Clinical efficacy and safety of autologous serum intramuscular injection in patients with mild-to-moderate atopic dermatitis: a prospective, open-label, uncontrolled study

Background Autologous blood therapy (ABT) has been used to treat atopic dermatitis (AD) for over a century, even though evidence supporting its efficacy is lacking. We aimed to investigate the effectiveness and safety of autologous serum intramuscular injection (ASIM), which is a modified form of ABT, in treating mild-to-moderate AD. Methods This study was a 12-week, open-label, prospective, uncontrolled trial. Following a 4-week run-in period, 22 out of 25 screened patients received ASIM once a week for 4 weeks in conjunction with standard treatment. The primary outcome measure was the Eczema Area and Severity Index (EASI), while the secondary outcomes included the Scoring Atopic Dermatitis (SCORAD) score, Dermatologic Life Quality Index (DLQI), and patient ratings of pruritus, sleep difficulty, disease status, and treatment effectiveness. Safety parameters were also assessed. Results EASI scores showed a non-statistically significant trend toward improvement during ASIM intervention. Patients with at least a 50% improvement in the EASI score at 4 weeks were older and had lower peripheral eosinophil counts (p<0.05). Secondary endpoints, including the SCORAD score, pruritus, sleep difficulty, and DLQI, demonstrated statistically significant improvements at week 4 compared to baseline (p<0.05). No significant adverse reactions were observed. Conclusions This pioneering study suggests that repeated ASIM may improve the clinical symptoms of mild-to-moderate AD, particularly in terms of pruritus and overall quality of life. However, further research with a larger sample size is required to establish the clinical significance of these findings

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

Background and Objectives: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. Subjects and Methods: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). Results: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 (from 81.5??5.3 to 71.8??9.9 beats/minute (difference, -9.9??9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6??8.2 to 132.9??13.5 mmHg, p<0.0001; SiDBP: from 96.9??5.4 to 88.3??8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4??13.5 to 133.8??11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7??8.7 to 87.5??9.5 mmHg, p<0.0001). Conclusion: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension. Copyright ?? 2010 The Korean Society of Cardiology

Characterization of subcellular localization of eukaryotic clamp loader/unloader and its regulatory mechanism

Proliferating cell nuclear antigen (PCNA) plays a critical role as a processivity clamp for eukaryotic DNA polymerases and a binding platform for many DNA replication and repair proteins. The enzymatic activities of PCNA loading and unloading have been studied extensively in vitro. However, the subcellular locations of PCNA loaders, replication complex C (RFC) and CTF18-RFC-like-complex (RLC), and PCNA unloader ATAD5-RLC remain elusive, and the role of their subunits RFC2-5 is unknown. Here we used protein fractionation to determine the subcellular localization of RFC and RLCs and affinity purification to find molecular requirements for the newly defined location. All RFC/RLC proteins were detected in the nuclease-resistant pellet fraction. RFC1 and ATAD5 were not detected in the non-ionic detergent-soluble and nuclease-susceptible chromatin fractions, independent of cell cycle or exogenous DNA damage. We found that small RFC proteins contribute to maintaining protein levels of the RFC/RLCs. RFC1, ATAD5, and RFC4 co-immunoprecipitated with lamina-associated polypeptide 2 (LAP2) alpha which regulates intranuclear lamin A/C. LAP2 alpha knockout consistently reduced detection of RFC/RLCs in the pellet fraction, while marginally affecting total protein levels. Our findings strongly suggest that PCNA-mediated DNA transaction occurs through regulatory machinery associated with nuclear structures, such as the nuclear matrix

Specific Intracellular Uptake of Herceptin-Conjugated CdSe/ZnS Quantum Dots into Breast Cancer Cells

Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). the mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. the in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. to clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined by confocal laser scanning microscopy. as a result, the QD-Her bound specifically to the membrane of SK-BR3, which became almost saturated after 6 hours incubation. This suggests that the growth signal of breast cancer cells is inhibited completely by the specific binding of herceptin to the Her-2 receptor of SK-BR3 membrane, resulting in cell death

Cu/CuO@ZnO Hollow Nanofiber Gas Sensor: Effect of Hollow Nanofiber Structure and P–N Junction on Operating Temperature and Sensitivity

For the fast and easy detection of carbon monoxide (CO) gas, it was necessary to develop a CO gas sensor to operate in low temperatures. Herein, a novel Cu/CuO-decorated ZnO hollow nanofiber was prepared with the electrospinning, calcination, and photodeposition methods. In the presence of 100 ppm CO gas, the Cu/CuO-photodeposited ZnO hollow nanofiber (Cu/CuO@ZnO HNF) showed twice higher sensitivity than that of pure ZnO nanofiber at a relatively low working temperature of 300◦ C. The hollow structure and p–n junction between Cu/CuO and ZnO would be considered to contribute to the enhancement of sensitivity to CO gas at 300◦ C due to the improved specific surface area and efficient electron transfer. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. T.1

Effects of Platycodon grandiflorum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia (BPH) is highly prevalent in the male population over the age of 60 years, manifesting as prostatic enlargement and distinctive changes in tissue histomorphology. In this study, we investigated whether a Platycodon grandiflorum methanolic extract (PGME) improved BPH in a testosterone propionate (TP)-induced model of BPH in rats. Castration was performed via the scrotal route under sodium pentobarbital anesthesia, and BPH was induced in the rats with a subcutaneous injection of TP (3 mg/kg) given every consecutive day for 4 weeks after castration. The control group of castrated rats received subcutaneous injections of corn oil. Experimentally, induced rat model of BPH, PGME led to significant reductions in prostate weight and dihydrotestosterone levels in the serum and prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and PGME treatment significantly reduced the severity of the lesion. Therefore, PGME was effective in reducing TP-induced BPH in a rat model, and may be useful for the clinical treatment of patients with BPH.Keywords: Benign prostatic hyperplasia (BPH), dihydrotestosterone, testosterone, Platycodon grandifloru

PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells

Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity

Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress