The Impact of Proinflammatory Cytokines and Imiquimod on GLUT1 in HaCaT Keratinocytes - a Potential Anti-Psoriatic Therapeutic Target?

BACKGROUND/AIMS: Glucose metabolism has been proven as an essential process for proliferating keratinocytes, which highlights the importance of glucose transporter-1 (GLUT1) not only in the onset of psoriasis but also in the progression and severity of this inflammation-driven disease. In this study, we attempted to find a connection between proinflammatory cytokines (IL-6, IL-17, IL-23, IL-36, TNF-α), a skin inflammation inducing agent - imiquimod (IMQ) and GLUT1 expression. METHODS: Human keratinocyte HaCaT cell line was incubated with exogenous cytokines: IL-6, IL-17A, IL-23, IL-36, TNF-α at a final concentration of 100 ng/ml, or with 1 µM of IMQ, for 48 h. Following the stimulation, glucose uptake and GLUT1 expression were evaluated. The activity of GLUT1 was measured in the presence of a selective GLUT1 inhibitor, BAY-876. The expression of GLUT1 was examined by immunofluorescence and quantified by qPCR, Western blotting and densitometry. RESULTS: The results from qPCR analysis showed that the administration of exogenous IL-6, IL-17, IL-23 and IL-36 to HaCaT cells resulted in upregulation of GLUT1-encoding SLC2A1 gene, while TNF-α had no significant effect. The same results were confirmed by immunofluorescence analysis, as the fluorescent intensity of GLUT1 was elevated following cytokine and IMQ stimulation. Western blot and densitometry showed that all examined cytokines, as well as IMQ, increased GLUT1 expression. HaCaT cells displayed an improved intracellular 2-deoxy-D-glucose (2-DG) uptake and GLUT1 activity after stimulation by exogenous cytokines and IMQ. The highest uptake of 2-DG was observed after IL-23 stimulation (1.93x) and the lowest after TNF-α stimulation (1.07x). BAY-876 inhibited the 2-DG uptake compared to control. CONCLUSION: Our findings suggest that cytokines and IMQ may play a key role in regulating GLUT1 expression in HaCaT cells. We believe that GLUT1 overexpression could potentially be utilized in the targeted treatment of psoriasis.

The Benefits of the Post-Transplant Cyclophosphamide in Both Haploidentical and Mismatched Unrelated Donor Setting in Allogeneic Stem Cells Transplantation.

Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies.

An Update on Photodynamic Therapy of Psoriasis-Current Strategies and Nanotechnology as a Future Perspective.

Psoriasis (PS) is an immune-mediated skin disease with substantial negative effects on patient quality of life. Despite significant progress in the development of novel treatment options over the past few decades, a high percentage of patients with psoriasis remain undertreated and require new medications with superior long-term efficacy and safety. One of the most promising treatment options against psoriatic lesions is a form of phototherapy known as photodynamic therapy (PDT), which involves either the systemic or local application of a cell-targeting photosensitizing compound, followed by selective illumination of the lesion with visible light. However, the effectiveness of clinically incorporated photosensitizers in psoriasis treatment is limited, and adverse effects such as pain or burning sensations are frequently reported. In this study, we performed a literature review and attempted to provide a pooled estimate of the efficacy and short-term safety of targeted PDT in the treatment of psoriasis. Despite some encouraging results, PDT remains clinically underutilized. This highlights the need for further studies that will aim to evaluate the efficacy of a wider spectrum of photosensitizers and the potential of nanotechnology in psoriasis treatment.

Phytochemicals in Gynecological Cancer Prevention.

Gynecological cancer confers an enormous burden among women worldwide. Accumulating evidence points to the role of phytochemicals in preventing cervical, endometrial, and ovarian cancer. Experimental studies emphasize the chemopreventive and therapeutic potential of plant-derived substances by inhibiting the early stages of carcinogenesis or improving the efficacy of traditional chemotherapeutic agents. Moreover, a number of epidemiological studies have investigated associations between a plant-based diet and cancer risk. This literature review summarizes the current knowledge on the phytochemicals with proven antitumor activity, emphasizing their effectiveness and mechanism of action in gynecological cancer.

In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment.

