Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

[Physiological response to drought stress and drought resistance of six Helleborus orientlis cultivars]. / å ­ä¸ªä¸œæ–¹é“ç­·å­å“ç§å¯¹å¹²æ—±èƒè¿«çš„ç”Ÿç†å“åº”åŠæŠ—æ—±æ€§è¯„ä»·.

We examined the responses of physiological and leaf anatomic structural characteristics of six Helleborus orientalis cultivars to different degrees of drought stress. A membership function was used to evaluate drought resis-tance and identify physiological and leaf anatomical indicators that exhibited a stronger correlation with drought tolerance. The results showed that leaf thickness, leaf area per unit mass and soluble protein levels of the six cultivars significantly decreased with the increases of drought stress. Net photosynthetic rate, stomatal conductance, and transpiration rate of leaves increased first and then decreased, while the intercellular CO2 concentration decreased. The relative electrical conductivity, MDA, and H2O2 contents of leaves were increased. Soluble saccharide and proline contents, and antioxidant enzyme activities were first elevated and then decreased. With the increases of drought stress, the ratio of palisade tissue thickness to sponge tissue thickness and stomatal density increased. Key indicators and relativities in evaluating drought resistance of those cultivars were proline, soluble sugars, and the ratio of palisade tissue thickness to sponge tissue thickness. H. orientalis 'Anemone Red' and H. orientalis 'Ane-mone Red spotted' had better drought resistance, which could be the excellent parental materials for the cultivation of new drought-resistant cultivars in the future.

Aggregating-agent-assisted surface-enhanced Raman spectroscopy-based detection of acrylamide in fried foods: A case study with potato chips.

This study developed a simple, rapid, stable, and reliable technique for acrylamide (AAm) detection through surface-enhanced Raman scattering (SERS) on an AgNPs substrate with an aggregating agent. Specifically, the agglomeration effects of five types of salt solutions (NaCl, KCl, MgCl2, Na2SO4, and MgSO4) were investigated at different concentrations and optimized using an orthogonal experiment. The optimal amounts of the aggregating agent, analytes, and AgNPs were 4, 4, and 12 µL, respectively. A linear relationship (peak area I1449 = 7.4197x + 5984.8, R2 = 0.9971) between the characteristic peak area and AAm concentration was established in the range of 10 to 500 µg/L, and the LOD was 2.5 µg/L. The recoveries and relative standard deviations in the analysis of potato chips samples were 94.67 %-117.50 % and 8.43 %-12.29 %, respectively. The results of the proposed method were consistent with those obtained by LC-MS/MS method. This study demonstrated that SERS has excellent potential for application in the qualitative and quantitative analyses of AAm in fried foods.

Silicon-based bulky group-induced remote control and conformational preference in the synthesis and application of isolable atropisomeric amides with secondary alcohol or amine moieties.

Remote stereocontrol through conformational transmission along a carbon chain is highly important in synthetic systems and molecular architectures. In this work, the interactional reactivity between a remote silicon-based bulky group and an O-/N-containing functional group has been revealed and determined by lateral lithiation-substitution, desilylation, as well as desilylation-olefination with benzaldehyde. The results suggest considerable information transmission and steric hindrance that can be exploited for the controllable synthesis of atropisomeric molecules. Based on the remote steric effect of a functional group across the aromatic ring of an amide, the construction of isolable atropisomeric amides with functional groups, such as alcohol, amine, and olefin was successfully achieved. All these new atropisomers were obtained in reasonable yield in pure diastereomeric form, and the specific configuration of representative products was confirmed by X-ray crystallography.

Modulation of multifunctional N,O,P ligands for enantioselective copper-catalyzed conjugate addition of diethylzinc and trapping of the zinc enolate.

In this work, we have successfully synthesized a new family of chiral Schiff base­phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp3-central chirality from axial BINOL and sp3-central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper-catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer-like bimetallic multinuclear Cu-Zn complex constructed in situ was found to be substrate-selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C2-axial binaphthol and sp3-central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)-L1- and (R,S)-L4-based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C = 20 000, turnover number (TON) = 17,600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper-L4-complex-catalyzed conjugate addition, which resulted in the high-yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4, and the corresponding mechanistic study of the copper catalyst system were investigated by 31P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.

[Clinical study of delivery method in modified vaginal hysterectomy for large uterus].

