Resveratrol Promotes Diabetic Wound Healing via SIRT1-FOXO1-c-Myc Signaling Pathway-Mediated Angiogenesis

Background/Aims: Diabetic non-healing skin ulcers represent a serious challenge in clinical practice, in which the hyperglycemia-induced disturbance of angiogenesis, and endothelial dysfunction play a crucial role. Resveratrol (RES), a silent information regulator 1 (SIRT1) agonist, can improve endothelial function and has strong pro-angiogenic properties, and has thus become a research focus for the treatment of diabetic non-healing skin ulcers; however, the underlying mechanism by which RES regulates these processes remains unclear. Therefore, the present study was intended to determine if RES exerts its observed protective role in diabetic wound healing by alleviating hyperglycemia-induced endothelial dysfunction and the disturbance of angiogenesis.Methods: We investigated the effects of RES on cell migration, cell proliferation, apoptosis, tube formation, and the underlying molecular mechanisms in 33 mM high glucose-stimulated human umbilical vein endothelial cells (HUVECs) by semi-quantitative RT-PCR, western blot analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and immunofluorescence in vitro. We further explored the role of RES on endothelial dysfunction and wound healing disturbance in db/db mice by TUNEL staining, immunofluorescence, and photography in vivo.Results: We observed an obvious inhibition of hyperglycemia-triggered endothelial dysfunction and a disturbance of angiogenesis, followed by the promotion of diabetic wound healing via RES, along with restoration of the activity of the hyperglycemia-impaired SIRT1 signaling pathway. Pretreatment with EX-527, a SIRT1 inhibitor, abolished the RES-mediated endothelial protection and pro-angiogenesis action, and then delayed diabetic wound healing. Furthermore, examination of the overexpression of forkhead box O1 (FOXO1), a transcription factor substrate of SIRT1, in HUVECs and db/db mice revealed that RES activated SIRT1 to restore hyperglycemia-triggered endothelial dysfunction and disturbance of angiogenesis, followed by the promotion of diabetic wound healing in a c-Myc-dependent manner. Pretreatment with 10058-F4, a c-Myc inhibitor, repressed RES-mediated endothelial protection, angiogenesis, and diabetic wound healing.Conclusion: Our findings indicate that the positive role of RES in diabetic wound healing via its SIRT1-dependent endothelial protection and pro-angiogenic effects involves the inhibition of FOXO1 and the de-repression of c-Myc expression

Analysis on the Live Coral Cover around Weizhou Island Using MODIS Data

Coral reefs are important as they can help to maintain ecological balance, biological resources, and species diversity on earth. However, they are globally threatened by human activities and climate change. As live coral cover (LCC) is regarded as an important measure of the health of coral reefs, analysis on LCC change associated with environmental parameters, such as chlorophyll-a concentration (Chl-a), sea surface temperature (SST), and photosynthetically active radiation (PAR), is of great value. Research on this front would help us comprehend the changes in coral reefs induced by human activities and global changes. Instead of using spasmodically in-field-measured environmental parameters, in this study, we chose to combine the successive Chl-a, SST, and PAR products of the Moderate Resolution Imaging Spectroradiometer (MODIS) with historic LCC records to establish an empirical relationship using nonlinear optimization. Thereafter, the established relationship was further used to discuss some possible developments of LCCs. According to the experiments, we concluded that the degradation of the LCC around Weizhou Island may be mainly caused by human-activity-caused eutrophication. Besides, we also showed that even if the Chl-a and the PAR can keep constant with current average levels, the corals around Weizhou Island may still be in a risk of disappearing between 2120–2140 as the SST continues to rise

Amebic Encephalitis in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib Therapy

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. A common first-line therapy offered to qualifying patients includes ibrutinib, an oral covalent inhibitor of Bruton’s tyrosine kinase. Treatment of CLL with ibrutinib therapy is generally well tolerated; however, serious opportunistic infections are being reported in patients treated with ibrutinib. In this report, we present a patient with CLL on ibrutinib therapy who developed rapidly declining neurological status concerning for the central nervous system (CNS) process related to his immunocompromised status. Despite multiple testing modalities, no evidence was found to explain the acute changes the patient was experiencing, and he had no improvement with common antimicrobial coverage. The patient ultimately expired, and autopsy of the brain revealed granulomatous amebic encephalitis due to opportunistic infection by Acanthamoeba species. As evidenced by this case, ibrutinib therapy, despite being generally well tolerated, has the potential to predispose patients to opportunistic infections like amebic encephalitis. Amebic encephalitis is a highly lethal CNS infection, and it is important for clinicians to recognize early on the potential for infection in patients on ibrutinib therapy presenting with CNS symptoms

Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple–negative breast cancer cells

