Genetic and pharmacological modulation of lamin A farnesylation determines its function and turnover.

Hutchinson-Gilford Progeria syndrome (HGPS) is a severe premature ageing disorder caused by a 50 amino acid truncated (Δ50AA) and permanently farnesylated lamin A (LA) mutant called progerin. On a cellular level, progerin expression leads to heterochromatin loss, impaired nucleocytoplasmic transport, telomeric DNA damage and a permanent growth arrest called cellular senescence. Although the genetic basis for HGPS has been elucidated 20 years ago, the question whether the Δ50AA or the permanent farnesylation causes cellular defects has not been addressed. Moreover, we currently lack mechanistic insight into how the only FDA-approved progeria drug Lonafarnib, a farnesyltransferase inhibitor (FTI), ameliorates HGPS phenotypes. By expressing a variety of LA mutants using a doxycycline-inducible system, and in conjunction with FTI, we demonstrate that the permanent farnesylation, and not the Δ50AA, is solely responsible for progerin-induced cellular defects, as well as its rapid accumulation and slow clearance. Importantly, FTI does not affect clearance of progerin post-farnesylation and we demonstrate that early, but not late FTI treatment prevents HGPS phenotypes. Collectively, our study unravels the precise contributions of progerin's permanent farnesylation to its turnover and HGPS cellular phenotypes, and how FTI treatment ameliorates these. These findings are applicable to other diseases associated with permanently farnesylated proteins, such as adult-onset autosomal dominant leukodystrophy.

A case report of SARS-CoV-2 encephalitis / 上海预防医学

A patient with SARS-CoV-2 infection was adimitted to Shanghai Shibei hospital of Jing'an District in early 2023. According to the patient's complaits， clinical manifestations， physical symptoms， laboratory examination， radiological image results， plus lumbar puncture， the patient was diagnosed with novel coronavirus encephalitis. The patient was discharged from the hospital after a combined treatment of Chinese and western medicine.

Extract of Zuojin Pill (characters: see text) induces apoptosis of SGC-7901 cells via mitochondria-dependent pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of water extract of Zuojin Pill ([characters: see text], ZJP) on inhibiting the growth of human gastric cancer cell line SGC-7901 and its potential mechanism.</p><p><b>METHODS</b>Effects of ZJP on SGC-7901 cells growth were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, cell apoptosis and cell cycle were determined by flow cytometry, and apoptosis induction was detected by means of DNA gel electrophoresis. The cellular mechanism of drug-induced cell death was unraveled by assaying oxidative injury level of SGC-7901 cell, mitochondrial membrane potentials, expression of apoptosis-related genes, such as B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cleaved caspase-3 and caspase-9.</p><p><b>RESULTS</b>ZJP exerted evident inhibitory effect on SGC-7901 cells by activating production of reactive oxygen species and elevating Bax/Bcl-2 ratio in SGC-7901 cells, leading to attenuation of mitochondrial membrane potential and DNA fragmentation.</p><p><b>CONCLUSIONS</b>ZJP inhibits the cancer cell growth via activating mitochondria-dependent apoptosis pathway. ZJP can potentially serve as an antitumor agent.</p>

Design and in vitro evaluation of simvastatin-hydroxyapatite coatings by an electrochemical process on titanium surfaces.

The aim of this study was to deposit simvastatin-hydroxyapatite (sim-HA) coatings on titanium surfaces by an electrochemical process and evaluate osteoprogenitor cell responses to sim-HA-coated surfaces. Simvastatin was prepared onto titanium surfaces with varying concentration (10(-7), 10(-6), 10(-5) and 10(-4) mol/L). Surface characteristics were performed by FSEM, XRD and FTIR. LC-MS/MS method was used for simvastatin quantification in Sim-HA-coated surfaces. Murine calvaria-derived pre-osteoblastic cell (MC3T3-E1) proliferation, alkaline phosphatase activity (ALP) and osteocalcin release were used to measure osteoblastic activities. FSEM observation showed rod-like HA crystals covered on all surfaces. As drug concentration increased, the crystal diameter decreased. XRD and FTIR observations showed all coatings consisted of HA. LC-MS/MS test showed the simvastatin concentration in 10(-6) mol/L group was 2.77 x 10(-7) mol/L/cm2, while in 10(-7) mol/L group was 1.89 x 10(-7) mol/L/cm2. MC3T3-E1 cells grown on 10(-7) mol/L and 10(-6) mol/L Sim-HA surfaces showed increased ALP activity as compared to HA-coated surfaces on day 7 (P < 0.05) while at 10 day, all Sim-HA groups were significantly increased than HA group (P < 0.05). Two Sim-HA groups showed significant increases in osteocalcin production on 7 10 and 14 day (P < 0.05). It showed that incubation with 10(-7) mol/L simvastatin enhanced the cell proliferation to a statistically significant extent (P < 0.05) compared with the HA group at day 7. It was concluded that simvastatin was successfully deposited into HA coatings using the electrochemical process and the sim-HA coatings enhanced differentiation of osteoprogenitor cells.

