Current Pharmaceutical Design - Volume 29, Issue 20, 2023

Obesity is considered as a chronic and high-prevalence disease on a global scale which affects all genders and ages. Although various drugs have been confirmed for the treatment of obesity, these medications have been shown to have a number of adverse effects on health. It is highlighted that natural products have an alleviative role in a broad spectrum of diseases, in particular obesity, and diabetes. Kaempferol (KMP), a plant- derived flavonol, is considerably engaged in the suppression of oxidative stress, radical scavenging, opposing cellular toxicity, and induction of the production and release of growth factors. This flavonol combats obesity by suppressing adipogenesis, regulating lipid and glucose metabolism, changing gut microbiota, and activating autophagy. Also, studies have shown that KMP exerts its anti-obesity actions by decreasing the accumulation of lipids and triglycerides (TGs), increasing fatty acid oxidation, and regulating multiple metabolic genes in the adipocytes. Considering that KMP may be a potential candidate for combating obesity, this paper summarizes the possible therapeutic roles of KMP in the treatment and prevention of this disease.

Cardiac resynchronization therapy (CRT) is the therapy of choice for patients with symptomatic systolic heart failure (HF) and left bundle branch block (LBBB), despite optimal medical therapy (OMT). The recently published 2021 European Society of Cardiology (ESC) Guidelines on cardiac pacing and cardiac resynchronization therapy highlight the importance of CRT on top of OMT in HF patients with left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm and typical LBBB with QRS duration ≥ 150 ms. In the presence of medically intractable or recurrent after catheter ablation atrial fibrillation (AF), AV nodal ablation as an adjuvant therapy becomes more relevant in patients qualifying for the implantation of a biventricular system. Furthermore, CRT may be considered in cases when increased pacing of the right ventricle is not desirable. However, alternative pacing sites and strategies are currently available, if the CRT is not feasible and effective in patients. However, strategies targeting “multi-sides” or using “multi-leads” have shown superiority over classic CRT. On the other hand, conduction system pacing seems to be a promising technique. Although early results are positive, consistency during the long term is pending. The indication for additional defibrillation therapy (ICD) may occasionally be unnecessary and has to be considered individually. Due to the great development and success of heart failure drug therapy, its positive effect on LV function can lead to enormous improvement. Physicians must await these effects and findings, which hopefully could lead to a relevant LV improvement resulting in a definitive decision against an ICD.

Peptides are of great importance in the areas of science because they can act as drug carriers and their therapeutic effect and their ability to generate an immune response. As culturing of viral agents for drugs and vaccine development is harmful, therefore, peptide-based drugs and vaccines have achieved great importance. Large immunoglobulins cannot pass the plasma membrane, so peptides are used to study this interaction because of their small size. Peptides with substituted amino acid sequences are also stable in blood serum, which makes them significant for drug development. Peptides with substituted amino acid sequences are stable in blood serum hence, their stability, small size, easy screening, cost-effectiveness, ease of administration and particularity (target specificity) make them effective to be used in pharmaceutical companies. Mostly branched peptides are used for the development of drugs because they are not prone to be degraded by proteolytic enzymes. In peptide-based vaccines, protein acts as the main constituent from which the main component that causes the infection is deleted by recombinant DNA technology, and these peptides act as antigens to stimulate the immune response. Self-assembled peptides have the main role in the delivery of drugs and vaccine molecules inside the living cells because they may also assemble into nano technological structures to improve their efficiency. This review focuses on the characteristics of peptides that make them effective to develop drugs and vaccines. Different peptides like synthetic peptides, antimicrobial peptides, signal peptides, carrier peptides, and their role against various viral, pathogenic, and microbial diseases and in cosmetics are described briefly.

