Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Antioxidant Activity and the Therapeutic Effect of Sinomenine Hydrochloride-Loaded Liposomes-in-Hydrogel on Atopic Dermatitis.

Sinomenine hydrochloride is an excellent drug with anti-inflammatory, antioxidant, immune-regulatory, and other functions. Atopic dermatitis is an inherited allergic inflammation that causes itchiness, redness, and swelling in the affected area, which can have a significant impact on the life of the patient. There are many therapeutic methods for atopic dermatitis, and sinomenine with immunomodulatory activity might be effective in the treatment of atopic dermatitis. In this study, the atopic dermatitis model was established in experimental mice, and physical experiments were carried out on the mice. In the experiment, sinomenine hydrochloride liposomes-in-hydrogel as a new preparation was selected for delivery. In this case, liposomes were dispersed in the colloidal hydrogel on a mesoscopic scale and could provide specific transfer properties. The results showed that the sinomenine hydrochloride-loaded liposomes-in-hydrogel system could effectively inhibit atopic dermatitis.

Evaluation of Antioxidant Activity and Treatment of Eczema by Berberine Hydrochloride-Loaded Liposomes-in-Gel.

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 µg/cm2. BBH-L-Gel had a good scavenging capacity on DPPH and H2O2, and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4-2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment.

Effects of Medium Additives on the Mycelial Growth and Polysaccharide Biosynthesis in Submerged Culture of Bjerkandera fumosa.

Medium additives have been shown to affect the synthesis of active products in fungi. This study investigated the effects of corn stalk, poplar sawdust, Tween-80, and oleic acid on mycelial biomass and physicochemical properties, as well as the bioactivity of polysaccharides, including exopolysaccharides (EPS) and intracellular polysaccharides (IPS), in the submerged culture of Bjerkandera fumosa. Results showed that the addition of corn stalk or poplar sawdust increased the production of EPS but decreased the production of IPS; Tween-80 had less effect on the production of EPS and IPS; and oleic acid stimulated polysaccharide production significantly. Polysaccharide property analysis showed that the addition of corn stalk or poplar sawdust promoted the production of high-molecular-weight components in polysaccharides and changed the monosaccharide composition of polysaccharides, as well as increased the mannose, glucuronic acid, and xylose contents of IPS. Tween-80 and oleic acid also changed the molecular weight distribution of polysaccharides but only slightly affected the composition of monosaccharides. The bioactivity assay indicated that the polysaccharides obtained by adding corn stalk possessed high hydroxyl radical scavenging and antitumor activities. The effect of poplar sawdust was slightly weaker than that of corn stalk. EPS and IPS obtained from a culture with Tween-80 and oleic acid possessed low antioxidant activity. Moreover, their antitumor activity was improved and lost, respectively. The results obtained in this work are useful for improving the understanding of the optimization and regulation of bioactive polysaccharide production in the submerged culture of B. fumosa.

Autophagy-related gene PXN as a prognostic marker: Promotion of ovarian cancer progression by suppressing the p110ß/Vps34/Beclin1 pathway.

Among gynecological malignancies, ovarian cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy-related genes that determine patient prognosis using limma differential expression and Kaplan-Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK-8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of autophagy proteins and the PI3K/Akt/mTOR and p110ß/Vps34/Beclin1 pathway proteins in ovarian cancer cells was detected using western blot; autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy-related genes were found to be overexpressed in ovarian -cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p < .05). PXN activates and regulates signaling pathways related to cellular autophagy, ubiquitination, lysosomes, PI3K-Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3Ⅰ, inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110ß) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian cancer and is associated with poor patient prognosis. It may promote ovarian cancer cell proliferation, migration, and invasion by inhibiting cellular autophagy via suppression of the p110ß/Vps34/Beclin1 pathway.

Left ventricular reverse remodeling after transcatheter aortic valve replacement for predominant aortic stenosis and mixed aortic valve disease.

BACKGROUND: Mixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients. METHODS: From January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non-occurrence of left ventricular reverse remodeling (non-LVRR). RESULTS: After the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end-diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post-operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08-48.57; p < .001) and coronary artery disease (OR: 2.82; 95% CI: 1.08-7.34; p = .034) were independent risk factors for non-LVRR. CONCLUSION: LVRR also occurs in patients with MAVD, post-operative MR and coronary artery disease were independent risk factors for non-LVRR.