Digital 3D anatomical modeling of the mandible with full teeth / 解剖学报

Objective To study and establish a high quality digital 3D anatomical modeling of the mandible with full teeth.Methods A set of accurate digital models of standard anatomical specimens of mandibular teeth were obtained by laser scanning, and the 3D mandible model was reconstructed by CT scan data;then, a registration deformation method based on the geometry and image anatomical landmark was employed to do the registration of each tooth to the mandible model, and finally the tooth enamel , dentin, periodontal ligament were generated .Results A high quality digital 3D anatomical modeling of the mandible with full teeth was built , each tooth had detail crown and whole root , the distinction between the enamel , dentin, periodontal ligament , and any anatomical regions can be zoomed and rotately displayed . Conclusion The digital 3D anatomical modeling of the mandible with full teeth has realistic 3D imaging view and convenient teaching-learning function , and has tremendous apllication futures in the stomatology , maxillofacial and other medical departments .

Proportion of Coptidis rhizoma and Evodiae fructus in the compound preparation: its effect in inducing apoptosis of SGC-7901 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of water extracts of Coptidis Rhizoma and Evodiae Fructus (CREF) on the proliferation and apoptosis of human gastric carcinoma cells (SGC-7901) and determine the optimal proportion of Coptidis rhizoma to Evodiae fructus.</p><p><b>METHODS</b>The growth inhibition of SGC-7901 cells treated with the water extracts of CREF of varying proportions was tested with MTT assay. The cell apoptotic rate and mitochondrial membrane potential were analyzed with flow cytometry.</p><p><b>RESULTS</b>The water extract of CREF with Coptidis Rhizoma: Evodiae Fructus proportions at 1:6, 2:5, 3:4, 4:3, 5:2, and 6:1 all significantly inhibited the growth of SGC-7901 cells after a 24-h or 48-h treatment (P<0.05). The growth inhibition and cell death ratio both exhibited a dose-dependent pattern of Coptidis Rhizoma. Flow cytometry analysis showed that, after treatment of the cells with CREF at the proportions of 1:6, 2:5, 3:4, 4:3, 5:2, and 6:1, the apoptotic rate were (8.50 ∓ 1.59)%, (9.90 ∓ 1.01)%, (17.15∓1.68)%, (21.55 ∓ 1.97)%, (34.10 ∓ 1.06)% and (34.40 ∓ 1.02)%, respectively, all significantly higher than that in the control group [(1.69 ∓ 1.91)%, P<0.05]. JC-1 Kit staining showed that mitochondrial membrane potential of SGC-7901 cells was decreased and the ratio of green to red fluorescence increased significantly after incubation with CREF.</p><p><b>CONCLUSION</b>CREF can inhibit the growth and induce apoptosis of SGC-7901 cells, and the strongest effect is achieved at the optimal proportion of Coptidis Rhizoma and Evodiae Fructus at 6:1.</p>

Research on Sailong boneextracts on proliferation and apoptosis of osteoblast cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the metabolic regulation and apoptosis of Sailong bone extracts on rat osteoblast cells in vitro.</p><p><b>METHOD</b>Sailong bone fat-soluble extract, Sailong bone ethanol extract and Sailong bone aqueous extract were extracted with super critical fluid extraction (SCFE) , and Sailong bone boiling water component was extracted with distilled water directly. MTT assay was applied to determine the proliferation of the cell promoted by four Sailong bone extracts and PAS assay for the aqueous proportion of the cell at different doses.</p><p><b>RESULT</b>Sailong bone fat-soluble and aqueous extract (each 10 mg x mL (-1)) could significantly improve the proliferation of rat osteoblast cells ROS 17/2. 8 (P < 0. 01). Compared with the blank, the proportion of xub-G, of the different extracts from Sailong bone is reduce evidently. The result have shown the extracts from Sailong bone could reduce the rate of aqueous of cell and could suspend the aqueous.</p><p><b>CONCLUSION</b>Sailong bone can promoting the proliferation, degrading the rate of the apoptosis and delay the development of osteoblast to be the substitute of the bone of tiger as a Chinese materia medica.</p>

Dosage adjustment during transition from short-term continuous subcutaneous insulin infusion to subcutaneous insulin injections / 中华内分泌代谢杂志

The relationship of insulin dosage during transition from continuous subcutaneous insulin infusion(CSII)to subcutaneous injections of premixed human insulin in 197 type 2 diabetic patients was analyzed. Positive correlation(r=0.60,P