Britanin - a beacon of hope against gastrointestinal tumors?

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties. It also exhibits significant anti-tumor activity, suppressing tumor growth in vitro and in vivo. The current body of research on Britanin includes thirty papers predominantly related to neoplasms, the majority of which are gastrointestinal tumors that have not been summarized before. To drive academic debate, the present paper reviews the available research on Britanin in gastrointestinal tumors. It also outlines novel research directions using data not directly concerned with the digestive system, but which could be adopted in future gastrointestinal research. Britanin was found to counteract liver, colorectal, pancreatic, and gastric tumors, by regulating proliferation, apoptosis, autophagy, immune response, migration, and angiogenesis. As confirmed in pancreatic, gastric, and liver cancer, its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation, as well as Bcl-2-associated X protein upregulation. Moreover, it has been found to induce the Akt kinase and Forkhead box O1 axis, activate the AMP-activated protein kinase pathway, elevate interleukin-2 and peroxisome proliferator-activated receptor-γ levels, reduce interleukin-10, as well as downregulate matrix metalloproteinase-9, Twist family bHLH transcription factor 1, and cyclooxygenase-2. It also inhibits Myc-HIF1α interaction and programmed death ligand 1 transcription by interrupting the Ras/ RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling. Future research should aim to unravel the link between Britanin and acetylcholinesterase, mast cells, osteolysis, and ischemia, as compelling data have been provided by studies outside the gastrointestinal context. Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells, while still being effective against the latter, further in-depth studies with the use of animal models are merited. The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent, which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors.

Resistance to olaparib is the major obstacle in targeted therapy for ovarian cancer (OC) with poly(ADP-ribose) polymerase inhibitors (PARPis), prompting studies on novel combination therapies to enhance olaparib efficacy. Despite identifying various mechanisms, understanding how OC cells acquire PARPi resistance remains incomplete. This study investigated microRNA (miRNA) expression in olaparib-sensitive (PEO1, PEO4) and previously established olaparib-resistant OC cell lines (PEO1-OR) using high-throughput RT-qPCR and bioinformatic analyses. The role of miRNAs was explored regarding acquired resistance and resensitization with the ATR/CHK1 pathway inhibitors. Differentially expressed miRNAs were used to construct miRNA-mRNA regulatory networks and perform functional enrichment analyses for target genes with miRNet 2.0. TCGA-OV dataset was analyzed to explore the prognostic value of selected miRNAs and target genes in clinical samples. We identified potential processes associated with olaparib resistance, including cell proliferation, migration, cell cycle, and growth factor signaling. Resensitized PEO1-OR cells were enriched in growth factor signaling via PDGF, EGFR, FGFR1, VEGFR2, and TGFßR, regulation of the cell cycle via the G2/M checkpoint, and caspase-mediated apoptosis. Antibody microarray analysis confirmed dysregulated growth factor expression. The addition of the ATR/CHK1 pathway inhibitors to olaparib downregulated FGF4, FGF6, NT-4, PLGF, and TGFß1 exclusively in PEO1-OR cells. Survival and differential expression analyses for serous OC patients revealed prognostic miRNAs likely associated with olaparib resistance (miR-99b-5p, miR-424-3p, and miR-505-5p) and resensitization to olaparib (miR-324-5p and miR-424-3p). Essential miRNA-mRNA interactions were reconstructed based on prognostic miRNAs and target genes. In conclusion, our data highlight distinct miRNA profiles in olaparib-sensitive and olaparib-resistant cells, offering molecular insights into overcoming resistance with the ATR/CHK1 inhibitors in OC. Moreover, some miRNAs might serve as potential predictive signature molecules of resistance and therapeutic response.

Biomedical Trends in Stimuli-Responsive Hydrogels with Emphasis on Chitosan-Based Formulations.

