Current Pharmaceutical Design - Volume 28, Issue 40, 2022

The emergence of multidrug-resistant bacterial strains with respect to commercially available antimicrobial drugs has marked a watershed in treatment therapies to fight pathogens and has stimulated research on alternative remedies. Proteins of the innate immune system of mammals have been highlighted as potentially yielding possible treatment options for infections. Lactoferrin (Lf) is one of these proteins; interestingly, no resistance to it has been found. Lf is a conserved cationic nonheme glycoprotein that is abundant in milk and is also present in low quantities in mucosal secretions. Moreover, Lf is produced and secreted by the secondary granules of neutrophils at infection sites. Lf is a molecule of approximately 80 kDa that displays multiple functions, such as antimicrobial, anti-viral, anti-inflammatory, and anticancer actions. Lf can synergize with antibiotics, increasing its potency against bacteria. Lactoferricins (Lfcins) are peptides resulting from the N-terminal end of Lf by proteolytic cleavage with pepsin. They exhibit several anti-bacterial effects similar to those of the parental glycoprotein. Synthetic analog peptides exhibiting potent antimicrobial properties have been designed. The aim of this review is to update understanding of the structure and effects of Lf and Lfcins as anti-bacterial compounds, focusing on the mechanisms of action in bacteria and the use of Lf in treatment of infections in patients, including those studies where no significant differences were found. Lf could be an excellent option for prevention and treatment of bacterial diseases, mainly in combined therapies with antibiotics or other antimicrobials.

In this narrative review, firstly, we describe the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of its infection in humans. Later, the importance of mast cells in SARS-CoV-2 infection and their role in Coronavirus Disease 2019 (COVID-19) will be discussed. SARS-CoV-2 is a transmissible agent frequently detected in some mammalian species and also in humans. Literature data published in PubMed that covered mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease were reviewed by the authors independently and collectively. Recommendations for the management of cytokine release syndrome and related manifestations were made by the authors. Mast cells are concentrated in environments where they encounter viruses, bacteria, and toxins, especially in the skin, nasal mucosa, lungs, airways, gastrointestinal tract, and meninges, to prevent their entry into the human body. Once SARS-CoV-2 enters the host, it stimulates one of the mast cells, together with pre-existing innate immune cells that form a defensive barrier in the submucosa of the respiratory tract and nasal cavities against pathogenic microorganisms. The roles of mast cells in SARS-CoV-2-induced hyperinflammation and cytokine storms have recently been one of the hot topics in the literature. Physicians should keep in mind the mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease. Mast cell-targeting therapies (e.g., H1 and H2 receptor antagonists) can reduce the severity and course of the disease when used after complications associated with COVID-19 are suspected or seen.

Hypothesis: This review article represents a brief layout of the risk factors and pathophysiology responsible for obesity, customary treatment strategies, and nanotechnology-based nutraceutical for the therapeutics of obesity. Experiments: An exhaustive search of the literature was done for this purpose, using Google Scholar, PubMed, and ScienceDirect databases. A literature study was conducted using publications published in peer-reviewed journals between 2000 and 2022. Findings: This was revealed that risk factors responsible for obesity were genetic abnormalities and environmental and socio-economic factors. Several research articles published between 2000 and 2022 were based on phytoconstituents-based nanoformulation for obesity therapeutics and, therefore, have been systematically compiled in this review. Various nutraceuticals like Garcinia cambogia, quercetin, resveratrol, capsaicin, Capsicum, Curcuma longa, Camella Sinensis, Zingiber officinalis, Citrus aurantium, Aegle marmelos, Coffea canephora, Asparagus officinalis, Gardenia jasminoides, Catha edulis, Clusia nemroisa, Rosmarinus officinalis, Cirsium setidens, Betula platyphylla, Tripterygium wilfordi possessing anti-obesity actions are discussed in this review along with their patents, clinical trials as well as their nanoformulation available. Conclusion: This review illustrates that nanotechnology has a great propensity to impart a promising role in delivering phytochemicals and nutraceuticals in managing obesity conditions and other related disorders.

