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KRAS mutation throughout pancreatic cancer malignancy.
Furthermore, as high throughput technology becomes more affordable and accessible, researchers continue to deepen their understanding of the factors that influence tumor heterogeneity and shape the TME over the course of treatment regimens. In this review, we will investigate the factors that give rise to tumor heterogeneity and the impact it has on the field of immunotherapy. We will discuss how tumor heterogeneity causes resistance to various treatments and review the strategies currently being employed to overcome this challenging clinical hurdle. Finally, we will outline areas of research that should be prioritized to gain a better understanding of tumor heterogeneity and develop appropriate solutions.Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer's disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug.Stress is a common belief among breast cancer patients and the public to explain variation in breast cancer incidence. Epidemiological studies interrogating the relationship between stress and cancer have reported mixed results. The impact of the topic and the lack of consensus has sparked this review of the literature to investigate gaps in knowledge and identify areas of research. We first present a brief summary of the biopsychosocial model generally used to conduct research on stress. We then divide the overview of the literature into areas of research focus. These include the role of distressing life events in breast cancer incidence, the role of adverse childhood events in later breast cancer incidence, the importance of race and socioeconomic status (SES) as social determinants of breast cancer incidence, and the specific role of chronic stress in relation to breast cancer. For each topic, we discuss the potential of stress as a risk factor and possible intervention strategies that could reduce the effects of stress. We then identify further research questions to be probed to fill the gaps in knowledge. We conclude with a discussion of future research directions for stress research as it relates to breast cancer incidence.(1) Background Cardiovascular autonomic dysfunction is a non-motor feature in Parkinson's disease with negative impact on functionality and life expectancy, prompting early detection and proper management. We aimed to describe the blood pressure patterns reported in patients with Parkinson's disease, as measured by 24-h ambulatory blood pressure monitoring. (2) Methods We conducted a systematic search on the PubMed database. Studies enrolling patients with Parkinson's disease undergoing 24-h ambulatory blood pressure monitoring were included. Data regarding study population, Parkinson's disease course, vasoactive drugs, blood pressure profiles, and measurements were recorded. (3) Results The search identified 172 studies. Forty studies eventually fulfilled the inclusion criteria, with 3090 patients enrolled. Abnormal blood pressure profiles were commonly encountered high blood pressure in 38.13% of patients (938/2460), orthostatic hypotension in 38.68% (941/2433), supine hypertension in 27.76% (445/1603) and nocturnal hypertension in 38.91% (737/1894). Dipping status was also altered often, 40.46% of patients (477/1179) being reverse dippers and 35.67% (310/869) reduced dippers. All these patterns were correlated with negative clinical and imaging outcomes. (4) Conclusion Patients with Parkinson's disease have significantly altered blood pressure patterns that carry a negative prognosis. Ambulatory blood pressure monitoring should be validated as a biomarker of PD-associated cardiovascular dysautonomia and a tool for assisting therapeutic interventions.Since it was first reported in Wuhan, China, in 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic outbreak resulting in a tremendous global threat due to its unprecedented rapid spread and an absence of a prophylactic vaccine or therapeutic drugs treating the virus. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a key player in the viral entry into cells through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor protein, and the RBD has therefore been crucial as a drug target. In this study, we used phage display to develop human monoclonal antibodies (mAbs) that neutralize SARS-CoV-2. A human synthetic Fab phage display library was panned against the RBD of the SARS-CoV-2 spike protein (SARS-2 RBD), yielding ten unique Fabs with moderate apparent affinities (EC50 = 19-663 nM) for the SARS-2 RBD. All of the Fabs showed no cross-reactivity to the MERS-CoV spike protein, while three Fabs cross-reacted with the SARS-CoV spike protein. Five Fabs showed neutralizing activities in in vitro assays based on the Fabs' activities antagonizing the interaction between the SARS-2 RBD and ACE2. Reformatting the five Fabs into immunoglobulin Gs (IgGs) greatly increased their apparent affinities (KD = 0.08-1.0 nM), presumably due to the effects of avidity, without compromising their non-aggregating properties and thermal stability. Furthermore, two of the mAbs (D12 and C2) significantly showed neutralizing activities on pseudo-typed and authentic SARS-CoV-2. Navitoclax mouse Given their desirable properties and neutralizing activities, we anticipate that these human anti-SARS-CoV-2 mAbs would be suitable reagents to be further developed as antibody therapeutics to treat COVID-19, as well as for diagnostics and research tools.
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