Pityriasis Rubra Pilaris - a difficult path to optimal treatment. Case report.

Pityriasis Rubra Pilaris is a rare, chronic inflammatory dermatosis of unknown etiology, presenting with erythema and papular eruptions. Treatment is difficult due to the lack of causal therapy, guidelines and requires an individualized approach. The most common treatments are systemic retinoids, immunosuppressants, phototherapy and biological therapy. This article presents the case of a 73-year-old man suffering from type 1 pityriasis rubra pilaris. The patient was initially treated with acitretin, which was discontinued due to hypogammaglobulinemia. This rare side effect of acitretin has not been previously published. As a second-line treatment, the patient received methotrexate, but with no clinical improvement after 3 months and an increase in skin pruritus. Finally, the use of isotretinoin resulted in significant clinical improvement and was well tolerated.

9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation.

BACKGROUND: Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are mainly Sertoli cells, which form the blood-testis barrier and produce immunosuppressive factors. Sertoli cells prevent inflammation in the testis and maintain immune tolerance by inhibiting proliferation and inducing lymphocyte apoptosis. It has been shown that 9-cis-retinoic acid (9cRA) blocks ex vivo apoptosis of peripheral blood lymphocytes and promotes the differentiation of Treg cells in the gut. However, the role of retinoid signaling in regulating the immune privilege of the testes remains unknown. OBJECTIVE: The aim of this study was to determine whether 9cRA, acting via the retinoic acid receptors (RAR) and the retinoic X receptors (RXR), controls the immunomodulatory functions of Sertoli cells by influencing the secretion of anti-inflammatory/pro-inflammatory factors, lymphocyte physiology and Treg cell differentiation. METHODS: Experiments were performed using in vitro model of co-cultures of murine Sertoli cells and T lymphocytes. Agonists and antagonists of retinoic acid receptors were used to inhibit/stimulate retinoid signaling in Sertoli cells. RESULTS: Our results have demonstrated that 9cRA inhibits the expression of immunosuppressive genes and enhances the expression of pro-inflammatory factors in Sertoli cells and lymphocytes, increases lymphocyte viability and decreases apoptosis rate. Moreover, we have found that 9cRA blocks lymphocyte apoptosis acting through both RAR and RXR and inhibiting FasL/Fas/Caspase 8 and Bax/Bcl-2/Caspase 9 pathways. Finally, we have shown that 9cRA signaling in Sertoli cells inhibits Treg differentiation. CONCLUSION: Collectively, our results indicate that retinoid signaling negatively regulates immunologically privileged functions of Sertoli cells, crucial for ensuring male fertility. 9cRA inhibits lymphocyte apoptosis, which can be related to the development of autoimmunity, inflammation, and, in consequence, infertility.

MMPs-responsive silk spheres for controlled drug release within tumor microenvironment.

Silk is a biocompatible and biodegradable material that enables the formation of various morphological forms, including nanospheres. The functionalization of bioengineered silk makes it possible to produce particles with specific properties. In addition to tumor cells, the tumor microenvironment (TME) includes stromal, immune, endothelial cells, signaling molecules, and the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are overexpressed in TME. We investigated bioengineered spider silks functionalized with MMP-responsive peptides to obtain targeted drug release from spheres within TME. Soluble silks MS12.2MS1, MS12.9MS1, and MS22.9MS2 and the corresponding silk spheres carrying MMP-2 or MMP-2/9 responsive peptides were produced, loaded with doxorubicin (Dox), and analyzed for their susceptibility to MMP-2/9 digestion. Although all variants of functionalized silks and spheres were specifically degraded by MMP-2/9, the MS22.9MS2 nanospheres showed the highest levels of degradation and release of Dox after enzyme treatment. Moreover, functionalized spheres were degraded in the presence of cancer cells releasing MMP-2/9. In the 2D and 3D spheroid cancer models, the MMP-2/9-responsive substrate was degraded and released from spheres when loaded into MS22.9MS2 particles but not into the control MS2 spheres. The present study demonstrated that a silk-based MMP-responsive delivery system could be used for controlled drug release within the tumor microenvironment.

Therapeutic Management and Outcomes of Hepatoblastoma in a Pediatric Patient with Mosaic Edwards Syndrome.