Biomedicine is constantly evolving to ensure a significant and positive impact on healthcare, which has resulted in innovative and distinct requisites such as hydrogels. Chitosan-based formulations stand out for their versatile utilization in drug encapsulation, transport, and controlled release, which is complemented by their biocompatibility, biodegradability, and non-immunogenic nature. Stimuli-responsive hydrogels, also known as smart hydrogels, have strictly regulated release patterns since they respond and adapt based on various external stimuli. Moreover, they can imitate the intrinsic tissues' mechanical, biological, and physicochemical properties. These characteristics allow stimuli-responsive hydrogels to provide cutting-edge, effective, and safe treatment. Constant progress in the field necessitates an up-to-date summary of current trends and breakthroughs in the biomedical application of stimuli-responsive chitosan-based hydrogels, which was the aim of this review. General data about hydrogels sensitive to ions, pH, redox potential, light, electric field, temperature, and magnetic field are recapitulated. Additionally, formulations responsive to multiple stimuli are mentioned. Focusing on chitosan-based smart hydrogels, their multifaceted utilization was thoroughly described. The vast application spectrum encompasses neurological disorders, tumors, wound healing, and dermal infections. Available data on smart chitosan hydrogels strongly support the idea that current approaches and developing novel solutions are worth improving. The present paper constitutes a valuable resource for researchers and practitioners in the currently evolving field.

Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

Emicizumab as a Promising Form of Therapy for Type A Hemophilia - A Review of Current Knowledge from Clinical Trials.

Hemophilia is a plasma bleeding disorder characterized by a deficiency of certain blood clotting factors. The most common forms of this disease, i.e., type A and type B, affect approximately 400,000 people worldwide. Without appropriate treatment ensuring the proper coagulation cascade, this disease may lead to serious disability. Minimizing patient discomfort is possible via replacement therapy, consisting of the substitution of a missing coagulation factor via intravenous administration. Frequent medication and the risk related to factor inhibitors are significant disadvantages, necessitating the improvement of current therapies or the development of novel ones. This review examines the humanized bispecific antibody Emicizumab which ensures hemostasis by mimicking the action of the coagulation factor VIII, a deficiency of which causes type A hemophilia. The paper outlines the topic and then summarizes available clinical trials on Emicizumab in type A hemophilia. Several interventional clinical trials have found Emicizumab to be effective in decreasing bleeding episodes and raising patient satisfaction among various hemophilia A populations. Current Emicizumab-related trials are forecast to be completed between 2024 and 2030, and in addition to congenital hemophilia A, the trials cover acquired hemophilia A and patients playing sports. Providing a more comprehensive understanding of Emicizumab may revolutionize the management of hemophilia type A and improve quality of life. Conclusively, Emicizumab is a gentler therapy owing to subcutaneous delivery and fewer injections, which reduces injection-site reactions and makes therapy less burdensome, ultimately decreasing hospital visits and indirect costs.

The Course of COVID-19 and Long COVID: Identifying Risk Factors among Patients Suffering from the Disease before and during the Omicron-Dominant Period.

SARS-CoV-2 has acquired many mutations that influence the severity of COVID-19's course or the risk of developing long COVID. In 2022, the dominant SARS-CoV-2 variant was Omicron. This study aimed to compare the course of COVID-19 in the periods before and during the dominance of the Omicron variant. Risk factors for developing long COVID were also assessed. This study was based on stationary visits of patients after COVID-19 and follow-up assessments after 3 months. Clinical symptoms, comorbidities, and vaccination status were evaluated in 1967 patients. Of the analyzed group, 1308 patients (66.5%) were affected by COVID-19 in the period before the Omicron dominance. The prevalence of long COVID was significantly lower among patients of the Omicron group (47.7% vs. 66.9%, p < 0.001). The risk of long COVID was higher for women (OR: 1.61; 95% CI: 1.31, 1.99]) and asthmatics (OR: 1.46; 95% CI: 1.03, 2.07]). Conclusively, infection during the Omicron-dominant period was linked to a lower risk of developing long COVID. Females are at higher risk of developing long COVID independent of the pandemic period. Individuals affected by COVID-19 in the Omicron-dominant period experience a shorter duration of symptoms and reduced frequency of symptoms, except for coughing, which occurs more often.

Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.

Clinical and electrocardiographic correlates of myocardial dysfunction after COVID-19 in nonhospitalised patients in long-term follow-up. Data from the polish long-covid cardiovascular study.

Clinical evidence indicates that COVID-19 is a multiorgan disease that significantly impacts the cardiovascular system. However, little is known about the predictors of myocardial dysfunction after SARS-CoV-2 infection. Therefore, this research aimed to evaluate the clinical and electrocardiographic correlates of myocardial dysfunction after SARS-CoV-2 infection in nonhospitalised patients without previously diagnosed cardiovascular disease. This observational study included 448 patients selected from the database of 4142 patients in the Polish Long-Covid Cardiovascular study. All patients underwent a 12-lead electrocardiogram (ECG); 24-h Holter ECG monitoring, 24/7 ambulatory blood pressure monitoring, echocardiography, and cardiac magnetic resonance imaging. According to the results of diagnostic tests, patients were divided into two groups depending on the occurrence of myocardial dysfunction after COVID-19. Group 1-without myocardial dysfunction after COVID-19-consisted of 419 patients, with a mean age of 48.82 (SD ± 11.91), and Group 2 (29 patients)-with myocardial dysfunction after COVID-19, with a mean age of 51.45 (SD ± 12.92). When comparing the analysed groups, there were significantly more men in Group 2 (p = 0.006). QRS (corresponds to the time of ventricular contraction in an electrocardiographic examination) fragmentation (p = 0.031), arrhythmias (atrial fibrillation, supraventricular extrasystole, ventricular extrasystole) (p = 0.008), and male gender (p = 0.007) were independently associated with myocardial dysfunction after COVID-19. The study showed that myocardial damage after COVID-19 affects men more often and is independent of typical clinical factors and the severity of the disease course. The QRS fragmentation and arrhythmias observed in the ECG indicate the possibility of myocardial dysfunction in patients after COVID-19, which may be a valuable marker for physicians.

Analysis of prognostic factors in patients diagnosed with bladder cancer complicated by hemorrhage treated by drug-eluting bead embolization.

Background: Transcatheter bladder arterial chemoembolization (TACE) is an alternative treatment used to control bladder cancer (BC) with bleeding, especially in older adult patients with comorbidities. This retrospective observational study evaluated the effect and prognostic factors of transcatheter drug-eluting bead (DEB) embolization in patients with advanced BC. Methods: We assessed 39 patients diagnosed with BC with hemorrhage who were either inoperable or unwilling to undergo surgery at our hospital between January 2018 and October 2022. All patients underwent TACE by DEB loaded with epirubicin and imaging scans after 2 months to evaluate the curative effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) standard to determine treatment. Re-examination and follow-up were performed every 3-6 months to observe hematuria recurrence and the curative effect. Results: A total of 95 interventional treatments were performed in 39 patients, and all participants achieved complete hemostasis within 5 days after the first intervention. Computed tomography or magnetic resonance imaging showed that the total effective rate [complete response (CR) + partial response (PR)] was 64.1%, and the disease benefit rate (CR +PR + stable disease) was 79.5%. A total of 30 patients (76.9%) had no hematuria recurrence. Logistic regression analysis indicated that the type of blood supply in BC may relate to whether the patients benefited from the intervention. Hematuria recurrence was significantly associated with the total number of tumors and the type of blood supply (P<0.05). Conclusions: Superselective embolization of bladder arteries with DEB can be used to treat BC with hemorrhage. However, hypovascular tumor blood supply may result in poor postoperative efficacy and hematuria recurrence. Additionally, multiple bladder tumors may be a risk factor for hematuria recurrence.

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression.

