Conflicting results identifying the association between tooth loss and cardiovascular disease and stroke have been reported. Therefore, a dose-response meta-analysis was performed to clarify and quantitatively assess the correlation between tooth loss and cardiovascular disease and stroke risk. Up to March 2017, seventeen cohort studies were included in current meta-analysis, involving a total of 879084 participants with 43750 incident cases. Our results showed statistically significant increment association between tooth loss and cardiovascular disease and stroke risk. Subgroups analysis indicated that tooth loss was associated with a significant risk of cardiovascular disease and stroke in Asia and Caucasian. Furthermore, tooth loss was associated with a significant risk of cardiovascular disease and stroke in fatal cases and nonfatal cases. Additionally, a significant dose-response relationship was observed between tooth loss and cardiovascular disease and stroke risk. Increasing per 2 of tooth loss was associated with a 3% increment of coronary heart disease risk; increasing per 2 of tooth loss was associated with a 3% increment of stroke risk. Subgroup meta-analyses in study design, study quality, number of participants and number of cases showed consistent findings. No publication bias was observed in this meta-analysis. Considering these promising results, tooth loss might provide harmful health benefits.

Chemodynamic therapy (CDT) is a kind of method utilizing hydroxyl radicals (•OH) generated by Fenton or Fenton-like reactions in situ to kill tumor cells. Copper, a cofactor of many intracellular enzymes, which has good biocompatibility, is a transition metal with extremely high efficiency in the Fenton-like reaction. However, when the intracellular free copper exceeds the threshold, it will bring serious side effects. Hence, we used the chelation between glutathione (GSH) and copper ions to produce a nanocatalytic drug, which was named as Cu–GSSG NPs, to fix free copper. With the aid of hydrogen peroxide (H2O2) in vitro, Cu–GSSG NPs catalyzed it to •OH radicals, which could be confirmed by the electron spin resonance spectrum and the degradation experiment of methylene blue. Based on these results, we further studied the intracellular properties of Cu–GSSG NPs and found that Cu–GSSG NPs could react with the overexpressed H2O2 in tumor cells to produce •OH radicals effectively by the Fenton-like reaction to induce cell death. Therefore, Cu–GSSG NPs could be a kind of potential “green” nanocatalytic drug with good biocompatibility to achieve CDT.

Objective: Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various cancers, but its cardiotoxicity cannot be ignored. Schisandrin B (SchB) has the ability to upregulate cellular antioxidant defense mechanism and promote mitochondrial function and antioxidant status. However, it has not been reported whether it can resist THP-induced cardiotoxicity. The aim of this study was to investigate the effect of SchB on THP cardiotoxicity and its mechanism.Methods: The rat model of cardiotoxicity induced by THP was established, and SchB treatment was performed at the same time. The changes of ECG, cardiac coefficient, and echocardiogram were observed. The changes of myocardial tissue morphology were observed by H&E staining. Apoptosis was detected by TUNEL. The levels of LDH, BNP, CK-MB, cTnT, SOD, and MDA in serum were measured to observe the heart damage and oxidative stress state of rats. The expression of cleaved-caspase 9, pro/cleaved-caspase 3, Bcl-2/Bax, and cytosol and mitochondrial Cyt C and Bax was evaluated by western blot. H9c2 cardiomyocytes were cocultured with THP, SchB, and mPTP inhibitor CsA to detect the production of ROS and verify the above signaling pathways. The opening of mPTP and mitochondrial swelling were detected by mPTP kit and purified mitochondrial swelling kit.Results: After 8 weeks, a series of cardiotoxicity manifestations were observed in THP rats. These adverse effects can be effectively alleviated by SchB treatment. Further studies showed that SchB had strong antioxidant and antiapoptotic abilities in THP cardiotoxicity.Conclusion: SchB has an obvious protective effect on THP-induced cardiotoxicity. The mechanism may be closely related to the protection of mitochondrial function, inhibition of mPTP opening, and alleviation of oxidative stress and apoptosis of cardiomyocytes.

Background: Kaempferide (Ka, 3,5,7-trihydroxy-4′-methoxy avone), an active ingredient of Tagetes erecta L has been demonstrated to possess many pharmacological effects, including antioxidant, antiin ammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro. Methods: High-fat diet (HFD) was used to induce the model of glycolipid metabolism disorder in mice.The hypolipidemic and hypoglycemic effect was detected by several indicators, like blood sample analysis blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocytes was prepared to con rm the target of Ka by co-culturing with PPARγ agonist or inhibitor. Results: Administration of Ka at a dose of 10mg/kg for 16 weeks effectively attenuated obesity, hyperlipidemia, hyperglycemia and insulin resistance in HFD mice. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 pathway and PPARγ/PI3K/AKT pathway, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further con rmed the above signaling pathway and key protein. Conclusion: Ka played an important role in improving glycolipid metabolism disorder, which were causally associated with weight loss. The underlying mechanisms might are associated with the activation of PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and provides theoretical basis for Ka in the effective treatment of obesity, diabetes and other metabolic diseases.