The mosaic form of Edwards syndrome affects 5% of all children with Edwards syndrome. The clinical phenotype is highly variable, ranging from the full spectrum of trisomy 18 to the normal phenotype. The purpose of this publication was to present the therapeutic process in an 18-month-old girl with the mosaic form of Edwards syndrome and hepatoblastoma, against the background of other cases of simultaneous occurrence of this syndrome and hepatoblastoma described so far. It appears that this particular group of patients with hepatoblastoma and Edwards syndrome can have good outcomes, provided they do not have life-threatening cardiac or other severe defects. Due to the prematurity of our patient and the defects associated with Edwards syndrome, the child required constant multidisciplinary care, but Edwards syndrome itself was not a reason to discontinue therapy for a malignant neoplasm of the liver. Regular abdominal ultrasound examination, along with AFP testing, may be helpful in the early detection of liver tumors in children with Edwards syndrome.

Echocardiographic findings in cancer-associated non-bacterial thrombotic endocarditis. Clinical series of 111 patients from single institution.

AIMS: Echocardiographic assessment of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) is limited to cases reports and small clinical series. Identifying heart valves abnormalities and its relation to embolic complications and cancer types. METHODS AND RESULTS: Manual review of echocardiographic images and medical records of Mayo Clinic patients (03/31/2002-06/30/2022) was performed. Ca-NBTE in 111 patients (mean age 63.2±9.7 years, 66.7% female) predominantly affected mitral valves (MV) (69), 56 aortic (AV), 8 tricuspid (TV) and rarely pulmonic (PV) (1). In 18 patients 2 valves were involved, 3 and 4 valves involvement in only a single patient each. Embolic complications were prevalent (n=102, 91.9%). Ca-NBTE affected MV more frequently the on upstream (atrial) (90% vs 49.3%) and TV downstream (ventricular) side (75% vs 37.5%). NBTE size (cm) varied significantly among valves, with TV hosting the largest masses (0.63-2.40 x 0.39-1.77), compared to MV [(0.11-1.81 x 0.11-1.62), (length p=0.001; width p=0.03)], and to AV [(0.20-2.70 x 0.11-1.51), (length p=0.001; width p=0.056)]; MV masses were borderline longer in systemic compared to cerebral emboli (p=0.057). Majority of MV (79.6%) and AV (69.6%) had thickened leaflets. NBTE lesions commonly affected closing margins (73.9%MV, 85.7% AV, and 62.5% of TV), but rarely commissures of MV (8.7%), yet fairly frequently of AV (41.1%). Five patients had severe regurgitation of MV and 5 AV. CONCLUSION: Ca-NBTE manifests mainly as thrombotic mobile masses attached to thickened MV and AV, with distinct variations in size based on valve type. Embolic destination but not cancer type is associated with NBTE mass size, and location.

Androgens and Notch signaling cooperate in seminiferous epithelium to regulate genes related to germ cell development and apoptosis.

It was reported previously that in adult males disruption of both androgen and Notch signaling impairs spermatid development and germ cell survival in rodent seminiferous epithelium. To explain the molecular mechanisms of these effects, we focused on the interaction between Notch signaling and androgen receptor (AR) in Sertoli cells and investigate its role in the control of proteins involved in apical ectoplasmic specializations, actin remodeling during spermiogenesis, and induction of germ cell apoptosis. First, it was revealed that in rat testicular explants ex vivo both testosterone and Notch signaling modulate AR expression and cooperate in the regulation of spermiogenesis-related genes (Nectin2, Afdn, Arp2, Eps8) and apoptosis-related genes (Fasl, Fas, Bax, Bcl2). Further, altered expression of these genes was found following exposure of Sertoli cells (TM4 cell line) and germ cells (GC-2 cell line) to ligands for Notch receptors (Delta-like1, Delta-like4, and Jagged1) and/or Notch pathway inhibition. Finally, direct interactions of Notch effector, Hairy/enhancer-of-split related with YRPW motif protein 1, and the promoter of Ar gene or AR protein were revealed in TM4 Sertoli cells. In conclusion, Notch pathway activity in Sertoli and germ cells regulates genes related to germ cell development and apoptosis acting both directly and indirectly by influencing androgen signaling in Sertoli cells.

