Targeting metabolism to enhance immunotherapy within tumor microenvironment.

Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Like cancer cells, immune cells within the tumor microenvironment or premetastatic niche also undergo extensive metabolic reprogramming, which profoundly impacts anti-tumor immune responses. Numerous evidence has illuminated that immunosuppressive TME and the metabolites released by tumor cells, including lactic acid, Prostaglandin E2 (PGE2), fatty acids (FAs), cholesterol, D-2-Hydroxyglutaric acid (2-HG), adenosine (ADO), and kynurenine (KYN) can contribute to CD8+ T cell dysfunction. Dynamic alterations of these metabolites between tumor cells and immune cells can similarly initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response. This review summarizes the new landscape beyond the classical metabolic pathways in tumor cells, highlighting the pivotal role of metabolic disturbance in the immunosuppressive microenvironment, especially how nutrient deprivation in TME leads to metabolic reprogramming of CD8+ T cells. Likewise, it emphasizes the current therapeutic targets or strategies related to tumor metabolism and immune response, providing therapeutic benefits for tumor immunotherapy and drug development in the future. Cancer metabolic reprogramming has been considered an emerging hallmark in tumorigenesis and the antitumor immune response. Dynamic alterations of metabolites between tumor cells and immune cells initiate metabolic competition in the TME, leading to nutrient deprivation and subsequent microenvironmental acidosis, which impedes immune response.

Neutrophils as potential therapeutic targets for breast cancer.

Breast cancer (BC) remains the foremost cause of cancer mortality globally, with neutrophils playing a critical role in its pathogenesis. As an essential tumor microenvironment (TME) component, neutrophils are emerging as pivotal factors in BC progression. Growing evidence has proved that neutrophils play a Janus- role in BC by polarizing into the anti-tumor (N1) or pro-tumor (N2) phenotype. Clinical trials are evaluating neutrophil-targeted therapies, including Reparixin (NCT02370238) and Tigatuzumab (NCT01307891); however, their clinical efficacy remains suboptimal. This review summarizes the evidence regarding the close relationship between neutrophils and BC, emphasizing the critical roles of neutrophils in regulating metabolic and immune pathways. Additionally, we summarize the existing therapeutic approaches that target neutrophils, highlighting the challenges, and affirming the rationale for continuing to explore neutrophils as a viable therapeutic target in BC management.

The Proteoglycan Glypican-1 as a Possible Candidate for Innovative Targeted Therapeutic Strategies for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, with a 5-year survival rate of 7% and 80% of patients diagnosed with advanced or metastatic malignancies. Despite recent advances in diagnostic testing, surgical techniques, and systemic therapies, there remain limited options for the effective treatment of PDAC. There is an urgent need to develop targeted therapies that are able to differentiate between cancerous and non-cancerous cells to reduce side effects and better inhibit tumor growth. Antibody-targeted strategies are a potentially effective option for introducing innovative therapies. Antibody-based immunotherapies and antibody-conjugated nanoparticle-based targeted therapies with antibodies targeting specific tumor-associated antigens (TAA) can be proposed. In this context, glypican-1 (GPC1), which is highly expressed in PDAC and not expressed or expressed at very low levels in non-malignant lesions and healthy pancreatic tissues, is a useful TAA that can be achieved by a specific antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy. In this review, we describe the main clinical features of PDAC. We propose the proteoglycan GPC1 as a useful TAA for PDAC-targeted therapies. We also provide a digression on the main developed approaches of antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy, which can be used to target GPC1.

Bone-Targeted Exosomes: Strategies and Applications.

As the global population ages, bone-related diseases have increasingly become a major social problem threatening human health. Exosomes, as natural cell products, have been used to treat bone-related diseases due to their superior biocompatibility, biological barrier penetration, and therapeutic effects. Moreover, the modified exosomes exhibit strong bone-targeting capabilities that may improve efficacy and avoid systemic side effects, demonstrating promising translational potential. However, a review of bone-targeted exosomes is still lacking. Thus, the recently developed exosomes for bone-targeting applications in this review are focused. The biogenesis and bone-targeting regulatory functions of exosomes, the constructive strategies of modified exosomes to improve bone-targeting, and their therapeutic effects for bone-related diseases are introduced. By summarizing developments and challenges in bone-targeted exosomes, It is striven to shed light on the selection of exosome constructive strategies for different bone diseases and highlight their translational potential for future clinical orthopedics.

