Hyperbaric oxygen (HBO) therapy is considered a safe and feasible method that to provide neuroprotection against ischemic stroke. However, the therapy mechanisms of HBO have not been fully ...elucidated. We hypothesized that the mechanism underlying the protective effect of HBO preconditioning (HBO-PC) against cerebral ischemia/reperfusion injury was related to inhibition of mitochondrial apoptosis and energy metabolism disorder. To test this hypothesis, an ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in rats. HBO-PC involved five consecutive days of pretreatment before MCAO. In additional experiments, X chromosome-linked inhibitor of apoptosis protein (XIAP) and second mitochondria-derived activator of caspases (SMAC) shRNA and NC plasmids were intraventricularly injected into rat brains after MCAO (2 h). After 24 h, all rats underwent motor function evaluation, which was assessed by modified Garcia scores. TTC staining for the cerebral infarct and cerebral edema, and TUNEL staining for cell apoptosis, were also analyzed. Reactive oxygen species and antioxidative enzymes in rat brains were detected, as well as mitochondrial complex enzyme activities, ATP levels, and Na
+
/K
+
ATPase activity. Western blot was used to detect apoptotic proteins including Bcl-2, Bax, caspase-3, caspase-9, cyc-c, XIAP, and SMAC. HBO-PC remarkably reduced the infarct volume and improved neurological deficits. Furthermore, HBO-PC alleviated oxidative stress and regulated the expression of apoptosis-related proteins. Moreover, HBO-PC inhibited the decrease in ATP levels, mitochondrial complex enzyme activities, and Na
+
/K
+
ATPase activity to maintain stable energy metabolism. XIAP knockdown weakened the protective effect of HBO, whereas SMAC knockdown strengthened its protective effect. The effects of HBO-PC can be attributed to inhibition of ischemia/hypoxia-induced mitochondrial apoptosis and energy metabolism disturbance. The action of HBO-PC is related to the XIAP and SMAC signaling pathways.
Although many surgical and nonsurgical therapeutic options have been well-established, hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related death worldwide. Therefore, ...the discovery of novel potential therapeutic strategies is still urgently required for improving survival and prognosis of HCC patients. As the most potent antigen-presenting cells in the human immune system, dendritic cells (DCs) play an important role in activating not only innate but also adaptive immune responses to specifically destroy tumor cells. As a result, DC-based vaccines, which are prepared by different tumor-antigen-pulsing strategies or maturation-stimulating reagents, either alone or in combination with various anticancer therapies and/or immune effector cells, have been developed as a promising personalized cancer immunotherapy. This review provides a comprehensive summary of the evidence from clinical trials evaluating the safety, feasibility, and efficacy of DC-based vaccines in treating HCC patients and highlights the data from recent preclinical studies regarding the development of promising strategies for optimizing the efficacy of DC-vaccine-based immunotherapy for HCC.
The theory of inflammation is one of the important theories in the pathogenesis of diabetic nephropathy (DN). We herein aimed to explore whether loganin affected macrophage infiltration and ...activation upon diabetic nephropathy (DN) by a spontaneous DN mice and a co-culture system of glomerular mesangial cells (GMCs) and macrophage cells (RAW264.7) which was induced by advanced glycation end products (AGEs).
Loganin showed remarkable capacity on protecting renal from damage by mitigating diabetic symptoms, improving the histomorphology of the kidney, decreasing the expression of extracellular matrix such as FN, COL-IV and TGF-β, reversing the production of IL-12 and IL-10 and decreasing the number of infiltrating macrophages in the kidney. Moreover, loganin showed markedly effects by suppressing iNOS and CD16/32 expressions (M1 markers), increasing Arg-1 and CD206 expressions (M2 markers), which were the phenotypic transformation of macrophage. These effects may be attributed to the inhibition of the receptor for AGEs (RAGE) /monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway, with significantly down-regulated expressions of RAGE, MCP-1 and CCR2 by loganin. Loganin further decreased MCP-1 secretion when RAGE was silenced, which means other target was involved in regulating the MCP-1 expression. While loganin combinated with the inhibitor of CCR2 exerted stronger anti-inhibition effects of iNOS expression, suggesting that CCR2 was the target of loganin in regulating the activation of macrophages.
