Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy.

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

Discovery, validation, and prodrug design of an ACE2 activator for treating bacterial infection-induced lung inflammation.

Exacerbated inflammatory responses can be detrimental and pose fatal threats to the host, as exemplified by the global impact of the COVID-19 pandemic, resulting in millions of fatalities. Developing novel drugs to combat the damaging effects of inflammation is essential for both preventive measures and therapeutic interventions. Accumulating evidence suggests that Angiotensin Converting Enzyme 2 (ACE2) possesses the ability to optimize inflammatory responses. However, the clinical applicability of this potential is limited due to the lack of dependable ACE2 activators. In this study, we conducted a screening of an FDA-approved drug library and successfully identified a novel ACE2 activator, termed H4. The activator demonstrated the capability to mitigate lung inflammation caused by bacterial lung infections, effectively modulating neutrophil infiltration. Importantly, to improve the clinical applicability of the poorly water-soluble H4, we developed a prodrug variant with significantly enhanced water solubility while maintaining a similar level of efficacy as H4 in attenuating inflammatory responses in the lungs of mice exposed to bacterial infections. This finding highlights the potential of formulated H4 as a promising candidate for the treatment and prevention of inflammatory diseases, including lung-related conditions.

Supramolecular nanomedicines through rational design of self-assembling prodrugs.

Advancements in the development of nanomaterials have led to the creation of a plethora of functional constructs as drug delivery vehicles to address many dire medical needs. The emerging prodrug strategy provides an alternative solution to create nanomedicines of extreme simplicity by directly using the therapeutic agents as molecular building blocks. This Review outlines different prodrug-based drug delivery systems, highlights the advantages of the prodrug strategy for therapeutic delivery, and demonstrates how combinations of different functionalities - such as stimuli responsiveness, targeting propensity, and multidrug conjugation - can be incorporated into designed prodrug delivery systems. Furthermore, we discuss the opportunities and challenges facing this rapidly growing field.

Local scaffold-assisted delivery of immunotherapeutic agents for improved cancer immunotherapy.

Cancer immunotherapy, which reprograms a patient's own immune system to eradicate cancer cells, has been demonstrated as a promising therapeutic strategy clinically. Immune checkpoint blockade (ICB) therapies, cytokine therapies, cancer vaccines, and chimeric antigen receptor (CAR) T cell therapies utilize immunotherapy techniques to relieve tumor immune suppression and/or activate cellular immune responses to suppress tumor growth, metastasis and recurrence. However, systemic administration is often hampered by limited drug efficacy and adverse side effects due to nonspecific tissue distribution of immunotherapeutic agents. Advancements in local scaffold-based delivery systems facilitate a controlled release of therapeutic agents into specific tissue sites through creating a local drug reservoir, providing a potent strategy to overcome previous immunotherapy limitations by improving site-specific efficacy and minimizing systemic toxicity. In this review, we summarized recent advances in local scaffold-assisted delivery of immunotherapeutic agents to reeducate the immune system, aiming to amplify anticancer efficacy and minimize immune-related adverse events. Additionally, the challenges and future perspectives of local scaffold-assisted cancer immunotherapy for clinical translation and applications are discussed.

In the time of COVID .

ABSTRACT: JAANP Fellow Dr. Leslie-Faith Morritt Taub, NYU Adult-Gerontology Primary Care Program Director, describes the emotional, political, and social impact of COVID-19 on one graduating cohort of nurse practitioner (NP) students at New York University and one incoming cohort of students. Through the lens of a seasoned professor she describes the changes to her teaching methods because she leads these students through the course work and clinical work required to take on the role of the NP in the midst of a global pandemic in the heart of New York City.

Biomaterial Platform To Establish a Hypoxic Metastatic Niche in Vivo.

Hypoxia is a hallmark of tumor microenvironments, exerting wide-ranging impacts on key processes of tumor progression and metastasis. However, our understanding of how hypoxia regulates these processes has been based primarily on studying the effects of hypoxia within the primary tumor. Recently, an increasing number of studies have suggested the importance of hypoxic regulation within metastatic target organs, but hypoxic metastatic niches in the body are difficult to access with current imaging techniques, hampering detailed in vivo investigation of hypoxia at metastatic sites. Here, we report an engineered biomaterial scaffold that is able to establish an in vivo hypoxic metastatic niche in a readily accessible area, enabling the investigation of hypoxic regulation at a metastatic site. We engineered hypoxic environments within microporous poly(lactide-co-glycolide) (PLG) scaffolds, which have previously been shown to act as premetastatic niche mimics, via the addition of CoCl2, a hypoxia-mimetic agent. When implanted into the subcutaneous region of mice, CoCl2-containing PLG (Co-PLG) scaffolds established hypoxic microenvironments, as evidenced by the stabilization of hypoxia-inducible factor 1α (HIF1α) and increased blood vessel formation in vitro and in vivo. Furthermore, implanted Co-PLG scaffolds were able to recruit 4T1 metastatic breast cancer cells. These results demonstrate that Co-PLG scaffolds can establish an in vivo hypoxic metastatic niche, providing a novel platform to investigate hypoxic regulation of disseminated tumor cells (DTCs) at target organs.

