A drug co-delivery platform made of magnesium-based micromotors enhances combination therapy for hepatoma carcinoma cells.

Combination therapy is an emerging strategy to overcome multidrug resistance (MDR) in hepatocellular carcinoma (HCC) chemotherapy treatment. However, the passive diffusion in traditional delivery systems greatly retards the approach and penetration of drugs into hepatocellular carcinoma cells and thus hinders the efficacy of combination therapy. Micro/nanomotors with autonomous locomotion in a tiny scale provide the possibility of tackling this issue. Herein, an active drug delivery micromotor platform delicately designed to load drugs with different physicochemical properties and enhance the drug permeability of cells is demonstrated for HCC chemotherapy treatment. The biocompatible micromotor platform Mg/PLGA/CHI comprised magnesium (Mg) coated with two polymer layers made of poly(lactic-co-glycolic acid) (PLGA) and chitosan (CHI), where the hydrophobic and hydrophilic drugs doxorubicin (Dox) and Curcumin (Cur) were loaded, respectively. The autonomous motion of the micromotors with velocity up to 45 µm s-1 greatly enhanced the diffusion of chemotherapeutic drugs and led to higher extracellular and intracellular drug distribution. Moreover, hydrogen produced during the motion eliminated the excess reactive oxygen species (ROS) in the human hepatocellular carcinoma (HepG2) cells. Compared with inert groups, the absorption of Dox and Cur from the active micromotors was about 2.9 and 1.5 times higher in human hepatocellular carcinoma (HepG2) cells. In addition, the anti-tumor activity also obviously improved at the micromotor concentration of 1 mg mL-1 (cell proliferation was reduced by almost 30%). Overall, this work proposes an approach based on loading different chemotherapy agents on an active delivery system to enhance drug permeability and overcome MDR and provides a potentially effective therapeutic strategy for the treatment of HCC.

Qufeng Xuanbi Formula Ameliorates Airway Remodeling in Asthmatic Mice by Suppressing Airway Smooth Muscle Cell Proliferation through MEK/ERK Signaling Pathway.

Asthma is a common chronic respiratory disease. The Qufeng Xuanbi formula (QFXBF), a Chinese herbal decoction, has shown efficacy in the management of asthma. The purpose of this study was to investigate the potential therapeutic effects of QFXBF in the treatment of asthma both in vitro and in vivo. Platelet-derived growth factor (PDGF)-induced airway smooth muscle cell (ASMC) proliferation and MTT assays were used to explore the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, ovalbumin (OVA) group, high QFXBF group, low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). A mouse allergic asthma model was established using the intranasally administered OVA sensitization method. Morphological changes in the lung tissue were examined by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Finally, the protein expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), phospho-mitogen-activated protein kinase (p-MEK1/2), mitogen-activated protein kinase (MEK1/2), phospho-extracellular signal-regulated kinases (p-ERK1/2), and extracellular signal-regulated kinases (ERK1/2) in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. PDGF significantly increased the viability of ASMCs. Compared with mice in the control group, the airway walls and airway smooth muscle of mice in the OVA group were thickened, and the number of inflammatory cells around the bronchus significantly increased. Moreover, the administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathological changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment with QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA, and PCNA. QFXBF inhibited the proliferation of ASMCs by suppressing MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

Effect of urban air pollution on CRP and coagulation: a study on inpatients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important event in the course of chronic obstructive pulmonary disease that negatively affects patients' quality of life and leads to higher socioeconomic costs. While previous studies have demonstrated a significant association between urban air pollution and hospitalization for AECOPD, there is a lack of research on the impact of particulate matter (PM) on inflammation and coagulation in AECOPD inpatients. Therefore, this study investigated the association of changes in coagulation function and C-reactive protein (CRP) with PM levels in the days preceding hospitalization. PATIENTS AND METHODS: We reviewed the medical records of AECOPD patients admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between March 2017 and September 2019. We analyzed the association of coagulation function and CRP level in AECOPD patients with PM levels in the days before hospitalization. Multivariate unconditional logistic regression analyses were used to evaluate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of CRP data with hospitalization day. Kruskal-Wallis tests were used to evaluate mean aerodynamic diameter of ≥ 2.5 µm (PM2.5) exposure on the day before hospitalization; we assessed its association with changes in prothrombin time (PT) in AECOPD inpatients with different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes. RESULTS: The peripheral blood PT of AECOPD patients with PM2.5 ≥ 25 mg/L on the day before hospitalization were lower than those of patients with PM2.5 < 25 mg/L (t = 2.052, p = 0.041). Patients with severe GOLD class exposed to greater than 25 mg/L of PM2.5on the day before hospitalization showed significant differences in PT (F = 9.683, p = 0.008). Peripheral blood CRP levels of AECOPD patients exposed to PM2.5 ≥ 25 mg/L and PM10 ≥ 50 mg/L on the day before hospitalization were higher than those of patients exposed to PM2.5 < 25 mg/L and PM10 < 50 mg/L (t = 2.008, p = 0.046; t = 2.637, p = 0.009). Exposure to < 25 mg/L of PM2.5 on the day before hospitalization was significantly associated with CRP levels (adjusted OR 1.91; 95% CI 1.101, 3.315; p = 0.024). CONCLUSION: Exposure of patients with AECOPD to high PM levels on the day before hospitalization was associated with an increased CRP level and shortened PT. Moreover, PM2.5 had a greater effect on CRP level and PT than mean aerodynamic diameter of ≥ 10 µm (PM10). AECOPD patients with severe GOLD class were more sensitive to PM2.5-induced shortening of PT than those with other GOLD classes.

