Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease\'s progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer. NEPC may arise de novo or develop following androgen deprivation therapy (ADT). NEPC that arise following ADT has the nomenclature \"treatment-emerging/induced NEPC (t-NEPC)\". t-NEPC would be anticipated in castration resistant prostate cancer (CRPC) and metastatic PCa. t-NEPC is characterized by low or absent androgen receptor (AR) expression, independence of AR signaling, and gain of neuroendocrine phenotype. t-NEPC is an aggressive metastatic tumor, develops from PCa in response to drug induced ADT, and shows very short response to conventional therapy. t-NEPC occurs in 10%-17% of patients with CRPC. De novo NEPC is rare and is accounting for less than 2% of all PCa. The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated. Sphingosine kinase 1 plays a significant role in t-NEPC development. Although neuroendocrine markers: Synaptophysin, chromogranin A, and insulinoma associated protein 1 (INSM1) are expressed in t-NEPC, they are non-specific for diagnosis, prognosis, and follow-up of therapy. t-NEPC shows enriched genomic alteration in tumor protein P53 (TP53) and retinoblastoma 1 (RB1). There are evidences suggest that t-NEPC might develop through epigenetic evolution. There are genomic, epigenetic, and transcriptional alterations that are reported to be involved in development of t-NEPC. Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC. PCa is resistant to immunotherapy, and at present there are running trials to approach immunotherapy for PCa, CRPC, and t-NEPC.

OBJECTIVE: To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease.
METHODS: According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished - \"post-infectious IBS\" (n=45), \"IBS in overweight and obese people\" (n=49), \"comorbid IBS\" (n=75) and \"essential IBS\" (n=51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS (COMT, SLC6A4, FTO), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied.
RESULTS: Patients with \"post-infectious IBS\" are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype \"IBS in overweight and obese individuals\" is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The \"comorbid IBS phenotype\" is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the \"essential phenotype\", there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism.
CONCLUSIONS: The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for \"postinfectious\") phenotypes of the disease: \"IBS in overweight and obese people\", \"comorbid\" and \"essential\".
Цель. Дать характеристику фенотипов заболевания для разработки индивидуализированных подходов к терапии синдрома раздраженного кишечника (СРК) на основе взаимодействия генетических и эпигенетических факторов. Материалы и методы. Согласно сформулированной концепции авторов из когорты пациентов с СРК выделены подгруппы – «постинфекционный СРК» (n=45), «СРК у лиц с избыточной массой тела и ожирением» (n=49), «коморбидный СРК» (n=75) и «эссенциальный СРК» (n=51). В каждой подгруппе изучена распространенность полиморфизмов генов-кандидатов, ассоциированных с СРК (COMT, SLC6A4, FTO), особенности питания, уровень тревоги и депрессии, секреция кортизола, серотонина, дофамина, уровень зонулина в кале. Результаты. Пациенты с «постинфекционным СРК» характеризуются носительством аллеля S гена SLC6A4, генотипа val/val гена COMT, преобладанием диареи, высоким уровнем тревоги, частым отказом от молока и молочных продуктов. При фенотипе «СРК у лиц с избыточной массой тела и ожирением» чаще встречаются генотипы L/L гена SLC6A4, met/met гена COMT и A/A гена FTO, запоры, низкий уровень дофамина в плазме, признаки депрессии, частые эпизоды переедания, пристрастие к жирной и сладкой пище, избыточное потребление сахара, дефицит овощей в рационе. Для «коморбидного фенотипа СРК» характерны более частое выявление генотипа val/val гена COMT и носительство аллеля S гена SLC6A4, клинически выраженной тревоги и депрессии, ранний дебют заболевания, тяжелое течение, существенные ограничения в еде, значимое повышение эпителиальной проницаемости. При «эссенциальном фенотипе» отсутствуют яркие стигмы заболевания, выделить отличительные генетические и эпигенетические факторы, а также ведущий патогенетический механизм не представляется возможным. Заключение. Анализ генетических и эпигенетических факторов, ведущих механизмов формирования и течения СРК позволяет выделить дополнительные (помимо «постинфекционного») фенотипы заболевания: «СРК у лиц с избыточной массой тела и ожирением», «коморбидный» и «эссенциальный».