Sleep disorders, glucose regulation, and type 2 diabetes.

Recent epidemiological, biological, and behavioral evidence suggests that sleep disorders may contribute to the development of diabetes; conversely, diabetes itself may contribute to sleep disorders. Sleep appears to moderate the neurohormones that regulate blood glucose. Sleep deprivation and sleep disorders contribute to pathophysiological changes associated with the development of type 2 diabetes. In people who already have diabetes, sleep deprivation contributes to elevations of hemoglobin A1c. Symptoms that occur as a result of diabetes, such as nocturia and neuropathic pain, may in turn contribute to sleep disturbance and exacerbate sleep deprivation. The purposes of this article are to examine the scientific basis for the associations between diabetes and sleep, identify gaps in the understanding of the empirical underpinnings of these relationships, and propose directions for future research.

A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl2.

BACKGROUND: While hypoxia has been well-studied in various tumor microenvironments, its role in cancer cell dormancy is poorly understood, in part due to a lack of well-established in vitro and in vivo models. Hypoxic conditions under conventional hypoxia chambers are relatively unstable and cannot be maintained during characterization outside the chamber since normoxic response is quickly established. To address this challenge, we report a robust in vitro cancer dormancy model under a hypoxia-mimicking microenvironment using cobalt chloride (CoCl2), a hypoxia-mimetic agent, which stabilizes hypoxia inducible factor 1-alpha (HIF1α), a major regulator of hypoxia signaling. METHODS: We compared cellular responses to CoCl2 and true hypoxia (0.1% O2) in different breast cancer cell lines (MCF-7 and MDA-MB-231) to investigate whether hypoxic regulation of breast cancer dormancy could be mimicked by CoCl2. To this end, expression levels of hypoxia markers HIF1α and GLUT1 and proliferation marker Ki67, cell growth, cell cycle distribution, and protein and gene expression were evaluated under both CoCl2 and true hypoxia. To further validate our platform, the ovarian cancer cell line OVCAR-3 was also tested. RESULTS: Our results demonstrate that CoCl2 can mimic hypoxic regulation of cancer dormancy in MCF-7 and MDA-MB-231 breast cancer cell lines, recapitulating the differential responses of these cell lines to true hypoxia in 2D and 3D. Moreover, distinct gene expression profiles in MCF-7 and MDA-MB-231 cells under CoCl2 treatment suggest that key cell cycle components are differentially regulated by the same hypoxic stress. In addition, the induction of dormancy in MCF-7 cells under CoCl2 treatment is HIF1α-dependent, as evidenced by the inability of HIF1α-suppressed MCF-7 cells to exhibit dormant behavior upon CoCl2 treatment. Furthermore, CoCl2 also induces and stably maintains dormancy in OVCAR-3 ovarian cancer cells. CONCLUSIONS: These results demonstrate that this CoCl2-based model could provide a widely applicable in vitro platform for understanding induction of cancer cell dormancy under hypoxic stress.

A case study of an older adult with severe anemia refusing blood transfusion.

PURPOSE: To discuss the diagnosis and treatment of severe anemia in an older adult who presents the challenge of declining blood transfusion in a real-world scenario where critical thinking, evidence-based care, and collaboration with other providers must come together to serve this patient's unique needs. DATA SOURCES: Extensive review of the scientific literature on anemia and the situation in which a patient refuses blood transfusion presented in a case study format. CONCLUSIONS: A thorough physical assessment, complete health history, and appropriate diagnostic workup should be used to distinguish the normal effects of senescence from the signs and symptoms of anemia. Common conditions that cause anemia in the elderly include chronic disease, iron deficiency, and gastrointestinal bleeding. These conditions may result in profound anemia. The challenge can be compounded when, because of religious tenets, a patient does not accept a blood transfusion. This case study challenges nurse practitioners to apply knowledge, seek guidance, and make appropriate referrals to care for a patient in order to render care within the parameters of the patient's belief system. IMPLICATIONS FOR PRACTICE: The astute primary care provider recognizes that anemia is not an expected physiological change associated with aging but a manifestation of an underlying disease process. Fatigue, weakness, and dyspnea are all symptoms of anemia that may be overlooked and attributed to the aging process. Further, in keeping with the principles of autonomy and self-determination, it is the clinician's duty to work with all patients to restore them to a state of optimal health while respecting deeply held spiritual beliefs.

Concordance of provider recommendations with American Diabetes Association's Guidelines.

PURPOSE: To determine if selected client characteristics were factors influencing the provision of provider advice for diet, exercise, smoking cessation, alcohol cessation, eye and foot care, and influenza and pneumonia vaccine for those told by a provider that they had diabetes. DATA SOURCES: Data from the 2001 National Health Interview Survey were used in a secondary analysis to answer the research question. This study used a subsample who self-reported having provider-diagnosed diabetes; the subsample comprised 2287 unweighted subjects that, when weighted, represent 6.38% of the civilian noninstitutionalized individuals with diabetes in the United States. CONCLUSIONS: This study suggests that many patients are not receiving all the eight processes of care studied, particularly those with new onset diabetes, elders, black people, and Hispanics. IMPLICATIONS FOR PRACTICE: This study suggests that the present paradigm is not early prevention but treatment of established disease. Changes in entrenched thinking about clinical care need to be addressed. Patients with diabetes need to have an awareness that there is a standard of optimal care, and they should be encouraged to seek those who provide this care. Further, system changes may be required to address changes that are not easily made at the provider level.