Study on the Antioxidant Effect of Shikonin-Loaded ß-Cyclodextrin Forming Host-Guest Complexes That Prevent Skin from Photoaging.

When the skin is overexposed to ultraviolet rays, free radicals will accumulate in the skin, causing lipid damage and even inducing photoaging of the skin. Combination therapy with antioxidant drugs is a good choice for topical treatment of skin photoaging due to its special physiological structure. In this paper, shikonin was encapsulated in ß-cyclodextrin (SH-ß-CD) by the precipitation crystallization method, which delayed the release of the drug and increased drug solubility. The average diameter of SH-ß-CD was 203.0 ± 21.27 nm with a zeta potential of -14.4 ± 0.5 mV. The encapsulation efficiency (EE%) was 65.9 ± 7.13%. The results of the in vitro permeation across the dialysis membrane and ex vivo transdermal release rates were 52.98 ± 1.21% and 88.25 ± 3.26%, respectively. In vitro antioxidant and antilipid peroxidation model assay revealed the antioxidant potential of SH and SH-ß-CD. In the mice model of skin photoaging, SH and SH-ß-CD had a recovery effect on the skin damage of mice, which could significantly increase the superoxide dismutase (SOD) activity in the skin. Briefly, SH-ß-CD had an obvious therapeutic effect on the skin photoaging of mice caused by UV, and it is promising in skin disease treatment and skin care.

Study on the controlled release and synergistic anti-oxidant activity in vitro and ex vivo of ligustrazine hydrochloride encapsulated into liposomes.

Ligustrazine with good antioxidant activity is one of the main active components of chuanxiong. We designed ligustrazine hydrochloride-loaded liposomes (LTH-L) by the thin film dispersion method. The particle size and zeta potential of liposomes was 118±10.61nm and -39.3±3.7mV, entrapment efficiency (EE%) was 75.05±10.67%. In vitro permeation across the dialysis membrane, the release rate (R%) of ligustrazine hydrochloride (LTH) and LTH-L were reached 80% and 60%. Ex Vivo transdermal behavior experiment showed the R% of LTH and LTH-L were between 30%-40%, the R% of LTH-L was slightly lower, because liposomes played the role on the sustained and controlled release of LTH. In addition, LTH, LTH-L and BL reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution for two hours, the scavenge rates (SR%) were 55.06±2.73%, 11.3±0.03% and 37.25±1.12% respectively (P<0.001) and the SR% of LTH, LTH-L and BL reacted with H2O2 were 4.13±0.02%, 0.52±0.01% and 75.15±6.10%. The inhibit rate (IR%) of LTH, LTH-L and BL on malondialdehyde (MDA) in liver homogenate were 35.44±1.79%, 1.22±0.01% and 17.92±0.29% (P<0.001), the IR% were 30.82±0.93%, 1.7±0.01% and 25.19±0.60% (P<0.001) in anti-low density lipoprotein (LDL) oxidation experiments, perhaps LTH prepared into LTH-L can play a better antioxidant role.

Pseudomonas hydrolytica sp. nov., multiple polymer-degrading bacteria isolated from soil in China.

A short rod-shaped, Gram-stain-negative strain that can degrade multiple polymers was isolated from forest soil in China and designated as DSWY01T. The results of 16S rRNA gene sequence analysis showed that this isolate shared high similarities with Pseudomonas alcaliphila NBRC 102411T (99.3 %), Pseudomonas mendocina NBRC 14162T (99.2%) and Pseudomonas oleovorans NBRC 13583T (99.0%). The results of phylogenetic analysis based on 16S rRNA gene sequence and multilocus sequence analysis (recA, gyrB, nuoD, glnS and rpoD) indicated that strain DSWY01T belongs to the genus Pseudomonas and is a member of the P. oleovorans group in an independent branch. The average nucleotide identity and digital DNA-DNA hybridization between the genome of strain DSWY01T and the genomes of other species (ANIb 77.72-89.65 %; GGDC 15.50-31.10 %) showed that the isolate represents a novel species. The DNA G+C content of strain DSWY01T was 63.67 mol%, and the major cellular fatty acids (>15 %) were a mixture of C18 : 1ω7c/C18 : 1ω6c and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and two unidentified lipids, and the major quinone was CQ-10. The morphological, physiological and biochemical characteristics of the isolate were then compared with those of reference type strains. The isolate differed considerably from its closest relatives and is representative of a novel species of Pseudomonas, for which the name Pseudomonas hydrolytica sp. nov. is proposed. The type strain is DSWY01T (=DSM 106702T=CCTCC AB 2018053T).