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose-methotrexate conjugate (GLU-MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter-1 (GLUT1). GLU-MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU-MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU-MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU-MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.

The Effect of a New Glucose-Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma Cell Lines.

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite-methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients' life. Therefore, novel targeted therapies based on the malignant cells' common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose-methotrexate conjugate (Glu-MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu-MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu-MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients' outcomes.

Glycoconjugation as a Promising Treatment Strategy for Psoriasis.

Despite the progress in the development of novel treatment modalities, a significant portion of patients with psoriasis remains undertreated relative to the severity of their disease. Recent evidence points to targeting the glucose transporter 1 and sugar metabolism as a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases. In this review, we discuss glycoconjugation, an approach that facilitates the pharmacokinetics of cytotoxic molecules and ensures their preferential influx through glucose transporters. We propose pathways of glycoconjugate synthesis to increase effectiveness, cellular selectivity, and tolerability of widely used antipsoriatic drugs. The presented approach exploiting the heightened glucose requirement of proliferating keratinocytes bears the potential to revolutionize the management of psoriasis. SIGNIFICANCE STATEMENT: Recent findings concerning the fundamental role of enhanced glucose metabolism and glucose transporter 1 overexpression in the pathogenesis of psoriasis brought to light approaches that proved successful in cancer treatment. Substantial advances in the emerging field of glycoconjugation highlight the rationale for the development of glucose-conjugated antipsoriatic drugs to increase their effectiveness, cellular selectivity, and tolerability. The presented approach offers a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases.

The impact of photodynamic therapy on immune system in cancer - an update.

Photodynamic therapy (PDT) is a therapeutic approach that has gained significant attention in recent years with its promising impact on the immune system. Recent studies have shown that PDT can modulate both the innate and adaptive arms of the immune system. Currently, numerous clinical trials are underway to investigate the effectiveness of this method in treating various types of cancer, as well as to evaluate the impact of PDT on immune system in cancer treatment. Notably, clinical studies have demonstrated the recruitment and activation of immune cells, including neutrophils, macrophages, and dendritic cells, at the treatment site following PDT. Moreover, combination approaches involving PDT and immunotherapy have also been explored in clinical trials. Despite significant advancements in its technological and clinical development, further studies are needed to fully uncover the mechanisms underlying immune activation by PDT. The main objective of this review is to comprehensively summarize and discuss both ongoing and completed studies that evaluate the impact of PDT of cancer on immune response.

In Vitro and In Vivo Antipsoriatic Efficacy of Protected and Unprotected Sugar-Zinc Phthalocyanine Conjugates.

Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose-ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose-ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.

Optimizing Outcomes in Mismatched Unrelated Donor Allogeneic Transplantation: Post-Transplant Cyclophosphamide's Dual Impact on Graft versus Host Disease Incidence and Overall Survival: Retrospective Analysis on Behalf of Polish Adult Leukemia Group.

Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) has emerged as a promising immunosuppressive strategy, revolutionizing haploidentical transplantation and demonstrating promise in MMUD settings. Background/Objectives: This study aimed to evaluate the impact of PTCy on MMUD allo-HSCT outcomes, specifically its effects on GvHD incidence and overall survival, compared to anthitymocyte globulin (ATG). Methods: One hundred seventy-four patients were classified into three groups based on the type of transplantation: PTCy-haplo (114/174; 65.5%), PTCy-MMUD (23/174; 13.2%), and ATG-MMUD (37/174; 21.2%). Results: Our findings showed that PTCy-MMUD significantly reduced acute GvHD occurrence compared to PTCy-haplo and ATG-MMUD approaches (p = 0.006). The delayed onset of acute GvHD in the PTCy-MMUD group suggests a more controlled immune reconstitution, contributing to the lower incidence. Importantly, PTCy-MMUD exhibited enhanced five-year overall survival rates, aligning with the notion that reduced GvHD correlates with improved patient outcomes (p = 0.032). Conclusions: We believe that this study contributes valuable insights into PTCy-MMUD's management, underscoring its potential to significantly reduce GvHD incidence and enhance survival outcomes. Although further investigations and clinical trials are warranted, this research underscores the promising role of PTCy-based GvHD prophylaxis in improving MMUD allo-HCT success.