A Retrospective Study of Ocular Cancer in Saudi Arabia: 25-Year Analysis.

Background: Ocular malignancies are uncommon among eye diseases; however, they jeopardize both vision and life. The main objective of this study was to use to describe the epidemiology of eye and ocular adnexa malignancies across different ages and sex. Methods: The King Khaled University institutional review board approved this study. Data on ocular cancer were retrieved from the Saudi Cancer Registry between 1994 and 2018. The registry collected important patient information such as demographic information (age, gender, and nationality), clinical details, and tumor classification. Results: The total number of cases with ocular cancer diagnosed was 1051 cases. The highest number was recorded in Riyadh (35.39%, n=372), followed by Makkah (16.93%, n=178). The incidence was higher in the 0-4 years' age group (55.21%), and it got down as people got older. The data also revealed differences in the number of reported cases over time, as well as in the representation of eye cancer cases by gender and nationality. While many ocular cancer pathologies were seen, with "Retinoblastoma, not otherwise specified" being the most common (53.32%), the incidence rates for males and females remained largely stable over time. Conclusion: The study emphasizes the need for continued monitoring, research, and analysis of potential of epidemiology of ocular cancer occurrence in Saudi Arabia. Identifying the geographical distribution and age pattern of Ocular malignancies have the potential to assist healthcare authorities and policymakers in developing precise strategies to reduce, recognize at an early stage, and successfully manage this condition.

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies.

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.

Evaluation of the Use of Digital Mental Health Platforms and Interventions: Scoping Review.

BACKGROUND: The increasing use of digital mental health (DMH) platforms and digital mental health interventions (DMHIs) is hindered by uncertainty over effectiveness, quality and usability. There is a need to identify the types of available evidence in this domain. AIM: This study is a scoping review identifying evaluation of the (1) DMH platform/s used; and (2) DMHI/s applied on the DMH platform/s. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guided the review process. Empirical studies that focused on evaluation of the use and application of DMH platforms were included from journal articles (published 2012-2022). A literature search was conducted using four electronic databases (Scopus, ScienceDirect, Sage and ACM Digital Library) and two search engines (PubMed and Google Scholar). RESULTS: A total of 6874 nonduplicate records were identified, of which 144 were analyzed and 22 met the inclusion criteria. The review included general/unspecified mental health and/or suicidality indications (n = 9, 40.9%), followed by depression (n = 5, 22.7%), psychosis (n = 3, 13.6%), anxiety and depression (n = 2, 9.1%), as well as anxiety, depression and suicidality (n = 1, 4.5%), loneliness (n = 1, 4.5%), and addiction (n = 1, 4.5%). There were 11 qualitative studies (50%), 8 quantitative studies (36.4%), and 3 mixed-methods studies (n = 3, 13.6%). The results contained 11 studies that evaluated the DMH platform/s and 11 studies that evaluated the DMHI/s. The studies focused on feasibility, usability, engagement, acceptability and effectiveness. There was a small amount of significant evidence (1 in each 11), notably the (cost-)effectiveness of a DMHI with significant long-term impact on anxiety and depression in adults. CONCLUSION: The empirical research demonstrates the feasibility of DMH platforms and DMHIs. To date, there is mostly heterogeneous, preliminary evidence for their effectiveness, quality and usability. However, a scalable DMHI reported effectiveness in treating adults' anxiety and depression. The scope of effectiveness may be widened through targeted strategies, for example by engaging independent young people.

Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas.

Amyotrophic lateral sclerosis (ALS) is an extremely heterogeneous disease of motor neurons that eventually leads to death. Despite impressive advances in understanding the genetic, molecular, and pathological mechanisms of the disease, the only drug approved to date by both the FDA and EMA is riluzole, with a modest effect on survival. In this opinion view paper, we will discuss how to address some challenges for drug development in ALS at the conceptual, technological, and methodological levels. In addition, socioeconomic and ethical issues related to the legitimate need of patients to benefit quickly from new treatments will also be addressed. In conclusion, this brief review takes a more optimistic view, given the recent approval of two new drugs in some countries and the development of targeted gene therapies.

Tackling prion diseases: a review of the patent landscape.

