The origins and spread of domestic horses from the Western Eurasian steppes.

Domestication of horses fundamentally transformed long-range mobility and warfare1. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling2-4 at Botai, Central Asia around 3500 BC3. Other longstanding candidate regions for horse domestication, such as Iberia5 and Anatolia6, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association7 between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC8,9 driving the spread of Indo-European languages10. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture11,12.

Rapidly growing uterine myoma - should we be afraid of it?

During a year, myomas may undergo radical changes in their dimensions - from decreasing by 90% to growing by 200%. On average, myomas of the uterus increase in volume by 20-30% annually in the premenopausal period. On the other hand, myomas regress spontaneously in about 20% of women. After menopause uterine fibroids stabilize or regress. Every new or growing lesion of the uterus after menopause has to be diagnosed. There is no general definition of fast growing uterine myoma. The presence of fast growing uterine myoma, regardless of its definition, is associated with some clinical issues: it may become symptomatic (pain, bleeding, bulk symptoms), may be responsible for infertility, and a malignant process (leiomyosarcoma) may be present. Regardless of common belief, the risk of sarcoma is not related to the size of the uterus or its fast enlargement. The prevalence of sarcoma in myomas is 0.26%, and in rapidly growing myomas is 0.27%. Treatment should be individualized, selected for the age of the woman and her expectations (preservation of fertility, uterus), symptoms, size and localization of the myomas. The methods of surgical treatment of unsuspected "rapidly growing myomas" are the same as those of common uterine fibroids. Minimally invasive surgery is optimal, but a decision has to be made after evaluation of the risk factors of sarcoma.

Analysis of the results of invasive diagnostic procedures in patients referred to gynecologic department due to abnormal uterine bleeding.

INTRODUCTION: Abnormal uterine bleeding (AUB) is one of the most common reason for visits to gynecologists. Endometrial biopsy is a routine procedure in gynecological practice to detect the etiology of AUB and to exclude precancerous and cancerous lesions of the endometrium. The aim of this study was to assess the causes of AUB among women, who had undergone invasive diagnostics due to AUB. MATERIAL AND METHODS: This study was carried among 531 women, who had undergone invasive diagnostics due to AUB between January 2018 and December 2018. Women were divided into premenopausal (with perimenopausal) and postmenopausal groups. Transvaginal ultrasound was performed. Endometrial thickness was compared with histopathological results in each subgroup and statistically analyzed. The incidence of histopathological findings and rate of anemia were also analyzed. RESULTS: In our series of patients the most common cause of AUB based on histopathological results was endometrial polyp, both before and after menopause. The most frequent pathologies at ultrasound findings were leiomyomas and endometrial polyps. The incidence of taken together: atypical hyperplasia and endometrial cancer was significantly higher in postmenopausal group (8.58%) than in pre- and perimenopausal (1.35%, p = 0.0001). The median endometrial thickness, both before and after menopause, was significantly greater in patients with pathological than with nonpathological endometrium. 31% of women with abnormal uterine bleeding before menopause and 10% after menopause had anemia. CONCLUSIONS: Measurements of endometrial thickness seems to be acceptable initial diagnostic tool to distinguish between benign and pathological endometrial changes both before and after menopause.

Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer.

PURPOSE: We aimed to compare expression levels of miRNA-21, -103, -129, -150 in primary tumour tissues and its omental metastases from patients operated for advanced ovarian serous cancer. Expression levels of selected miRNAs were correlated with clinicopathological features, including chemosensitivity and survival. METHODS: We performed total RNA extraction from archival formalin-fixed paraffin-embedded tissue samples of primary serous ovarian cancer and omental metastases. The study included 48 patients with advanced ovarian cancer. The reference group consisted of 48 normal ovarian tissue samples. We performed cDNA synthesis, real time polymerase chain reaction and assessed relative expression of selected miRNAs. RESULTS: Samples derived from serous ovarian cancer were characterized by higher expression levels of miRNA-150 in comparison to omental metastases (p = 0.045). Furthermore, we observed that shorter progression free-survival was associated with lower levels of miRNA-150 in metastatic tissues. We did not find similar relationships for other miRNAs. CONCLUSIONS: MiRNA-150 may potentially serve as a prognostic factor in advanced ovarian cancer. However, further studies are required to clearly confirm such hypothesis.