Effects of different household cooking methods on the biological properties of Chinese yam.

Yam (Dioscorea opposite Thunb) is used as a staple food and a traditional medicine in China. This study investigated the effects of different household cooking methods on the bioactive components (phenolic compounds, diosgenin and allantoin) and their bioaccessibility as well as the biological properties (antioxidant activity, hypoglycemic activity, anti-angiotensin I-converting enzyme (ACE) or anti-acetylcholinesterase (AChE)) of Chinese yam using an in vitro simulated digestion model. The results demonstrated that cooking caused significant losses of total soluble phenolic compounds (lowest loss of 20% for boiling at atmospheric pressure) and diosgenin content (lowest loss of 27.37% for microwaving) but no changes in the allantoin content. The cooking methods affected the bioaccessibility of the bioactive components differently. Normal steaming resulted in the highest amount of bioaccessible phenolic compounds (71.21%) and allantoin (79.07%), whereas high-pressure boiling in the highest content of diosgenin (75.58%). The concentration of bioactive components in the digesta fluid was correlated with the antioxidant activity and enzymatic inhibitory activities. Overall, household cooking processes allow the biological activity of yam to be retained by changing the profile of bioactive components potentially available for intestinal absorption. Thus, a household cooking method such as normal pressure steaming appeared to be most suitable for achieving the expected health benefits of yam.

The diagnostic value of prostate cancer between holmium laser enucleation of the prostate and transurethral resection of the prostate for benign prostatic hyperplasia: A retrospective comparative study.

BACKGROUND: To compare the diagnostic value of prostate cancer (PCa) between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data of 2909 patients who underwent surgery for benign prostatic hyperplasia (BPH) from January 2008 to June 2018. A total of 1362 patients received HoLEP, and 1547 patients received TURP. The baseline patient characteristics were collected. We then compared the perioperative outcomes of these patients who diagnosed with incidentally diagnosed prostatic carcinoma (IDPC) or PCa after BPH surgeries. RESULTS: The total detection rate of PCa in HoLEP group was higher than that in TURP group (85/6.24% vs. 61/3.94%, p = 0.005). Specifically, 55(4.6%) patients were diagnosed with IDPC in HoLEP group with prostate-specific antigen (PSA) less than 4 ng/ml, and 37(2.7%) patients in TURP group (p = 0.014). For the patients with PSA between 4 and 10 ng/ml, 15(13.9%) patients were diagnosed with PCa after HoLEP, and 6(5.0%) patients after TURP (p = 0.023). But the detection rate of PCa was not significantly different between the two groups when PSA was over 10 ng/ml. On the other hand, 57 in 1215 patients with no prostate biopsy preoperatively were diagnosed with PCa after HoLEP, while 42 in 1370 patients after TURP (4.7% vs. 3.1%, p = 0.040), respectively. Twenty-six patients received once biopsy and diagnosed with PCa in HoLEP group, while 15 patients in TURP group (18.4% vs. 8.9%, p = 0.018), respectively. However, no significant difference was observed for patients who received twice prostate biopsy in the two groups. CONCLUSIONS: The present study showed that HoLEP can provide a higher total detection rate of PCa when compared with TURP. Besides, this superiority was especially embodied in patients with PSA less than 10 ng/ml.

The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells.

AIM: To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. METHODS: The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm2 , 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. RESULTS: Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/ß-catenin signaling pathways by MAP is the potential mechanism. CONCLUSIONS: MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/ß-catenin signaling pathway.

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.

Electrical twitch-obtaining intramuscular stimulation in lower back pain: a pilot study.

OBJECTIVES: To determine if electrical twitch-obtaining intramuscular stimulation (ETOIMS) provides greater myofascial lower back pain relief than muscle stimulation or skin stimulation. DESIGN: In this single-blinded, crossover, pilot trial performed at a university-affiliated outpatient rehabilitation medicine department in Taiwan, 12 acupuncture-naive patients with lower back pain of 3-60 mos duration received one crossover treatment every 2 wks by monopolar needle electrode insertion at bilateral T10-S1 levels to: (1) paraspinal muscles, (2) overlying skin, and (3) paraspinal muscles with ETOIMS applied via the needle electrode at individual treatment sites. A total of 30 manual insertions per side per treatment were performed, with withdrawal after 2 secs. Beginning 1 wk before each trial and continuing until 2 wks after, patients completed a visual analog scale twice daily. In addition, on the day of treatment, patients received a physical examination and completed a visual analog scale both before and after treatment. RESULTS: Significant and immediate reduction in the visual analog scale levels was noted only with ETOIMS. Immediate improvement occurred in one of nine physical tests with muscle stimulation and ETOIMS only. In the 2 wks after treatment, absolute visual analog scale levels for ETOIMS were significantly lower than muscle stimulation and skin stimulation. ETOIMS resulted in a greater percentage of pain relief in the first week after treatment, although it was not statistically significant from muscle stimulation and skin stimulation. CONCLUSIONS: ETOIMS provided significantly greater immediate and sustained myofascial lower back pain relief than muscle stimulation and skin stimulation. Although a greater percentage of pain reduction occurred with ETOIMS, it was not statistically significant.