NIR-Light-Triggered Mild-Temperature Hyperthermia to Overcome the Cascade Cisplatin Resistance for Improved Resistant Tumor Therapy.

Currently, cisplatin resistance has been recognized as a multistep cascade process for its clinical chemotherapy failure. Hitherto, it remains challenging to develop a feasible and promising strategy to overcome the cascade drug resistance (CDR) issue for achieving fundamentally improved chemotherapeutic efficacy. Herein, a novel self-assembled nanoagent is proposed, which is constructed by Pt(IV) prodrug, cyanine dye (cypate), and gadolinium ion (Gd3+), for systematically conquering the cisplatin resistance by employing near-infrared (NIR) light activated mild-temperature hyperthermia in tumor targets. The proposed nanoagents exhibit high photostability, GSH/H+-responsive dissociation, preferable photothermal conversion, and enhanced cellular uptake performance. In particular, upon 785-nm NIR light irradiation, the generated mild temperature of ≈ 43 °C overtly improves the cell membrane permeability and drug uptake, accelerates the disruption of intracellular redox balance, and apparently enhances the formation of Pt-DNA adducts, thereby effectively overcoming the CDR issue and achieves highly improved therapeutic efficacy for cisplatin-resistant tumor ablation.

Entropy by Neighbor Distance as a New Measure for Characterizing Spatiotemporal Orders in Microscopic Collective Systems.

Collective systems self-organize to form globally ordered spatiotemporal patterns. Finding appropriate measures to characterize the order in these patterns will contribute to our understanding of the principles of self-organization in all collective systems. Here we examine a new measure based on the entropy of the neighbor distance distributions in the characterization of collective patterns. We study three types of systems: a simulated self-propelled boid system, two active colloidal systems, and one centimeter-scale robotic swarm system. In all these systems, the new measure proves sensitive in revealing active phase transitions and in distinguishing steady states. We envision that the entropy by neighbor distance could be useful for characterizing biological swarms such as bird flocks and for designing robotic swarms.

Toddalia asiatica extract attenuates adjuvant-induced arthritis by modulating colon Th17/Treg balance and colony homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Given the adverse effects of the current principal treatments, there is still a great need for effective cures for rheumatoid arthritis (RA), an immune-mediated disease. Toddalia asiatica (L.) Lam is a traditional medicinal herb that can be used for RA treatment because of its anti-inflammatory and analgesic properties. AIM OF THE STUDY: To investigate the possible effects of Toddalia asiatica extract (TAE) on intestinal immunity and the intestinal bacterial flora in a rat model of RA. MATERIALS AND METHODS: The anti-arthritis effect of TAE was evaluated in arthritis rats induced by complete Freund's adjuvant-induced arthritis (AIA). Arthritis index (AI) scores, systemic inflammation scores, histopathologic changes in the colon and ankle were detected by hematoxylin and eosin staining. Western blot analysis was performed to assess the protein expression of IL-17A, RORC, IL-1ß, IL-6, FOXP3, IL-10 in the colon. RT-PCR was performed to assess the expression of the colon's mRNA. Finally, changes to the gut microbiome by sequencing 16S rDNA. Microbial function prediction was performed using PICRUSt with the KEGG databases and correlation analysis was carried out by computing Spearman's rank correlations. RESULTS: demonstrated that TAE administration at a dose of 3 g/kg dramatically decreased AI scores, systemic inflammation scores, and histopathologic lesions of the ankle and colon in AIA rats. TAE was found to significantly reduce the expression levels of Th17-related proteins and mRNAs (IL-17A, RORC, IL-1ß and IL-6) in the colon, while increasing the expression levels of Treg-related proteins and mRNA (IL-10 and FOXP3), which helped restore the balance of Th17/Treg immune cells in the colon. Meanwhile, TAE was also found to be capable of remodeling the gut microbiota in AIA rats. Depleting RA-associated genera and thereby increasing α-diversity enriched the gut microbiota's diversity and shifted the community composition dramatically, leading to the increase of Firmicutes_unclassified, Ruminococcaceae_unclassified, Muribaculum, Subdoligranulum, Lachnospira, Marvinbryantia, and the reduction of RA-related bacteria Ligilactobacillus, Streptococcus and Eubacterium-eligens-group. Furthermore, PICRUSt analysis revealed that metabolic pathways were associated with TAE treatment, with metabolic pathways dominating. Among them, metabolic pathways were predominant. Correlation studies showed that a total of 9 microorganisms, including Ligilactobacillus, Eubacterium-eligens-group and Subdoligranulum, were significantly associated with Th17/Treg expression. CONCLUSIONS: This study demonstrates that TAE is a low-toxicity poly alkaline drug that can rapidly and effectively improve joint symptoms in RA rats and increases beneficial intestinal bacteria and decreases harmful ones, which is associated with modulating Th17/Treg interactions in intestinal T cells and reversing microbial disorders.

Microscopic Swarms: From Active Matter Physics to Biomedical and Environmental Applications.

