Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma.

BACKGROUND: Liver cancer, particularly hepatocellular carcinoma (HCC), is a significant gastrointestinal disease with a mortality rate as high as nearly 80% within five years. The disease's pathophysiology involves deranged immune responses and bile acid metabolism, with the gut microbiota (GM) playing a crucial role. Recent research highlights the potential of GM in influencing HCC treatment outcomes, especially regarding immune checkpoint inhibitors (ICIs). However, few patients currently benefit from ICIs due to a lack of effective response biomarkers. AIMS AND METHODS: This review aimed to explore the literature on HCC treatment issues, focusing on immune response, bile acid metabolism, and GM dysbiosis. This review included studies from PubMed, Medline, and major gastroenterology and hepatology meetings, using keywords like gut microbiota, immune system, liver cancer, and checkpoint inhibitors. RESULTS: GM dysbiosis significantly impacts immune response and bile acid metabolism, making it a promising biomarker for ICI response. Modulating GM can enhance ICI treatment efficacy, although more research is needed to confirm its direct therapeutic benefits for HCC. CONCLUSIONS: GM dysbiosis is integral to liver cancer pathogenesis and treatment response. Its modulation offers promising therapeutic avenues for improving HCC prognosis and response to immunotherapy.

Digital pathology implementation in cancer diagnostics: towards informed decision-making.

Digital pathology (DP) has become a part of the cancer healthcare system, creating additional value for cancer patients. DP implementation in clinical practice provides plenty of benefits but also harbors hidden ethical challenges affecting physician-patient relationships. This paper addresses the ethical obligation to transform the physician-patient relationship for informed and responsible decision-making when using artificial intelligence (AI)-based tools for cancer diagnostics. DP application allows to improve the performance of the Human-AI Team shifting focus from AI challenges towards the Augmented Human Intelligence (AHI) benefits. AHI enhances analytical sensitivity and empowers pathologists to deliver accurate diagnoses and assess predictive biomarkers for further personalized treatment of cancer patients. At the same time, patients' right to know about using AI tools, their accuracy, strengths and limitations, measures for privacy protection, acceptance of privacy concerns and legal protection defines the duty of physicians to provide the relevant information about AHI-based solutions to patients and the community for building transparency, understanding and trust, respecting patients' autonomy and empowering informed decision-making in oncology.

Gender Differences in Patients with Prolactinoma: Single-center Ukrainian Experience.

INTRODUCTION: Prolactinomas are the most common type of pituitary gland tumors that secrete overly prolactin. They account for approximately 60% of all hormone-secreting hypophysis tumors. AIM: This study aims to analyze gender differences in patients with prolactinomas who were operated on transsphenoidal surgery and conduct a single-center retrospective analysis of patient data. MATERIAL AND METHODS: This study evaluated the medical records of 109 patients (61 females and 48 males) from 2009 to 2019 at Feofaniya Clinical Hospital of the State Administration of Affairs in Kyiv, Ukraine. The primary criterion for including patients was a Serum Prolactin (PRL) level of over 100 ng/ml and the presence of a pituitary adenoma (PA) as observed on MRI. Additionally, the histological examination needed to confirm the presence of Prolactin-Secreting Pituitary Adenomas (PSPAs) without plurihormonal activity through both microscopy and immunohistochemical (IHC) staining. RESULTS: Significant differences in preoperative PRL levels were not observed. However, males had significantly larger tumor sizes and prevalence of macroadenomas. In male patients, the preoperative PLR levels showed a weak negative correlation with age (r=-0.304, p < 0.036) and a positive correlation with tumor size (r=0.555, p < 0.001) and cavernous sinus invasion (r=0.339, p < 0.018). In females, preoperative PRL was significantly associated only with tumor size and Knosp grade. CONCLUSION: Prolactin-Secreting Pituitary Adenomas (PSPAs) are more common in women than men and are characterized by larger and more invasive tumors with high PRL levels at diagnosis. The PRL level and tumor size before surgery can predict early biochemical remission in both males and females with an accuracy of 58.3% and 68.8%, respectively.