Attitudes of Internal Medicine Nurses, Surgical Nurses and Midwives towards Reporting of Clinical Adverse Events.

Understanding the attitudes of medical staff contributes to shaping a culture of safety in health care. The aim of this study was the measurement of attitudes of nurses and midwives towards reporting clinical adverse events. Various research tools were used, including the Reporting of Clinical Adverse Events Scale (RoCAES; Polish: P-RoCAES), the Justice Sensitivity Inventory, the Feelings in Moral Situations Scale, the Perceived Stress at Work Scale and the Author's Survey Questionnaire. The cross-sectional survey was conducted from October 2022 to April 2023. The study used assessment-based sampling. The study included 745 midwives and nurses working in internal medicine-surgical wards in nine hospitals in a large provincial city in Poland. One-way analysis of variance ANOVA, post hoc test (Fisher's NIR), and r-Spearman correlation test were used. The level of significance (p) did not exceed 0.05. Respondents did not differ in terms of sensitivity to justice, moral feelings, and perceived stress at work, all of which variables were at moderate levels. Respondents' attitudes towards reporting clinical adverse events in the P-RoCAES were positive (surgical nurses 71.10; internal medicine nurses 72.04; midwives 71.26; F(2.741) = 1.14, p = 0.319), especially those with a master's degree, longer work experience and older age. Respondents with a master's degree were most likely to perceive a benefit from reporting adverse events (P-RoCAES subscale) (F(2.737) = 8.45, p = 0.001). The longer employment tenure (F(3.716) = 4.63, p = 0.003) and having a master's degree (F(2.737) = 3.10, p = 0.045) were associated with a higher feeling of guilt among the respondents (P-RoCAES subscale). The longer the participants worked, the more positive their attitude became towards the importance of transparency in procedures (F(2.741) = 3.56, p = 0.029), but the more negative their attitude was towards the benefits of reporting adverse events (P-RoCAES subscale) (r(686) = -0.08, p = 0.037). Individual attitudes of nurses and midwives as well as their age, length of service or education can influence the formation of a culture of safety in health care (including the reporting of clinical adverse events). Attitudes can motivate corrective action, can be reinforced and shaped by educational programs, good quality management and monitoring system solutions.

Professional challenges of nurses working during the SARS-CoV-2 virus pandemic.

OBJECTIVES: The diverse list of tasks and needs related to the SARS-CoV-2 pandemic may lead to different professional experiences in nurses working with patients infected with and not infected with SARS-CoV-2. The aim of the study was to measure the professional challenges of nurses working during the SARS-CoV-2 pandemic in Poland. MATERIAL AND METHODS: The study was conducted in 2021 in a group of 151 nurses. The following scales were used: the Perceived Stress Scale (PSS-10), the General Self-Efficacy Scale (GSES), the Impact of Event Scale - Revised (IES-R), the Minnesota Satisfaction Questionnaire (MSQ-SF), the Areas of Worklife Survey (AWS) and the Maslach Burnout Inventory - Human Services Survey (MBIHSS). RESULTS: Nurses working with patients infected with SARS-CoV-2 showed a positive correlation between workload and emotional exhaustion (ρ = 0.26, p = 0.02), as well as positive correlations among control, community and depersonalization (ρ = 0.25, p = 0.02; ρ = 0.23, p = 0.04). Among nurses working with uninfected patients, positive correlations were found among control, community, fairness and emotional exhaustion (ρ = 0.40, p = 0.000; ρ = 0.41, p = 0.000; ρ = 0.25, p = 0.03), as well as correlations between control and depersonalization (ρ = 0.33, p = 0.01), and among control, community and personal accomplishment (ρ = 0.23, p = 0.05; ρ = 0.27, p = 0.02). CONCLUSIONS: Nurses working during the SARS-CoV-2 pandemic with infected and uninfected patients both experienced a variety of psychosocial challenges in coping with the demands of their work, social relationships and personal life. Int J Occup Med Environ Health. 2023;36(1):112-24.

Opinion of nurses of internal medicine wards regarding factors determining their work - observational and cross-sectional studies.

