Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy.

Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.

The Current and Promising Oral Delivery Methods for Protein- and Peptide-Based Drugs.

Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy.

PURPOSE: Neutropenia, defined as a number of neutrophils in patients' blood specimen lower than 1500 cells/µm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60-89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN. METHODS: The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. RESULTS: Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45-27.29; p < 0.01). CONCLUSIONS: Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN. Authors are advised to check the author instructions for the journal they are submitting to for word limits and if structural elements like subheadings, citations, or equations are permitted.

Adverse Renal Effects of Anticancer Immunotherapy: A Review.

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients' outcomes. However, stimulation of the immune system, beneficial in terms of fighting against cancer, generates the risk of harm to other cells in a patient's body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, superficially, are renal AEs in patients treated with ICIs. International guidelines issued by the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are fewer data concerning real occurrence and possible presentations of renal adverse drug reactions of other immunotherapeutic methods. This implies the need for the collection of safety data during ongoing clinical trials and in the real-life world to characterize the hazard related to the use of new immunotherapies and management of irAEs.