Secretion of cytokines and heat shock protein (HspA1A) by ovarian cancer cells depending on the tumor type and stage of disease.

Epithelial ovarian cancer is a heterogeneous disease comprising several tumor types that each have multiple histopathological features and different biological behaviors. Recent morphologic and molecular genetic studies have allowed for the categorization of various types of ovarian cancer into two groups: type I and type II. Type I tumors are low-grade and are genetically more stable, while type II tumors are high-grade and genetically unstable. The determination of the type of ovarian cancer may have implications in terms of the appropriate therapeutic strategy because different prognoses and responses to chemotherapeutic agents are observed. Therefore, the current challenge is better recognition of the features of cancer cells, which may result in more individualized therapy. The aim of the current studies was to compare the ability of ovarian cancer cells isolated from tumors, which were classified as type I or type II ovarian cancer, to release pro-inflammatory and immunosuppressive cytokines and heat shock protein (HspA1A). These factors are known to facilitate tumor cell survival, invasion and metastasis. Our studies demonstrated that ovarian cancer cells isolated from patients with type II tumors released high levels of immunosuppressive cytokines (i.e., interleukin 10 and transforming growth factor ß) and HspA1A in vitro. Conversely, ovarian cancer cells obtained from of type I tumors were significantly less active. We did not observe any difference in the ability of the isolated cancer cells to secrete pro-inflammatory cytokines, regardless of the type of ovarian cancer. In this study, we found that cancer cells from patients with type II tumors demonstrated more intense activity in regards to survival and metastasis, which should be considered during therapy.

Women's fertility after laparoscopic cystectomy of endometrioma and other benign ovarian tumors - a 24-month follow-up retrospective study.

OBJECTIVES: The golden standard in treatment benign ovarian cysts is laparoscopic cystectomy, but it may also influence women's fertility. The aim of the study was to compare women's fertility after laparoscopic cystectomy of endometrioma versus other benign ovarian tumors. MATERIALS AND METHODS: Out of the 123 patients operated because of benign ovarian tumor (OT), 66 underwent laparoscopic cystectomy of endometrioma (endometrioma group) and 57 underwent laparoscopic cystectomy of other benign ovarian tumor like: functional cyst, hemorrhagic cyst, yellow body cyst or mature teratoma (reference group). OT-related data were obtained from medical documentation (diagnostic tests, medical reproductive and surgical history, clinical status during OT surgery). Follow-up data were collected by means of a telephone interview. The survey included questions focused on women's fertility during a 24-month period following the surgical treatment of OT (conception, subsequent pregnancies, recurrence of OT). RESULTS: A 24-month follow-up period revealed that the cumulative pregnancy rate was significantly higher in reference group (RG) as compared to endometrioma group (EG), i.e. 52.6% vs. 32.3%. Lower pregnancy risk was demonstrated in a EG group vs. other benign ovarian tumors, HR=0.57 (CI 0.33-0.99; p=0.049), log-rank test p=0.045. Benign OT returned in 19.3% vs. EG 36.3%, HR= 2.5 (CI 1.16-5.55 ; p=0.019) log-rank test: p=0.0136. The EG was divided on two subgroups: women with solitary endometrioma and women with endometrioma and coexistent peritoneal endometriosis. The study showed insignificantly lower risk of pregnancy in a group of advanced endometriosis vs. solitary endometrioma group (HR= 0.79 (CI 0.34-1.83; log-rank test p=0.57; pregnancy rate 29.3% vs. 40.0%). Statistically nonsignificant higher pregnancy rate occurred in a group of women with tumor ≤50mm in size among patients with benign ovarian tumor and solitary endometrioma vs. group of women with tumor >50mm (30% vs. 61%; p=0.09). CONCLUSIONS: There is a low pregnancy rate after laparoscopic cystectomy of benign OT. Moreover, pregnancy rate after cystectomy of endometrioma is significantly lower and the percentage of reccurence of endometrioma is significantly higher. That is why, the decision about surgical treatment among childbearing women must be well-considered because of the risk of subsequent surgery in the future.

The significance of markers in the diagnosis of endometrial cancer.

Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy.