OBJECTIVES: The aim of the study was to assess the factors determining the work of nurses in internal medicine departments. METHODS: The study was multicentre, cross-sectional, and observational. The selection of the research group was intentional. The subject of the study were 209 nurses working in 11 internal medicine departments in 10 hospitals in the region of southern Poland. RESULTS: The number of patients cared for by one nurse, nurses' participation in the decision-making process, and nurses' age were shown to be direct predictors of emotional exhaustion. The number of patients cared for by a single nurse, nurses' participation in the decision-making process, and age were direct predictors of depersonalization. It was shown that significant (p < 0.05) independent (multivariate analysis) variables of the job satisfaction subscale were information on support for nurses at work by managerial staff and nurses' participation in the decision-making process. After analysing the impact of socio-demographic factors on the nurses' working environment, it was found that the participation of nurses in the decision-making process was significantly lower in the youngest group than in the other age groups (p = 0.006). CONCLUSIONS: Participation of nurses in the decision-making process is a direct determinant of occupational burnout. A higher number of patients under the care of a nurse, lack of participation in the decision-making process and a higher age of nurses are predictors of emotional exhaustion and depersonalization.

Factors Influencing the Rationing of Nursing Care in Selected Polish Hospitals.

Introduction: The rationalization of nursing care can be a direct consequence of the low employment rate or unfavorable working environment of nurses. Aim: The aim of the study was to learn about the factors influencing the rationing of nursing care. Methods: The study group consisted of 209 nurses working in internal medicine departments. The study used the method of a diagnostic survey, a survey technique with the use of research tools: the BERNCA-R questionnaire and the PES-NWI questionnaire (which includes the occupational burnout questionnaire). Results: The mean total BERNCA score for rationing nursing care was 1.94 ± 0.75 on a scale from 0 to 4. A statistically significant relationship was demonstrated between the work environment and the rationing of nursing care. The results of the BERNCA-R scale correlated statistically significantly and positively (r > 0) with two (out of three) subscales of the occupational burnout questionnaire (MBI­Maslach Burnout Inventory): emotional exhaustion and depersonalization (p < 0.001), and with all types of adverse events analyzed (p < 0.05). Conclusions: The higher the frequency of care rationing, the worse the assessment of working conditions by nurses, and, therefore, more frequent care rationing determined the more frequent occurrence of adverse events. The more frequent the care rationing, the more frequent adverse events occur.

Follicle-stimulating hormone regulates Notch signalling in the seminiferous epithelium of continuously and seasonally breeding rodents.

CONTEXT: Juxtacrine (contact-dependent) communication between the cells of seminiferous epithelium mediated by Notch signalling is of importance for the proper course of spermatogenesis in mammals. AIMS: The present study was designed to evaluate the role of follicle-stimulating hormone (FSH) in the regulation of Notch signalling in rodent seminiferous epithelium. METHODS: We explored the effects (1) of pharmacological inhibition of the hypothalamus-pituitary-gonadal (HPG) axis and FSH replacement in pubertal rats, and (2) of photoinhibition of HPG axis followed by FSH substitution in seasonally breeding rodents, bank voles, on Notch pathway activity. Experiments on isolated rat Sertoli cells exposed to FSH were also performed. Gene and protein expressions of Notch pathway components were analysed using RT-qPCR, western blot and immunohistochemistry/immunofluorescence. KEY RESULTS: Distribution patterns of Notch pathway proteins in bank vole and rat seminiferous epithelium were comparable; however, levels of activated Notch1 and Notch3, hairy/enhancer of split 1 (HES1) and hairy/enhancer of split-related with YRPW motif 1 (HEY1) in bank voles were dependent on the length of the photoperiod. In response to FSH similar changes in these proteins were found in both species, indicating that FSH is a negative regulator of Notch pathway activity in seminiferous epithelium. CONCLUSIONS: Our results support a common mechanism of FSH action on Notch pathway during onset and recrudescence of spermatogenesis in rodents. IMPLICATIONS: Interaction between FSH signalling and Notch pathway in Sertoli cells may be involved in spermatogenic activity changes of the testes occurring during puberty or photoperiod shift in continuously and seasonally breeding rodents, respectively.

Nuclear and Membrane Receptors for Sex Steroids Are Involved in the Regulation of Delta/Serrate/LAG-2 Proteins in Rodent Sertoli Cells.