Loganin could ameliorate DN kidney damage by inhibiting macrophage infiltration and activation via the MCP-1/CCR2 signaling pathway in DN.
Conotoxins are disulfide-rich small peptides, which are invaluable peptides that target ion channel and neuronal receptors. Conotoxins have been demonstrated as potent pharmaceuticals in the ...treatment of a series of diseases, such as Alzheimer's disease, Parkinson's disease, and epilepsy. In addition, conotoxins are also ideal molecular templates for the development of new drug lead compounds and play important roles in neurobiological research as well. Thus, the accurate identification of conotoxin types will provide key clues for the biological research and clinical medicine. Generally, conotoxin types are confirmed when their sequence, structure, and function are experimentally validated. However, it is time-consuming and costly to acquire the structure and function information by using biochemical experiments. Therefore, it is important to develop computational tools for efficiently and effectively recognizing conotoxin types based on sequence information. In this work, we reviewed the current progress in computational identification of conotoxins in the following aspects: (i) construction of benchmark dataset; (ii) strategies for extracting sequence features; (iii) feature selection techniques; (iv) machine learning methods for classifying conotoxins; (v) the results obtained by these methods and the published tools; and (vi) future perspectives on conotoxin classification. The paper provides the basis for in-depth study of conotoxins and drug therapy research.
Organic electrochemical transistors (OECTs) have been successfully employed for a variety of applications , especially chemical and biological sensing. Although the device response to analytes can be ...directly monitored by measuring steady-state channel currents of the devices, it is challenging to obtain stable signals with high signal-to-noise ratios. In this work, we developed a novel method for electrochemical sensing by measuring both the transconductance and the phase of the AC channel current for the first time. Then we successfully realized highly sensitive ion strength sensors and dopamine sensors based on the AC method. Our results indicate that the AC method is more sensitive than typical DC methods and can provide more stable data in sensing applications. Considering that the sensors can be conveniently integrated with AC circuits, this technology is expected to find broad applications in the future.
This study investigates how environmental, social, and governance (ESG) strategy and implementation, along with governance structure, influence sustainable development goals (SDGs). In recognizing ...the SDG gap between intent and implementation, our study places a special focus on the mediating role of ESG implementation, the moderating role of governance structure, and the pivotal concept of embeddedness of strategy in shaping SDG impact. To test the hypotheses, we analyze firm‐level data from 552 Taiwanese listed companies. The results suggest that ESG implementation mediates the relationship between a firm's ESG strategy and SDG impact. The governance structure plays a moderating role on the relationship between ESG implementation and SDG impact. Furthermore, the embeddedness of strategy shows a positive effect on SDG impact. The empirical findings contribute substantially to the theoretical landscape of ESG studies. The findings offer practical implications for business leaders striving to elevate their firms' SDG impacts.
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated ...the role of different NPS
nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS
neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS
neurons are not important for sleep/wake modulation. Further, we found that a NPS
nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS
neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of
supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS
neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti‐inflammatory, antibacterial, antifungal, and antihelminthic ...effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle‐treated mice. Berberine suppressed the viral infection‐induced up‐regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF‐κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection‐induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.
Abstract
The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a dramatic loss of human life worldwide. Despite many ...efforts, the development of effective drugs and vaccines for this novel virus will take considerable time. Artificial intelligence (AI) and machine learning (ML) offer promising solutions that could accelerate the discovery and optimization of new antivirals. Motivated by this, in this paper, we present an extensive survey on the application of AI and ML for combating COVID-19 based on the rapidly emerging literature. Particularly, we point out the challenges and future directions associated with state-of-the-art solutions to effectively control the COVID-19 pandemic. We hope that this review provides researchers with new insights into the ways AI and ML fight and have fought the COVID-19 outbreak.
PDF