Microbiota substances modulate dendritic cells activity: A critical view.

Contemporary research in the field of microbiota shows that commensal bacteria influence physiological activity of different organs and systems of a human organism, such as brain, lungs, immune and metabolic systems. This influence is realized by various processes. One of them is trough modulation of immune mechanisms. Interactions between microbiota and the human immune system are known to be complex and ambiguous. Dendritic cells (DCs) are unique cells, which initiate the development and polarization of adaptive immune response. These cells also interconnect native and specific immune reactivity. A large set of biochemical signals from microbiota in the form of different microbiota associated molecular patterns (MAMPs) and bacterial metabolites that act locally and distantly in the human organism. As a result, commensal bacteria influence the maturity and activity of dendritic cells and affect the overall immune reactivity of the human organism. It then determines the response to pathogenic microorganisms, inflammation, associated with different pathological conditions and even affects the effectiveness of vaccination.

Prognostic factors for surgical treatment of prolactin-secreting pituitary adenomas.

Introduction: Usually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy. Aim: This study aims to determine the early and late outcomes of surgery, with particular emphasis on developing prognostic factors for surgical treatment and analyzing risk factors affecting the recurrence of hyperprolactinemia and prolactinoma. Material and methods: This retrospective study was conducted at the Feofaniya Clinical Hospital of the State Administration of Affairs (Kyiv, Ukraine), evaluating 109 patients' records from 2009 to 2019. The main patients' inclusion criteria were: serum prolactin (PRL) level of more than 100 ng/ml, presence of pituitary adenoma (PA) on MRI, histologically approved PA by microscopy. According to the size of the prolactin-secreting PA (PSPAs) the selected 109 patients were divided into two groups: micro- (≤10 mm, n = 75) and macroadenoma group (10-40 mm, n = 34). Results: 1 month after the operation, PRL levels decreased by 87% (p < 0.001), 12 months-by 93% (p < 0.001). After receiving surgery and DA therapy for 12 months 77.1% of patients achieved biochemical remission. Out of the total number of patients observed, 15.6% (n = 17) had a Knosp score greater than 3. Additionally, in the macroadenoma group, the percentage of patients with a Knosp score greater than 3 was 41,2%, which was significantly higher as compared to the microadenoma group (4%, p < 0.001). In patients with microadenomas a weak reverse correlation between patients' age (r = -0.258, p < 0.026) and positive with tumor size (r = 0.251, p < 0.030) was revealed. In the macroadenoma group significant association was found only between preoperative serum PRL level and tumor size (r = 0.412, p < 0.016). The preoperative PRL can be used as a diagnostic marker for lack of early biochemical remission in patients with PSPAs with diagnostic accuracy 66.9%. Conclusions: This study found that primary transsphenoidal surgery is an effective treatment in reaching PRL level control in patients with both micro- and macroprolactinomas. The correct and thorough selection of candidates for surgery is crucial to achieve postoperative serum PRL normalization in the vast majority of patients.

Probiotic co-supplementation with absorbent smectite for pancreatic beta-cell function in type 2 diabetes: a secondary-data analysis of a randomized double-blind controlled trials.