[Evaluation of applicability of HE4 and ROMA in the preoperative diagnosis of adnexal masses]. / Ocena uzytecznosci oznaczen bialka HE4 i algorytmnu ROMA w przedoperacyjnej diagnostyce guzow przydatków.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA 125 (ROMA) in selecting patients at high risk of adnexal malignancy. MATERIAL AND METHODS: Serum CA 125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. RESULTS: Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA 125 and 95.4% and 81.3% for HE4, respectively ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA 125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively Serum levels of both CA 125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA 125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. CONCLUSIONS: CA 125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA 125.

Current clinical application of serum biomarkers to detect ovarian cancer.

For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression.

Hemostatic disorders of the menopausal period: the role of microRNA.

Adverse changes in hemostasis of menopausal women, observed e.g. in atherosclerotic or neoplastic cases, are of multicausal origin. It is believed that in the development and regulation of these processes, an important role is played by microRNA particles, which presence is ascertained in endothelial cells, atherosclerotic plaques and systemic circulation. Discovered for the first time over 20 years ago, up to now over two and a half thousand types of microRNA have been identified in the human body. MicroRNAs are single stranded RNA molecules of 20-24 nucleotides, encoded by the cell's genome and then transcribed by polymerase II. They regulate the expression of a large gene pool, approximately 30% of all genes, in the human body. MicroRNA molecules, like other bioactive molecules - RNA, protein - both play important roles in tumor invasion, metastasis, inflammation, coagulation, and regeneration. What is important, they can be detected not only in tissues (e.g. tumor tissues), but also in circulation (blood serum), where they are released. Accurate understanding of the role played by certain types of microRNA (e.g. miR-126, miR-17-92, miR-33, miR-613, miR-27a/b, miR-143, miR-335, miR-370, miR-122, miR-19b, miR-520, or miR-220) in hemostatic processes may allow in the future for their use not only as specific biomarkers of cardiovascular diseases but also as the target for innovative gene therapies.

Nitric oxide donors reduce the invasion ability of ovarian cancer cells in vitro.

The most important factors involved in tumor metastasis and angiogenesis are metalloproteinases (MMPs), vascular endothelial growth factor, and multifunctional transforming growth factor ß1. These factors are responsible for extracellular matrix degradation, induction of vascular permeability, and enhancement of tumor cells' invasion and metastasis. Elevated expression and secretion of the above-mentioned factors are correlated with the higher aggressiveness of tumors and low patient survival for example, patients with ovarian cancer. Therefore, regulation of the expression, secretion, and activity of these factors is still considered a potent target for therapeutic intervention in cancer patients. Nitric oxide (NO) donors belong to the class of agents with multivalent targeted activities in cancer cells and are considered potential anticancer therapeutics. Our studies have shown that NO donors such as spermine/NO and diethylenetriamine/NO decrease the secretion of vascular endothelial growth factor-A from the OVCAR-3 ovarian cancer cell line, but not from the SK-OV-3 ovarian cancer cell line. The release of MMP-2 from both cell lines was reduced in a soluble guanylate cyclase-dependent manner by spermine/NO and diethylenetriamine/NO. Nevertheless, MMP-2 activity was only affected in SK-OV-3 cells. Both NO donors reduced the transmigration of the ovarian cancer cell lines. We did not observe any significant effect of spermine/NO and diethylenetriamine/NO on mRNA expression of the tested aggressiveness factors. In conclusion, our data indicated that NO donors reduced the metastatic potential of ovarian cancer cells, but its impact is rather low and requires high concentrations of donors. Moreover, both the tested cell lines differed in the susceptibility to NO donors.

Measurement of free radicals using electron paramagnetic resonance spectroscopy during open aorto-iliac arterial reconstruction.