Delta/Serrate/LAG-2 (DSL) proteins, which serve as ligands for Notch receptors, mediate direct cell-cell interactions involved in the determination of cell fate and functioning. The present study aimed to explore the role of androgens and estrogens, and their receptors in the regulation of DSL proteins in Sertoli cells. To this end, primary rat Sertoli cells and TM4 Sertoli cell line were treated with either testosterone or 17ß-estradiol and antagonists of their receptors. To confirm the role of particular receptors, knockdown experiments were performed. mRNA and protein expressions of Jagged1 (JAG1), Delta-like1 (DLL1), and Delta-like4 (DLL4) were analyzed using RT-qPCR, Western blot, and immunofluorescence. Testosterone caused downregulation of JAG1 and DLL1 expression, acting through membrane androgen receptor ZRT- and Irt-like protein 9 (ZIP9) or nuclear androgen receptor (AR), respectively. DLL4 was stimulated by testosterone in the manner independent of AR and ZIP9 in Sertoli cells. The expression of all studied DSL proteins was upregulated by 17ß-estradiol. Estrogen action on JAG1 and DLL1 was mediated chiefly via estrogen receptor α (ERα), while DLL4 was controlled via estrogen receptor ß (ERß) and membrane G-protein-coupled estrogen receptor (GPER). To summarize, the co-operation of nuclear and membrane receptors for sex steroids controls DSL proteins in Sertoli cells, contributing to balanced Notch signaling activity in seminiferous epithelium.

Religiously Conditioned Health Behaviors within Selected Religious Traditions.

BACKGROUND: Health is a value of paramount importance for human existence. It has a special place in every religious system, both on the doctrinal and practical levels. Most religions view health as a priority value to be cared for, and require followers of individual religious groups to take care of their physical and mental health, and to maintain a balance between body and spirit. The aim of the study was to verify whether the level of religious commitment significantly influences health behaviors and whether in selected religions the faithful have a different approach to health behaviors. METHODS: This cross-sectional study was conducted on a group of 296 people-118 Seventh-day Adventists (SDA), 134 Catholics, and 14 Jews living in southern Poland, and 31 Muslims living in southern and north-eastern Poland. The following research tools were used as part of the diagnostic survey method: a questionnaire survey designed by us; the International Physical Activity Questionnaire (IPAQ); the Inventory of Health Behaviours (IHB); the Perceived Stress Scale (PSS 10) and anthropometric measurements, physical examination, laboratory tests. RESULTS: Only 75% of Catholics who participated in the study declared a high level of religious commitment. On the other hand, all (100%) of SDA, Jews, and Muslim respondents declared their religious commitment at a high level. SDA were characterized by the most desirable health behaviors on the IHB (high and average levels), especially eating habits. They did not consume alcohol, did not smoke cigarettes. The physical activity of most ADS was high and moderate. Most of the SDA subjects were characterized by an average and low level of stress intensity. The most common correct scores for homocysteine, triglycerides, and CRP were SDA, cholesterol by Jews, glucose by Muslims, and HDL by Catholics. The most common negative results were: homocysteine, glucose and triglycerides among Jews, cholesterol and CRP among Catholics, HDL among Muslims. Optimal blood pressure was most common among Catholics, and hypertension was most often diagnosed among Jews. Most often, Muslims had the correct body weight, and at the same time it was the group of respondents most often diagnosed with obesity. In contrast, underweight was observed only among Catholics. The SDA subjects were most often overweight. CONCLUSIONS: The results suggest that public health professionals and nurses should develop culturally specific educational interventions, especially among Catholics.

Flutamide treatment reveals a relationship between steroidogenic activity of Leydig cells and ultrastructure of their mitochondria.

Our present knowledge on interrelation between morphology/ultrastructure of mitochondria of the Leydig cell and its steroidogenic function is far from satisfactory and needs additional studies. Here, we analyzed the effects of blockade of androgen receptor, triggered by exposure to flutamide, on the expression of steroidogenic proteins (1) and ultrastructure of Leydig cells' constituents (2). We demonstrated that increase in the expression level of steroidogenic (StAR, CYP11A1, 3ß-HSD, and CYP19A1) proteins (and respective mRNAs) in rat testicular tissue as well as elevation of intratesticular sex steroid hormone (testosterone and estradiol) levels observed in treated animals correspond well to morphological alterations of the Leydig cell ultrastructure. Most importantly, up-regulation of steroidogenic proteins' expression apparently correlates with considerable multiplication of Leydig cell mitochondria and subsequent formation of local mitochondrial networks. Interestingly, we showed also that the above-mentioned processes were associated with elevated transcription of Drp1 and Mfn2 genes, encoding proteins implicated in mitochondrial dynamics. Collectively, our studies emphasize the importance of mitochondrial homeostasis to the steroidogenic function of Leydig cells.