Evaluation of the Approach towards Vaccination against COVID-19 among the Polish Population-In Relation to Sociodemographic Factors and Physical and Mental Health.

Due to the rapid development of COVID-19 vaccines, the world has faced a huge challenge with their general acceptance, including Poland. For this reason, we attempted to determine the sociodemographic factors influencing the decision of positive or negative attitudes toward COVID-19 vaccination. The analysis included 200,000 Polish participants-80,831 women (40.4%) and 119,169 men (59.6%). The results revealed that the most common reasons for vaccine refusal and hesitancy were the fear of post-vaccination complications and their safety (11,913/31,338, 38.0%; 9966/31,338, 31.8%). Negative attitudes were observed more often among male respondents with primary or secondary education (OR = 2.01, CI95% [1.86-2.17] and OR = 1.52, CI95% [1.41-1.63], respectively). On the other hand, older age ≥ 65 (OR = 3.69; 95%CI [3.44-3.96]), higher education level (OR = 2.14; 95%CI [2.07-2.22]), living in big cities with a range of 200,000-499,999 inhabitants and more than 500,000 inhabitants (OR = 1.57, CI95% [1.50-1.64] and OR = 1.90, CI95% [1.83-1.98], respectively), good physical conditions (OR = 2.05; CI95% [1.82-2.31]), and at last normal mental health conditions (OR = 1.67, CI95% [1.51-1.85]) were significantly associated with COVID-19 vaccine acceptance. Our study indicates which population group should be further supplied with data and information by health education, the government, and healthcare professionals to alleviate the negative attitude toward COVID-19 vaccines.

The Impact of Different Types of Diet on the Prevention of Diseases among Polish Inhabitants, Including COVID-19 Disease.

Proper nutrition may help in preventing deaths or at least alleviating the symptoms of many chronic diseases. While the COVID-19 disease was still taking its toll, the world had to adjust to new life conditions, which could change nutritional habits. In this observational, cross-sectional study, we aimed to identify the potential correlations between sociodemographic factors and diet and the presence of common chronic diseases among Polish inhabitants. Furthermore, we tried to determine whether the COVID-19 pandemic led to changes in nutritional habits. Therefore, based on the online study (the National Test for Poles' Health (NTPH), we collected data from 376,102 and 200,000 respondents in two different time frames (before the COVID-19 pandemic: 2019-2020 and during the COVID-19 pandemic: 2021-2022, respectively). Despite the rapid global rise of the COVID-19 pandemic, among our study group, hypertension was still the most commonly occurring disease in both time frames (32.33% in 2019-2020 and 34.95% in 2021-2022, p < 0.001). Furthermore, more chronic diseases were reported during the COVID-19 pandemic than in 2019-2020. Regarding sociodemographic factors, male respondents were more likely to develop hypertension and diabetes (OR = 1.35 CI 95% (1.28-1.43), p < 0.001; and OR = 1.20 CI 95% (1.11-1.30), p < 0.001). Vegetarian diet decreases the likelihood of hypertension, neurological disease, and diabetes (OR = 0.69, CI 95% (0.60-0.81), p < 0.001; OR = 0.72, CI 95% (0.59-0.88), p = 0.001; and OR = 0.73, CI 95% (0.55-0.96), p = 0.026). In line with this, consuming meat meals increases the risk of hypertension (OR = 1.09, CI 95% (1.02-1.17), p = 0.009). Interestingly, a reduced-sodium diet has an association with decreased morbidity of COVID-19 disease (OR = 0.72, CI 95% (0.63-0.82), p < 0.001). This result brings new light to more research to be done to allow efficient prevention of this disease. In conclusion, our study shows the beneficial role of a balanced diet in reducing the incidence rate of common chronic diseases. Our findings may be educational for those who would like to change their nutritional habits and/or for public health professionals to suggest the implementation of proper diets to their patients.

Identification of Barriers Limiting the Use of Preventive Vaccinations against Influenza among the Elderly Population: A Cross-Sectional Analysis.

