Protection against acute cerebral ischemia/reperfusion injury by QiShenYiQi via neuroinflammatory network mobilization

Cerebral ischemia/reperfusion injury (CI/RI) is a common feature of ischemic stroke, involving a period of impaired blood supply to the brain, followed by the restoration of cerebral perfusion through medical intervention. Although ischemia and reperfusion brain damage is a complex pathological process with an unclear physiological mechanism, more attention is currently focused on the neuroinflammatory response of an ischemia/reperfusion origin, and anti-inflammatory appears to be a potential therapeutic strategy following ischemic stroke. QiShenYiQi (QSYQ), a component-based Chinese medicine with Qi-tonifying and blood-activating property, has pharmacological actions of anti-inflammatory, antioxidant, mitochondrial protectant, anti-apoptosis, and antiplatelet aggregation. We have previously reported that the cardioprotective effect of QSYQ against ischemia/reperfusion injury is via improvement of mitochondrial functional integrity. In this research work, we aimed to investigate the possible mechanism involved in the neuroprotection of QSYQ in mice model of cerebral ischemia/reperfusion injury based on the inflammatory pathway. The cerebral protection was evaluated in the stroke mice after 24 h reperfusion by assessing the neurological deficit, cerebral infarction, brain edema, BBB functionality, and via histopathological assessment. TCM-based network pharmacology method was performed to establish and analyze compound-target-disease & function-pathway network so as to find the possible mechanism linking to the role of QSYQ in CI/RI. In addition, RT-qPCR was used to verify the accuracy of predicted signaling gene expression. As a result, improvement of neurological outcome, reduction of infarct volume and brain edema, a decrease in BBB disruption, and amelioration of histopathological alteration were observed in mice pretreated with QSYQ after experimental stroke surgery. Network pharmacology analysis revealed neuroinflammatory response was associated with the action of QSYQ in CI/RI. RT-qPCR data showed that the mice pretreated with QSYQ could significantly decrease IFNG-γ, IL-6, TNF-α, NF-κB p65, and TLR-4 mRNA levels and increase TGF-β1 mRNA level in the brain compared to the untreated mice after CI/RI (p \u3c 0.05). In conclusion, our study indicated the cerebral protective effect of pretreatment with QSYQ against CI/RI, which may be partly related to its potential to the reduction of neuroinflammatory response in a stroke subject

Galectin-3 Mediated Inflammatory Response Contributes to Neurological Recovery by QiShenYiQi in Subacute Stroke Model

Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke via modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly via regulating galectin-3 mediated inflammatory reaction

A socio-ecological analysis of factors influencing HIV treatment initiation and adherence among key populations in Papua New Guinea

Background: In Papua New Guinea (PNG) members of key populations, including female sex workers (FSW), men who have sex with men (MSM) and transgender women (TGW), have higher rates of HIV compared to the general adult population and low engagement in HIV care. This paper examines the socio-ecological factors that encourage or hinder HIV treatment initiation and adherence among HIV positive members of key populations in PNG. Methods: As part of a larger biobehavioural survey of key populations in PNG, 111 semi-structured interviews were conducted with FSW, MSM and TGW, of whom 28 identified as living with HIV. Interviews from 28 HIV positive participants are used in this analysis of the influences that enabled or inhibited HIV treatment initiation and treatment adherence. Results: Enablers included awareness of the biomedical benefits of treatment; experiences of the social, familial and health benefits of early treatment initiation and adherence; support provided by family and friends; and nonjudgmental and supportive HIV service provision. Factors that inhibited treatment initiation and adherence included perception of good health and denial of HIV diagnosis; poor family support following positive diagnosis; and anonymity and stigma concerns in HIV care services. Conclusion: Exploring health promotion messages that highlight the positive health impacts of early treatment initiation and adherence; providing client-friendly services and community-based treatment initiation and supply; and rolling out HIV viral load testing across the country could improve health outcomes for these key populations

Confidential, accessible point-of-care sexual health services to support the participation of key populations in biobehavioural surveys: lessons for Papua New Guinea and other settings where reach of key populations is limited