BACKGROUND: Aortic cross-clamping during abdominal aortic aneurysm (AAA) open repair leads to development of ischemia-reperfusion injury. Electron paramagnetic resonance spectroscopy (EPR) spin-trapping is a valuable method of direct measurement of free radicals. The objective of the study was to evaluate the results of EPR as a direct method of free radical measurement and degree of inflammatory response in open operative treatment of patients with AAA and aorto-iliac occlusive disease (AIOD). MATERIAL/METHODS: The study was performed on a group of 32 patients with AAA and 25 patients with AIOD scheduled for open repair. Peripheral venous blood for EPR spectroscopy and for SOD, GPx, ox-LDL, Il-6, TNF-alfa, CRP, and HO-1 were harvested. Selected parameters were established accordingly to specified EPR and immunohistochemical methods and analyzed between groups by Mann-Whitney U test and Wilcoxon matched-pairs signed-ranks test with Bonferroni correction. RESULTS: Free radicals level was correlated with the time of the aortic cross-clamping after the reperfusion of he first and second leg in AAA (r=0.7; r=0.47). ox-LDL in AAA decreased 5 min after reperfusion of the first leg (32.99 U/L, range: 14.09-77.12) and 5 min after reperfusion of the second leg (26.75 U/L, range: 11.56-82.12) and 24 h after the operation (25.85 U/L, range: 14.29-49.70). HO-1 concentration increased to above the level before intervention 24 h after surgery. The activities of GPx and SOD decreased 5 min after the first-leg reperfusion in AAA. Twenty-four hours after surgery, inflammatory markers increased in AAA to CRP was 14.76 ml/l (0.23-38.55), IL-6 was 141.22 pg/ml (84.3-591.03), TNF-alfa was 6.82 pg/ml (1.76-80.01) and AIOD: CRP was 18.44 mg/l (2.56-33.14), IL-6: 184.1 pg/ml (128.46-448.03), TNF-alfa was 7.74 pg/ml (1.74-74.74). CONCLUSIONS: EPR spin-trapping demonstrates temporarily elevated level of free radicals in early phase of reperfusion, leading to decrease antioxidants in AAA. Elevated free radical levels decreased 24 h after surgery due to various endogenous antioxidants and therapies.

The use of panniculectomy in morbidly obese patients undergoing gynecological surgery.

Panniculectomy is a surgical procedure that involves removal of the skin and fat excess which facilitates access to the peritoneal cavity. In the paper we present three cases of morbidly obese women (BMI: 46.3-59.5) who were treated in the Department of Gynecology and Oncological Gynecology in Lodz. One of the patients underwent an operation due to the presence of a large cervical myoma. Two another women were treated for endometrial cancer. During all of the three procedures panniculectomy was the first stage of the operation.

Interdisciplinary treatment of the patient with adenoid cystic carcinoma of the Bartholin's gland resulting in 15 years' survival: a case report and review of literature.

Carcinoma of the Bartholin's gland is very rare, comprises below 2% of Bartholin's gland lesions and adenoid cystic carcinoma (ADC) is one of the most uncommon variants and accounts for 10-15% of Bartholin's gland malignancies. There is no consensus on treatment of ADC of the Bartholin's gland: reported cases were treated with local excision or vulvectomy with or without lymphadenectomy followed or not by radiotherapy. The survival of patients varies significantly, so we present a case of interdisciplinary treatment of ADC resulting in 15 years' survival. The patient was initially treated with local excision, but the margins were not clear. Then vulvectomy, inguinal lymphadenectomy and adjuvant brachytherapy were performed resulting in 7 years free of the disease. Relapses were excised by abdominoperineal amputation of the rectum and distal part of the vagina with sigmoideostomy, excisions of local recurrences in vagina and metastasectomy of isolated lung metastases. The patient died manifesting multiple lung metastases 15 years after the initial diagnosis. Based on our experience and world literature, in cases of adenoid cystic carcinoma of the Bartholin's gland, vulvectomy with or without lymphadenectomy should be considered as a treatment of choice and in patients with positive margin, surgery should be extended by adjuvant radiotherapy.

Classical radical hysterectomy and nerve-sparing radical hysterectomy in the treatment of cervical cancer.