Introduction: Glioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure and a grim prognosis. WWOX is one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated in GBM for reliable associations with prognosis or disease progression despite known alterations. Recently, we observed a phenotypic heterogeneity between GBM cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among which the anti-GBM activity of WWOX was generally corresponding, but colony growth and formation were inconsistent in DBTRG-05MG. This prompted us to investigate the molecular landscapes of these cell lines, intending to translate them into the clinical context. Methods: U87MG/T98G/U251MG/DBTRG-05MG were subjected to high-throughput sequencing, and obtained data were explored via weighted gene co-expression network analysis, differential expression analysis, functional annotation, and network building. Following the identification of the most relevant DBTRG-distinguishing driver genes, data from GBM patients were employed for, e.g., differential expression analysis, survival analysis, and principal component analysis. Results: Although most driver genes were unique for each cell line, some were inversely regulated in DBTRG-05MG. Alongside driver genes, the differentially-expressed genes were used to build a WWOX-related network depicting protein-protein interactions in U87MG/T98G/U251MG/DBTRG-05MG. This network revealed processes distinctly regulated in DBTRG-05MG, e.g., microglia proliferation or neurofibrillary tangle assembly. POLE4 and HSF2BP were selected as DBTRG-discriminating driver genes based on the gene significance, module membership, and fold-change. Alongside WWOX, POLE4 and HSF2BP expression was used to stratify patients into cell lines-resembling groups that differed in, e.g., prognosis and treatment response. Some differences from a WWOX-related network were certified in patients, revealing genes that clarify clinical outcomes. Presumably, WWOX overexpression in DBTRG-05MG resulted in expression profile change resembling that of patients with inferior prognosis and drug response. Among these patients, WWOX may be inaccessible for its partners and does not manifest its anti-cancer activity, which was proposed in the literature but not regarding glioblastoma or concerning POLE4 and HSF2BP. Conclusion: Cell lines data enabled the identification of patients among which, despite high expression of WWOX tumor suppressor, no advantageous outcomes were noted due to the cancer-promoting profile ensured by other genes.

Carboxymethyl Chitosan Hydrogels for Effective Wound Healing-An Animal Study.

Hydrogels have various applications in medicine, for example, in systems for controlled drug release or as wound dressings, where they provide an appropriate environment for healing and constitute a barrier to microorganisms. The aim of this study was to evaluate the action of carboxymethyl chitosan (CMCS) hydrogels in wound healing therapy in vivo using a laboratory rat model. The hydrogels were formed from aqueous solutions of a CMCS biopolymer via electron beam irradiation, with the presence of a crosslinking agent of poly(ethylene glycol) diacrylate. A histopathological examination of injured tissue, using a model of a hard-to-heal wound, indicated that the CMCS hydrogel supported healing. The new gel dressing, being noncytotoxic, presents great potential in wound treatment, with positive effects on the amount of inflammatory infiltration, young collagen formation, and the degree of epidermalization. A key advantage of the current approach (i.e., using competitive radiation technology for synthesis) is that it includes only one step, with the product being sterilized as it is synthesized. The hydrogel effectively supports wound healing and can serve as a bio-based and biodegradable platform for other medical applications.

The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine.

The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.

LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer.

