Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways.

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.

Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents.

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are of limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver cancer initiation, thus providing a new way to combat liver cancer. Ferroptosis is a distinct form of controlled cell death that differs from conventional cell death routes like apoptosis, necrosis, and pyroptosis. It results from intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads to the accumulation of lipid peroxides that further result in oxidative damage to cell membranes, disrupt normal functioning, and ultimately speed up the ferroptosis phenomenon. Ferroptosis regulation is intricately linked to cellular physiological processes, encompassing iron metabolism, lipid metabolism, and the equilibrium between oxygen-free radical reactions and lipid peroxidation. This review intends to summarize the natural compounds targeting ferroptosis in liver cancer to offer new therapeutic ideas for liver cancer. Furthermore, it serves as the foundation for identifying and applying chemical medicines and natural chemicals that target ferroptosis to treat liver cancer efficiently.

Obstacles for using assistive technology in centres of special needs in the UAE.

Assistive technology (AT) represents one way to improve access and participation in the school and home environments of people with disabilities (PWDs). This study analyzed the obstacles to AT acquisition, knowledge, use, recommendation, and training in special needs centers in the United Arab Emirates (UAE) from the perspective of professionals (teachers and therapists). A questionnaire was developed and its validity and reliability were confirmed. The questionnaire was distributed to all special-needs centers in the UAE via Survey Monkey, and 78 responses were received. The results indicate the nature of obstacles to AT use in special education centers in the UAE, with obstacles related to parents having the highest mean. The results also indicated a statistically significant difference in professionals' perception of obstacles to using AT based on experience level, center location, and level of education. Implications for further research and recommendations for policy and practice are provided.

Use of assistive technology (AT) enhances accessibility for students with disabilities. Therefore, it is imperative for centers and schools to actively seek access to AT tools and services to meet the needs of students with disabilities.Educational institutions must establish clear AT policies and legislation to provide AT tools for students with disabilities and address barriers to their implementation.Qualitative studies should be conducted to better understand the obstacles perceived by students with disabilities, teachers, principals, other staff, and parents as well as to gather recommendations for improvement.

miRNA expression in PCOS: unveiling a paradigm shift toward biomarker discovery.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects a substantial percentage of women, estimated at around 9-21%. This condition can lead to anovulatory infertility in women of childbearing age and is often accompanied by various metabolic disturbances, including hyperandrogenism, insulin resistance, obesity, type-2 diabetes, and elevated cholesterol levels. The development of PCOS is influenced by a combination of epigenetic alterations, genetic mutations, and changes in the expression of non-coding RNAs, particularly microRNAs (miRNAs). MicroRNAs, commonly referred to as non-coding RNAs, are approximately 22 nucleotides in length and primarily function in post-transcriptional gene regulation, facilitating mRNA degradation and repressing translation. Their dynamic expression in different cells and tissues contributes to the regulation of various biological and cellular pathways. As a result, they have become pivotal biomarkers for various diseases, including PCOS, demonstrating intricate associations with diverse health conditions. The aberrant expression of miRNAs has been detected in the serum of women with PCOS, with overexpression and dysregulation of these miRNAs playing a central role in the atypical expression of endocrine hormones linked to PCOS. This review takes a comprehensive approach to explore the upregulation and downregulation of various miRNAs present in ovarian follicular cells, granulosa cells, and theca cells of women diagnosed with PCOS. Furthermore, it discusses the potential for a theragnostic approach using miRNAs to better understand and manage PCOS.

Unraveling the relationship between the renin-angiotensin system and endometrial cancer: a comprehensive review.

Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin-angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure.

Nanotube breakthroughs: unveiling the potential of carbon nanotubes as a dual therapeutic arsenal for Alzheimer's disease and brain tumors.

