Project description:With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.
Project description:The first coronavirus disease 2019 (COVID-19) report in Brazil occurs by the end of February, and 4 months later, there was more than 1 million infected patients and 54,971 deaths. The health-care system in Brazil is universal, meaning that all inhabitants are covered by the Unified Health Care System, and 20% of Brazilian citizens are covered by private health-care insurances. In this scenario, the government adopted some actions to combat the pandemics, including guidelines for COVID-19 prevention and management, allocation of funds to support primary care, extension of medical services in primary health units, increase in the number of health-care professionals, distribution of COVID-19 tests, use of telemedicine to monitor patients with flu-like symptoms, and teleconsulting with psychiatrist and psychologists. Since the pandemic offers a unique opportunity for research and management in Brazil, a coalition initiative conducted several therapeutic trials in search of safe treatments for patients with COVID-19. Other issue in this field was the organization of health system, both in private and public organizations.
Project description:BackgroundGallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC.ResultsBioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC.ConclusionOverall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.
Project description:Biofilm-related infections have been a major clinical problem and include chronic infections, device-related infections and malfunction of medical devices. Since biofilms are not fully available for the human immune system and antibiotics, they are difficult to eradicate and control; therefore, imposing a global threat to human health. There have been avenues to tackle biofilms largely based on the disruption of their adhesion and maturation. Nowadays, the use of probiotics and their derivatives has gained a growing interest in battling against pathogenic biofilms. In the present review, we have a close look at probiotics with the ultimate objective of inhibiting biofilm formation and maturation. Overall, insights into the mechanisms by which probiotics and their derivatives can be used in the management of biofilm infections would be warranted.
Project description:Cervical cancer is the first identified human papillomavirus (HPV) associated cancer and the most promising malignancy to be eliminated. However, the ever-changing virus subtypes and acquired multiple drug resistance continue to induce failure of tumor prevention and treatment. The exploration of cervical cancer heterogeneity is the crucial way to achieve effective prevention and precise treatment. Tumor heterogeneity exists in various aspects including the immune clearance of viruses, tumorigenesis, neoplasm recurrence, metastasis and drug resistance. Tumor development and drug resistance are often driven by potential gene amplification and deletion, not only somatic genomic alterations, but also copy number amplifications, histone modification and DNA methylation. Genomic rearrangements may occur by selection effects from chemotherapy or radiotherapy which exhibits genetic intra-tumor heterogeneity in advanced cervical cancers. The combined application of cervical cancer therapeutic vaccine and immune checkpoint inhibitors has become an effective strategy to address the heterogeneity of treatment. In this review, we will integrate classic and recently updated epidemiological data on vaccination rates, screening rates, incidence and mortality of cervical cancer patients worldwide aiming to understand the current situation of disease prevention and control and identify the direction of urgent efforts. Additionally, we will focus on the tumor environment to summarize the conditions of immune clearance and gene integration after different HPV infections and to explore the genomic factors of tumor heterogeneity. Finally, we will make a thorough inquiry into completed and ongoing phase III clinical trials in cervical cancer and summarize molecular mechanisms of drug resistance among chemotherapy, radiotherapy, biotherapy, and immunotherapy.
Project description:The coronavirus disease 2019 (COVID-19) is a public health emergency of international concern. The rising number of cases of this highly transmissible infection has stressed the urgent need to find a potent drug. Although repurposing of known drugs currently provides an accelerated route to approval, there is no satisfactory treatment. Polyphenols, a major class of bioactive compounds in nature, are known for their antiviral activity and pleiotropic effects. The aim of this review is to assess the effects of polyphenols on COVID-19 drug targets as well as to provide a perspective on the possibility to use polyphenols in the development of natural approaches against this viral disease.
Project description:Breast cancer is the most prevalent malignancy in women and the second most common cause of cancer-related death worldwide. Despite major innovations in early detection and advanced therapeutics, up to 30% of women with node-negative breast cancer and 70% of women with node-positive breast cancer will develop recurrence. The recognition that breast tumors are infiltrated by a complex array of immune cells that influence their development, progression, and metastasis, as well as their responsiveness to systemic therapies has sparked major interest in the development of immunotherapies. In fact, not only the native host immune system can be altered to promote potent antitumor response, but also its components can be manipulated to generate effective therapeutic strategies. We present here a review of the major approaches to immunotherapy in breast cancers, both successes and failures, as well as new therapies on the horizon.
Project description:Previous research has shown that people care less about men than about women who are left behind. We show that this finding extends to the domain of labor market discrimination: In identical scenarios, people judge discrimination against women more morally bad than discrimination against men. This result holds in a representative sample of the US population and in a larger but not representative sample of Amazon Mechanical Turk (Mturk) respondents. We test if this gender gap is driven by statistical fairness discrimination, a process in which people use the gender of the victim to draw inferences about other characteristics which matter for their fairness judgments. We test this explanation with a survey experiment in which we explicitly hold information about the victim of discrimination constant. Our results provide only mixed support for the statistical fairness discrimination explanation. In our representative sample, we see no meaningful or significant effect of the information treatments. By contrast, in our Mturk sample, we see that providing additional information partly reduces the effect of the victim's gender on judgment of the discriminator. While people may engage in statistical fairness discrimination, this process is unlikely to be an exhaustive explanation for why discrimination against women is judged as worse.