AIM OF THE STUDY: To compare Piver III radical hysterectomy (RH) with nerve-sparing radical hysterectomy (NSRH) for cervical cancer patients in terms of postoperative physiology of pelvic autonomic nerves and perioperative complications. MATERIAL AND METHODS: Seventy-three consecutive patients with invasive cervical cancer underwent RH (53 cases) or NSRH (20 cases) from 2001 to 2012 at the Department of Gynecology and Gynecologic Oncology of Polish Mother's Memorial Hospital - Research Institute in Lódz. RESULTS: Compared with patients treated with RH, patients who underwent NSRH presented no significant difference in terms of operative time (146 vs. 143 minutes, p > 0.05), blood loss and hospital stay (9.2 vs. 7.5 days, p > 0.05). A positive surgical margin was found in 6 cases of RH. No serious surgical complications were found in the NSRH group, while there were 4 cases in the RH group. CONCLUSIONS: Nerve-sparing radical hysterectomy is safe and feasible surgical management for cervical cancer patients, which should improve the physiology of the pelvic autonomic nerve system postoperatively. The technique is relatively new and its oncologic efficiency has not been fully established yet, moreover it requires sophisticated anatomical knowledge and high operative skills.

Vaginal hysterectomy vs. laparoscopically assisted vaginal hysterectomy in women with symptomatic uterine leiomyomas: a retrospective study.

INTRODUCTION: Uterine leiomyomas are the most common benign tumors of the female reproductive system. Although the majority of myomas are asymptomatic, some patients have symptoms or signs of varying degrees and require a hysterectomy. THE AIM OF THE STUDY: The aim of the study was to compare the clinical results of two minimally invasive hysterectomy techniques: vaginal hysterectomy (VH) and laparoscopically assisted vaginal hysterectomy (LAVH). MATERIAL AND METHODS: A retrospective, observational study was performed at a tertiary care center: the Gynecology and Gynecologic Oncology Department, Polish Mother's Memorial Hospital Research Institute. The study period was from January 2003 to December 2012. A total of 159 women underwent either vaginal hysterectomy (VH, n = 120) or laparoscopically assisted vaginal hysterectomy (LAVH, n = 39) for symptomatic uterine myomas. Outcome measures, including past medical history, blood loss, major complications, operating time and discharge time were assessed and compared between the studied groups. Statistical analysis was performed using Student t-test, U-Mann Whitney test, χ(2) test and Yates'χ(2) test. P < 0.05 was considered statistically significant. RESULTS: There were no differences in patients' mean age. Parity was significantly higher in the VH group (VH 1.9 ± 0.7 vs. LAVH 1.5 ± 0.8; p = 0.008). No difference was found in the mean ± standard deviation (SD) uterine volume between vaginal hysterectomy and LAVH groups (179 ± 89 vs. 199 ± 88 cm(3)), respectively. The mean operative time was significantly longer for the LAVH group (83 ± 29 vs. 131 ± 30 min; p = 0.0001). The intraoperative blood loss (VH 1.3 ± 1.1 vs. LAVH 1.4 ± 0.9 g/dl; p = 0.2) and the rate of intra- and postoperative complications were similar in both groups studied. The mean discharge time was longer for LAVH than for VH (VH 4.2 ± 1.2 vs. LAVH 5.3 ± 1.3 days, p = 0.0001). CONCLUSIONS: Laparoscopically assisted vaginal hysterectomy and VH are safe hysterectomy techniques for women with the myomatous uterus. Concerning the LAVH, the abdominal-pelvic exploration and the ability to perform adnexectomy safely represent the major advantages comparing with VH. Vaginal hysterectomy had a shorter operating time and the mild blood loss making it a suitable method of hysterectomy for cases in which the shortest duration of surgery and anesthesia is preferable.

MiRNAs as Regulators of Immune Cells in the Tumor Microenvironment of Ovarian Cancer.

Ovarian cancer is one of the leading causes of cancer deaths among women. There is an ongoing need to develop new biomarkers and targeted therapies to improve patient outcomes. One of the most critical research areas in ovarian cancer is identifying tumor microenvironment (TME) functions. TME consists of tumor-infiltrating immune cells, matrix, endothelial cells, pericytes, fibroblasts, and other stromal cells. Tumor invasion and growth depend on the multifactorial crosstalk between tumor cells and immune cells belonging to the TME. MiRNAs, which belong to non-coding RNAs that post-transcriptionally control the expression of target genes, regulate immune responses within the TME, shaping the landscape of the intrinsic environment of tumor cells. Aberrant expression of miRNAs may lead to the pathological dysfunction of signaling pathways or cancer cell-regulatory factors. Cell-to-cell communication between infiltrating immune cells and the tumor may depend on exosomes containing multiple miRNAs. MiRNAs may exert both immunosuppressive and immunoreactive responses, which may cause cancer cell elimination or survival. In this review, we highlighted recent advances in the field of miRNAs shaping the landscape of immune cells in the TME.