Alzheimer's disease (AD) and brain tumors are debilitating neurological conditions that pose significant challenges in current medical practices. Existing treatment options for AD primarily focus on symptom management, and brain tumors often require aggressive therapeutic approaches. Novel disease-modifying strategies and therapeutic agents are urgently needed to address the underlying causes of AD pathogenesis and improve brain tumor management. In recent years, nanoparticles (NPs) have shown promise as valuable tools in diagnosing and managing various brain disorders, including AD. Among these, carbon nanotubes (CNTs) have garnered attention for their unique properties and biomedical potential. Their ability to cross the blood-brain barrier (BBB) with ease opens up new possibilities for targeted drug delivery and neuroprotection. This literature review aims to explore the versatile nature of CNTs, which can be functionalized with various biomolecules or substances due to their sp2 hybridization. This adaptability enables them to specifically target cells and deliver medications under specific environmental conditions. Moreover, CNTs possess an exceptional capacity to penetrate cell membranes, making them valuable tools in the treatment of AD and brain tumors. By delving into the role of CNTs in biomedicine, this review sheds light on their potential in managing AD, offering a glimpse of hope for effective disease-modifying options. Understanding the mechanisms of CNTs' action and their capabilities in targeting and delivering medication to affected cells will pave the way for innovative therapeutic strategies that can improve the lives of those afflicted with these devastating neurological conditions. The exploration of CNTs as a dual therapeutic arsenal for both brain tumors and Alzheimer's disease holds great promise and may usher in a new era of effective treatment strategies for these challenging conditions.

COVID-19: Psychological distress, fear, and coping strategies among community members across the United Arab Emirates.

BACKGROUND: The COVID-19 pandemic impacted the psychosocial well-being of the United Arab Emirates [UAE] population like other communities internationally. OBJECTIVES: We aimed to identify the factors associated with psychological distress, fear, and coping amongst community members across the UAE. METHODS: We conducted a cross-sectional online survey across the UAE during November 2020. Adults aged ≥18 years, living in the UAE who were able to respond to an online questionnaire in English or Arabic were considered eligible to participate in the study. We used standard validated tools to measure psychological distress, fear and coping. Kessler Psychological Distress Scale [K10] was used to assess psychological distress, Fear of COVID-19 Scale [FCV-19S] was used to assess the level of fear, and Brief Resilient Coping Scale [BRCS] was used to assess the coping strategies. RESULTS: A total of 417 individuals participated in this study with a mean age of 29 [± 10.7] years. More than half of the participants experienced high to very high levels of psychological distress [55%] and a quarter experienced high levels of fear of COVID-19 [23.3%] with almost a third of them [36.2%] having low resilient coping. About 37.4% of the participants had work-related mental health impacts and 32.4% were perceived to have moderate to a great deal of distress due to a change of employment status during the pandemic. One in ten participants [9.4%] reported increased smoking. Increased smoking [AOR 8.66, 95% CIs 1.08-69.1,], increased alcohol drinking [AOR 2.39, 95% CIs 1.05-5.47] and higher levels of fear of COVID-19 [AOR 2.93, 95% CIs 1.83-4.67] were associated with moderate to very high levels of psychological distress. Being female [AOR 1.82, p = 0.030], having a pre-existing mental health condition [AOR 9.88, 95% p = 0.027], engaging in high-risk behaviors such as increased smoking [AOR 21.14, p = 0.003], increased alcohol drinking [AOR 1.48, p = 0.359] in the previous four weeks, and higher levels of fear of COVID-19 [AOR 4.18, p <0.001] were associated with moderate to very high levels of psychological distress. Also, being a smoker [AOR, 0.840, p = 0.011], and having a high level of fear [AOR 0.372, p = 0.001] were found to be associated with low resilient coping. CONCLUSION: Community members in the UAE are at a higher risk of psychosocial distress and fear during the COVID-19 pandemic. Thus, healthcare providers and policymakers would need to be more alert to provide specific mental health support strategies for their wellbeing.

Non-steroidal anti-inflammatory drugs and biomarkers: A new paradigm in colorectal cancer.

