Current Pharmaceutical Design - Volume 27, Issue 21, 2021

Gastric cancer is the second most common cause of cancer-related deaths in the world. The surgical management of the tumor is the best therapeutic option for gastric cancer patients. A combination of a heterogeneous distribution of genetic and environmental factors appears to be required to explain patients' poor prognosis. A search for targeted and molecular-based approaches is affected by the optimal gastric cancer drug management. The modern multidisciplinary approach to treating the pathology used worldwide prolongs the overall patient survival and decreases the rate of recurrence. An understanding of the mechanisms that underlie therapies will provide new insights into gastric cancer treatment. The improvement in medicine will probably be associated with a study of tumor biology, followed by a personalized and molecular-based approach development in anticancer drugs administration. The modern perspective in gastric cancer detection and treatment is the application of nanoparticles. Nanoparticles affecting the intensity of biological processes in cancer cells can be used to treat cancers to increase the effectiveness of anti-tumor therapy. Their cytotoxicity involves a wide range of pathological events. Their targets are the extracellular matrix degradation, epithelial-mesenchymal transition, tumor angiogenesis, tumor microenvironment modulation. These are accompanied by lipid peroxidation, apoptosis, and autophagic flux. Preliminary studies on the efficacy of the use of nanoparticles in cultured gastric cancers open new opportunities for anti-tumor treatment to overcome the toxicity of therapeutic agents and decrease the rate of resistance to anticancer drugs and therapies.

Low aqueous solubility and poor bioavailability are the major hurdles during drug development for the oral route. A large number of the newly discovered drug molecules fall under the BCS II class and have solubility related issues and hence pose low oral bioavailability, which, in turn, render them non-suitable candidates for further development. A multitude of solubility enhancement approaches are available. Notable among them are salt formation, solid dispersions, inclusion complexes, cocrystallization, nanonization, etc. Cocrystallization and nanonization are among the most widely used approaches in the pharmaceutical field that offer multiple enhancements to the active pharmaceutical ingredients. This review endeavours to cover the recent work, important findings, advantages offered by nano-sized cocrystals, future aspects and challenges in the implementation of this newer approach in pharmaceutical research and development.

Carbon Nanotubes (CNT) are the allotropes of carbon in nanosize dimension and are popular in medicinal field. These nano-based technologies are gaining high interest in the recent years for the treatment of diseases that are previously considered to be impossible to cure. CNTs have gained significance in the treatment of the majority of disorders such as Malaria, Alzheimer’s disease, Infectious disease, and Asthma. Moreover, patient’s responsiveness also increased in cardiovascular and pulmonary diseases. To date, a number of reviews are available in the literature covering applications of CNT in cancer. However, the purpose of this review is to focus on the use of CNTs in drug delivery of non-cancerous diseases. The novelty of this review is that it is focused on the applicability of CNT in the various non-cancerous diseases. Detailed information was collected from the literature which will guide and encourage researchers to explore the applicability of CNT in various non-cancerous diseases in the future.

Rheumatoid arthritis (RA) is the most commonly occurring, progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti-rheumatic drugs and herbal drugs in passive and receptor-mediated active targeting against RA. On reviewing the conventional and current therapeutics against RA, we conclude that although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

This review article mainly focuses on the revolution of the synthesis of gold nanoplatform from the previous era to the present era. Initially, the gold nanoplatform was widely used by the electrical and electronic industries for their products due to its remarkable properties, such as large surface volume, redox activity, fluorescence quenching, and optical-electronic properties. In this era, due to the invention of localised surface plasmonic resonance, optoacoustic, photothermal and theragnostic characteristics of the gold nanoplatforms and their application in biosensors and various diagnostic methods, the pharmaceutical and biotechnological companies have started showing their interest in manufacturing gold nanoplatforms for their new product development. This colloidal dispersion is synthesized in various forms, such as a gold nanoparticle, gold nanoplatform, plasmonic gold nanoparticle, amphiphilic gold nanoparticle, and gold nanocrystal. This review article describes various methods for preparation of gold nanoplatforms with different size, shape, and physiobiological properties and their applications in different fields.