To achieve the UNAIDS 90-90-90 targets at a national level, many countries must accelerate service coverage among key populations. To do this, key population programs have adopted methods similar to those used in respondent-driven sampling (RDS) to expand reach. A deeper understanding of factors from RDS surveys that enhance health service engagement can improve key population programs. To understand the in-depth lives of key populations, acceptance of expanded point-of-care biological testing and determine drivers of participation in RDS surveys, we conducted semi-structured interviews with 111 key population participants (12–65 years) were purposefully selected from six biobehavioral surveys (BBS) in three cities in Papua New Guinea. Key populations were female sex workers, men who have sex with men, and transgender women. Four reasons motivated individuals to participate in the BBS: peer referrals; private, confidential, and stigma-free study facilities; "one-stop shop" services that provided multiple tests and with same-day results, sexually transmitted infection treatment, and referrals; and the desire to know ones’ health status. Biobehavioral surveys, and programs offering key population services can incorporate the approach we used to facilitate key population engagement in the HIV cascade

A View from the Top: International Politics, Norms and the Worldwide Growth of NGOs

This article provides a top-down explanation for the rapid growth of nongovernmental organizations (NGOs) in the postwar period, focusing on two aspects of political globalization. First, I argue that international political opportunities in the form of funding and political access have expanded enormously in the postwar period and provided a structural environment highly conducive to NGO growth. Secondly, I present a norm-based argument and trace the rise of a pro-NGO norm in the 1980s and 1990s among donor states and intergovernmental organizations (IGOs), which has actively promoted the spread of NGOs to non-Western countries. The article ends with a brief discussion of the symbiotic relationship among NGOs, IGOs, and states promoting international cooperation

The Politics, Power, and Pathologies of International Organizations.

Do international organizations really do what their creators intend them to do? In the past century the number of international organizations (1Os) has increased exponentially, and we have a variety of vigorous theories to explain why they have been created. Most of these theories explain IO creation as a response to problems of incomplete information, transaction costs, and other barriers to Pareto efficiency and welfare improvement for their members. Research flowing from these theories, however, has paid little attention to how IOs actually behave after they are created. Closer scrutiny would reveal that many IOs stray from the efficiency goals these theories impute and that many IOs exercise power autonomously in ways unintended and unanticipated by states at their creation. Understanding how this is so requires a reconsideration of IOs and what they do. In this article we develop a constructivist approach rooted in sociological institutionalism to explain both the power of IOs and their propensity for dysfunctional, even pathological, behavior. Drawing on long-standing Weberian arguments about bureaucracy and sociological institutionalist approaches to organizational behavior, we argue that the rational-legal authority that IOs embody gives them power independent of the states that created them and channels that power in particular directions. Bureaucracies, by definition, make rules, but in so doing they also create social knowledge. They define shared international tasks (like "development"), create and define new categories of actors (like "refugee"), create new interests for actors (like "promoting human rights"), and transfer models of political organization around the world (like markets and democracy.) However, the same normative valuation on impersonal, generalized rules that defines bureaucracies and makes them powerful in We are grateful t

Globalization, educational targeting and stable inequalities : a comparative analysis of Argentina, Brazil and Chile

This article analyzes educational targeting in Argentina, Brazil and Chile from a sociological point of view. In essence, it presents the 'logic of induction' as an ideal type. This pedagogic discourse is the vehicle of an educational anti-poverty strategy that expects to induce clearly targeted groups to improve on their own. The analysis explores the influence of the global educational agenda, the empirical connection between this discourse and the mechanism of emulation as well as the territorialization of educational inequality. Emulation plays the main role inasmuch as the logic of induction eventually leads the target groups to compare their adverse situation with more privileged groups, what legitimizes the current structures of categorical inequality (Tilly 1998). Finally, a brief statistical summary reports that the trends of educational inequality have remained stable as far as urban- rural ratios (in Brazil and Chile) and regional disparities (in the three countries) are concerned

Assumption without representation: the unacknowledged abstraction from communities and social goods

We have not clearly acknowledged the abstraction from unpriceable “social goods” (derived from communities) which, different from private and public goods, simply disappear if it is attempted to market them. Separability from markets and economics has not been argued, much less established. Acknowledging communities would reinforce rather than undermine them, and thus facilitate the production of social goods. But it would also help economics by facilitating our understanding of – and response to – financial crises as well as environmental destruction and many social problems, and by reducing the alienation from economics often felt by students and the public