The use of large healthcare data sets in pursuit of a clinical question.

The use of large healthcare databases may be of interest to nurse practitioners who wish to answer clinical questions. This column will provide information about access to selected large healthcare databases, requirements for statistical software, and the skills required to utilize these databases.

Advanced practice nursing: shaping health through policy.

PURPOSE: To highlight the importance of advanced practice nurses (APNs) becoming politically engaged as key to promoting the healthcare interests of patients, communities and the profession and to offer specific strategies on how to become politically competent. DATA SOURCES: Robert Wood Johnson Foundation, CINAHL, PubMed. CONCLUSIONS: APNs must come to see political engagement as a professional obligation and health policy as something that they can shape rather than something that happens to them. IMPLICATIONS FOR PRACTICE: The overall goal of healthcare reform is the provision of quality, safe and cost-effective healthcare for all Americans. APNs are graduate prepared clinicians that focus on health and illness management and are strategically positioned to lead the way in shaping and implementing health policy priorities.

Monitoring for and preventing the long-term sequelae of bariatric surgery.

PURPOSE: To present a case study of a patient with multiple comorbid diseases who undergoes bariatric surgery. DATA SOURCES: Recent clinical and research articles, bariatric professional society guidelines, and government sources were culled to provide recommendations for the care of the person who chooses bariatric surgery as the treatment for the comorbid conditions of obesity, type 2 diabetes, obstructive sleep apnea, hypertension, and hyperlipidemia. CONCLUSIONS: As surgical management of obesity becomes more prevalent in an attempt to improve health-related quality of life, reduce mortality, and address the comorbidities that are prevalent in this population, nurse practitioners (NPs) need to understand what long-term management these patients will require. IMPLICATIONS FOR PRACTICE: NPs are primary care providers for patients with chronic diseases. It is likely that they will make referrals for this surgery and follow the patient after the procedure at some point. Knowledge of what the procedures involve, what changes to expect in the comorbid conditions, and what long-term monitoring and treatment should take place in the care of these patients will provide these patients with optimal care.

Making the diagnosis: idiopathic rapid eye movement sleep behavior disorder.

PURPOSE: To present a clinical case of idiopathic rapid eye movement sleep behavior disorder (RBD), differential diagnoses, selected treatments, and the pathology involved. DATA SOURCES: An Ovid data base search (covering 635 medical, neurologic, and psychiatric journals) was conducted using the search term RBD and limited to the years 2005-2009. This search strategy was used to locate clinical, research, and review articles providing the state of the science about RBD. A hand search was also conducted for seminal research papers as well as recent publications within the specialty of sleep disorders. CONCLUSIONS: RBD is a parasomnia with symptoms common to other disorders making it important to identify unique symptoms and diagnostic testing that helps differentiates these diseases. RBD can put the patient and the bed partner at risk for injury. Its prevalence is estimated to be 0.5% in older adults. IMPLICATIONS FOR PRACTICE: Nurse practitioners are primary care providers for older adults who may have complaints about behaviors associated with RBD. Knowledge of this disease process as well as its relationship with four other neurodegenerative diseases may provide an opportunity for early diagnosis and treatment of RBD and surveillance for and early diagnosis of the other neurodegenerative diseases in these patients.

If pelvic inflammatory disease is suspected empiric treatment should be initiated.

PURPOSE: To assist the nurse practitioner (NP) to make a rapid diagnosis and develop a treatment plan for pelvic inflammatory disease (PID) in order to assist women to promote their health and reduce their risk of the unnecessary sequelae of infertility, tubal damage, and the possibility of a subsequent ectopic pregnancy. DATA SOURCES: Centers for Disease Control guidelines and recent clinical practice literature were searched to provide guidance on how to diagnose, treat, and educate the patient with PID. CONCLUSIONS: The incidence of PID is approximately 1 million women annually. PID is diagnosed in 1%-2% of sexually active women under the age of 25, with a higher incidence in African American women. Women with PID produce over 2 million emergency room and office visits and incur health care costs of over 4 billion dollars annually. IMPLICATIONS FOR PRACTICE: PID is associated with chronic pelvic pain, infertility, and ectopic pregnancy. Symptoms can range from subtle and indolent to acute and fulminant. Having a high index of suspicion for the diagnosis will assist the NP in treating patients with this disease. Empiric antibiotic therapy should be initiated in all women at risk who have uterine, adnexal, or cervical motion tenderness on a bimanual exam with no other explanation for these symptoms. Without response to treatment, if the diagnosis is unclear, or if a surgical emergency is being considered, prompt referral to a specialist is warranted. Secondary preventive measures are discussed.