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Neurologic Clinics Aug 2024This article provides a comprehensive review of widely utilized stroke scales in both routine clinical settings and research. These scales are crucial for planning... (Review)
Review
This article provides a comprehensive review of widely utilized stroke scales in both routine clinical settings and research. These scales are crucial for planning treatment, predicting outcomes, and helping stroke patients recover. They also play a pivotal role in planning, executing, and comprehending stroke clinical trials. Each scale presents distinct advantages and limitations, and the authors explore these aspects within the article. The authors' intention is to provide the reader with practical insights for a clear understanding of these scales, and their effective use in their clinical practice.
Topics: Humans; Stroke; Cerebrovascular Disorders; Severity of Illness Index
PubMed: 38937040
DOI: 10.1016/j.ncl.2024.03.008 -
Pharmacological Research Jun 2024The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that... (Review)
Review
The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that mediates the classical WNT signaling pathway and other non-classical pathways. Besides, the FZDs also play a core role in tissue regeneration and tumor occurrence. With the structure and mechanism of FZDs activation becoming clearer, a series of FZDs modulators (inhibitors and agonists) have been developed, with the hope of bringing benefits to the treatment of cancer and degenerative diseases. Most of the FZDs inhibitors (small molecules, antibodies or designed protein inhibitors) block WNT signaling through binding to the cysteine-rich domain (CRD) of FZDs. Several small molecules impede FZDs activation by targeting to the third intracellular domain or the transmembrane domain of FZDs. However, three small molecules (FZM1.8, SAG1.3 and purmorphamine) activate the FZDs through direct interaction with the transmembrane domain. Another type of FZDs agonists are bivalent or tetravalent antibodies which activate the WNT signaling via inducing FZD-LRP5/6 heterodimerization. In this article, we reviewed the FZDs modulators reported in recent years, summarized the critical molecules' discovery processes and the elucidated relevant structural and pharmacological mechanisms. We believe the summaried molecular mechanisms of the relevant modulators could provide important guidance and reference for the future development of FZD modulators.
PubMed: 38936522
DOI: 10.1016/j.phrs.2024.107286 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as "genomic junk" to key players in cancer progression.... (Review)
Review
Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as "genomic junk" to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including LINE-1, Alus, and LTRs, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.
PubMed: 38936517
DOI: 10.1016/j.bbcan.2024.189143 -
JMIR MHealth and UHealth Jun 2024Rising rates of psychological distress (symptoms of depression, anxiety, and stress) among adults in the United States necessitate effective mental wellness...
BACKGROUND
Rising rates of psychological distress (symptoms of depression, anxiety, and stress) among adults in the United States necessitate effective mental wellness interventions. Despite the prevalence of smartphone app-based programs, research on their efficacy is limited, with only 14% showing clinically validated evidence. Our study evaluates Noom Mood, a commercially available smartphone-based app that uses cognitive behavioral therapy and mindfulness-based programming. In this study, we address gaps in the existing literature by examining postintervention outcomes and the broader impact on mental wellness.
OBJECTIVE
Noom Mood is a smartphone-based mental wellness program designed to be used by the general population. This prospective study evaluates the efficacy and postintervention outcomes of Noom Mood. We aim to address the rising psychological distress among adults in the United States.
METHODS
A 1-arm study design was used, with participants having access to the Noom Mood program for 16 weeks (N=273). Surveys were conducted at baseline, week 4, week 8, week 12, week 16, and week 32 (16 weeks' postprogram follow-up). This study assessed a range of mental health outcomes, including anxiety symptoms, depressive symptoms, perceived stress, well-being, quality of life, coping, emotion regulation, sleep, and workplace productivity (absenteeism or presenteeism).
RESULTS
The mean age of participants was 40.5 (SD 11.7) years. Statistically significant improvements in anxiety symptoms, depressive symptoms, and perceived stress were observed by week 4 and maintained through the 16-week intervention and the 32-week follow-up. The largest changes were observed in the first 4 weeks (29% lower, 25% lower, and 15% lower for anxiety symptoms, depressive symptoms, and perceived stress, respectively), and only small improvements were observed afterward. Reductions in clinically relevant anxiety (7-item generalized anxiety disorder scale) and depression (8-item Patient Health Questionnaire depression scale) criteria were also maintained from program initiation through the 16-week intervention and the 32-week follow-up. Work productivity also showed statistically significant results, with participants gaining 2.57 productive work days from baseline at 16 weeks, and remaining relatively stable (2.23 productive work days gained) at follow-up (32 weeks). Additionally, effects across all coping, sleep disturbance (23% lower at 32 weeks), and emotion dysregulation variables exhibited positive and significant trends at all time points (15% higher, 23% lower, and 25% higher respectively at 32 weeks).