Colorectal cancer is a sporadic, hereditary, or familial based disease in its origin, caused due to diverse set of mutations in large intestinal epithelial cells. Colorectal cancer (CRC) is a common and deadly disease that accounts for the 4th worldwide highly variable malignancy. For the early detection of CRC, the most common predictive biomarker found endogenously are KRAS and ctDNA/cfDNA along with SEPT9 methylated DNA. Early detection and screening for CRC are necessary and multiple methods can be employed to screen and perform early diagnosis of CRC. Colonoscopy, an invasive method is most prevalent for diagnosing CRC or confirming the positive result as compared to other screening methods whereas several non-invasive techniques such as molecular analysis of breath, urine, blood, and stool can also be performed for early detection. Interestingly, widely used medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation have reported chemopreventive impact on gastrointestinal malignancies, especially CRC in several epidemiological and preclinical types of research. NSAID acts by inhibiting two cyclooxygenase enzymes, thereby preventing the synthesis of prostaglandins (PGs) and causing NSAID-induced apoptosis and growth inhibition in CRC cells. This review paper majorly focuses on the diversity of natural and synthetic biomarkers and various techniques for the early detection of CRC. An approach toward current advancement in CRC detection techniques and the role of NSAIDs in CRC chemoprevention has been explored systematically. Several prominent governing mechanisms of the anti-cancer effects of NSAIDs and their synergistic effect with statins for an effective chemopreventive measure have also been discussed in this review paper.

Frontiers of Ferroptosis in Cancer Treatment.

Recent phenomenal advancements in genomic and proteomic technologies and rapid breakthroughs in the interpretation of large gene expression datasets have enabled scientists to comprehensively characterize the gene signatures involved in ferroptosis. Ferroptosis is an iron-dependent form of non-apoptotic cell death that has gained the worthwhile attention of both basic and clinical researchers. Ferroptosis has dichotomous, context-dependent functions both as a tumor suppressor and promoter of carcinogenesis. Essentially, pharmacological modulation of ferroptosis by its induction as well as its inhibition holds enormous potential to overcome drug resistance and to improve the therapeutic potential of chemotherapeutic drugs in a wide variety of cancers.

The Impact of the COVID-19 "Infodemic" on Well-Being: A Cross-Sectional Study.

INTRODUCTION: The COVID-19 pandemic created a crisis in the world of information and digital literacy. The amount of misinformation surrounding COVID-19 that has circulated through social media (SM) since January 2020 is notably significant and has been linked to rising levels of anxiety and fear amongst SM users. AIM: This study aimed to assess SM practices during COVID-19 and investigated their impact on users' well-being. METHODS: An online survey was distributed between June 10 and July 31 2020 via different SM platforms in the United Arab Emirates and other Arabic-speaking countries. Adults above 18 years of age who spoke Arabic or English were invited to complete the survey which covered multiple domains, use and practices related to social media platforms and mental health questions, including the WHO-5 Well-Being Index. RESULTS: Out of 993 participants, 73% were females, 76% were non-Emirati, 91% were university graduates, and 50% were employed in various occupations, of which 20% were health care professionals. Participants indicated that they acquired COVID-19 related information primarily from social media and messaging applications of which WhatsApp was the most used. Most participants reported sharing information after verification. The mean well-being score was 12.6 ±5.6, with 49% of participants reporting poor well-being (WHO-5 score <12.5). Adjusted linear regression showed that Facebook usage was negatively associated with well-being scores. Additionally, high time use was associated with poorer well-being. When adjusting for other factors, including low confidence in information around COVID-19 and poor knowledge overall, SM usage was significantly associated with poorer well-being. CONCLUSION: The study sheds light on the use of SM during the pandemic and its impact on well-being throughout the novel coronavirus pandemic. Social media practices during emergencies and disasters may impact public well-being. Authorities are advised to step in to minimize the spread of misinformation and more frequent use of social media as it may influence well-being. Public health specialists, information technology and communication experts should collaborate to limit the infodemic effect on communities.

Psychological impact of COVID-19 on healthcare workers: cross-sectional analyses from 14 countries.