OBJECTIVE: To prospectively explore the techniques, feasibility and safety of modified vaginal hysterectomy for large uterus. METHODS: A total of 158 patients undergoing hysterectomy at Beijing Hospital from January 2008 to December 2010 were divided into three groups: 12-16 gestational weeks large uterus for vaginal hysterectomy (n = 65, group 1), 12-16 gestational weeks uterus for abdominal hysterectomy (n = 47, group 2) and <10 gestational weeks uterus for vaginal hysterectomy (n = 46, group 3). The pattern and techniques of delivery in group 1 was based on the location of fibroids/adenomyoma (in anterior wall, posterior wall, uterine horn or broad ligament, cervix) and the direction of overall shape maximum diameter (direction towards abdomen defined as long type while the direction towards lateral pelvic wall wide type). The completion and safety were observed intraoperatively. The outpatient follow-up period was 1 month. RESULTS: A total of 158 cases of hysterectomy were performed successfully. The locations of fibroids/adenomyoma included anterior wall (n = 17), posterior wall (n = 24), unilateral uterine horn (n = 6), broad ligament (n = 3) and cervix (n = 2). in group 1, and there were long (n = 6) and wide (n = 7) types. They were all successfully delivered through vagina through various techniques. No case was converted into laparotomy. The average largest size (judged by as large as number of gestational weeks) and weight of uterus was group 2 and followed by group 1. But the difference of size and weight between two groups was insignificant (P > 0.05). Sorted by mean operative duration, mean amount of bleeding and decrease of hemoglobin, the declining order was the group 2, group 1 and group 3. The amount of bleeding for group 1 was less than that for group 2 (P < 0.05). But it was more than group 3 (P > 0.05). According to postoperative hospitalization duration, flatus time and indwelling catheter time, no statistical differences existed between groups 1 and 3. But the values of group 1 were significantly better than those of group 2 (P < 0.01, <0.05, <0.01). CONCLUSION: Vaginal hysterectomy is a safe and effective option for removing enlarged uterus. This pattern of operation can reduce the postoperative hospitalization time, flatus time and indwelling catheter time.

[Vaginal repair operation for anterior pelvic organ prolapse in elderly women].

OBJECTIVE: To identify the safety and efficacy of individualized vaginal surgery for anterior pelvic organ prolapse (POP) in elderly women so as to provide a clinical basis for studies on improving life quality by treatment in elderly women. METHODS: The individuation group consisted of 90 patients with a diagnosis of anterior POP. All over 60 years old, they underwent individualized vaginal surgery. The safety and efficacy, POP quantitative examination POP-Q change, cure and recurrence rate and life quality scores on incontinence and pelvic floor distress and impact were assessed. The control group (n = 60) was composed of patients (> 60 yr old) with a diagnosis of anterior POP were performed with Kelly-Kennedy operation. Their safety, efficacy, cure and recurrence rates were compared. RESULTS: Individualized vaginal surgery in elderly women was both safe and effective. The post-therapeutic recovery time was shorter (P < 0.05), the cure rate higher and the recurrence rate lower (P < 0.05) than that of control group. The life quality after individualized surgery improved (P < 0.01). CONCLUSION: The individualized vaginal surgery is safe and effective for a correction of anterior POP in elderly women. The life quality improves after operation.

[Expression of estrogen sulfotransferase (EST) gene and bridging integrator protein-1 (BIN1) gene and their significance in breast tissues].

BACKGROUND & OBJECTIVE: Estrogen sulfotransferase (EST) is an enzyme which metabolizes estrogen into inactive estrogen sulphate. Bridging integrator protein-1 (BIN1) is a novel c-myc-interacting protein with the features of tumor suppressor. EST and BIN1 may be protective in tumorigenesis. This study was to detect the gene expression of EST and BIN1 in breast cancer tissues,and further investigate the carcinogenesis mechanism of breast cancer. METHODS: The mRNA levels of EST and BIN1 in 12 specimens of normal human breast tissue, and 24 specimens of breast cancer were measured by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: EST mRNA and BIN1 mRNA were expressed in all normal human breast tissues, while EST mRNA was decreased in 75.0% (18/24), and lost in 25.0% (6/24) breast cancer specimens; BIN1 mRNA was decreased in 25.0%(16/24), and lost in 66.7.0% (16/24) breast cancer specimens. CONCLUSION: Down-regulation of EST mRNA and BIN1 mRNA may play an important role in the molecular mechanisms of breast carcinogenesis.