Introduction: There is growing evidence from animal and clinical studies suggesting probiotics can positively affect type 2 diabetes (T2D). In a previous randomized clinical study, we found that administering a live multistrain probiotic and absorbent smectite once a day for eight weeks to patients with T2D could reduce chronic systemic inflammatory state, insulin resistance, waist circumference and improve the glycemic profile. However, there is a lack of evidence supporting the efficacy of probiotic co-supplementation with absorbent smectite on pancreatic ß-cell function in T2D. Aim: This secondary analysis aimed to assess the effectiveness of an alive multistrain probiotic co-supplementation with absorbent smectite vs placebo on ß-cell function in T2D patients. Material and methods: We performed a secondary analysis on a previously published randomized controlled trial (NCT04293731, NCT03614039) involving 46 patients with T2D. The main inclusion criteria were the presence of ß-cell dysfunction (%B<60%) and insulin therapy alone or combined with oral anti-diabetic drugs. The primary outcome was assessing ß-cell function as change C-peptide and %B. Results: We observed only a tendency for improving ß-cell function (44.22 ± 12.80 vs 55.69 ± 25.75; р=0.094). The effectiveness of the therapy probiotic-smectite group was confirmed by fasting glycemia decreased by 14% (p=0.019), HbA1c - 5% (p=0.007), HOMA-2 - 17% (p=0.003) and increase of insulin sensitivity by 23% (p=0.005). Analysis of the cytokine profile showed that statistical differences after treatment were in the concentration of both pro-inflammatory cytokines: IL-1ß (22.83 ± 9.04 vs 19.03 ± 5.57; p=0.045) and TNF-α (31.25 ± 11.32 vs 26.23 ± 10.13; p=0.041). Conclusion: Adding a live multistrain probiotic and absorbent smectite supplement slightly improved ß-cell function and reduced glycemic-related parameters in patients with T2D. This suggests that adjusting the gut microbiota could be a promising treatment for diabetes and warrants further investigation through more extensive studies.

Ethical navigation of biobanking establishment in Ukraine: learning from the experience of developing countries.

Building a biobank network in developing countries is essential to foster genomic research and precision medicine for patients' benefit. However, there are serious barriers to establishing biobanks in low-income and middle-income countries (LMICs), including Ukraine. Here, we outline key barriers and essential milestones for the successful expansion of biobanks, genomic research and personalised medicine in Ukraine, drawing from the experience of other LMICs. A lack of legal and ethical governance in conjunction with limited awareness about biobanking and community distrust are the principal threats to establishing biobanks. The experiences of LMICs suggest that Ukraine urgently needs national guidelines covering ethical and legal aspects of biospecimen-related research. National guidelines must be consistent with international ethical recommendations for safeguarding participants' rights, welfare and privacy. Additionally, efforts to educate and engage physicians and patient communities are essential for achieving biobanking goals and benefits for precision medicine and future patients.

Accuracy of attenuation coefficient measurement (ACM) for real-time ultrasound hepatic steatometry: Comparison of simulator/phantom data with magnetic resonance imaging proton density fat fraction (MRI-PDFF).

Objectives: To evaluate the accuracy and reproducibility of real time ultrasound (US) steatometry with the Attenuation Coefficient (AC) measurement in comparison with magnetic resonance imaging with proton density software module (MRI-PDFF). Methods: This study was conducted between January 2021 and October 2021. The comparison of instrumental methods for assessing and grading hepatic steatosis using a multimodal phantom simulator of different fat and water ratios was performed. The study involved 3 radiological centers. The steatophantom was simultaneously investigated using three methods: magnetic resonance imaging with proton density software module (MRI-PDFF) and 128-slice multidetector computed tomography, and then by 2 different US scanner for steatosis assessment via Measurement Attenuation Imaging (ATI) ant Attenuation Coefficient Measurement (ACM). Results: Modeling of hepatic steatosis using a series of phantom simulators allows evidence-based medicine to determine the diagnostic accuracy of the latest US techniques for steatosis. The ACM and ATI of both US systems on phantoms correlated well with each other and with MRI-PDFF and, thus, can provide good diagnostic value in the assessment of hepatic steatosis. MDCT was less sensitive to mild steatosis than AC and MRI-PDFF. Conclusion: Measurement of ACs in US studies by devices from different vendors compared to other modalities of radiological imaging (MDCT and MRI-PDFF) by special phantoms is an accurate and promising method for noninvasive quantification of hepatic steatosis.