Structural, Electrical and Corrosion Properties of Bulk Ti-Cu Alloys Produced by Mechanical Alloying and Powder Metallurgy.

Binary Ti100-x-Cux (x = 1.6 and 3.0 wt.%) alloys were produced by the application of mechanical alloying and powder metallurgy processes. The influence of the copper concentration in titanium on the microstructure and properties of bulk alloys was investigated. The synthesized materials were characterized by an X-ray diffraction technique, scanning electron microscopy, and chemical composition determination. The electrochemical and corrosion properties were also investigated. Cold compaction and sintering reduced the content of α-Ti content in Ti98.4-Cu1.6 and Ti97-Cu3 alloys to 92.4% and 83.7%, respectively. Open Circuit Potential measurements showed a positive shift after the addition of copper, suggesting a potential deterioration in the corrosion resistance of the Ti-Cu alloys compared to pure Ti. Electrochemical Impedance Spectroscopy analysis revealed significant improvement in electrical conductivity after the addition of copper. Corrosion testing results demonstrated compromised corrosion resistance of Ti-Cu alloys compared to pure Ti. In summary, the comprehensive investigation of Ti100-x-Cux alloys provides valuable insights for potential applications in biosensing.

Chemical Stability of High-Entropy Spinel in a High-Pressure Pure Hydrogen Atmosphere.

This paper focuses on high-entropy spinels, which represent a rapidly growing group of materials with physicochemical properties that make them suitable for hydrogen energy applications. The influence of high-pressure pure hydrogen on the chemical stability of three high-entropy oxide (HEO) sinter samples with a spinel structure was investigated. Multicomponent HEO samples were obtained via mechanochemical synthesis (MS) combined with high-temperature thermal treatment. Performing the free sintering procedure on powders after MS at 1000 °C for 3 h in air enabled achieving single-phase (Cr0.2Fe0.2Mg0.2Mn0.2Ni0.2)3O4 and (Cu0.2Fe0.2Mg0.2Ni0.2Ti0.2)3O4 powders with a spinel structure, and in the case of (Cu0.2Fe0.2Mg0.2Ti0.2Zn0.2)3O4, a spinel phase in the amount of 95 wt.% was achieved. A decrease in spinel phase crystallite size and an increase in lattice strains were established in the synthesized spinel powders. The hydrogenation of the synthesized samples in a high-pressure hydrogen atmosphere was investigated using Sievert's technique. The results of XRD, SEM, and EDS investigations clearly showed that pure hydrogen at temperatures of up to 250 °C and a pressure of up to 40 bar did not significantly impact the structure and microstructure of the (Cr0.2Fe0.2Mg0.2Mn0.2Ni0.2)3O4 ceramic, which demonstrates its potential for application in hydrogen technologies.

Microstructure, Mechanical and Corrosion Properties of Copper-Nickel 90/10 Alloy Produced by CMT-WAAM Method.

In the case of copper and its alloys, Wire Arc Additive Manufacturing (WAAM) 3D printing technology is mainly used to produce elements for the maritime industry and research has focused on the use of Cu-Al alloys. There is little information devoted to the use of Cu-Ni alloys in this technology, which are also widely used in the maritime industry. In this work, tests were carried out on the microstructure, mechanical properties, and corrosion properties in a 1M NaCl solution of Cu-Ni 90/10 alloy 3D walls printed using the WAAM method. The obtained objects are characterized by a microstructure with elongated column grains and particles of the Ni-Ti phase, hardness in the range of 138-160 HV10, ultimate tensile strength of 495-520 MPa, yield strength of 342-358 MPa, elongation of 16.6-17.9%, and a low average corrosion rate of 7.4 × 10-5 mm/year. The work shows that it is possible to obtain higher mechanical properties of Cu-Ni 90/10 alloy 3D objects produced using the WAAM method compared to cast materials, which opens up the possibility of using this alloy to produce objects with more complex shapes and for use in corrosive working conditions.