Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture.

Good's buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers. However, the emergence of severe adverse effects, such as cellular uptake, lysosomal autophagic activation, and visible light-induced cytotoxicity, raises serious questions over its biocompatibility while underlying mechanism was unclear. Here we report that riboflavin (RF, component of cell culture medium) generates 1O2, ·OH, and O2 •- under visible light exposure during regular cell manipulation. These short half-life reactive oxygen species (ROS) react with tertiary amine groups of HEPES, producing 106.6 µM of H2O2. Orders of magnitude elevated half-life of ROS in the medium caused severe cytotoxicity and systematic disorder of normal cell functions. We have further designed and validated zwitterionic betaines as the new generation biocompatible organic pH buffers, which is able to completely avoid the adverse effects that found on HEPES and derivate Good's buffers. These findings may also open a new avenue for zwitterionic betaine based materials for biomedical applications.

Phosphonate/quaternary ammonium copolymers as high-efficiency antibacterial coating for metallic substrates.

Designing a coating material with efficient bactericidal property to cope with bacterial associated infections is highly desirable for metallic implants and devices. Here, we report phosphonate/quaternary ammonium copolymers, p(DEMMP-co-TMAEMA), as the new type of metal anchorable high-efficiency antibacterial coating. Seven p(DEMMP-co-TMAEMA) polymers with varied cationic components were precisely prepared via random radical polymerization. Copolymers were constructed on titanium alloy (TC4) substrates based on strong covalent bonding between the phosphonate group and metallic substrates through a one-step process as evidenced by XPS and water contact angle tests. A robust relationship between the composition of the copolymers and the bactericidal ability endowed to TC4 substrates was established. Results showed that the copolymer, with the pDEMMP content even as low as 6.3%, was able to anchor onto TC4 substrates. With the increase of cationic pTMAEMA content from 4.0 to 93.7% in the coating copolymer, the bactericidal ability endowed to the TC4 substrates was steadily increased from 39.4 to 98.8% for S. aureus and from 70.0 to 99.4% for E. coli after 8 h's of contacting. All p(DEMMP-co-TMAEMA) coating on TC4 substrates showed limited cytotoxicity to C2C12 cells. Notably, the phosphonate/quaternary amine copolymers can be easily constructed on diverse biomedical metals such as titanium (Ti), stainless steel (SS), and Ni/Cr alloys with significantly increased antibacterial performance, demonstrating the potency of the copolymer as the general high-efficiency antibacterial coating for diverse bio-metals.

Impact of dietary intake of sodium and potassium on short-term blood pressure variability.

BACKGROUND: Dietary Approaches to Stop Hypertension (DASH)-Sodium trial showed that dietary sodium and potassium affect blood pressure (BP). We aimed to investigate whether dietary sodium and potassium affect short-term BP variability (BPV) in addition to BP. METHODS: A total of 343 participants from the DASH-Sodium trial (age 48.4 ±â€Š9.7, 42.5% men) and 323 individuals from the Jackson Heart Study (JHS) (age 56.7 ±â€Š11.2, 30.7% men) with satisfactory ambulatory BP monitoring records and 24-h urine collection were included. Average real variability (ARV) was calculated as a measure of short-term BPV. RESULTS: By estimating dietary intake from urinary excretion, we observed that higher urinary sodium-to-potassium ratio was significantly associated with higher diastolic ARV in both studies. Among the DASH-Sodium trial, potassium-rich DASH diet alone had insignificant effect on both systolic (-0.1 ±â€Š1.7 mmHg, P = 0.343) or diastolic ARV (-0.2 ±â€Š1.5 mmHg, P = 0.164), whereas combined DASH diet and low sodium intake significantly reduced both systolic (8.5 ±â€Š1.6 vs. 8.9 ±â€Š1.7 mmHg, P = 0.032) and diastolic ARV (7.5 ±â€Š1.5 vs. 7.8 ±â€Š1.6 mmHg, P = 0.025) as compared with control diet and high sodium intake. As the reduction of systolic ARV was majorly derived from the change of mean SBP, diastolic ARV was significantly determined by urinary sodium-to-potassium ratio (ß coefficient ±â€Šstandard error: 0.012 ±â€Š0.004; P = 0.006) after adjusting for age, sex, smoking, mean DBP, BMI, and race. CONCLUSION: Dietary sodium and potassium can jointly modulate short-term BPV in addition to BP. Combined DASH diet and low sodium intake may reduce systolic and diastolic ARV via different mechanisms.

Phosphonate/zwitterionic/cationic terpolymers as high-efficiency bactericidal and antifouling coatings for metallic substrates.

Bacteria associated infection is a critical challenge for metallic implants and devices in biomedical applications. Here, we report phosphonate/zwitterionic/quaternary amine terpolymers as a new type of antifouling and bactericidal coating for metallic substrates. Through reversible-addition fragmentation chain transfer polymerization (RAFT) and quaternization, well-controlled phosphonate/zwitterionic/cationic terpolymers with identical phosphonate segments (repeat units of 15) and varied zwitterionic and cationic components (nSBMA : nTMAEMA = 64 : 0, 54 : 18, 18 : 32, 9 : 52, and 0 : 70) were precisely prepared. The polymers can be coated on TC4 substrates based on the strong coordination between phosphonate groups and metallic substrates, as evidenced by water contact angle and XPS tests. Bactericidal evaluation revealed that the antibacterial efficiency was enhanced with the increase of cationic content in the coating polymers. TC4 substrates coated with the polymer coating with a cationic segment of 70 repeat units were able to kill 97.5 and 94.0% of S. aureus and E. coli, respectively. By virtue of the antifouling ability of the zwitterionic component and the bactericidal ability of the cationic component, the antibacterial efficiency was increased to 99.5% without significant compromising of the cytocompatibility. Meanwhile, the dual functional terpolymers could be easily applied on other metallic substrates, such as titanium, stainless steel, and Ni/Cr alloy, which were able to kill up to 97.9% of S. aureus and 99.9% of E. coli, respectively, endowing the excellent antibacterial properties to general bio-metals. The high-efficiency antibacterial modification strategy demonstrated here may find many applications on metallic implants and devices to combat bacterial associated infections.

Acupuncture therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Fibromyalgia (FM) can cause chronic widespread pain and seriously affect the quality of patient lives. Acupuncture therapy is widely used for pain management. However, the effect of acupuncture on FM is still uncertain. The aim of this review was to determine the effect and safety of acupuncture therapy on the pain intensity and quality of life in patients with FM. MATERIALS AND METHODS: We searched PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and the Chinese Biomedical Literature Database to collect randomized controlled trials (RCTs) of acupuncture for FM published before May 2018. A meta-analysis was performed according to the Cochrane systematic review method by using RevMan 5.3 software, and GRADE was used to evaluate the quality of the evidence. RESULTS: We identified 12 RCTs that compared acupuncture therapy to sham acupuncture or conventional medication. Meta-analysis showed that acupuncture was significantly better than sham acupuncture for relieving pain (MD =-1.04, 95% CI [-1.70, -0.38], P=0.002, I 2=78%) and improving the quality of life (MD =-13.39, 95% CI [-21.69, -5.10], P=0.002, I 2=82%), with low- to moderate-quality evidence in the short term. At follow-up in the long term, the effect of acupuncture was also superior to that of sham acupuncture. No serious adverse events were found during acupuncture. CONCLUSION: Acupuncture therapy is an effective and safe treatment for patients with FM, and this treatment can be recommended for the management of FM.