Probiotic for Pancreatic ß-Cell Function in Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

INTRODUCTION: Many clinical studies have proved the effectiveness of probiotics in metabolic disorders associated with insulin resistance. However, the impact of probiotic therapy on pancreatic ß-cell function is ambiguous. The influence of probiotic supplementation vs. placebo on ß-cell function in people with type 2 diabetes (T2D) was assessed in a double-blind, single-center, randomized, placebo-controlled trial (RCT). METHODS: Sixty-eight patients with T2D were selected for participation in the RCT. Patients were randomly allocated to consumption of live multistrain probiotics or a placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. The primary main outcome was the assessment of ß-cell function as change in C-peptide and HOMA-ß (homeostasis model assessment-estimated ß-cell function), which was calculated using the HOMA2 calculator (Diabetes Trials Unit, University of Oxford). Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables, and cytokines levels. Analysis of covariance was used to assess the difference between groups. RESULTS: Supplementation with live multiprobiotic was associated with slight significant improvement of ß-cell function (HOMA-ß increased from 32.48 ± 13.12 to 45.71 ± 25.18; p = 0.003) and reduction of fasting glucose level (13.03 ± 3.46 vs 10.66 ± 2.63 mmol/L and 234.63 ± 62.36 vs 192.07 ± 47.46 mg/dL; p < 0.001) and HbA1c (8.86 ± 1.28 vs 8.48 ± 1.22; p = 0.043) as compared to placebo. Probiotic therapy significantly affects chronic systemic inflammation in people with T2D by reducing pro-inflammatory cytokine levels. CONCLUSIONS: Probiotic therapies modestly improved ß-cell function in patients with T2D. Modulating the gut microbiota represents a new diabetes treatment and should be tested in more extensive studies. TRIAL REGISTRATION: NCT05765292.

Antimicrobial activity of dietary supplements based on bacterial lysate of Lactobacillus rhamnosus DV.

Introduction: According to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary. Aim: To determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures. Material and methods: Antimicrobial activity of Del-Immune V® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative (Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive (Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast (Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures. Results: The MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC-12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant. Conclusions: It was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents.

Probiotics for pancreatic ß-cell function: from possible mechanism of action to assessment of effectiveness.

Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycemia because of insulin resistance (IR) and\or pancreatic ß-cell dysfunction. Last century research showed that gut microbiota has a direct effect on metabolism and metabolic diseases. New studies into the human microbiome and its connection with the host is making it possible to develop new therapies for a wide variety of diseases. Inflammation is a well-known precursor to metabolic syndrome, which increases the risk of hypertension, visceral obesity, and dyslipidemia, which can lead to T2D through the damage of pancreatic ß-cell and reduce insulin secretion. Current understanding for beneficial effects of probiotics in T2D strictly rely on both animal and clinical data, which mostly focused on their impact on IR, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic ß-cell function in terms of T2D and related metabolic disorders. Therefore, current review will focus on the efficacy of probiotics for the protection of ß-cells damage and it`s mechanism in patients with T2D.

Protective effect of vaginal resveratrol administration on joint tissues in ovariectomized rats: Targeting mTOR and сaspase 3.

INTRODUCTION: Estrogens play a considerable role in maintaining bone and articular cartilage homeostasis. Menopause provokes joint disorders due to metabolic syndrome and altered signaling pathways. Phytoestrogen resveratrol was demonstrated to provide chondroprotective and osteoprotective effects. However, the mechanisms of such action of Resveratrol are still being explored. AIM: The study aims to determine the effect of Resveratrol on the joints and its therapeutic mechanism in ovariectomized rats. MATERIAL AND METHODS: The study was carried out on Wistar female rats that were divided into three groups, including control animals; ovariectomized rats (OVX); and the OVX group treated with an intravaginal gel containing Resveratrol (0.5 % 0.1 mL, daily 28 days). Knee joint tissues (articular cartilage, subchondral plate, subchondral bone) were assessed by histomorphometry. The expression of mTOR, PTEN, Caspase 3 and BCL-2 in articular cartilage and subchondral bone were evaluated immunohistochemically. RESULTS: Resveratrol treatment of OVX rats prevented weight gain by 17 % (P < 0.001), demonstrating the systemic effect on metabolic pathways. Although there were no statistically significant differences in the thickness of articular cartilage between groups, OVX rats possessed degenerative changes in chondrocytes, associated with the enhanced expression of mTOR (P < 0.001) and Casp-3 (P = 0.005). Resveratrol decreased mTOR (P = 0.007) and Casp-3 (P = 0.011) expression in chondrocytes, reducing degenerative changes. At the same time, resveratrol attenuated the deterioration of trabecular bone in OVX rats (P = 0.002). This effect was through the up-regulation of BCL-2 (P = 0.018) and down-regulation of Casp-3 expression (P < 0.001). CONCLUSIONS: Intravaginal administration of resveratrol provided systemic effects and ameliorated joint tissue structure and signaling in OVX rats through stimulation of BCL-2 and reduced Casp-3 expression.

