Near-Infrared-II Light Induced Mild Hyperthermia Activate Cisplatin-Artemisinin Nanoparticle for Enhanced Chemo/Chemodynamic Therapy and Immunotherapy.

Chemodynamic therapy (CDT) is an effective cancer treatment that uses Fenton reaction to induce cancer cell death. Current clinical applications of CDT are limited by the dependency of external supply of metal ions as well as low catalytic efficiency. Here, a highly efficient metal-free CDT by using endoperoxide bridge-containing artesunate as free radical-generating substance is developed. A Pt(IV) prodrug (A-Pt) containing two artesunate molecules in the axial direction is synthesized, which can be decomposed into cisplatin and artesunate under reducing intracellular environment in tumor cells. To improve the catalytic efficiency for Fenton reaction, a near-infrared-II (NIR-II) photothermal agent IR1048 is incorporated to achieve a mild hyperthermia effect. By encapsulating the A-Pt and IR1048 with human serum albumin, A-Pt-IR NP are formulated for efficient drug delivery in 4T1 tumor-bearing mice. NIR-II light irradiation of A-Pt-IR NP treated mice show accelerated Fenton reaction. In addition, A-Pt-IR NP could also induce strong immunogenic cell death, which effectively reverses the immunosuppressive tumor microenvironment, and augments antitumor immunity. This study demonstrates that A-Pt-IR NP are potent biodegradable NIR-II active chemotherapy/CDT nanomedicine for clinical translation.

Albumin-based lipoprotein nanoparticles for improved delivery and anticancer activity of curcumin for cancer treatment.

Aim: To prepare curcumin (CUR)-loaded, dioleoyl phosphoethanolamine-conjugated human serum albumin nanoparticles (NPs) and to evaluate their effectiveness in breast cancer therapy. Materials & methods: The CUR-loaded NPs were physicochemically characterized and evaluated for their cytotoxicity in murine (4T1) and human breast cancer (MDA-MB-231) cell lines. The antitumor efficacy of the nanomedicine was evaluated in 4T1 tumor bearing mice. Results: The prepared NPs exhibited encapsulation and drug loading efficiencies of approximately 79 and 21%, respectively. The NPs were taken up efficiently and markedly hindered the proliferation of breast cancer cells compared with free drug. NPs exhibited greater suppression of tumor growth in 4T1 tumor bearing mice. Conclusion: CUR-human serum albumin-dioleoyl phosphoethanolamine NPs could be a potential treatment alternative for solid tumors, including breast cancer.

Nephrotic syndrome due to preeclampsia before 20 weeks of gestation: a case report.

BACKGROUND: Preeclampsia (PE) refers to the development of hypertension and new-onset proteinuria or progressive organ damage (especially kidney) in a previously normotensive pregnant women after 20 weeks of gestation. Thus, new-onset nephrotic syndrome due to PE before 20 weeks of gestation seems to be rare, making its diagnosis difficult in this time period. CASE PRESENTATION: A 28-year-old woman presented with a new-onset nephrotic syndrome at 16 weeks of gestation. A high dose of oral glucocorticoids (prednisolone, 40 mg) was initiated for presumed glomerulonephritis since she presented with severe nephrotic syndrome before 20 weeks of gestation, however, the treatment was not effective. At 21 weeks of gestation, we confirmed that the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high (sFlt-1, 13,400 pg/mL; PlGF, 21.9 pg/mL; serum sFlt-1/PlGF ratio 611.9). Therefore, we diagnosed nephrotic syndrome due to PE, and oral glucocorticoids were discontinued. After she underwent a cesarean section at 24 weeks & 3 days, we performed a kidney biopsy. Focal segmental sclerotic lesions with epithelial cell hyperplasia and foam cells in the tubular poles were seen on light microscopy. On immunofluorescence tests, C4d staining showed linear peripheral patterns in the glomeruli. Electron microscopy revealed diffuse subendothelial edema with focal foot process effacement. The histological diagnosis was severe glomerular endotheliosis with focal segmental glomerulosclerosis. Furthermore, the histology of placenta was consistent with PE. Eight months after delivery, her proteinuria disappeared completely. CONCLUSIONS: We not only confirmed an abnormal serum sFlt-1/PlGF ratio but also presented the histology compatible with pure PE in the kidney and placenta in a case of nephrotic syndrome before 20 weeks of gestation. The serum sFlt-1/PlGF ratio may be useful in determining the treatment strategy for atypical cases of pregnant women with nephrotic syndrome, particularly before 20 weeks of gestation.

[Effect of postoperative hypoalbuminemia and supplement of human serum albumin on the development of poor wound healing following lumbar internal fixation surgery].