Lactoferrin (LF) is a protein molecule with a wide variety of physiological properties. LF has broadspectrum antibacterial, antiviral, antioxidant, and antitumor, and possesses immunomodulatory properties to regulate immunity and gastrointestinal function. The main aim of this review is to explore the recent investigations on the functional role of LF against several human disorders and diseases through monotherapy or combinatorial regimens with other biological/chemotherapeutic agents through novel nanoformulations. We significantly searched public databases such as Pubmed, National Library of Medicine, relemed, Scopus and collected published reports pertaining to these recent reports on lactoferrin as a monotherapy or combination therapy, and its nanoformulations. We have discussed vividly the role of LF as a growth factor with substantial potential that can promote cell growth and regeneration potential for repairing tissues such as bone, skin, mucosa, and tendons. In addition, we have discussed novel perspectives on the role of LF as an inductive factor for the proliferation of stem cells in tissue recovery and discussed its novel modulating effects in ameliorating cancer and microbial growth through several signaling cascades via monotherapy or combinatorial regimens. Furthermore, the regeneration potential of this protein is reviewed to explore the efficacy and prospects of new treatment methods. This review benefits various microbiologists, stem cell therapists, and oncologists to explore the efficacy of LF in several segments of medicine by examining its ability as a stem cell differentiation factor, and anticancer agent or antimicrobial agent through novel formulations in preclinical or clinical study.

Heart failure is a major problem in developed countries, leading to a high number of hospitalizations and healthcare costs. The most common symptom of heart failure is congestion, which is also the primary reason for hospitalization. Diuretics, particularly loop diuretics, are the cornerstone of the treatment of congestion. Likewise, there are other types of diuretics with different pathways of action, bioavailability profiles, adverse reactions, and effects on the cardiovascular and renal systems. Moreover, in recent years, new therapeutic alternatives have been proposed for challenging cases of diuretic resistance, such as ultrafiltration through peripheral access or peritoneal dialysis. The main objective of this article is to provide a step-guided approach to the management of congestion in patients with heart failure in order to guide the medical practice. Despite the significant amount of research published in recent years, there are no clear algorithms for managing acute heart failure. Diuretics remain the primary treatment of acute heart failure, and nephron blockade is key, but new therapies are emerging, and ongoing research is needed to develop better strategies for managing this condition.

Despite significant advancements in CNS research, CNS illnesses are the most important and serious cause of mental disability worldwide. These facts show a tremendous unmet demand for effective CNS medications and pharmacotherapy since it accounts for more hospitalizations and extended care than practically all other disorders combined. The site-targeted kinetics of the brain and, pharmacodynamics of CNS effects are determined/regulated by various mechanisms after the dose, including blood-brain barrier (BBB) transport and many other processes. These processes are condition-dependent in terms of their rate and extent because they are dynamically controlled. For effective therapy, drugs should access the CNS “at the right place, time, and concentration”. Details on inter-species and inter-condition variances are required to translate target site pharmacokinetics and associated CNS effects between species and illness states, improving CNS therapeutics and drug development. The present review encircles a short discussion about the barriers that affect effective CNS treatment and precisely focuses on the pharmacokinetics aspects of efficient CNS therapeutics.

Wilms' tumor (WT) is the most common renal malignancy in children, accounting for more than 90% of all pediatric renal cancers. Although this tumor is generally responsive to treatment, relapses and deaths still occur in a significant proportion of patients. The genetic alterations commonly found in WT and also its unique histological features and the tumor microenvironment suggest that the immune system may play a crucial role in the disease's development and progression. The limitations of conventional therapies, including surgery, chemotherapy, and radiotherapy, in preventing recurrence in WT patients and their potential for exerting long-term side effects, necessitate the application of novel therapeutic strategies, like immunotherapy, in this disease. Immunotherapy is an emerging cancer treatment approach based on the concept of harnessing the patient's immune system to fight tumor cells. This approach has demonstrated promising results in various types of cancers due to its relatively high specificity, efficacy, and tolerability. However, the precise effects of immunotherapy in WT remain to be explored. For this purpose, this review highlights the potential implication of different immunotherapy approaches, like monoclonal antibodies, adoptive cell therapy, and immune checkpoint inhibitors, in patients with WT, with a particular emphasis on the tumor's genetic and histological features. Although much remains to be learned about the optimal use of immunotherapy for this disease, the available evidence suggests that immunotherapy has the potential to significantly improve outcomes for patients with WT. However, there is still a substantial need for conducting further studies, especially randomized controlled trials, to determine the most effective immunotherapy strategy for this tumor. Moreover, the potential beneficiary roles of the combination of immunotherapy and conventional treatments should be investigated in future research.