Background: Healthcare workers (HCWs) have been impacted psychologically due to their professional responsibilities over the prolonged era of the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to identify the predictors of psychological distress, fear, and coping during the COVID-19 pandemic among HCWs. Methods: A cross-sectional online survey was conducted among self-identified HCWs across 14 countries (12 from Asia and two from Africa). The Kessler Psychological Distress Scale, the Fear of COVID-19 Scale, and the Brief Resilient Coping Scale were used to assess the psychological distress, fear, and coping of HCWs, respectively. Results: A total of 2447 HCWs participated; 36% were doctors, and 42% were nurses, with a mean age of 36 (±12) years, and 70% were females. Moderate to very-high psychological distress was prevalent in 67% of the HCWs; the lowest rate was reported in the United Arab Emirates (1%) and the highest in Indonesia (16%). The prevalence of high levels of fear was 20%; the lowest rate was reported in Libya (9%) and the highest in Egypt (32%). The prevalence of medium-to-high resilient coping was 63%; the lowest rate was reported in Libya (28%) and the highest in Syria (76%). Conclusion: COVID-19 has augmented the psychological distress among HCWs. Factors identified in this study should be considered in managing the wellbeing of HCWs, who had been serving as the frontline drivers in managing the crisis successfully across all participating countries. Furthermore, interventions to address their psychological distress should be considered.

COVID-19: Factors associated with psychological distress, fear, and coping strategies among community members across 17 countries.

BACKGROUND: The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. OBJECTIVES: We aimed to examine the extent and identify factors associated with psychological distress, fear of COVID-19 and coping. METHODS: We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. RESULTS: A total of 8,559 people participated; mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping; the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]); nurses had medium to high resilient coping (1.30 [1.03-1.65]). CONCLUSIONS: The extent of psychological distress, fear of COVID-19 and coping varied by country; however, we identified few higher risk groups who were more vulnerable than others. There is an urgent need to prioritise health and well-being of those people through well-designed intervention that may need to be tailored to meet country specific requirements.

Airplug-mediated isolation and centralization of single T cells in rectangular microwells for biosensing.

Sorting cells in a single cell per microwell format is of great interest to basic biology studies, biotherapeutics, and biosensing including cell phenotyping. For instance, isolation of individual immune T cells in rectangular microwells has been shown to empower the multiplex cytokine profiling at the single cell level for therapeutics applications. The present study, however, shows that there is an existing bias in temporal cytokine sensing that originates from random "unpredicted" positions of loaded cells within the rectangular microwells. To eliminate this bias, the isolated cells need to be well-aligned with each other and relative to the sensing elements. Hence, an approach that utilizes the in situ formation and release of airplugs to localize cells towards the center of the rectangular microwells is reported. The chip includes 2250 microwells (each 500 × 50 × 20 µm3) arranged in 9 rows. Results showed 20% efficiency in trapping single T cells per microwells, where cells are localized within ±3% of the center of microwells. The developed platform could provide real-time dynamic and unbiased multiplex cytokine detection from single T cells for phenotyping and biotherapeutics studies.

Vitamin D deficiency in mothers, neonates and children.

Vitamin D is produced in response to the exposure of skin to sunlight through UV-B synthesis. It can also be obtained from diet and dietary supplements. Vitamin D is essential for strong bones as it helps to absorb calcium from diet. Vitamin D deficiency mainly occurs if strict vegetarian diet is followed as mostly the source of vitamin D is animal based; therefore, exposure to sunlight is restricted or having dark skin color. Low vitamin D levels results in increased possibility of gestational diabetes among pregnant women, low birth weight and pre-eclampsia in infants, and mothers may suffer bone impairment, osteoporosis, hypocalcaemia, and hypertension. Vitamin D deficiency is directly linked with severe complication in mothers and neonates, causing rickets, poor fetal growth and infantile eczema in neonates. Higher prevalence rate of vitamin D deficiency has led professionals to emphasize on development of relevant precautionary measures.

Cytokine profiles at birth and the risk of developing severe respiratory distress and chronic lung disease.