[Effects of phytoestrogen alpha-zearalanol on normal human breast].

OBJECTIVE: To study the effects of phytoestrogen alpha-zearalanol (alpha-ZAL) on normal human breast. METHODS: Ten specimens of normal human breast tissues were subcutaneously implanted into 30 athymic nude mice aged 9-10 weeks, one for 3 mice. These mice were then randomly divided into three groups: control group (without hormone treatment, n = 10), 1 mg/kg alpha-ZAL group (n = 10), and 5 mg/kg alpha-ZAL group (n = 10). All breast tissues were taken out 6 weeks later. Immunohistochemistry was used to determine the protein expressions of proliferating cell nuclear antigen (PCNA), inhibiting apoptosis gene Bcl-2, estrogen receptor (ER), and progesterone receptor (PR). Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression levels of estrogen sulfotransferase (EST) mRNA and bridging integrator protein-1 (BIN1) mRNA. Morphological features of grafts before and after treatment were also observed. RESULTS: Alpha-ZAL had no significant effects on Bcl-2, PCNA, ER, and PR expression of mammary epithelial cells in graft specimens. Alpha-ZAL upregulated BIN1 mRNA expression in grafts, but had no significant effect on ESTmRNA expression. CONCLUSIONS: Alpha-ZAL does not affect the morphology, proliferating, and apoptosis of epithelial cells in normal human breast tissues implanted into nude mice, but it may increase the gene expression of tumor-inhibiting BIN1, suggesting that alpha-ZAL may have potential proteotive effect on normal human breast.

[Expression of estrogen sulfotransferase in breast tissues and the regulation of ESTmRNA by estrogen].

OBJECTIVE: To detect the expression of estrogen sulfotransferase (EST) in breast tissues, and to investigate its significance in breast carcinogenesis and the relationship between EST mRNA and estrogen. METHODS: Seven specimens of normal human breast tissues from patients with benign breast diseases were implanted subcutaneously into athymic nude mice, one specimen divided into many pieces to be implanted into 2 groups of mice, totalling 14 mice. Then the 14 mice were divided into 2 groups: as control and the other injected intramuscularly with estradiol benzoate (B-E(2)) every other day for 6 weeks. Six weeks after, the implanted tissues were taken out. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of EST mRNA in 24 specimens of breast cancer, 6 specimens of normal breast tissues around the breast fibroadenoma, all resected during operation, and the specimens of implanted normal breast tissues from the mice (control group and B-E(2) group). The protein expression of estrogen receptor (ER) was detected by immunohistochemistry in the 24 specimens of breast cancer. RESULTS: EST mRNA was expressed in all normal human breast tissues and the expression was increased in the grafts from mice of B-E(2) group. However, the specimens of breast cancer showed decrease or absence of EST mRNA expression. CONCLUSION: EST mRNA expression is decreased or lost in breast cancer tissues. EST mRNA can be regulated by estrogen in normal breast tissues.

[The effect of estrogen benzoate on normal human breast tissue implanted into athymic nude mice].

OBJECTIVE: To investigate the proliferating effect of estradiol benzoate on normal human breast tissue. METHODS: Three specimens of normal human breast tissue were implanted into nine 9-10-week-old intact female athymic nude mice which were randomly divided into group A, B and C. Each specimen was divided into three parts, and each part was implanted into mice of each group of three (A, B and C) respectively. Two weeks later, part of xenografts was taken out from group A as control group, and then group A, B and C were injected muscularly with 3, 6, 9 micrograms estradiol benzoate once daily, respectively. After therapy for 28 days, the grafts were taken out and expression of proliferating cell nuclear antigen (PCNA), estrogen receptor (ER) and proliferating receptor (PR) in grafts were examined using immunohistochemical method. RESULTS: Compared with control group, PCNA was increased in group B and C (P < 0.05), but in group A had no significant change. ER was gradually down regulated by 3, 6 and 9 micrograms estradiol benzoate (P < 0.05); however, PR was increasingly up regulated (P < 0.05). CONCLUSIONS: Certain dosage of estradiol benzoate has proliferating effect on normal human breast tissue.