Management of Refractory Functional Gastrointestinal Disorders: What Role Should Psychiatrists Have?

Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways.

Metformin (MET) is a preferred drug for the treatment of type 2 diabetes mellitus. Recent studies show that apart from its blood glucose-lowering effects, it also inhibits the development of various tumours, by inducing autophagy. Various studies have confirmed the inhibitory effects of MET on cancer cell lines' propagation, migration, and invasion. The objective of the study was to comprehensively review the potential of MET as an anticancer agent, particularly focusing on its ability to induce autophagy and inhibit the development and progression of various tumors. The study aimed to explore the inhibitory effects of MET on cancer cell proliferation, migration, and invasion, and its impact on key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and PI3K. This review noted that MET exerts its anticancer effects by regulating key signalling pathways such as phosphoinositide 3-kinase (PI3K), LC3-I and LC3-II, Beclin-1, p53, and the autophagy-related gene (ATG), inhibiting the mTOR protein, downregulating the expression of p62/SQSTM1, and blockage of the cell cycle at the G0/G1. Moreover, MET can stimulate autophagy through pathways associated with the 5' AMPK, thereby inhibiting he development and progression of various human cancers, including hepatocellular carcinoma, prostate cancer, pancreatic cancer, osteosarcoma, myeloma, and non-small cell lung cancer. In summary, this detailed review provides a framework for further investigations that may appraise the autophagy-induced anticancer potential of MET and its repurposing for cancer treatment.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

A comprehensive immunobiology review of IBD: With a specific glance to Th22 lymphocytes development, biology, function, and role in IBD.

The two primary forms of inflammatory disorders of the small intestine andcolon that make up inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). While ulcerative colitis primarily affects the colon and the rectum, CD affects the small and large intestines, as well as the esophagus,mouth, anus, andstomach. Although the etiology of IBD is not completely clear, and there are many unknowns about it, the development, progression, and recurrence of IBD are significantly influenced by the activity of immune system cells, particularly lymphocytes, given that the disease is primarily caused by the immune system stimulation and activation against gastrointestinal (GI) tract components due to the inflammation caused by environmental factors such as viral or bacterial infections, etc. in genetically predisposed individuals. Maintaining homeostasis and the integrity of the mucosal barrier are critical in stopping the development of IBD. Specific immune system cells and the quantity of secretory mucus and microbiome are vital in maintaining this stability. Th22 cells are helper T lymphocyte subtypes that are particularly important for maintaining the integrity and equilibrium of the mucosal barrier. This review discusses the most recent research on these cells' biology, function, and evolution and their involvement in IBD.

Tumor-derived lncRNAs: Behind-the-scenes mediators that modulate the immune system and play a role in cancer pathogenesis.

Having been involved in complex cellular regulatory networks and cell-to-cell communications, non-coding RNAs (lncRNAs) have become functional carriers that transmit information between cells and tissues, modulate tumor microenvironments, encourage angiogenesis and invasion, and make tumor cells more resistant to drugs. Immune cells' exosomal lncRNAs may be introduced into tumor cells to influence the tumor's course and the treatment's effectiveness. Research has focused on determining if non-coding RNAs affect many target genes to mediate regulating recipient cells. The tumor microenvironment's immune and cancer cells are influenced by lncRNAs, which may impact a treatment's efficacy. The lncRNA-mediated interaction between cancer cells and immune cells invading the tumor microenvironment has been the subject of numerous recent studies. On the other hand, tumor-derived lncRNAs' control over the immune system has not gotten much attention and is still a relatively new area of study. Tumor-derived lncRNAs are recognized to contribute to tumor immunity, while the exact mechanism is unclear.

Role of genetically engineered mesenchymal stem cell exosomes and LncRNAs in respiratory diseases treatment.

The term acute respiratory disease encompasses a wide range of acute lung diseases, which in recent years have been ranked among the top three deadly diseases in the world. Since conventional treatment methods, including the use of anti-inflammatory drugs, have had no significant effect on the treatment process of these diseases, the attention of the medical community has been drawn to alternative methods. Mesenchymal stem cells (MSC) are multipotential stem/progenitor cells that have extensive immunomodulatory and anti-inflammatory properties and also play a critical role in the microenvironment of injured tissue. MSC secretomes (containing large extracellular vesicles, microvesicles, and exosomes) are a newly introduced option for cell-free therapies that can circumvent the hurdles of cell-based therapies while maintaining the therapeutic role of MSC themselves. The therapeutic capabilities of MSCs have been showed in many acute respiratory diseases, including chronic respiratory disease (CRD), novel coronavirus 2019 (COVID -19), and pneumonia. MSCs offer novel therapeutic approaches for chronic and acute lung diseases due to their anti-inflammatory and immunomodulatory properties. In this review, we summarize the current evidence on the efficacy and safety of MSC-derived products in preclinical models of lung diseases and highlight the biologically active compounds present in the MSC secretome and their mechanisms involved in anti-inflammatory activity and tissue regeneration.

Shedding Light on the Role of Exosomal PD-L1 (ExoPD-L1) in Cancer Progression: an Update.

Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.

Exploring the detailed role of interleukins in cancer: A comprehensive review of literature.

