Current Pharmaceutical Design - Volume 28, Issue 38, 2022

The conventional treatment is faced with limitations in treating solid tumors due to their specific pathophysiology. Several novel therapeutics have been introduced in recent decades to treat solid tumors. Among these new methods, tumor therapy using bacterial products like bacteriocins and peptides has been of great interest due to their unique characteristics and advantages of them in comparison to the conventional treatment, including that they can precisely target tumor cells, selective toxicity for tumor cells, low side effect on normal cells, toxicity activity for MDR cancer cells, used as the target delivery vehicles and enhancing drug delivery. Moreover, their small size and low molecular weight have made them easy to synthesize and modify. Furthermore, in recent years, genetic engineering has expanded the therapeutic ability of peptides to treat solid tumors, which results in overcoming the peptide drawbacks. The present review mainly focuses on the new advances in applying bacterial peptides and bacteriocins in treating human solid tumors.

Breast cancer is the second leading cause of cancer-related deaths. It is important to target the complex pathways using a suitable targeted delivery system. Targeted delivery systems can effectively act on cancer cells and lead to the annihilation of tumor proliferation. They mainly employ targeting agents like aptamers linked to the formulation. Based on the expression of the receptors on the surface of the cancer cells, suitable aptamers can be developed. AS1411 is one such aptamer that has the ability to bind to the over-expressed nucleolin present in breast cancer cells. Nucleolin is a phosphoprotein that is involved in various aspects, like cell growth, differentiation and survival. Mostly they are found in the nucleolus, nucleus, cytoplasm and cell surface. The shuttling effect of the nucleolin between the nucleus and cytoplasm serves as a bonus for the AS1411 aptamer. Because of the shutting effect, the internalization of the drug compound or chemotherapeutic drug inside the cell can be achieved. In this article, we have discussed nucleolin, anti-nucleolin aptamer, namely, AS1411, and its application in exhibiting various anticancer activities, including apoptosis, anti-angiogenesis, anti-metastasis, stimulation of tumor suppressor (i.e., P53), and inhibition of tumor inducer. Further, the ways of internalization, namely macropinocytosis, are also discussed. Additionally, we have also discussed the superiority of the aptamer compared to the antibodies as well as the limitations of the aptamers. By considering all the above parameters, we hope this aptamer will be effective in the management and eradication of breast cancer cells.

Poor dietary habits such as overconsumption of hypercaloric diets characterized by a high content of fructose and fat are related to metabolic abnormalities development such as obesity, diabetes, and dyslipidemia. Accumulating evidence supports the hypothesis that if energy intake gradually exceeds the body's ability to store fat in adipose tissue, the prolonged metabolic imbalance of circulating lipids from endogenous and exogenous sources leads to ectopic fat distribution in the peripheral organs, especially in the heart, liver, and kidney. The kidney is easily affected by dyslipidemia, which induces lipid accumulation and reflects an imbalance between fatty acid supply and fatty acid utilization. This derives from tissue lipotoxicity, oxidative stress, fibrosis, and inflammation, resulting in structural and functional changes that lead to glomerular and tubule-interstitial damage. Some authors indicate that a lipid-lowering pharmacological approach combined with a substantial lifestyle change should be considered to treat chronic kidney disease (CKD). Also, the new therapeutic target identification and the development of new drugs targeting metabolic pathways involved with kidney lipotoxicity could constitute an additional alternative to combat the complex mechanisms involved in impaired kidney function. In this review article, we first provide the pathophysiological evidence regarding the impact of hypercaloric diets, such as high-fat diets and high-fructose diets, on the development of metabolic disorders associated with impaired renal function and the molecular mechanisms underlying tissue lipid deposition. In addition, we present the current progress regarding translational strategies to prevent and/or treat kidney injury related to the consumption of hypercaloric diets.

Cancer is one of the leading causes of death worldwide. Chemotherapy and radiation therapy are the major treatments used for the management of cancer. Multidrug resistance (MDR) is a major hindrance faced in the treatment of cancer and is also responsible for cancer relapse. To date, several studies have been carried out on strategies to overcome or reverse MDR in cancer. Unfortunately, the MDR reversing agents have been proven to have minimal clinical benefits, and eventually, no improvement has been made in therapeutic efficacy to date. Thus, several investigational studies have also focused on overcoming drug resistance rather than reversing the MDR. In this review, we focus primarily on nanoformulations regarded as a novel approach to overcome or bypass the MDR in cancer. The nanoformulation systems serve as an attractive strategy as these nanosized materials selectively get accumulated in tumor tissues, thereby improving the clinical outcomes of patients suffering from MDR cancer. In the current work, we present an overview of recent trends in the application of various nano-formulations, belonging to different mechanistic classes and functionalization like carbon nanotubes, carbon nanohorns, carbon nanospheres, liposomes, dendrimers, etc., to overcome MDR in cancer. A detailed overview of these techniques will help researchers in exploring the applicability of nanotechnologybased approaches to treat MDR.

Background: Ageing is characterized by a gradual decline in body function, representing the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria, and its serum level is lower in prefrail and frail subjects. Objective: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre-frail older patients. Methods: We scheduled 3 months of treatment and then 3 months of follow-up. A total of 92 subjects were selected from May, 2009 to July, 2017, in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo groups were used. Results: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p < 0.001 and an increase in serum-free carnitine and acetylcarnitine (p < 0.05) in Mini-Mental state (MMSE) p < 0.0001 and 6-walking distance (p < 0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and CRP (p < 0.01), an increase in MMSE score (p < 0.001) and in the 6-walking distance (p < 0.001). Conclusions: ALCAR treatment delays the incidence and severity of onset of degenerative disorders of the elderly in prefrail subjects with improvement in memory and cognitive processes.

Background: Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response. Objective: To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients. Methods: One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology. Results: Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis. Conclusion: Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.