression, and the activation of ERK and Akt, a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. In conclusion, β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK- and Akt-dependent manner, and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.
Animals ; Cell Death ; drug effects ; genetics ; Cell Line, Tumor ; Heme Oxygenase-1 ; genetics ; Hydrolyzable Tannins ; pharmacology ; MAP Kinase Signaling System ; drug effects ; genetics ; PC12 Cells ; Piperidines ; adverse effects ; Proto-Oncogene Proteins c-akt ; genetics ; Pyrazoles ; adverse effects ; Rats

This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting. The viability of the PC12 cells treated with different medicines was examined by MTT assay. The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA. The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP(+)-induced oxidative injury. Moreover, β-PGG induced Nrf2 nuclear translocation, which was found to be upstream of β-PGG-induced HO-1 expression, and the activation of ERK and Akt, a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. In conclusion, β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK- and Akt-dependent manner, and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.