BACKGROUND: Neonates with the diagnosis of respiratory distress syndrome (RDS) were studied to investigate possible associations between cytokine levels at birth and developing severe RDS or chronic lung disease (CLD). MATERIALS AND METHODS: This was a cross-sectional study on serum and bronchoalveolar lavage (BAL) samples collected within hours of birth from infants with moderate and severe RDS. Twenty infants with moderate RDS and 20 infants with severe RDS were studied. RDS was diagnosed on the basis of radiographic findings, respiratory distress, and an increasing oxygen requirement. RDS severity was graded based on the radiological findings and Downe's Score. CLD was diagnosed when infants were still on supplemented O2 by at least 28 days of age. Levels of the cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor alpha were measured using enzyme-linked immunosorbent assay. "Statistical analysis was performed using the SPSS for Windows, (SPSS Inc., Chicago, IL, USA)." RESULTS: Levels of the proinflammatory cytokines IL-8 and IL-1ß were significantly higher in BAL of infants with severe RDS than those with moderate RDS (P = 0.007 and P = 0.02, respectively). IL-8 levels were also significantly higher in BAL and serum of infants who later progressed to CLD than in those who did not (P = 0.03 for both). The IL-8/IL-10 cytokine ratio was significantly higher in the BAL of severe RDS infants than in moderate RDS (P = 0.01) and in the serum of infants who progressed to CLD than in those who did not (P = 0.03). CONCLUSION: Levels of IL-8 and the IL-8/IL-10 ratio measured soon after birth were associated with severity of RDS as well as progression to CLD. Early measurement of cytokines levels and ratios may contribute to the prognosis and management of RDS and CLD.

What is a midwife? A survey of pregnant women in Abu Dhabi.

Evidence suggests that, throughout the world, there is a lack of understanding of the midwife's role. It has previously been found that most pregnant women in Dubai did not understand the role of the midwife and felt safer being cared for by doctors This paper presents findings from a survey conducted in Abu Dhabi, where midwifery is well established, which sought to explore whether the role of the midwife is generally acknowledged and understood. Overall a lack of knowledge of the role and scope of practice of the midwife was evident amongst a third of respondents. Since midwifery care has been shown to provide high quality maternity care, marketing and promoting the role of the midwife both to service users and to other professionals is crucial.

Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1.

AIMS: Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O2⁻) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identified for Dectin-1. Our hypothesis was that inflammation generates endogenous ligands for Dectin-1 that activate O2⁻ production and thereby contributes to atherogenesis. METHODS AND RESULTS: Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O2⁻ production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O2⁻ is produced. CONCLUSION: We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O2⁻ production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.

Protein kinase Cδ is a critical component of Dectin-1 signaling in primary human monocytes.

Zymosan, a mimic of fungal pathogens, and its opsonized form (ZOP) are potent stimulators of monocyte NADPH oxidase, resulting in the production of O(2)(.-), which is critical for host defense against fungal and bacterial pathogens and efficient immune responses; however, uncontrolled O(2)(.-) production may contribute to chronic inflammation and tissue injury. Our laboratory has focused on characterizing the signal transduction pathways that regulate NADPH oxidase activity in primary human monocytes. In this study, we examined the involvement of various pattern recognition receptors and found that Dectin-1 is the primary receptor for zymosan stimulation of O(2)(.-) via NADPH oxidase in human monocytes, whereas Dectin-1 and CR3 mediate the activation by ZOP. Further studies identified Syk and Src as important signaling components downstream of Dectin-1 and additionally identified PKCδ as a novel downstream signaling component for zymosan-induced O(2)(.-) as well as phagocytosis. Our results show that Syk and Src association with Dectin-1 is dependent on PKCδ activity and expression and demonstrate direct binding between Dectin-1 and PKCδ. Finally, our data show that PKCδ and Syk but not Src are required for Dectin-1-mediated phagocytosis. Taken together, our data identify Dectin-1 as the major PRR for zymosan in primary human monocytes and identify PKCδ as a novel downstream signaling kinase for Dectin-1-mediated regulation of monocyte NADPH oxidase and zymosan phagocytosis.