Abstract Background Adipose tissue, which is mainly composed of adipocytes, is a crucial component of the tumor microenvironment, particularly in breast cancer. Adipocytes surround breast cancer cells and may participate in cell‒cell interactions in the breast microenvironment. However, little is currently known about how adipocytes influence the biological behavior of the surrounding breast cancer cells. Hence, this study sought to investigate the role and underlying mechanisms of periostin in triple–negative breast cancer (TNBC) cells cocultured with adipogenic conditioned medium (ACM) and palmitic acid (PA). Methods Human TNBC cell lines (MDA‒MB‒231 and SUM159PT) were treated with ACM and PA, then the expression of periostin, matrix metalloproteinases (MMPs) and stemness–related molecules were assessed by Western blotting and RT‒qPCR. The cellular viability was assessed using CCK‒8 assay. Plasmid transfection, RNA sequencing, and pathway inhibitor were used to explore the specific mechanisms of periostin. Results ACM and PA elevated the expression of both MMPs and stemness–related molecules in TNBCs. MMPs can promote tumor cell infiltration and migration by degrading the extracellular matrix, and stemness expression increases the development of tumor chemoresistance. Additionally, ACM and PA increased periostin expression, while inhibiting periostin disrupted the involvement of ACM and PA in promoting extracellular matrix degradation, stemness, and chemoresistance in TNBCs. Furthermore, this study found that periostin promoted TNBC progression by activating the MAPK/ERK signaling pathway and that inhibition of MAPK/ERK signaling reduced the phenotype caused by periostin upregulation in TNBCs treated with ACM or PA. Finally, the present results showed that the high expression of POSTN, which encodes periostin, was substantially related to worse survival in TNBC patients. Conclusions The results of the study elucidated for the first time how periostin is the key protein secreted in TNBCs in response to the adipocyte–regulated tumor microenvironment, while periostin–neutralizing antibodies may serve as potential therapeutic agents in relation to TNBC progression

A Glutathione Precursor Reduces Oxidative Injury to Cultured Embryonic Cardiomyocytes

BACKGROUND: Newborn infants are highly vulnerable to oxidative stress. Following birth asphyxia, oxidative injury due to ischemia-reperfusion can result in significant brain and heart damage, leading to death or long-term disability. STUDY QUESTION: The study objective was to evaluate the effectiveness of antioxidant gamma-L-glutamyl-L-cysteine (γGlu-Cys) in inhibiting oxidative injury to cultured embryonic cardiomyocytes (H9c2 cells). STUDY DESIGN: Control and γGlu-Cys-treated (0.5 mM) H9c2 cells were incubated under 6-hour ischemic conditions followed by 2-hour simulated reperfusion. MEASURES AND OUTCOMES: To quantify oxidative stress-induced apoptosis sustained by cardiomyocytes, lactate dehydrogenase (LDH) release and the presence of cytosolic cytochrome c were measured, as well as the number of secondary lysosomes visualized under electron microscopy. RESULTS: Compared to controls, H9c2 cells coincubated with γGlu-Cys during ischemia-reperfusion exhibited a significant reduction in both LDH release into the incubation medium [23.88 ± 4.08 (SE) vs. 9.95 ± 1.86% of total; P = 0.02] and the number of secondary lysosomes [0.070 ± 0.009 (SD) vs. 0.043 ± 0.004 per μm; P = 0.01]. Inhibition of LDH release with γGlu-Cys was the same (P = 0.67) as that of a caspase inhibitor. The significant increase in cytosolic cytochrome c (P = 0.01) after ischemia-reperfusion simulation further supports γGlu-Cys\u27s role in apoptosis prevention. CONCLUSIONS: It is concluded that the glutathione precursor γGlu-Cys protects cultured embryonic cardiomyocytes from apoptosis-associated oxidative injury

PINK1/Parkin pathway-mediated mitophagy by AS-IV to explore the molecular mechanism of muscle cell damage

Background: Functional disorders of mitochondria are closely related to muscle diseases. Many studies have also shown that oxidative stress can stimulate the production of a large number of reactive oxygen species (ROS), which have various adverse effects on mitochondria and can damage muscle cells. Purpose: In this study, based on our previous research, we focused on the PINK1/Parkin pathway to explore the mechanism by which AS-IV alleviates muscle injury by inhibiting excessive mitophagy. Methods: L6 myoblasts were treated with AS-IV after stimulation with hydrogen peroxide (H2O2) and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Then, we detected the related indices of oxidative stress and mitophagy by different methods. A PINK1 knockdown cell line was established by lentiviral infection to obtain further evidence that AS-IV reduces mitochondrial damage through PINK1/Parkin. Results: After mitochondrial damage, the expression of malondialdehyde (MDA) and intracellular ROS in L6 myoblasts significantly increased, while the expression of superoxide dismutase (SOD) and ATP decreased. The mRNA and protein expression levels of Tom20 and Tim23 were decreased, while those of VDAC1 were increased. PINK1, Parkin, and LC3 II mRNA and protein expression increased, and P62 mRNA and protein expression decreased·H2O2 combined with CCCP strongly activated the mitophagy pathway and impaired mitochondrial function. However, abnormal expression of these factors could be reversed after treatment with AS-IV, and excessive mitochondrial autophagy could also be reversed, thus restoring the regulatory function of mitochondria. However, AS-IV-adjusted function was resisted after PINK1 knockdown. Conclusion: AS-IV is a potential drug for myasthenia gravis (MG), and its treatment mechanism is related to mediating mitophagy and restoring mitochondrial function through the PINK1/Parkin pathway

Path planning for mobile-anchor based wireless sensor network localization: Static and dynamic schemes

In wireless sensor networks, node locations are required for many applications. Usually, anchors with known positions are employed for localization. Sensor positions can be estimated more efficiently by using mobile anchors (MAs). Finding the best MA trajectory is an important problem in this context. Various path planning algorithms are proposed to localize as many sensors as possible by following the shortest path with minimum number of anchors. In this paper, path planning algorithms for MA assisted localization are proposed for both static and dynamic schemes. These approaches use MAs by stopping at minimum number of nodes to cover the monitoring area with shortest path length. A novel node localization algorithm based on alternating minimization is proposed. The performances of the proposed path planning algorithms are compared with previous approaches through simulations. The results show that more sensors are localized with less anchors in a shorter path and time for both schemes