The cancer cells that are not normal can grow into tumors, invade surrounding tissues, and travel to other parts of the body via the lymphatic or circulatory systems. Interleukins, a vital class of signaling proteins, facilitate cell-to-cell contact within the immune system. A type of non-coding RNA known as lncRNAs mediates its actions by regulating miRNA-mRNA roles (Interleukins). Because of their dual function in controlling the growth of tumors and altering the immune system's response to cancer cells, interleukins have been extensively studied concerning cancer. Understanding the complex relationships between interleukins, the immune system, the tumor microenvironment, and the components of interleukin signaling pathways that impact the miRNA-mRNA axis, including lncRNAs, has advanced significantly in cancer research. Due to the significant and all-encompassing influence of interleukins on the immune system and the development and advancement of cancers, lncRNAs play a crucial role in cancer research by modulating interleukins. Their diverse effects on immune system regulation, tumor growth encouragement, and tumor inhibition make them appealing candidates for potential cancer treatments and diagnostics. A deeper understanding of the relationship between the biology of interleukin and lncRNAs will likely result in more effective immunotherapy strategies and individualized cancer treatments.

Therapeutic Potential of Microvesicles in Cell Therapy and Regenerative Medicine of Ocular Diseases With an Especial Focus on Mesenchymal Stem Cells-Derived Microvesicles.

These days, mesenchymal stem cells (MSCs), because of immunomodulatory and pro-angiogenic abilities, are known as inevitable factors in regenerative medicine and cell therapy in different diseases such as ocular disorder. Moreover, researchers have indicated that exosome possess an essential potential in the therapeutic application of ocular disease. MSC-derived exosome (MSC-DE) have been identified as efficient as MSCs for treatment of eye injuries due to their small size and rapid diffusion all over the eye. MSC-DEs easily transfer their ingredients such as miRNAs, proteins, and cytokines to the inner layer in the eye and increase the reconstruction of the injured area. Furthermore, MSC-DEs deliver their immunomodulatory cargos in inflamed sites and inhibit immune cell migration, resulting in improvement of autoimmune uveitis. Interestingly, therapeutic effects were shown only in animal models that received MSC-DE. In this review, we summarized the therapeutic potential of MSCs and MSC-DE in cell therapy and regenerative medicine of ocular diseases.

The Role of Janus Kinase/STAT3 Pathway in Hematologic Malignancies With an Emphasis on Epigenetics.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been known to be involved in cell growth, cellular differentiation processes development, immune cell survival, and hematopoietic system development. As an important member of the STAT family, STAT3 participates as a major regulator of cellular development and differentiation-associated genes. Prolonged and persistent STAT3 activation has been reported to be associated with tumor cell survival, proliferation, and invasion. Therefore, the JAK-STAT pathway can be a potential target for drug development to treat human cancers, e.g., hematological malignancies. Although STAT3 upregulation has been reported in hematopoietic cancers, protein-level STAT3 mutations have also been reported in invasive leukemias/lymphomas. The principal role of STAT3 in tumor cell growth clarifies the importance of approaches that downregulate this molecule. Epigenetic modifications are a major regulatory mechanism controlling the activity and function of STAT3. So far, several compounds have been developed to target epigenetic regulatory enzymes in blood malignancies. Here, we discuss the current knowledge about STAT3 abnormalities and carcinogenic functions in hematopoietic cancers, novel STAT3 inhibitors, the role of epigenetic mechanisms in STAT3 regulation, and targeted therapies, by focusing on STAT3-related epigenetic modifications.

A New Concept for the Treatment and Rehabilitation of Patients with Pathologic Comorbidities Using Cutting-Edge Digital Technologies in Dental Orthopaedics.

OBJECTIVES: This article investigates the specific aspects of overactive or exaggerated vomiting reflexes affecting the procedure of dental examination and impression in patients with complete secondary adentia, who need orthopaedic dental treatment. MATERIALS AND METHODS: The prevailing manifestation degree of exaggerated vomiting reflex was diagnosed among patients with complete secondary adentia and exaggerated vomiting reflex. STATISTICAL ANALYSIS: Exaggerated vomiting reflexes occur when a patient suffers from dentophobia, the term, which is otherwise known as the fear of dentists. The study was performed using methods of mathematical statistics, including the Pearson χ2 criterion and the statistical probability criterion (p). RESULTS: The role of an exaggerated vomiting reflex was revealed in the development of patients' dentophobic experiences, and the nature of such experiences was established. Variations in dentophobic reactions were distinguished and management strategies were studied for patients with complete secondary adentia and exaggerated vomiting reflex. CONCLUSIONS: These studies were aimed at preventing the development of vomiting reflex during dental procedures and at identifying an optimal strategy for stopping exaggerated vomiting reflex. The role of the vomiting reflex in the orthopaedic treatment of dental patients was determined.

Electronic APPS in assessing risk and monitoring of patients with arterial hypertension

The medical social significance of the arterial hypertension (AH) in the world is determined by its high prevalence, which allows to call it a non-infectious pandemic of today. The AH still remains the most common chronic disease that triggers the cardiovascular continuum, significantly reduces the body's adaptive capacity, worsens the living standards for people of socially minded age, and represents the leading global risk of increased cardiovascular mortality. The purpose of the study was comparison of informative value of various methods for measuring the arterial blood pressure (ABP) (office-based, home-based using electronic apps, and daily) in order to improve the risk assessment of the condition and monitoring the treatment efficiency for the AH patients. The method of qualitative and quantitative analysis of scientific literature and public online sources was used in the study. It has been established that the ABP analysis is an important tool to prevent the negative consequences of the AH. The results of the experimental study have revealed that hourly home-based ABP monitoring using a mobile electronic app is more informative than monitoring at long intervals, and provides information which is close to the average daily indicators obtained in the daily ABP monitoring.