CONCLUSIONS
This study contributes insights into the promising positive impact of Noom Mood on mental health and well-being outcomes, extending beyond the intervention phase. Though more rigorous studies are necessary to understand the mechanism of action at play, this exploratory study addresses critical gaps in the literature, highlighting the potential of smartphone-based mental wellness programs to lessen barriers to mental health support and improve diverse dimensions of well-being. Future research should explore the scalability, feasibility, and long-term adherence of such interventions across diverse populations.
Topics: Humans; Prospective Studies; Male; Female; Adult; Middle Aged; Surveys and Questionnaires; Mobile Applications; Health Promotion; Cognitive Behavioral Therapy; Program Evaluation; United States; Mindfulness; Quality of Life
PubMed: 38935946
DOI: 10.2196/54634 -
Radiographics : a Review Publication of... Jul 2024Bile leaks arise from various causes such as trauma, complications after hepatobiliary surgery, and intrahepatic malignancies or their associated liver-directed... (Review)
Review
Bile leaks arise from various causes such as trauma, complications after hepatobiliary surgery, and intrahepatic malignancies or their associated liver-directed treatments. Bile leaks can result in significant morbidity and mortality. Delayed diagnosis is not uncommon due to nonspecific manifestations; therefore, a high clinical suspicion is needed. A multidisciplinary approach for treatment of biliary leaks with prompt referral to tertiary care centers with experienced hepatobiliary surgeons, advanced endoscopists, and interventional radiologists is needed to address these challenging complications. Management of biliary leaks can range from conservative management to open surgical repair. Minimally invasive procedures play a crucial role in biliary leak treatment, and the interventional radiologist can help guide appropriate management on the basis of a clear understanding of the pathophysiology of biliary leaks and a current knowledge of the armamentarium of treatment options. In most cases, a simple diversion of bile to decompress the biliary system may prove effective. However, persistent and high-output biliary leaks require delineation of the source with tailored treatment options to control the leak. This may be done by additional diversions, occluding the source, reestablishing connections, or using a combination of therapies to bridge to more definitive surgical interventions. The authors describe the different treatment options and emphasize the role of interventional radiology. RSNA, 2024.
Topics: Humans; Postoperative Complications; Biliary Tract Diseases; Anastomotic Leak; Patient Care Team
PubMed: 38935550
DOI: 10.1148/rg.230155 -
Expert Opinion on Pharmacotherapy Jun 2024The treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune... (Review)
Review
INTRODUCTION
The treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune checkpoint inhibitors (ICIs). However, chemotherapy remains a cornerstone of treatment, alone or in combination. Microtubule-targeting agents, such as taxanes and vinca alkaloids, play a crucial role in clinical practice in both early and advanced settings in NSCLC.
AREA COVERED
This review outlines the mechanisms of action, present significance, and prospective advancements of microtubule-targeting agents (MTAs), with a special highlight on new combinations in phase 3 trials. The online databases PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'Microtubule-targeting agents' and 'non-small cell lung cancer' or synonyms, with a special focus over the last 5 years of publications.
EXPERT OPINION
Despite the emergence of immunotherapy, MTA remains crucial, often used alongside or after immunotherapy, especially in squamous cell lung cancer. Next-generation sequencing expands treatment options, but reliable biomarkers for immunotherapy are lacking. While antibody-drug conjugates (ADCs) show promise, managing toxicities remain vital. In the early stages, MTAs, possibly with ICIs, are standard, while ADCs may replace traditional chemotherapy in the advanced stages. Nevertheless, MTAs remain essential in subsequent lines or for patients with contraindications.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Tubulin Modulators; Antineoplastic Agents; Immune Checkpoint Inhibitors; Immunotherapy; Animals; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38935538
DOI: 10.1080/14656566.2024.2369196 -
Molecular Carcinogenesis Jun 2024Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles in regulating tumor...
Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles in regulating tumor progression and therapy resistance by transferring exosomes to cancer cells. However, how CAFs modulate esophageal squamous cell carcinoma (ESCC) progression and radioresistance remains incompletely understood. The expression of fibroblast activation protein (FAP) in CAFs was evaluated by immunohistochemistry in 174 ESCC patients who underwent surgery and 78 pretreatment biopsy specimens of ESCC patients who underwent definitive chemoradiotherapy. We sorted CAFs according to FAP expression, and the conditioned medium (CM) was collected to culture ESCC cells. The expression levels of several lncRNAs that were considered to regulate ESCC progression and/or radioresistance were measured in exosomes derived from FAP CAFs and FAP CAFs. Subsequently, cell counting kit-8, 5-ethynyl-2'-deoxyuridine, transwell, colony formation, and xenograft assays were performed to investigate the functional differences between FAP CAFs and FAP CAFs. Finally, a series of in vitro and in vivo assays were used to evaluate the effect of AFAP1-AS1 on radiosensitivity of ESCC cells. FAP expression in stromal CAFs was positively correlated with nerve invasion, vascular invasion, depth of invasion, lymph node metastasis, lack of clinical complete response and poor survival. Culture of ESCC cells with CM/FAP CAFs significantly increased cancer proliferation, migration, invasion and radioresistance, compared with culture with CM/FAP CAFs. Importantly, FAP CAFs exert their roles by directly transferring the functional lncRNA AFAP1-AS1 to ESCC cells via exosomes. Functional studies showed that AFAP1-AS1 promoted radioresistance by enhancing DNA damage repair in ESCC cells. Clinically, high levels of plasma AFAP1-AS1 correlated with poor responses to dCRT in ESCC patients. Our findings demonstrated that FAP CAFs promoted radioresistance in ESCC cells through transferring exosomal lncRNA AFAP1-AS1; and may be a potential therapeutic target for ESCC treatment.
PubMed: 38934786
DOI: 10.1002/mc.23782 -
Immunity, Inflammation and Disease Jun 2024Asthma, a chronic inflammatory disease with diverse pathomechanisms, presents challenges in developing personalized diagnostic and therapeutic approaches. This review... (Review)
Review
OBJECTIVE
Asthma, a chronic inflammatory disease with diverse pathomechanisms, presents challenges in developing personalized diagnostic and therapeutic approaches. This review aims to provide a comprehensive overview of the role of exosomes, small extracellular vesicles, in asthma pathophysiology and explores their potential as diagnostic biomarkers and therapeutic tools.
METHODS
A literature search was conducted to identify recent studies investigating the involvement of exosomes in asthma. The retrieved articles were analyzed to extract relevant information on the role of exosomes in maintaining lung microenvironment homeostasis, regulating inflammatory responses, and their diagnostic and therapeutic potential for asthma.
RESULTS
Exosomes secreted by various cell types, have emerged as crucial mediators of intercellular communication in healthy and diseased conditions. Evidence suggest that exosomes play a significant role in maintaining lung microenvironment homeostasis and contribute to asthma pathogenesis by regulating inflammatory responses. Differential exosomal content between healthy individuals and asthmatics holds promise for the development of novel asthma biomarkers. Furthermore, exosomes secreted by immune and nonimmune cells, as well as those detected in biofluids, demonstrate potential in promoting or regulating immune responses, making them attractive candidates for designing new treatment strategies for inflammatory conditions such as asthma.
CONCLUSION
Exosomes, with their ability to modulate immune responses and deliver therapeutic cargo, offer potential as targeted therapeutic tools in asthma management. Further research and clinical trials are required to fully understand the mechanisms underlying exosome-mediated effects and translate these findings into effective diagnostic and therapeutic strategies for asthma patients.
Topics: Exosomes; Humans; Asthma; Biomarkers; Animals; Lung; Cell Communication
PubMed: 38934401
DOI: 10.1002/iid3.1325 -
Frontiers in Cell and Developmental... 2024Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and... (Review)
Review
Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.
PubMed: 38933330
DOI: 10.3389/fcell.2024.1399065 -
Viruses Jun 2024Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host... (Review)
Review
Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.
Topics: Humans; Respiratory Tract Infections; SARS-CoV-2; Peptide Hydrolases; Viral Tropism; COVID-19; Virus Diseases; Antiviral Agents; Host-Pathogen Interactions; Protease Inhibitors
PubMed: 38932275
DOI: 10.3390/v16060984