The detrimental consequences of two consecutive disasters impacting cytopathology in Ukraine: COVID followed by the war.

The Covid-19 pandemic and ongoing war in Ukraine caused unprecedented disruption in healthcare, including cytopathology activities. This paper elucidates the effect of two consecutive disasters-the COVID-19 pandemic followed by the war-on cytopathology practice in Ukraine through a single-centre retrospective study. Total testing volumes, geographic distribution, and indicators of laboratory operations were assessed during three periods of 3 months each: the first 3 months of the acute phase of the war (March-May 2022, period 1); summer (June-August 2022, period 2); and the fall (September-November 2022, period 3, associated with massive attacks on the energy infrastructure in Ukraine). These data were compared with the corresponding periods in 2020, during the COVID-19 pandemic, and in 2021, the post-lockdown period. The ongoing war in Ukraine has caused a dramatic disruption in routine health maintenance and cytological practice. A net decline in both PAP testing and non-gynaecological pathology was associated with a geographic redistribution of cytopathological testing, and an increase in the rate of abnormal sample reporting. Despite these challenges, cytopathology practice in Ukraine demonstrates resilience, allowing for maintaining the healthcare system and addressing the needs of the civil population during the war. The ongoing war in Ukraine heavily affected cytological practice. The decline in PAP testing during the early period of the war was associated with an increase in the abnormal sample rate. Further study of the war's impact on the cervical pathology rate and the health of the population in the next decades is needed.

Association between intestinal microflora and obesity.

Obesity has become one of modern society's most serious health problems. Studies from the last 30 years revealed a direct relationship between imbalanced energy intake and increased healthcare costs related to the treatment or management of obesity. Recent research has highlighted significant effects of gut microbial composition on obesity. We aimed to report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature searching for the following key words: metabolism, gut microbiota, dysbiosis, and obesity. There is evidence that an association between intestinal microbiota and obesity exists at any age. There are complex genetic, metabolic, and inflammatory mechanisms involved in the pathogenesis of obesity. Revision of indications for use of probiotics, prebiotics, and antibiotics in obese patients should be considered. Microbial composition of the gut may be an important factor involved in the development of obesity. Changes in the gut microbiota may result in changes in human metabolism and weight loss.

Efficacy of interferon alpha for the treatment of hospitalized patients with COVID-19: A meta-analysis.

Introduction: IFN-α intervention may block SARS-CoV-2 replication and normalize the deregulated innate immunity of COVID-19. Aim: This meta-analysis aimed to investigate the efficacy of interferon IFN-α-containing regimens when treating patients with moderate-to-severe COVID-19. Material and methods: PubMed, SCOPUS, and ClinicalTrials.gov were searched from inception to 15 January 2022. A systematic literature search was conducted by applying relevant terms for 'COVID-19' and 'interferon-α'. The primary outcome enclosed the all-cause hospital mortality. The secondary outcomes constituted the length of hospital stay; hospital discharge; nucleic acid negative conversion. Results: Eleven studies are enclosed in the meta-analysis. No significant difference in the all-cause mortality rate was found between the study and control groups (OR 0.2; 95% CI 0.05-1.2; I2 = 96%). The implementation of interferon did not influence such outcomes as the length of hospital stay (OR 0.9; 95% CІ, 0.3-2.6; I2 = 91%), nucleic acid negative conversion (OR 0.8; 95% CI, 0.04-17.2; I2 = 94%). Nevertheless, IFN-α treatment resulted in a higher number of patients discharged from the hospital (OR 26.6; 95% CІ, 2.7-254.3; I2 = 95%). Conclusions: Thus, IFN-α does not benefit the survival of hospitalized COVID-19 patients but may increase the number of patients discharged from the hospital. Systematic review registration: www.crd.york.ac.uk/prospero, identifier (CRD42022374589).