Older adults are at a high risk of experiencing severe complications of influenza. Receiving a vaccination is a beneficial strategy to prevent the disease and reduce the severity of influenza illnesses. This cross-sectional questionnaire-based study aimed to evaluate the influence of sociodemographic, clinical, and mental parameters as well as other potential risk factors on refusal to vaccinate against influenza among the elderly population in Poland. Furthermore, due to the prevailing COVID-19 pandemic, we put efforts into finding any statistical correlations between the fear of COVID-19 infection in patients and their attitudes toward receiving an influenza vaccination. The study was conducted in November−December 2020 in Poland on a representative nationwide sample of 500 individuals aged > 60. Of the respondents, 62 (12.4%) and 51 (10.2%) underwent influenza vaccination in 2019 and 2020, respectively. Out of ten different factors analyzed in this study, three were significantly associated with attitudes towards influenza vaccination. Participants with net income below the national average of PLN 3000 (OR = 2.37, CI 95% [1.26−4.47]), compared to those earning more than PLN 3000, had significantly higher odds of having a negative attitude towards influenza vaccination. Furthermore, respondents with <174 cm height (OR = 2.56, CI 95% [1.51−4.33]) and those with strong fear of COVID-19 infection (OR = 1.65, CI95% [1.02−2.66]) were also more likely to refrain from influenza vaccination. We believe the identification of factors limiting the willingness to receive influenza vaccination is an effective way to help clinicians focus their efforts on educating the groups of patients with the highest odds of refusing to receive the vaccine. Moreover, it may aid the design and enforcement of national solutions or the implementation of novel legislative measures and preventive programs, increasing public confidence and promoting vaccination, especially among groups at high risk of developing this disease.

Sociodemographic and Health-Related Factors Influencing Drug Intake among the Elderly Population.

Excessive drugs intake among the elderly population, including self-medication, constitutes an important public health problem. Polypharmacy may lead to numerous adverse health effects, which become more prevalent when combined with biological changes in seniors. In this cross-sectional study, 500 Polish adults aged ≥60 years (M = 67.9 ± 4.2) were asked to complete a questionnaire via telephone calls, allowing us to identify sociodemographic and health-related factors influencing the daily medications consumption. Our findings revealed that all of the participants were receiving medications; 60.2% of them receive at least 1 to 3 drugs per day (301/500). The most commonly used medications included antihypertensive drugs and analgesics (51.0% and 46.0%, respectively). Taking into account clinical conditions, independent predictors of receiving over 3 medications per day turned out to be (1) coronary artery disease (OR = 6.77; CI 95%, 2.86-16.1), (2) diabetes (OR = 3.23, CI 95%, 1.75-5.95), (3) asthma (OR = 4.87, CI 95%, 2.13-11.1), (4) heart failure (OR = 3.38, CI 95%, 1.59-7.19) and (5) gastroesophageal reflux disease (OR = 1.93, CI 95%, 1.03-3.62). Participants suffering from depression were more likely to take drugs for hypertension (OR = 1.70, CI 95%, 1.04-2.78), while those with anxiety and social loneliness took more painkillers (OR = 2.59, CI 95%, 1.58-4.26 and OR = 2.08, CI 95%, 1.38-3.13, respectively). The most significant sociodemographic factors increasing the drugs intake among the population included in our study were high body mass and subsequent increased BMI values (OR = 2.68, CI 95%, 1.50-4.77). Furthermore, living in a city with over 400,000 inhabitants increased the likelihood of taking antidepressants (OR = 2.18, CI 95%, 1.20-3.94). Our study revealed factors increasing the risk of excessive medications intake and hence, increased susceptibility to some iatrogenic diseases among the elderly population. These factors should be considered by primary care physicians while prescribing appropriate drugs to elderly patients.

Correction: Agrawal et al. The Assessment of Fear of COVID-19 among the Elderly Population: A Cross-Sectional Study. J. Clin. Med. 2021, 10, 5537.

In the original publication [...].

The Impact of Hypoglycemia on Patients with Diabetes Mellitus: A Cross-Sectional Analysis.