Sociodemographic Factors Affecting Older People's Care Dependency in Their Daily Living Environment According to Care Dependency Scale (CDS).

The aim of the research was to determine the influence of sociodemographic factors on older people's care dependency in their living environment according to the Care Dependency Scale (CDS). Methods: The research was conducted in a group of 151 older people staying in their own homes. The methods applied in the research included a sociodemographic questionnaire and scales including the Abbreviated Mental Test Score (AMTS), CDS, Katz Index of Independence in Activities of Daily Living (ADL), Lawton's Instrumental Activities of Daily Living (I-ADL), Mini Nutritional Assessment (MNA), and Geriatric Depression Scale (GDS). Results: Gender had a significant impact on the level of care dependency. The surveyed females obtained the medium or high level of dependency more often than males (22.4% vs. 6.1%), and the low level of dependency was significantly more frequent among men than women (p = 0.006). Moreover, the age of the respondents determined their level of care dependency. The subjects with a medium or high level of care dependency were significantly older (p = 0.001). The subjects with a low level of care dependency were more likely to be married than people with a medium/high level (p < 0.001). The level of education had a significant impact on care dependency. A higher level of education correlated with a medium/high level of dependency (p = 0.003). Conclusions: The survey results confirmed that sociodemographic factors have a significant impact on the level of care dependency. When planning care in the home environment, special attention should be paid to older women, who are more likely to lose their independence than men. These women should be given additional support.

Comparison of Lifestyle of Catholics and Seventh-Day Adventists and the Relationship with Homocysteine as Risk Factor for Cardiovascular Diseases, a Cross-Sectional Study in Polish Males and Females.

BACKGROUND: A review of epidemiological data demonstrates relationships between defined health behaviours linked with religious affiliation and a reduced risk of developing and dying from Cardiovascular Disease (CVD). The aim of the study was to compare the lifestyle of Seventh-day Adventists (SDA) and Catholics (CA), to determine the relationship between the lifestyle of SDA, CA and the level of serum homocysteine as a risk factor for CVD. METHODS: A cross-sectional study was conducted on 252 SDA and CA. The following tools were used: interview questionnaire, anthropometric measurement, the International Physical Activity Questionnaire (IPAQ), the Inventory of Health Behaviours (IHB), the Perceived Stress Scale (PSS-10), laboratory tests (homocysteine level), and the Fagerström Test for Nicotine Dependence (FTND). RESULTS: Selected lifestyle elements, such as smoking cigarettes, drinking alcohol, physical activity, diet, Body Mass Index (BMI), health behaviours on the IHB, psychosocial factors and level of stress for CA were significantly different in comparison to SDA. The religion professed by the respondents was not significantly associated with the increased level of homocysteine as a risk factor for cardiovascular diseases (CVD). The level of homocysteine for CA were significantly different in comparison to SDA. The studied group of CA was significantly influenced by socio-demographic factors: gender, age, education, place of residence, BMI and lifestyle: drinking alcohol and smoking cigarettes, consumption of dark bread, pasta, and groats. For the studied group of SDA, the level of homocysteine was significantly influenced by socio-demographic factors such as gender, age, professional activity, and consumption of legumes. CONCLUSIONS: Public health professionals and nurses should develop culturally specific educational interventions.

Crosstalk between Androgen-ZIP9 Signaling and Notch Pathway in Rodent Sertoli Cells.