Ventricular strain analysis in patients with no structural heart disease using a vendor-independent speckle-tracking software.

BACKGROUND: Ventricular strain measurements vary depending on cardiac chamber (left ventricle [LV] or right ventricle [RV]), type of strain (longitudinal, circumferential, or radial), ventricular level (basal, mid, or apical), myocardial layer (endocardial or epicardial), and software used for analysis, among other demographic factors such as age and gender. Here, we present an analysis of ventricular strain taking all of these variables into account in a cohort of patients with no structural heart disease using a vendor-independent speckle-tracking software. METHODS: LV and RV full-thickness strain parameters were retrospectively measured in 102 patients (mean age 39 ± 15 years; 62% female). Within this cohort, we performed further layer-specific strain analysis in 20 subjects. Data were analyzed for global and segmental systolic strain, systolic strain rate, early diastolic strain rate, and their respective time-to-peak values. RESULTS: Mean LV global longitudinal, circumferential, and radial strain values for the entire cohort were - 18.4 ± 2.0%, - 22.1 ± 4.1%, and 43.9 ± 12.1% respectively, while mean RV global and free wall longitudinal strain values were - 24.2 ± 3.9% and - 26.1 ± 5.2% respectively. Women on average demonstrated higher longitudinal and circumferential strain and strain rate than men, and longer corresponding time-to-peak values. Longitudinal strain measurements were highest at the apex compared with the mid ventricle and base, and in the endocardium compared with the epicardium. Longitudinal strain was the most reproducible measure, followed closely by circumferential strain, while radial strain showed suboptimal reproducibility. CONCLUSIONS: We present an analysis of ventricular strain in patients with no structural heart disease using a vendor-independent speckle-tracking software.

The Controlled Release and Anti-Inflammatory Activity of a Tetramethylpyrazine-Loaded Thermosensitive Poloxamer Hydrogel.

PURPOSE: Tetramethylpyrazine-loaded poloxamer hydrogel materials were studied to achieve the controlled release of tetramethylpyrazine. METHODS: First, hydrogels having different concentrations of poloxamer 407 and poloxamer 188 were prepared. The gelling temperature and viscosity were measured. Second, we investigated the tetramethylpyrazine release rate from the thermosensitive poloxamer hydrogel materials in vitro and ex vivo. Finally, further study of the pharmacological efficacy of the tetramethylpyrazine-loaded thermosensitive poloxamer hydrogel materials was also investigated in vivo. RESULTS: The in vitro, ex vivo and in vivo experimental results showed that the tetramethylpyrazine-loaded poloxamer hydrogel with the appropriate gelling temperature, good adhesion and easy preparation controlled the release of tetramethylpyrazine. CONCLUSIONS: The hydrogel with the suitable nasal temperature and a satisfactory adhesion was selected. The relevant tests were carried out, including the determination of the concentration of drugs in the brain homogenate and the anti-inflammatory test after different modes of administration. So the poloxamer hydrogel was a novel carrier to deliver TMP to pass across the blood brain barrier via nasal administration.

Left ventricular metabolic remodeling and accompanied dysfunction in type 2 diabetic patients: A 3D speckle tracking analysis.

PURPOSES: The purposes of our study were to determine the risk factors related to metabolic left ventricular remodeling (LVR) in type 2 diabetes mellitus (T2DM) patients and to assess the LV function with different geometry in such population. METHODS: Seventy-eight T2DM patients with normal 2D-LVEF (≥55%) were enrolled and divided into two groups with LV normal geometry (LVN) and with LV remodeling (LVR). The control group was composed of forty age- and sex-matched healthy individuals with LVN. A multifactor logistic regression was used to determine the risk factors for LVR, and their diagnostic values were evaluated using the area under the ROC curves (AUC). Three-dimensional speckle tracking echocardiography (3DSTE) was used to measure LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). RESULTS: Fasting plasma glucose (FPG), hyperlipidemia, and BMI were independently associated with LVR in T2DM patients, and the AUC values were 0.699, 0.697, and 0.732, respectively. The T2DM patients with LVN showed significantly lower GLS than the controls (P < 0.05), whereas the T2DM patients with LVR showed significantly lower GLS, GCS, GAS, and GRS than the T2DM patients with LVN (all P < 0.01). Additionally, GLS, GAS, and GRS values decreased significantly in the T2DM patients with LV hypertrophy than in those with LV concentric remodeling (all P < 0.05). CONCLUSIONS: The routine echocardiography and 3DSTE could be used in combining way to detect the metabolic LV remodeling and accompanied dysfunction in T2DM patients.

