Current Pharmaceutical Design - Volume 27, Issue 44, 2021

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis, and cardiovascular disease (CVD), which significantly deteriorate patients’ quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process, including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoid agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.

Background: It is known that vitamin D can increase the body’s immunity against some viral infections. Many people worldwide have vitamin D deficiency; therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D in immunity and recovery from viral infections, especially novel Coronavirus disease (COVID- 19), are reviewed. Methods: The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE), and Medical and Health Education (Medrix) were searched. Results: Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can increase cellular immunity, reduce cytokine storm, and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect. Conclusion: Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection.

Background: Human respiratory syncytial virus (RSV) has been shown to be linked with various forms of respiratory diseases, such as common cold and lower respiratory tract illnesses like pneumonia and bronchiolitis. TLRs play critical role in generating host immune response against RSV. TLRs are expressed not only on leukocytes but also on many other cell types and can recognize RSV. Previous studies have established that RSV can interact with TLR4 and initiate inflammatory cascade of cytokines. The data from a recent study indicated that TLR2/TLR6 is involved in RSV recognition and subsequent innate immune activation. However, the nature of binding and the envelope protein of RSV involved in this interaction with TLRs are not studied yet. Objective: We hypothesized that RSV G protein can bind to TLRs and mediate the inflammatory immune response against the virus infection. Therefore, we investigated whether RSV G protein could activate innate immune response through TLR signaling. Methods: Different TLR antagonists were used to assess the effect of the exposure of RSV and RSV G ectodomain in human primary small airway epithelial cells (HSAECs). Various inflammatory cytokines, chemokines and type I IFNs were measured by ELISA along with their mRNA expression by qPCR. In silico interaction of RSV G protein with TLR2/TLR6 was also analyzed. Results: Results of ELISA and qPCR analysis have shown that TLR2/TLR6 signaling is activated in HSAECs upon RSV and RSV G protein exposure which initiates innate immune response against RSV. Moreover, RSV envelope protein G plays a crucial role in binding and activation of TLR2/TLR6 signaling. Conclusion: In summary, our study shows that TLR2/TLR6 play important role in the activation of innate immune response upon RSV recognition which could be helpful in promoting RSV clearance and preventing RSV-induced disease.

The issue of poor aqueous solubility is a major hurdle in pharmaceutical dosage form design. A large number of active molecules in the research and development pipeline possess poor aqueous solubility and, hence, are not suitable for further development. Therefore, the pharmaceutical industry is continuously in search of techniques to tackle the issue of poor solubility. Cocrystallization has gained popularity as one such technique for the modulation of physicochemical properties of an active pharmaceutical ingredient (API). Pharmaceutical cocrystals consist of an API non-covalently linked to a crystal former or coformer that plays an important role in imparting the desired properties to the cocrystal. Cocrystallization of an API with a suitable coformer not only enhances solubility but also helps in improving physicochemical properties such as stability, bioavailability, mechanical properties, etc., without changing the pharmacological activity of the API. The past decade has experienced enormous growth in cocrystal research which paved the way for drug-drug, higherorder, and nano-sized cocrystals, and further exploration of the applications of cocrystals is still going on. Recently FDA and EMA have released regulatory guidelines for pharmaceutical cocrystals, which grant them a status similar to that of polymorphs and salts, which in turn opens a wider prospect for pharmaceutical cocrystals in terms of intellectual property.

Background: Spinal surgeries are often accompanied by significant blood loss both intraoperatively and postoperatively. Excessive blood loss caused by surgery may lead to several unsatisfactory medical consequences. Tranexamic acid (TXA) is a kind of antifibrinolytic agent that has been widely used in spinal surgery. Currently, it is widely accepted that intravenous TXA (ivTXA) can clearly reduce blood loss in spinal fusion surgeries. Compared with ivTXA, topical TXA (tTXA) seems to be much easier to administer, and this advantage provides a maximum concentration of TXA at the haemorrhagic site with little to no TXA entering the circulation. Objective: To evaluate the effect of tTXA on blood loss during and after spinal surgery via a comprehensive metaanalysis of the published data in randomized controlled trials (RCTs) and other comparative cohort studies. Methods: A comprehensive search of PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for RCTs and other comparative cohort studies on the effect of tTXA on blood loss during and after spinal surgery. The outcomes were total blood loss, hidden blood loss, intraoperative blood loss, total postoperative drainage volume, drainage tube duration postoperatively, drainage volume and drainage of blood content at postoperative day (POD) 1 and POD2, length of hospital stay, number of patients who received a blood transfusion, serum HB level at POD1, operative timespan, side effects and complications. The final search was performed in October, 2020. We followed the PRISMA guideline, and the registration number is INPLASY202160028. Results: In total, 6 studies with 481 patients were included. tTXA treatment, compared with the control conditions, can significantly reduce the total blood loss, hidden blood loss, total postoperative drainage volume, and number of patients receiving blood transfusions; reduce the drainage volume and drainage of blood content at POD1; shorten the drainage tube duration postoperatively and length of hospital stay; and enhance the serum HB level at POD1 for spinal surgery. tTXA treatment did not significantly influence the intraoperative blood loss, drainage volume or drainage of blood content at POD2 or the operative duration. Conclusion: Compared with control conditions, tTXA has high efficacy in reducing blood loss and drainage volume, enables quick rehabilitation, and has a relatively high level of safety in spinal surgery.

Background: Myocardial fibrosis after myocardial infarction (MI) has been considered a core factor in the deterioration of cardiac function. Previous studies have shown that miRNA plays an important role in various pathophysiological processes of the heart. However, the role of miRNA in myocardial fibrosis regulation after MI remains unclear. In the present study, we documented that miR-218-5p was significantly decreased in myocardial fibroblasts after MI. Methods: The miRNA expression profiles of MI were downloaded from GEO Datasets. The expression of a fibrosis-related gene in vivo and in vitro was analyzed by RT-PCR, western blotting, and immunohistochemical staining. Results: Total 7 up- and 9 downregulated common miRNAs were found in the two profiles. Among these common genes, miR-218-5p was downregulated in the MI mice. MiR-218-5p mediated the myocardial fibrosis in vivo and in vitro. Mechanistically, we found that GJA1 (CX43) may be the target of miR218-5p, and overexpressed CX43 can partly block the function of miR-218-5p in fibrosis inhibition. Conclusion: Our results suggested that miR-218-5p plays an important role in myocardial fibrosis after MI by targeting CX43. Thus, miR-218-5p promises to be a potential diagnosis and treatment of myocardial fibrosis after MI.