Gut microbiota in patients with COVID-19 and type 2 diabetes: A culture-based method.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) continues to affect people around the world, with one of the most frequent comorbidities being Type 2 Diabetes (T2D). Studies have suggested a link between disbalances in gut microbiota and these diseases, as well as with COVID-19, potentially due to inflammatory dysfunction. This study aims to analyze the changes in gut microbiota in COVID-19 patients with T2D using a culture-based method. Methods: The stool samples were taken from 128 patients with confirmed COVID-19. Changes in the composition of gut microbiota were analyzed by culture-based method. The study used chi-squared and t-test to find significant differences in gut bacteria between samples and non-parametric correlation analysis to examine relationship between gut bacteria abundance, C-reactive protein (CRP) levels and length of stay (LoS) in COVID-19 patients without T2D. Results: The gut microbiota of T2D patients with COVID-19 showed increased Clostridium spp., Candida spp., and decreased Bifidobacterium spp., Lactobacillus spp. Metformin-treated patients with T2D and COVID-19 without antibiotic treatment showed increased Bacteroides spp., Lactobacillus spp., and decreased Enterococcus, Clostridium compared to the same group with antibiotic treatment. The study also found a positive correlation between the abundance of certain gut microbiota genera, such as Klebsiella spp. and Enterococcus spp., and CRP levels and LoS in COVID-19 patients without and with T2D, while the abundance of other genera, such as Bifidobacterium spp. and Lactobacillus spp., was found to have a negative correlation. Conclusion: In conclusion, this study provides important insights into the gut microbiota composition of SARS-CoV-2-infected individuals with T2D and its potential impact on the course of the disease. The findings suggest that certain gut microbiota genera may be associated with increased CRP levels and longer hospital stays. The significance of this study lies in the fact that it highlights the potential role of gut microbiota in the progression of COVID-19 in patients with T2D, and may inform future research and treatment strategies for this patient population. The future impact of this study could include the development of targeted interventions to modulate gut microbiota in order to improve outcomes for COVID-19 patients with T2D.

Incidence of BRAF mutations in cutaneous melanoma: histopathological and molecular analysis of a Ukrainian population.

Aim: This study aimed to investigate the incidence of BRAF mutation in cutaneous melanoma in the Ukrainian population with respect to clinical and histopathological data. Materials & methods: This single-center retrospective cohort study enrolled 299 primary CM with known BRAF status assessed by RT-PCR. Results: The overall BRAF mutation rate was 56.5% in CM and demonstrated a link with the younger age (p < 0.001), anatomical site (p < 0.001) and histological type of CM (p = 0.022). BRAF-positive CM possessed a slightly higher mitotic rate (p = 0.015) and Breslow thickness (p = 0.028) but did not relate to tumor-infiltrating lymphocytes. Conclusion: The high rate of BRAF mutations in CM patients in the Ukrainian cohort was associated with superficial spreading histology, higher depth of invasion and proliferation.

Fecal microbiota transplantation in patients with post-infectious irritable bowel syndrome: A randomized, clinical trial.

Introduction: Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified. Aim: The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT's safety, clinical and microbiological efficacy in patients with PI-IBS. Materials and methods: Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale). Results: FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted. Conclusion: This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.

Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms.

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel's therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4−4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.