Introduction: Prion diseases are a class of rare and fatal neurodegenerative diseases for which no cure is currently available. They are characterized by conformational conversion of cellular prion protein (PrPC) into the disease-associated 'scrapie' isoform (PrPSc). Under an etiological point of view, prion diseases can be divided into acquired, genetic, and idiopathic form, the latter of which are the most frequent.Areas covered: Therapeutic approaches targeting prion diseases are based on the use of chemical and nature-based compounds, targeting either PrPC or PrPSc or other putative player in pathogenic mechanism. Other proposed anti-prion treatments include passive and active immunization strategies, peptides, aptamers, and PrPC-directed RNA interference techniques. The treatment efficacy has been mainly assessed in cell lines or animal models of the disease testing their ability to reduce prion accumulation.Expert opinion: The assessed strategies focussing on the identification of an efficient anti-prion therapy faced various issues, which go from permeation of the blood brain barrier to immunological tolerance of the host. Indeed, the use of combinatory approaches, which could boost a synergistic anti-prion effect and lower the potential side effects of single treatments and may represent an extreme powerful and feasible way to tackle prion disease.

Mucosal vaccines: Strategies and challenges.

Mucosal immunization has potential benefits over conventional parenteral immunization, eliciting immune defense in both mucosal and systemic tissue for protecting from pathogen invasion at mucosal surfaces. To provide a first line of protection at these entry ports, mucosal vaccines have been developed and hold a significant promise for reducing the burden of infectious diseases. However, until very recently, only limited mucosal vaccines are available. This review summarizes recent advances in selected aspects regarding mucosal vaccination, including appropriate administration routes, reasonable formulations, antigen-sampling and immune responses of mucosal immunity, and the strategies used to improve mucosal vaccine efficacy. Finally, the challenges of developing successful mucosal vaccines and the potential solutions are discussed.

Key Factors Influencing Low-Carbon Behaviors of Staff in Star-Rated Hotels-An Empirical Study of Eastern China.

To guide sustainable development in the hospitality industry requires hotel staff engagement, so what causes and how to facilitate the implementation of low-carbon behaviors should be high priorities. However, most prior studies focused on hotel guest behavior or discussed, on an individual level, the psychological aspects of the factors of the low-carbon behavior of either managers or employees. Therefore, this research aims to examine the effect of influencing factors inside and outside of the hotel context on hotel staff's low-carbon behaviors in star-rated hotels. A set of influencing factors were identified by using literature retrieval, ground theory and in-depth interviews. Structural equation modelling was then applied with 440 valid questionnaires collected from representative star-rated hotels in Eastern China. The results revealed that low-carbon managerial activities, strategic orientation, social norms, and perceived behavior control were four key factors affecting the low-carbon behavior adoption of staff from star-rated hotels. Among them, low-carbon managerial activities were found to be the strongest factor affecting hotel staff's low-carbon behaviors. Consumer attitude, however, exerted no significant impact. Targeted strategies were finally proposed for the improvement of hotel staff's low-carbon behavior from the perspectives of hoteliers and governments. This study contributes to the generation mechanism of low-carbon behavior among staff and, in practice, towards behavioral improvement by providing comprehensive insights about the attribution of factors belonging to multiple dimensions related to the low-carbon behavior of staff in the hotel industry.

Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.

Ovarian cancer is one of the leading causes of death in patients with gynecological malignancy. Despite optimal cytoreductive surgery and platinum-based chemotherapy, ovarian cancer disseminates and relapses frequently, with poor prognosis. Hence, it is urgent to find new targeted therapies for ovarian cancer. Recently, the tumor microenvironment has been reported to play a vital role in the tumorigenesis of ovarian cancer, especially with discoveries from genome-, transcriptome- and proteome-wide studies; thus tumor microenvironment may present potential therapeutic target for ovarian cancer. Here, we review the interactions between the tumor microenvironment and ovarian cancer and various therapies targeting the tumor environment.

The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy.