Echocardiographic and pathomorphological features in fetuses with ductal-dependent congenital heart diseases.

OBJECTIVE: To individually analyze echocardiographic features in fetuses with ductal-dependent congenital heart diseases (DDCHD) and to verify the anatomical characteristics corresponding to the echocardiogram scan views. BACKGROUND: Ductal-dependent congenital heart diseases depends on the ductus arteriosus (DA) remaining open to maintain suitable pulmonary or systemic circulation after birth. An accurate diagnosis using prenatal echocardiography has important clinical significance in evaluating disease prognosis and ensuring timely treatment. METHODS: Fetuses were followed in the prenatal and postpartum periods via echocardiography. The results of postpartum echocardiography or autopsy specimens were compared with the prenatal echocardiography findings. RESULTS: One hundred and eight fetuses displayed various types of DDCHD including 66 fetuses with ductal-dependent pulmonary circulation, and 42 fetuses with ductal-dependent systemic circulation. Prenatal echocardiography revealed the typical characteristics of no forward flow signal from right ventricular outflow tract to the pulmonary trunk proximally and a reverse flow in the DA in most fetuses for ductal-dependent pulmonary circulation, a reverse flow in the transverse aortic arch for aorta atresia, and a loss of continuity between aortic arch and descending aorta for interruption of the aortic arch (IAA). All 108 fetuses displayed various types of complex CHD, including right ventricular dysplasia with pulmonary atresia (PA), severe Ebstein anomaly, double outlet right ventricle with PA, tetralogy of fallot with PA, single ventricle with PA or aorta atresia, hypoplastic left heart syndrome, and IAA. CONCLUSIONS: The identification of reverse flow in the aortic arch or DA aids in the subsequent accurate diagnosis of DDCHD associated with complex malformation of the heart.

A Nasal Temperature and pH Dual-Responsive In Situ Gel Delivery System Based on Microemulsion of Huperzine A: Formulation, Evaluation, and In Vivo Pharmacokinetic Study.

Huperzine A (hup A), extracted from the Chinese medicinal plant Huperzia serrata, is a reversible and highly selective second-generation acetylcholine esterase (AchE) inhibitor for treating Alzheimer's disease (AD), but it suffers from low bioavailability in the brain. This study aimed to develop a nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of hup A (hup A-M-TPISG). The optimal formulation was obtained by central composite design and response surface methodology. The optimized mucoadhesive formulation, hup A-M-TPISG, was composed of pluronic F127 (20.80%), pluronic F68 (2.8%), and chitosan (0.88%) as the gel matrix, which could gelatinize under physiological conditions (29-34°C, pH 6.5) because of its temperature and pH responsiveness. The optimized hup A-M-TPISG formulation was further evaluated by in vitro release and in vivo pharmacokinetic studies via microdialysis. The in vitro release study showed continuous and steady drug release from hup A-M-TPISG, which was in accordance with the first-order model. Moreover, the pharmacokinetic results revealed that the optimized formulation for nasal administration, with convenient administration and improved patient compliance, could achieve similar brain-targeting properties as intravenous administration. In conclusion, the hup A-M-TPISG for intranasal administration, as an effective and safe vehicle, could enhance the absorption of hup A in vivo and would be a promising noninvasive alternative for partially improving brain-targeting therapy.

Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer.