Microscopic swarms consisting of, e.g., active colloidal particles or microorganisms, display emergent behaviors not seen in equilibrium systems. They represent an emerging field of research that generates both fundamental scientific interest and practical technological value. This review seeks to unite the perspective of fundamental active matter physics and the perspective of practical applications of microscopic swarms. We first summarize experimental and theoretical results related to a few key aspects unique to active matter systems: the existence of long-range order, the prediction and observation of giant number fluctuations and motility-induced phase separation, and the exploration of the relations between information and order in the self-organizing patterns. Then we discuss microscopic swarms, particularly microrobotic swarms, from the perspective of applications. We introduce common methods to control and manipulate microrobotic swarms and summarize their potential applications in fields such as targeted delivery, in vivo imaging, biofilm removal, and wastewater treatment. We aim at bridging the gap between the community of active matter physics and the community of micromachines or microrobotics, and in doing so, we seek to inspire fruitful collaborations between the two communities.

Near-infrared light-triggered nanobomb for in situ on-demand maximization of photothermal/photodynamic efficacy for cancer therapy.

Currently, the in situ on/off switch of PTT/PDT reagents for tumor treatment has evoked considerable interest in the field of cancer therapy. However, the actual PTT/PDT therapy efficacy in tumor treatment is largely restricted by the PTT/PDT reagents' aggregation issues during their release from the hydrophobic carrier to the hydrophilic tumor microenvironment. Thus, it remains a challenge to break through the therapy barrier caused by the PTT/PDT agent aggregation and achieve substantial improvement of anticancer efficacy. In this work, we developed a novel near-infrared (NIR) light-responsive and gas bubble-generated liposomal nanobomb (Cy/Ce6/CO2-Lip-FA) through the co-encapsulation of PTT/PDT reagents with gas precursor into the hydrophobic and hydrophilic regions of liposomes, respectively, in order to overcome the aggregation issues and substantially improve the synergistic PTT/PDT efficacy. Upon arrival at the tumor region, the PS phototoxicity of Cy/Ce6/CO2-Lip-FA could be effectively switched on through CO2 generation induced by the PTT effect of Cypate upon NIR irradiation. The gas bubble burst can remarkably suppress the aggregation of Cypate/Ce6 and extremely enhance the synergistic PTT/PDT efficacy. These results indicate that the proposed NIR-responsive and gas bubble-functionalized liposomal nanobomb is a highly promising platform for tumor treatment with better therapeutic efficacy.

Chinese herbal compound prescription for systemic lupus erythematosus: A protocol for systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE), known as lupus, is a chronic autoimmune disease and there is no cure for SLE. The western medication can improve syndromes to some extent; however, severe adverse drug reactions appear at the same time. Recently, it is confirmed that Chinese medicine also can have an excellent clinical efficacy on SLE. METHODS AND ANALYSIS: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. MAJOR RESULTS: levels of total remission rate, SLEDAI. Secondary results: The laboratory index about C3 levels, Hb levels, white blood cell levels, and adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions." All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. RESULTS: The curative effect and safety of Chinese herbal compound prescription treatment for SLE patients will be evaluated systematically. CONCLUSION: The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for SLE to further guide its promotion and application. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OPEN SCIENCE FRAMEWORK (OSF)REGISTRATION NUMBER:: https://osf.io/wvfrx/.

Efficacy of electroacupuncture combined with probiotics for depression and chronic diarrhea in patients and effect on serum inflammatory cytokines, NE and BDNF.

Efficacy of electroacupuncture combined with probiotics for depression and chronic diarrhea in patients, and its effect on the levels of serum inflammatory cytokines, norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) were investigated. A total of 104 patients with depression and chronic diarrhea admitted to The First Clinical Faculty, Guangxi University of Traditional Chinese Medicine from July 2014 to June 2018 were randomly divided into the observation group (n=56) and the control group (n=48). The observation group was treated with electroacupuncture combined with probiotics, and the control group was given conventional drugs for depression and chronic diarrhea. The Hamilton Depression Rating Scale (HAM-D) score and the abdominal symptom score were evaluated before treatment and at 3 weeks after treatment. Changes in the levels of serum inflammatory cytokines [interleukin (IL)-6, IL-2 and tumor necrosis factor (TNF)-α] as well as the levels of NE and BDNF in the two groups of patients before and after treatment were determined using radioimmunoassay. Compared with those in the control group, the symptoms of depression and diarrhea in the observation group were remarkably alleviated (p<0.05). After treatment, the serum cytokine levels in the two groups of patients were decreased, and the decreased level of serum inflammatory cytokines in the observation group was not obviously different from that in the control group. Besides, the serum BDNF level in the observation group was also reduced (p<0.05). The overall efficacy of the observation group was superior to that of the control group, showing a statistical difference. Electroacupuncture combined with probiotics brings good efficacy to patients with depression and chronic diarrhea, which is worthy of clinical promotion and development.

Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo.

BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. METHODS: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.