Breast cancer is the most common form of tumor in women and the leading cause of cancer-related mortality. Even though the major cellular burden in breast cancer is constituted by the so-called bulk tumor cells, another cell subpopulation named cancer stem cells (CSCs) has been identified. The latter have stem features, a self-renewal capacity, and the ability to regenerate the bulk tumor cells. CSCs have been described in several cancer types but breast cancer stem cells (BCSCs) were among the first to be identified and characterized. Therefore, many efforts have been put into the phenotypic characterization of BCSCs and the study of their potential as prognostic indicators and therapeutic targets. Many dysregulated pathways in BCSCs are involved in the epithelial-mesenchymal transition (EMT) and are found up-regulated in circulating tumor cells (CTCs), another important cancer cell subpopulation, that shed into the vasculature and disseminate along the body to give metastases. Conventional therapies fail at eliminating BCSCs because of their quiescent state that gives them therapy resistance. Based on this evidence, preclinical studies and clinical trials have tried to establish novel therapeutic regimens aiming to eradicate BCSCs. Markers useful for BCSC identification could also be possible therapeutic methods against BCSCs. New approaches in drug delivery combined with gene targeting, immunomodulatory, and cell-based therapies could be promising tools for developing effective CSC-targeted drugs against breast cancer.

Viral-Targeted Strategies Against EBV-Associated Lymphoproliferative Diseases.

Epstein-Barr virus (EBV) is strongly associated with a spectrum of EBV-associated lymphoproliferative diseases (EBV-LPDs) ranging from post-transplant lymphoproliferative disorder, B cell lymphomas (e.g., endemic Burkitt lymphoma, Hodgkin lymphoma, and diffuse large B cell lymphoma) to NK or T cell lymphoma (e.g., nasal NK/T-cell lymphoma). The virus expresses a number of latent viral proteins which are able to manipulate cell cycle and cell death processes to promote survival of the tumor cells. Several FDA-approved drugs or novel compounds have been shown to induce killing of some of the EBV-LPDs by inhibiting the function of latent viral proteins or activating the viral lytic cycle from latency. Here, we aim to provide an overview on the mechanisms by which EBV employs to drive the pathogenesis of various EBV-LPDs and to maintain the survival of the tumor cells followed by a discussion on the development of viral-targeted strategies based on the understanding of the patho-mechanisms.

Different Targeting Strategies for Treating Breast Cancer Bone Metastases.

BACKGROUND: Breast cancer is the most frequently diagnosed malignancy in women worldwide. Breast cancer tends to metastasize to bone. Around 70% of the breast cancer patients eventually develop bone metastasis. After the bone invasion, metastatic cells disrupt the balance between osteoblastic and osteoclastic activities, leading to skeletal complications, characterized by pain and pathological fractures and hence worsening the patient's quality of life. Once tumor invades the bone, it is hard to treat it with, the so-far available treatments options (e.g. bisphosphonates and denosumab). Bone metastasis should be essentially controlled, in cancer treatment and there is a strong need to explore new, more efficient therapeutic targets. This review discusses the bone physiological processes and the recent advances in exploring different pathways involved in bone metastasis. Furthermore, some novel treatment options, which are under preclinical and clinical investigations, are highlighted. CONCLUSION: A deeper understanding of these metastatic pathways can provide oncology researchers with novel avenues for treating bone metastasis, one of the main challenges to cure breast cancer. The restoration of healthy bone environment will not only improve the patient's quality of life but also reduces the tumor burden.

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies.

Superparamagnetic iron oxide nanoparticles (SPION)-based magnetic resonance imaging is a powerful, noninvasive tool in biomedical imaging. The recent embedding of SPIO in nanoencapsulations that had different controllable surface properties has now made it possible to use SPIO in the imaging of metabolic processes. The two major issues to realize maximized and selective SPIO cancer targeting are the minimization of macrophage uptake and the preferential binding to cancerous cells over healthy neighbor cells. The utility of SPIO has been shown in clinical applications using a series of marketed SPION-based contrast agents. Applications have ranged from detecting inflammatory diseases to the specific identification of cell surface markers expressed on tumors. This review focuses on iron-oxide-based nanoparticles, to include the physiochemical properties of SPION surface engineering and its synthetic methods as well as SPIO imaging applications and specifically targeted SPIO conjugates (e.g. targeted probes) for labeling cancerous, cell-surface molecules. As a specific application of this technology, we discuss its use in the imaging of pancreatic duct adenocarcinoma in addition to its potential for use in early diagnosis through targeted strategies.

Trachoma in Asia-A disappearing scourge.

Trachoma is an ancient blinding eye disease. With improvements in hygiene and living conditions and development of targeted strategies by the World Health Organization, trachoma is being progressively eliminated. Great progress is being seen in Asian countries, many of which are becoming trachoma free.