Objective: To analyze the association between postoperative hypoalbuminemia and poor wound healing, and to evaluate whether postoperative supplementation of human serum albumin can improve postoperative wound healing after lumbar internal fixation surgery. Methods: From January 2014 to December 2018, 602 patients who underwent lumbar internal fixation surgery in the Department of Orthopedics, Zhujiang Hostiptal of Southern Medical University were identified. There were 250 males (41.5%) and 352 females (58.5%), with an average age of (60±12) years. All patients' clinical records were reviewed, including demographics data, comorbidity data, preoperative serum laboratory values, intraoperative factor, postoperative serum laboratory values and wound healing, and the incidence rate of poor wound healing was calculated. The statistical analyses were performed with R software and Empower(R) to analyze the factors related to poor wound healing. Multiple logistic regression models were performed with adjustment for the potential confounders to evaluate the effect of postoperative hypoalbuminemia and supplementation of human serum albumin on the development of poor wound healing. Results: Poor wound healing occurred in 51(8.47%) patients. After adjusting for the confounding factors, multiple regression analysis showed that there was no correlation between postoperative albumin levels and poor wound healing(OR=1.00, 95%CI: 0.91-1.10, P=1.000). Compared with patients with postoperative normal albumin level, postoperative hypoalbuminemia would increase the risk of poor wound healing by 13% (OR=1.13, 95%CI: 0.47-2.70, P=0.787). There was no correlation between supplementation of human serum albumin and poor wound healing in patients with normal albumin levels or postoperative hypoalbuminemia (P>0.05). Conclusions: There is no correlation between postoperative hypoalbuminemia and poor wound healing after lumbar internal fixation surgery. Postoperative supplementation of human serum albumin can't improve wound healing.

Green Synthesized Nanomaterials as Theranostic Platforms for Cancer Treatment: Principles, Challenges and the Road Ahead.

With the emergence of nanotechnology, new methods have been developed for engineering various nanoparticles for biomedical applications. Nanotheranostics is a burgeoning research field with tremendous prospects for the improvement of diagnosis and treatment of various cancers. However, the development of biocompatible and efficient drug/gene delivery theranostic systems still remains a challenge. Green synthetic approach of nanoparticles with low capital and operating expenses, reduced environmental pollution and better biocompatibility and stability is a latest and novel field, which is advantageous over chemical or physical nanoparticle synthesis methods. In this article, we summarize the recent research progresses related to green synthesized nanoparticles for cancer theranostic applications, and we also conclude with a look at the current challenges and insight into the future directions based on recent developments in these areas.

Alternatives to Biologics in Management of Knee Osteoarthritis: A Systematic Review.

BACKGROUND: Knee osteoarthritis (KOA) is a common condition encountered by physicians. KOA is addressed by a wide array of modalities including a number of nonbiological treatments. METHODS: PubMed, ISI Web of Science, and SPORTDiscus were searched for level 1 to 4 studies published from inception to August 2017. RESULTS: A total of 18 studies were evaluated and results demonstrated moderate supporting evidence for prolotherapy and limited evidence for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin. Evidence for local anesthetic agents was conflicting. CONCLUSION: There is moderate supportive evidence for the effectiveness of prolotherapy in improving pain and function in both, short-term and long-term. Limited supporting evidence found for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin in improving pain and function. There is conflicting evidence for the use of local anesthetic agents in patients with KOA.

Intra-Arterial Perimortem Resuscitation Using a Micellar Colloid.

OBJECTIVE: The following were studied in a perimortem mouse model of rapid blood loss: (a) efficacy of a prototypical micellar colloid, Intralipid 20%, (IL20), compared to albumin (b) comparison of intra-arterial and intravenous resuscitation, (c) efficacy of IL20 at a volume 2 × the volume of blood removed, and (d) efficacy of oxygenated IL20 after clinical death (CD). METHODS: CD, the absence of breathing and zero blood pressure (BP), was produced by removing 55% of the blood volume within 3 minutes. After CD, the chest was opened to observe ventricular contraction. IL20, Ringer's lactate (RL), or albumin was infused perimortem. RESULTS: Without resuscitation CD occurred in 2.85 ± 0.40 minutes. Ventricular contraction persisted 20.50 ± 1.11 minutes after CD. RL infused immediately after CD restored breathing if given intra-arterially but not intravenously. IL20 was superior to the prototypical colloid, albumin in maintaining the BP. Increasing the volume of IL20 further increased BP. Delayed RL infusion after CD failed to restore breathing. Delayed resuscitation after CD with oxygenated IL20 restored breathing and BP. CONCLUSIONS: Micellar colloid is superior to the prototypical colloid albumin and can possibly be of use when signs of life are no longer present. In extremis, intra-arterial infusion is superior to intravenous infusion.