No abstract

To maximize the utilization and response to the high oxidative stress environment of tumor sites while avoiding the dilemma of enhancing reactive oxygen species (ROS) response in a single way, mitochondrial targeting combined with fluorescent self-reporting polymeric nanocarriers (1K-TPP and 2K-TPP) with grafted structures were synthesized via a chemoenzymatic method in a high yield to simultaneously enhance the drug delivery of endogenous ROS responses. 1K-TPP and 2K-TPP loaded doxorubicin (DOX) at a high content over 12% and formed homogeneous spherical micelles. In vitro, both of them showed promising high sensitivity (detection limit below 200 nM H2O2), fast response, and ratiometric fluorescent self-reporting properties (fluorescent enhancement more than 200 times) to ROS and excellent stability under physiological conditions, while achieving a rapid release of the DOX in response to 1 mM H2O2. Cell co-localization experiments exhibited that they had favorable mitochondrial targeting, and mitochondrial isolation experiments also confirmed that the TPP-modified 1K-TPP selectively accumulated nearly three times in mitochondria than that in total cells. The internalization of 1K-TPP and 2K-TPP into cancer cells was greatly improved by nearly 200% compared to that of unmodified control (1K-OH and 2K-OH) and also explored a unique energy-dependent endocytosis. Furthermore, stimulation of endogenous ROS enhanced the green fluorescence intensity (up to 51.4%) of the linked probe so as to destroy the internal structure of the nanocarriers, achieving self-reporting of the drug’s intracellular release and tracking of the intracellular location of nanocarriers. The cytotoxicity of DOX-loaded 1K-TPP and 2K-TPP in tumor cells with a higher ROS content showed statistical superiority to that of 1K-OH and 2K-OH, benefiting from the extremely good endogenous ROS response sensitivity leading to the differential selective release of drugs. These results demonstrate the potential of 1K-TPP and 2K-TPP, especially for 1K-TPP, as mitochondria-targeted, fluorescent self-reporting nanocarriers for combined enhancement of endogenous ROS responsiveness.

Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various types of cancer, but its cardiotoxicity cannot be ignored. Canagliflozin, the first sodium-glucose co-transporter-2 inhibitor approved by the USA FDA, has been shown to have a significant effect on cardiovascular damage caused by diabetes. However, it has not been reported whether it can resist THP-induced cardiotoxicity. The aim of the present study was to investigate the effect of canagliflozin on THP-induced cardiotoxicity and its mechanism. A rat model of cardiotoxicity induced by THP was established and canagliflozin treatment was performed at the same time. The changes of electrocardiography, cardiac coefficient and echocardiogram were observed. The levels of lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB, cardiac troponin T, superoxide dismutase (SOD) and malondialdehyde were detected. The expression of SOD2, NADPH oxidase 2, pro/cleaved-caspase-and Bcl-2/Bax were evaluated by western blotting. The primary culture of cardiomyocytes was prepared to explore the effect in vitro. After eight weeks, a series of cardiotoxicity manifestations were observed in THP rats. However, canagliflozin treatment had no significant effect on the above adverse reactions. Similarly, further studies showed that canagliflozin had no significant effect on THP-induced cardiomyocyte injury in vitro. The present study showed that there was no significant protective effect of canagliflozin on THP-induced cardiotoxicity and cardiomyocyte injury.

Covalent organic frameworks (COFs) are widely used in photocatalysis due to their periodic π–π arrays, high crystallinity, and adjustable bandgap. Herein, a new strategy for integrating polyphenyl building blocks in COFs is presented to improve the photocatalytic efficiency. To implement this strategy, a series of COFs with different numbers of phenyl groups are successfully designed and synthesized. By varying the number of phenyl units in the precursor, the COFs exhibit different bandgaps, band‐edge positions, carrier mobilities, and interfacial transfer resistances. The corresponding characterization reveals that the photocatalytic capacity of COFs increases with the number of phenyls in the basic structural unit. Further, under visible light irradiation, the COFs prepared from 1,3,5‐tris [4‐amino(1,1‐biphenyl‐4‐yl)] benzene (TABB) and 1,4‐benzenedicarboxaldehyde (BDB) (named TABB‐BDB COF) exhibit superior light‐responsive oxidase‐mimicking characteristic, which can catalyze the oxidation of 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS). Based on the aforementioned characteristics, TABB‐BDB COF is designed as a robust colorimetric probe for the inexpensive, highly sensitive, and rapid detection of uric acid (UA) with a linear range of 5–160 mg L−1. This study not only demonstrates COFs‐based light‐response oxidase mimicking for efficient UA detection but also provides an intelligent tactic for boosting the photocatalytic competence of COFs.