Introduction: The discovery of non-coding RNA (ncRNA) dates back to the pre-genomics era, but the progress in this field is still dynamic and leverages current post-genomics solutions. WWOX is a global gene expression modulator that is scarcely investigated for its role in regulating cancer-related ncRNAs. In bladder cancer (BLCA), the link between WWOX and ncRNA remains unexplored. The description of AP-2α and AP-2γ transcription factors, known as WWOX-interacting proteins, is more commonplace regarding ncRNA but still merits investigation. Therefore, this in vitro and in silico study aimed to construct an ncRNA-containing network with WWOX/AP-2 and to investigate the most relevant observation in the context of BLCA cell lines and patients. Methods: RT-112, HT-1376, and CAL-29 cell lines were subjected to two stable lentiviral transductions. High-throughput sequencing of cellular variants (deposited in the Gene Expression Omnibus database under the GSE193659 record) enabled the investigation of WWOX/AP-2-dependent differences using various bioinformatics tools (e.g., limma-voom, FactoMineR, multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE), miRDB, Arena-Idb, ncFANs, RNAhybrid, TargetScan, Protein Annotation Through Evolutionary Relationships (PANTHER), Gene Transcription Regulation Database (GTRD), or Evaluate Cutpoints) and repositories such as The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia. The most relevant observations from cap analysis gene expression sequencing (CAGE-seq) were confirmed using real-time PCR, whereas TCGA data were validated using the GSE31684 cohort. Results: The first stage of the whole study justified focusing solely on WWOX rather than on WWOX combined with AP-2α/γ. The most relevant observation of the developed ncRNA-containing network was LINC01137, i.e., long non-coding RNAs (lncRNAs) that unraveled the core network containing UPF1, ZC3H12A, LINC01137, WWOX, and miR-186-5p, the last three being a novel lncRNA/miRNA/mRNA axis. Patients' data confirmed the LINC01137/miR-186-5p/WWOX relationship and provided a set of dependent genes (i.e., KRT18, HES1, VCP, FTH1, IFITM3, RAB34, and CLU). Together with the core network, the gene set was subjected to survival analysis for both TCGA-BLCA and GSE31684 patients, which indicated that the increased expression of WWOX or LINC01137 is favorable, similar to their combination with each other (WWOX↑ and LINC01137↑) or with MIR186 (WWOX↑/LINC01137↑ but MIR186↓). Conclusion: WWOX is implicated in the positive feedback loop with LINC01137 that sponges WWOX-targeting miR-186-5p. This novel WWOX-containing lncRNA/miRNA/mRNA axis should be further investigated to depict its relationships in a broader context, which could contribute to BLCA research and treatment.

Prevalence and assessment of risk factors among Polish adults with post-COVID-19 syndrome: a 12-month follow-up study.

INTRODUCTION: Previous studies have indicated that COVID-19 symptoms may persist for up to 12 months after recovery; however, data on this phenomenon are still limited. OBJECTIVES: The aim of this study was to assess the prevalence, the most common symptoms, and the risk factors for development of post-COVID syndrome in hospitalized and nonhospitalized patients during a 12-month follow-up after recovery from COVID-19. PATIENTS AND METHODS: This longitudinal study was based on medical data collected at follow-up visits at 3 and 12 months post-COVID-19. Sociodemographic data, chronic conditions, and the most common clinical symptoms were assessed. A total of 643 patients were enrolled in the final analysis. RESULTS: A majority of the study group were women (63.1%), and the median age of the entire group was 52 years (interquartile range [IQR] 43-63). After 12 months, a median of 65.7% (IQR, 62.1%-69.6%) of the patients declared the presence of at least 1 clinical symptom of post-COVID syndrome. The most common complaints were asthenia (median, 45.7% [IQR, 41.9%-49.6%]) and neurocognitive symptoms (median, 40% [IQR, 36%-40.1%]). In a multivariable analysis, female sex (odds ratio [OR] 1.49; P = 0.01) and severe COVID-19 course (OR, 3.05; P <0.001) were associated with persistence of clinical symptoms for up to 12 months after recovery. CONCLUSIONS: After 12 months, persistent symptoms were declared by 65.7% of the patients. The most common symptoms 3 and 12 months after the infection were worse tolerance to exercise, fatigue, palpitations, and memory or concentration problems. Women are at a higher risk of experiencing persistent symptoms, and COVID-19 severity was a predictor of persistent post-COVID-19 symptoms.

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up.

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry. In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization. The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations.

Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness, the latter is one responsible for potentiating the resistance to treatment, inter alia due to increased invasiveness. In recent years, glioblastoma stemness research has bashfully introduced a key aspect of cytoskeletal rearrangements, whereas the impact of the cytoskeleton on invasiveness is well known. Although non-stem glioblastoma cells are less invasive than glioblastoma stem cells (GSCs), these cells also acquire stemness with greater ease if characterized as invasive cells and not tumor core cells. This suggests that glioblastoma stemness should be further investigated for any phenomena related to the cytoskeleton and metabolism, as they may provide new invasion-related insights. Previously, we proved that interplay between metabolism and cytoskeleton existed in glioblastoma. Despite searching for cytoskeleton-related processes in which the investigated genes might have been involved, not only did we stumble across the relation to metabolism but also reported genes that were found to be implicated in stemness. Thus, dedicated research on these genes in GSCs seems justifiable and might reveal novel directions and/or biomarkers that could be utilized in the future. Herein, we review the previously identified cytoskeleton/metabolism-related genes through the prism of glioblastoma stemness.

Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.

The transcription factor family activator protein 2 (TFAP2) is vital for regulating both embryonic and oncogenic development. The TFAP2 family consists of five DNA-binding proteins, including TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E. The importance of TFAP2 in tumor biology is becoming more widely recognized. While TFAP2D is not well studied, here, we mainly focus on the other four TFAP2 members. As a transcription factor, TFAP2 regulates the downstream targets directly by binding to their regulatory region. In addition, the regulation of downstream targets by epigenetic modification, posttranslational regulation, and interaction with noncoding RNA have also been identified. According to the pathways in which the downstream targets are involved in, the regulatory effects of TFAP2 on tumorigenesis are generally summarized as follows: stemness and EMT, interaction between TFAP2 and tumor microenvironment, cell cycle and DNA damage repair, ER- and ERBB2-related signaling pathway, ferroptosis and therapeutic response. Moreover, the factors that affect TFAP2 expression in oncogenesis are also summarized. Here, we review and discuss the most recent studies on TFAP2 and its effects on carcinogenesis and regulatory mechanisms.

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications.

In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

Substances of Natural Origin in Medicine: Plants vs. Cancer.

Continuous monitoring of the population's health is the main method of learning about disease prevalence. National and international data draw attention to the persistently high rates of cancer incidence. This necessitates the intensification of efforts aimed at developing new, more effective chemotherapeutic and chemopreventive drugs. Plants represent an invaluable source of natural substances with versatile medicinal properties. Multidirectional activities exhibited by natural substances and their ability to modulate key signaling pathways, mainly related to cancer cell death, make these substances an important research direction. This review summarizes the information regarding plant-derived chemotherapeutic drugs, including their mechanisms of action, with a special focus on selected anti-cancer drugs (paclitaxel, irinotecan) approved in clinical practice. It also presents promising plant-based drug candidates currently being tested in clinical and preclinical trials (betulinic acid, resveratrol, and roburic acid).

Antineoplastic Nature of WWOX in Glioblastoma Is Mainly a Consequence of Reduced Cell Viability and Invasion.

Following the discovery of WWOX, research has moved in many directions, including the role of this putative tumor suppressor in the central nervous system and related diseases. The task of determining the nature of WWOX in glioblastoma (GBM) is still considered to be at the initial stage; however, the influence of this gene on the GBM malignant phenotype has already been reported. Because most of the available in vitro research does not consider several cellular GBM models or a wide range of investigated biological assays, the present study aimed to determine the main processes by which WWOX exhibits anticancer properties in GBM, while taking into account the phenotypic heterogeneity between cell lines. Ectopic WWOX overexpression was studied in T98G, DBTRG-05MG, U251MG, and U87MG cell lines that were compared with the use of assays investigating cell viability, proliferation, apoptosis, adhesion, clonogenicity, three-dimensional and anchorage-independent growth, and invasiveness. Observations presenting the antineoplastic properties of WWOX were consistent for T98G, U251MG, and U87MG. Increased proliferation and tumor growth were noted in WWOX-overexpressing DBTRG-05MG cells. A possible explanation for this, arrived at via bioinformatics tools, was linked to the TARDBP transcription factor and expression differences of USP25 and CPNE2 that regulate EGFR surface abundance. Collectively, and despite various cell line-specific circumstances, WWOX exhibits its anticancer nature mainly via a reduction of cell viability and invasiveness of glioblastoma.