Background: Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients. Methods: We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis. Results: Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events’ rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group. Conclusion: Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.

Background: Transcatheter closure of patent foramen ovale (PFO) is a highly effective therapy for patients with left circulation thromboembolism, not attributable to other conditions. Objectives: This retrospective cohort study investigates the impact of baseline foramen ovale anatomy on the severity of the postclosure shunt. Methods: Patients with PFO, who underwent percutaneous closure, were followed up for at least 5 years postimplantation. Patients were classified into two groups based on the presence of high-risk features of the baseline PFO anatomy. At the follow-up follow-up, residual right-to-left shunt was assessed for the high and non-highrisk anatomy groups, via transcranial Doppler at rest and after performing the Valsalva maneuver, with the injection of agitated saline. Results: 38 patients were examined after a mean follow-up period of 9 ± 3 years after implantation. After retrospective evaluation of the baseline transthoracic and transesophageal echo studies, 14 patients with high-risk PFO anatomy were identified. The degree of the residual right-to-left shunt, as assessed by the number of microbubbles was higher in the high-risk PFO anatomy group compared to the non-high-risk group, both at rest [1.50 (IQR: 0.00-3.25) vs. 0.00 (IQR: 0.00-0.00), p < 0.001] and post-Valsalva maneuver [7.50 (IQR: 1.50- 10.25) vs. 0.00 (IQR: 0.00-3.75), p = 0.003]. Furthermore, in the high-risk group, more microbubbles were detected at rest (p = 0.008) and post-Valsalva (p = 0.002) in subjects without antiplatelet treatment compared to subjects on prolonged antiplatelet therapy. Conclusion: Baseline PFO anatomy affects the severity of the residual right-to-left shunt. Prolonged antiplatelet therapy may benefit patients with high-risk anatomical features.

Background: Cholestatic liver damage is a chronic disease caused by dysfunction of the hepaticbiliary system. Oxidative stress and inflammation are essential factors in the pathogenesis of cholestasis. Thus, the current study was designed to examine the effect of empagliflozin on bile duct ligation-induced liver damage in rats. Methods: This study was done on male Wistar rats, which were randomly assigned to the four experimental groups: sham control (SC), bile duct ligation (BDL), SC plus empagliflozin (SC+EMPA) (receiving 10 mg of EMPA orally for 7 days), BDL plus empagliflozin 10 mg/kg (BDL+ EMPA). At the end of the study, the rats were sacrificed, and serum and tissue samples were collected to analyze biochemical parameters, biomarkers of oxidative stress, inflammatory markers, and histopathological changes. The molecular docking technique was performed to elucidate the interaction of EMPA and Cu/Zn-superoxide dismutase (SOD1). Results: The results showed that BDL elevated the serum activity of ALT, AST, ALP, and levels of TBIL and TPro. BDL also intensifies the oxidative stress state in rats, which was confirmed by augmenting lipid peroxidation (MDA), protein oxidation (PCO), and altering antioxidant defense parameters through decreased SOD, catalase (CAT), and glutathione peroxidase (GPX) levels. Furthermore, the histopathological changes in the liver demonstrated the aggravation of inflammation and oxidative stress. In contrast, treatment with EMPA has shown anti-inflammatory and anti-oxidant effects by reducing TNF-α and IL-6 pro-inflammatory marker proteins, restoring the antioxidant status (increased SOD and GPX), reducing ALT, AST, ALP, TBIL levels, and protein oxidation, and improving the histopathological alterations through reducing bile duct proliferation, fibrosis, focal and portal inflammation. According to the attained findings, the SOD1 activity can be regulated by the EMPA. Our documentation presents direct evidence at the molecular level related to the ability of EMPA to exert its antioxidant performance through certain measures in a particular molecular route. Conclusion: The results showed EMPA to have hepatic protective effects in rats against cholestatic liver injury, an effect mediated by its antioxidant and anti-inflammatory properties.