BACKGROUND: Combined anthracycline-trastuzumab chemotherapy has been associated with LV dysfunction. We aimed to assess early changes in left ventricular (LV) and right ventricular (RV) mechanics associated with combined anthracycline-trastuzumab treatment for breast cancer. As well as explore whether early changes in 2-dimensional (2D)-speckle tracking echocardiography (STE) could predict later chemotherapy-induced cardiotoxicity. METHODS: Sixty-six patients with breast cancer who received anthracycline-trastuzumab treatment were included (mean [±SD] age, 52 [9] years). Echocardiograms were available for analysis with 2D-STE at the following time points: pretreatment (T0), first cycle (T1), and second cycle (T2) of combined chemotherapy. All patients had a normal pretreatment LV ejection fraction (LVEF). Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. RESULTS: Cardiotoxicity developed in 13 of the 66 patients (20%). The mean (±SD) LVEF at T0 was 66% (±6); at T1 60% (±7); and at T2, 54% (±6). For the 53 patients without cardiotoxicity, the LVEF was 65% (±4%) at T0, 63% (±5%) at T1, and 62% (±4) at T2. Global longitudinal strain (GLS) at T1 was the strongest indicator of subsequent cardiotoxicity (area under the curve, 0.85; cutoff value, - 14.06; sensitivity, 91%; specificity, 83%; P = .003). Compared with baseline (T0), left ventricular longitudinal strain, LV circumferential strain, circumferential peak systolic strain rate (SR), circumferential peak early diastolic SR, right ventricular longitudinal strain, and longitudinal peak systolic SR at T1 and T2 were reduced significantly in patients with cardiotoxicity (P < .05). CONCLUSIONS: Anthracycline-trastuzumab treatment leads to early deterioration of LV GLS, circumferential strain, and systolic SR. Right ventricular GLS and SR were also affected. Early changes in GLS are good predictors of subsequent development of anthracycline-trastuzumab-induced cardiotoxicity.

Left ventricular structural alterations are accompanied by subclinical systolic dysfunction in type 2 diabetes mellitus patients with concomitant hyperlipidemia: An analysis based on 3D speckle tracking echocardiography.

AIMS: The aims of the current study were to analyze and compare the left ventricular (LV) structure and function in type 2 diabetes mellitus (T2DM) patients with or without hyperlipidemia using conventional echocardiography and real-time three-dimensional speckle tracking echocardiography (3DSTE) and to determine the variables that could affect LV strain values in these patients. METHODS: Eighty-one T2DM patients with normal LVEF (≥55%) were included, 41 of whom had hyperlipidemia as comorbidity. Forty age- and gender-matched healthy volunteers were recruited as the control group. Conventional echocardiography and 3DSTE were performed, and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured. RESULTS: Significant differences in two-dimensional LV geometry were found among three groups (P = .015). Compared with the control group, LV remodeling was more prevalent in the patients with T2DM, and LV hypertrophy was most prevalent in the T2DM patients with hyperlipidemia. GLS and GCS values decreased significantly in the T2DM patients without hyperlipidemia relative to the control group (P < .01 and P < .05). The GLS, GCS, GAS, and GRS values in the T2DM patients with hyperlipidemia were all significantly lower than those in the control group (all P < .001) and were also significantly lower than those in the T2DM patients without hyperlipidemia (P < .01 or P < .05). Both fasting plasma glucose (FPG) and hyperlipidemia were independently associated with all strain values in patients with T2DM. CONCLUSIONS: The combination of conventional echocardiography and 3DSTE could detect subclinical LV abnormalities in T2DM patients with or without hyperlipidemia.

Association of pulse pressure with left ventricular geometry and function in elderly nonhypertensive patients with diabetes: A 3D speckle tracking echocardiography study.

PURPOSE: The aims of this study were to investigate and compare the left ventricular (LV) geometry and function in elderly nonhypertensive type 2 diabetic patients with normal (NPP, <60 mm Hg) and with high (HPP, ≥60 mmHg) 24-hour pulse pressure, and to explore the independent predictors of LV strain values in these patients. METHODS: A total of 76 elderly nonhypertensive type 2 diabetic patients with normal (≥55%) LV ejection fraction (LVEF) were included, 36 of whom had HPP. The control group included 40 age- and sex-matched healthy volunteers with normal NPP. Conventional echocardiography and three-dimensional speckle-tracking echocardiography (3DSTE) were performed and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured. RESULTS: Significant differences in the two-dimensional LV geometry were found among the three groups (p = 0.015), and concentric geometry was most prevalent in the diabetic patients with HPP. The diabetic patients with NPP only showed significantly lower GLS than the controls (p < 0.05). However, the diabetic patients with HPP showed significantly lower LVEF and severely lower strain values in all directions than the controls and the diabetic patients with NPP (p < 0.01or p < 0.05 or p < 0.001). Fasting plasma glucose, HPP, and body mass index were independently associated with all strain parameters in diabetic patients. CONCLUSIONS: The combination of conventional echocardiography and 3DSTE could detect LV subclinical abnormalities in nonhypertensive type 2 diabetic patients with NPP and HPP. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:416-425, 2017.