Trauma-related disorders are debilitating psychiatric conditions that affect people who have directly or indirectly witnessed adversities. Experiencing multiple types of traumas appears to be common during childhood, and even more so during adolescence. Dramatic brain/body transformations occurring during adolescence may provide a highly responsive substrate to external stimuli and lead to trauma-related vulnerability conditions, such as internalizing (anxiety, depression, anhedonia, withdrawal) and externalizing (aggression, delinquency, conduct disorders) problems. Analyzing relations among neuronal, endocrine, immune, and biochemical signatures of trauma and internalizing and externalizing behaviors, including the role of personality traits in shaping these conducts, this review highlights that the marked effects of traumatic experience on the brain/body involve changes at nearly every level of analysis, from brain structure, function and connectivity to endocrine and immune systems, from gene expression (including in the gut) to the development of personality.

BACKGROUND: Pre-harvest sprouting (PHS) is a major problem for wheat production due to its direct detrimental effects on wheat yield, end-use quality and seed viability. Annually, PHS is estimated to cause > 1.0 billion USD in losses worldwide. Therefore, identifying PHS resistance quantitative trait loci (QTLs) is crucial to aid molecular breeding efforts to minimize losses. Thus, a doubled haploid mapping population derived from a cross between white-grained PHS susceptible cv AAC Innova and red-grained resistant cv AAC Tenacious was screened for PHS resistance in four environments and utilized for QTL mapping.
RESULTS: Twenty-one PHS resistance QTLs, including seven major loci (on chromosomes 1A, 2B, 3A, 3B, 3D, and 7D), each explaining ≥10% phenotypic variation for PHS resistance, were identified. In every environment, at least one major QTL was identified. PHS resistance at most of these loci was contributed by AAC Tenacious except at two loci on chromosomes 3D and 7D where it was contributed by AAC Innova. Thirteen of the total twenty-one identified loci were located to chromosome positions where at least one QTL have been previously identified in other wheat genotype(s). The remaining eight QTLs are new which have been identified for the first time in this study. Pedigree analysis traced several known donors of PHS resistance in AAC Tenacious genealogy. Comparative analyses of the genetic intervals of identified QTLs with that of already identified and cloned PHS resistance gene intervals using IWGSC RefSeq v2.0 identified MFT-A1b (in QTL interval QPhs.lrdc-3A.1) and AGO802A (in QTL interval QPhs.lrdc-3A.2) on chromosome 3A, MFT-3B-1 (in QTL interval QPhs.lrdc-3B.1) on chromosome 3B, and AGO802D, HUB1, TaVp1-D1 (in QTL interval QPhs.lrdc-3D.1) and TaMyb10-D1 (in QTL interval QPhs.lrdc-3D.2) on chromosome 3D. These candidate genes are involved in embryo- and seed coat-imposed dormancy as well as in epigenetic control of dormancy.
CONCLUSIONS: Our results revealed the complex PHS resistance genetics of AAC Tenacious and AAC Innova. AAC Tenacious possesses a great reservoir of important PHS resistance QTLs/genes supposed to be derived from different resources. The tracing of pedigrees of AAC Tenacious and other sources complements the validation of QTL analysis results. Finally, comparing our results with previous PHS studies in wheat, we have confirmed the position of several major PHS resistance QTLs and candidate genes.

Takotsubo syndrome (TTS), recognized as stress\'s cardiomyopathy, or as left ventricular apical balloon syndrome in recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the limited understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in recent years, and particularly correlated to the SARS-CoV-2 pandemic, leads us to the imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and of targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial forms of TTS have been described. However, a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we here conducted a systematic review of the literature before June 2021, to contribute to the identification of potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but few in number and with diverse limitations. Consequently, we concluded that further work is needed to address the gaps discussed, and clear evidence may arrive by using multi-omics investigations.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

Autoimmune thyroid disease (AITD) accounts for 90% of all thyroid diseases and affects 2-5% of the population with remarkable familial clustering. Among AITDs, Graves\' disease (GD) is a complex disease affecting thyroid function. Over the last two decades, case-control studies using cutting-edge gene sequencing techniques have detected various susceptible loci that may predispose individuals to GD. It has been presumed that all likely associated genes, variants, and polymorphisms might be responsible for 75-80% of the heritability of GD. As a result, there are implications concerning the potential contribution of environmental and epigenetic factors in the pathogenesis of GD, including its initiation, progression, and development. Numerous review studies have summarized the contribution of genetic factors in GD until now, but there are still some key questions and notions that have not been discussed concerning the interplay of genetic, epigenetic, and immunological factors. With this in mind, this review discusses some newly-identified loci and their potential roles in the pathogenicity of GD. This may lead to the identification of new, promising therapeutic targets. Here, we emphasized principles, listed all the reported disease-associated genes and polymorphisms, and also summarized the current understanding of the epigenetic basis of GD.