The increasing mortality and morbidity in patients with diabetes mellitus constitute a severe public health problem. The condition is recognized as a cause of impaired quality of life, high costs, and diminished productivity. In this study, we performed a cross-sectional analysis among 300 Polish participants with type 1 and type 2 diabetes to determine and classify risk factors associated with increased incidences of hypoglycemia. Including an open-access knowledge about the correlations between diabetes rates and human's lifestyle, we confirm that the frequency of smoking and drinking alcohol, low BMI, inappropriate diet, low physical activity, lack of vaccination against influenza and pneumococci, and co-existence of other comorbidities such as cardiovascular diseases, thyroid diseases, hyperlipidemia, retinopathy, and asthma elevate the risk of hypoglycemia. Furthermore, hypoglycemic patients were more often malnourished, depressed, irritated, and exposed to stress. In sum, the analysis of the interaction between diabetes and sociodemographic, environmental, or other disease-related risk factors provides strategies to optimize glycemic control and reduce the incidence of hypoglycemia. Furthermore, we believe our findings may constitute a basis for promoting health by adjusting available and implementing new preventive services reducing hypoglycemic episodes in diabetic patients.

BKV Related Hemorrhagic Cystitis-An Insight into Risk Factors and Later Complications-An Analysis on Behalf of Polish Adult Leukemia Group.

BK virus reactivation increases the likelihood of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplant (HCT). In this study, we aimed to identify predictive and risk factors associated with the increased occurrence of this condition following HCT. On a group of 124 patients aged ≤71 years old (median 40 years) who underwent HCT, we analyzed sex, age, time from diagnosis to transplantation, type of conditioning, donor's relationship, age, and sex, the impact of immunosuppression with different drugs, and acute and chronic GVHD, BK viremia and viruria as potential factors increasing the risk of BK-related HC after HCT. HC occurred among 24 patients (24/124; 29.2%). A significant correlation was observed between HC incidences after HCT, BK viremia and viruria, and acute GVHD occurrence. Furthermore, the level of BKV DNA in serum at day +21 (>0.75 × 103) significantly impacted the patients' survival time. According to our results, the likelihood ratio of BKV-DNA on day +21 in serum is 6.25, indicating that this diagnostic test has the potential to be utilized in a clinical setting. These findings may be used as a voice in the discussion on implementing an optimal preemptive treatment in BKV reactivation after allogeneic HCT.

Prevalence of Use of Preventive Services in Poland: Result from a Population-Based Nationwide Study.

Systematic reviews of scientific evidence have identified clinical services that prevent or ameliorate illness and reduce mortality. This study aimed to assess the prevalence of all recommended evidence-based preventive services in a publicly funded healthcare setting. We conducted a population-based nationwide cross-sectional computer-assisted telephone survey of 1000 Polish adults (response rate 42%). The self-reported use of all recommended clinical preventive services was assessed, including mammography, colonoscopy, blood glucose screening, vaccination, blood pressure screening, and preventive counselling. The results showed that only 6.4% of adults had received all recommended preventive screening, whereas only 4.3% had received appropriate counselling. General practitioner (GP) visits, blood pressure screening, blood glucose screening, and cervical smear were among the most commonly provisioned interventions, while flu vaccination, PSA assessment, and preventive counselling were among the least prevalent services. Despite the low uptake of preventive interventions, over 75% is interested in remote access to preventive services using telemedicine platforms and e-consultations. Our findings suggest that there are significant gaps in the receipt of preventive interventions. Further improvements require not only changes in the incentive system for healthcare providers, but also system-level innovation such as telemedicine solutions to deliver preventive services remotely and engage individuals in the monitoring process.

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a widespread chronic autoimmune disorder affecting the joints, causing irreversible cartilage, synovium, and bone degradation. During the course of the disease, many immune and joint cells are activated, causing inflammation. Immune cells including macrophages, lymphocytes, neutrophils, mast cells, natural killer cells, innate lymphoid cells, as well as synovial tissue cells, like fibroblast-like synoviocytes, chondrocytes, and osteoclasts secrete different proinflammatory factors, including many cytokines, angiogenesis-stimulating molecules and others. Recent studies reveal that curcumin, a natural dietary anti-inflammatory compound, can modulate the response of the cells engaging in RA course. This review comprises detailed data about the pathogenesis and inflammation process in rheumatoid arthritis and demonstrates scientific investigations about the molecular interactions between curcumin and immune cells responsible for rheumatoid arthritis development to discuss this herbal drug's immunoregulatory role in RA treatment.