Speckle tracking echocardiography predicts early subclinical anthracycline cardiotoxicity in patients with breast cancer.

PURPOSE: This study aimed to assess the early changes of left ventricular (LV) and right ventricular (RV) mechanics associated with anthracycline treatment for breast cancer and to determine whether two-dimensional speckle tracking echocardiography (2D-STE) analysis could predict chemotherapy-induced cardiotoxicity. BACKGROUND: Anthracycline generates progressive LV dysfunction associated with a poor prognosis. Early detection of minor change of myocardial mechanics is thus important. METHODS: Pretreatment (T0), first (T1), and second (T2) on-treatment echocardiograms were available for analysis with 2D-STE. All patients had normal pretreatment left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a drop in LVEF to ≤53% or an absolute decrease of 10% on a follow-up echocardiogram. Analysis of variance receiver operating curve and area under the curve (AUC) analysis was performed. RESULTS: Eighty-six patients with breast cancer who received anthracycline treatment were included. Compared with T0, LV and RV global longitudinal strain (GLS), and LV global circumferential strain (GCS) at T1 and T2 were reduced significantly (p < 0.005 for all). There was a significant decrease in the LV GLS with increasing age at both T1 and T2 (p < 0.05 for all). GLS at T1 (AUC 0.83; cutoff -14.06; sensitivity 83%; specificity 84%; p = 0.0033) and at T2 (AUC 0.90; cutoff -13.84; sensitivity 93%; specificity 84%; p < 0.0001) was the strongest indicator of subsequent cardiotoxicity. CONCLUSIONS: Anthracycline treatment induces early deterioration of LV global longitudinal and circumferential strain, involving also the RV. Early change in the GLS seems to be a good predictor of the development of chemotherapy-induced cardiotoxicity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:222-230, 2017.

Tetramethylpyrazine-Loaded Hydrogels: Preparation, Penetration Through a Subcutaneous-Mucous-Membrane Model, and a Molecular Dynamics Simulation.

Tetramethylpyrazine (TMP) was extracted from Ligusticum chuanxiong hort. The compound is known to have a variety of medicinal functions; in particular, it is used for the treatment of cerebral ischemic diseases. TMP-loaded hydrogels offer an excellent preparation with the capacity to bypass the blood-brain barrier, allowing treatment of the brain through intranasal administration. We prepared TMP-loaded hydrogels using carbomer 940 and evaluated the release of TMP from the hydrogel. We determined the release rate using Franz-type diffusion cell experiments with a subcutaneous-mucous-membrane model and also by a molecular dynamics (MD) simulation. In general, the former method was more complicated than the latter was. The dynamic behavior of TMP release from the hydrogel was revealed by analysis of the mean square displacement of the trajectory in the MD simulation. The coefficient of TMP diffusion from the hydrogel was calculated at different temperatures (277, 298, and 310 K) by using MD software. The results showed that the coefficient of diffusion increased with an increase in temperature. This trend was observed both experimentally and in the MD simulation. Therefore, the MD simulation was a complementary method to verify the experimental data.

Purification and characterization of a novel extracellular alkaline protease from Cellulomonas bogoriensis.

An extracellular alkaline protease produced by the alkali-tolerant Cellulomonas bogoriensis was purified by a combination of ammonium sulfate precipitation and cation exchange chromatography. The purity of the protease was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its molecular weight was confirmed to be 18.3 kDa. The enzyme showed optimum activity at 60 °C and pH 11. The stability of the protease was maintained at a wide temperature range of 4-60 °C and pH range of 3-12. Irreversible inhibition of the enzyme activity by phenylmethylsulfonyl fluoride and tosyl-l-phenylalanine chloromethyl ketone demonstrated that the purified enzyme is a chymotrypsin of the serine protease family. The Km and Vmax of the protease activity on casein were 19.2 mg/mL and 25000 µg/min/mg, respectively. The broad substrate specificity and remarkable stability in the presence of organic solvents, salt, and commercial detergents, as well as its excellent stain removal and dehairing capability, make the purified alkaline protease a promising candidate for industrial applications.