Our recent study demonstrated altered expression of Notch ligands, receptors, and effector genes in testes of pubertal rats following reduced androgen production or signaling. Herein we aimed to explore the role of nuclear androgen receptor (AR) and membrane androgen receptor (Zrt- and Irt-like protein 9; ZIP9) in the regulation of Notch pathway activation in rodent Sertoli cells. Experiments were performed using TM4 and 15P-1 Sertoli cell lines and rat primary Sertoli cells (PSC). We found that testosterone (10-8 M-10-6 M) increased the expression of Notch1 receptor, its active form Notch1 intracellular domain (N1ICD) (p < 0.05, p < 0.01, p < 0.001), and the effector genes Hey1 (p < 0.05, p < 0.01, p < 0.001) and Hes1 (p < 0.05, p < 0.001) in Sertoli cells. Knockdown of AR or ZIP9 as well as antiandrogen exposure experiments revealed that (i) action of androgens via both AR and ZIP9 controls Notch1/N1ICD expression and transcriptional activity of recombination signal binding protein (RBP-J), (ii) AR-dependent signaling regulates Hey1 expression, (iii) ZIP9-dependent pathway regulates Hes1 expression. Our findings indicate a crosstalk between androgen and Notch signaling in Sertoli cells and point to cooperation of classical and non-classical androgen signaling pathways in controlling Sertoli cell function.

Silk Particles as Carriers of Therapeutic Molecules for Cancer Treatment.

Although progress is observed in cancer treatment, this disease continues to be the second leading cause of death worldwide. The current understanding of cancer indicates that treating cancer should not be limited to killing cancer cells alone, but that the target is the complex tumor microenvironment (TME). The application of nanoparticle-based drug delivery systems (DDS) can not only target cancer cells and TME, but also simultaneously resolve the severe side effects of various cancer treatment approaches, leading to more effective, precise, and less invasive therapy. Nanoparticles based on proteins derived from silkworms' cocoons (like silk fibroin and sericins) and silk proteins from spiders (spidroins) are intensively explored not only in the oncology field. This natural-derived material offer biocompatibility, biodegradability, and simplicity of preparation methods. The protein-based material can be tailored for size, stability, drug loading/release kinetics, and functionalized with targeting ligands. This review summarizes the current status of drug delivery systems' development based on proteins derived from silk fibroin, sericins, and spidroins, which application is focused on systemic cancer treatment. The nanoparticles that deliver chemotherapeutics, nucleic acid-based therapeutics, natural-derived agents, therapeutic proteins or peptides, inorganic compounds, as well as photosensitive molecules, are introduced.

Flutamide Alters the Expression of Chemerin, Apelin, and Vaspin and Their Respective Receptors in the Testes of Adult Rats.

Adipokines influence energy metabolism and have effects on male reproduction, including spermatogenesis and/or Sertoli cell maturation; however, the relationship between these active proteins and androgens in testicular cells is limited. Here, we studied the impact of short-term exposure to flutamide (an anti-androgen that blocks androgen receptors) on the expression of chemerin, apelin, vaspin and their receptors (CCRL2, CMKLR1, GPR1, APLNR, GRP78, respectively) in adult rat testes. Moreover, the levels of expression of lipid metabolism-modulating proteins (PLIN1, perilipin1; TSPO, translocator protein) and intercellular adherens junction proteins (nectin-2 and afadin) were determined in testicular cells. Plasma levels of adipokines, testosterone and cholesterol were also evaluated. Gene expression techniques used included the quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) and immunohistochemistry (IHC). The androgen-mediated effects observed post-flutamide treatment were found at the gonadal level as chemerin, apelin, and vaspin gene expression alterations at mRNA and protein levels were detected, whereas the cellular targets for these adipokines were recognised by localisation of respective receptors in testicular cells. Plasma concentrations of all adipokines were unchanged, whereas plasma cholesterol content and testosterone level increased after flutamide exposure. Differential distribution of adipokine receptors indicates potential para- or autocrine action of the adipokines within the rat testes. Additionally, changes in the expression of PLIN1 and TSPO, involved in the initial step of testosterone synthesis in Leydig cells, suggest that testicular cells represent a target of flutamide action. Increase in the gene expression of PLIN1 and TSPO and higher total plasma cholesterol content indicates enhanced availability of cholesterol in Leydig cells as a result of androgen-mediated effects of flutamide. Alterations in adherens junction protein expression in the testis confirm the flutamide efficacy in disruption of androgen signalling and presumably lead to impaired para- and autocrine communication, important for proper functioning of adipokines.