Background/Objective: Carbon nanoparticles (CNs) are a novel injected suspension used during thyroidectomy in order to black stain the thyroid gland and the lymph nodes while maintaining the anatomic color of the parathyroid glands and the laryngeal nerves. The aim of this systematic review is to investigate the benefits of carbon nanoparticles in thyroid surgical procedures and examine their role in lymph node tracing, parathyroid preservation, and recurrent laryngeal nerve protection. Methods: A systematic review of the literature in the PubMed/Medline database was performed. Articles reporting randomized clinical trials, prospective, and retrospective studies that compared the use of carbon nanoparticles in one group of patients with a control-blank group were included. The article was reported in accordance with PRISMA guidelines (CRD42021243015). Results: The search strategy retrieved 22 studies of the literature. Fourteen studies calculated a greater number of lymph nodes detected/dissected in the central neck zone to the patients using CN solution and 1 article noted a higher rate of lymph nodes resected in the lateral neck zone in the same group of patients. A significant increase in the number of metastatic lymph nodes retrieved in the CN group was found in 7 studies. Twenty-one studies suggested that the use of CNs for the protection of the parathyroid glands was beneficial. Transient hypoparathyroidism and transient hypocalcemia were presented with a significantly lower incidence in the CN group in 13 and in 8 studies, respectively. Conclusion: Carbon nanoparticles may improve both central and lateral neck dissection and enhance parathyroid gland identification and preservation.

Obesity is associated with an exacerbated synthesis and secretion of several molecules, which culminates in chronic low-grade inflammation and insulin resistance. Such conditions affect molecular and physiological responses of several organs and, if not resolved, predispose the obese patients to other diseases such as Type 2 diabetes, atherosclerosis, cancer, neural injuries, and cognitive impairments. A microenvironment with an excess of pro-inflammatory cytokines released by different cells, including immune and adipose cells lead to metabolic and non-metabolic diseases during obesity. In this context, the role of neuronal guidance cues named netrin, semaphorin and ephrin is novel. Specifically, the available literature indicates that besides their classic role as molecules that guide the axon to its target site, the neuronal guidance cues exhibit immunomodulatory functions from adipose tissue to the neural environment. In the current narrative review, we discuss the participation of the neuronal guidance cues on the physiology and pathophysiology of obesity. We also discuss the feedback loop of obesity on the netrin, semaphorin and ephrin functions that impair the structure and function of the brain. The integrative view of the neuronal guidance cues can be relevant in designing new treatments focus on attenuating metabolic and immune disorders in obese patients and reduce the risk of acquiring diseases such as Type 2 diabetes, atherosclerosis, cancer, and neural injuries.

Coronavirus disease 2019 (SARS-CoV-2) (COVID-19) has recently raised worldwide public health concerns. The available data on COVID-19 in patients with diabetes is limited but generally indicate that there is an increased risk of developing COVID-19 infection in diabetic patients, which ultimately impacts the overall patient’s survival. Various aspects might be involved; however, the exact mechanisms and interrelationships between diabetes and the novel COVID-19 have not yet been fully elucidated. This review summarizes the possible mechanisms by which present diabetes predispose individuals to COVID-19 infection, modulates the hostviral interactions and increases the risk of mortality. We hope this review can provide beneficial information for further studies and contribute to improved disease management of diabetic patients with COVID-19.

Background: Epigenetic regulation concerning histone lysine methylation and demethylation play a crucial role in cerebral ischemic injury. Dysregulation of histone methylation modifiers has been identified in cerebral ischemia. However, the function and the underlying mechanisms of histone demethylase KDM4A on neuroinflammation and functional recovery in ischemic stroke remains unclear. Methods: In the present study, the rat model of transient middle cerebral artery occlusion (MCAO) was established, and the expression level of KDM4A was assessed in brain tissues. KDM4A inhibition was carried out by intrathecal injection with Lv-shKDM4A, and then pro-inflammatory cytokines and neurological functional tests were assessed. Results: We demonstrated that rats subjected to MCAO showed a markedly increased expression of KDM4A, pro-inflammatory cytokines IL-1β and TNF-α, and vascular endothelial growth factor (VEGF), whereas KDM4A inhibition repressed the expression of IL-1β, TNF-α and VEGF both in MCAO and oxygen-glucose deprivation (OGD) models. Furthermore, KDM4A inhibition showed a marked improvement in spatial learning and sensorimotor function, as suggested by mNSS and foot-fault test, respectively. Mechanistically, KDM4A inhibition repressed NF-ΚB signaling activation in microglia as indicated by decreased expression and nuclear translocation of p65 in vitro and in vivo. The effects of KDM4A overexpression on exacerbating neuroinflammation was inhibited by additional treatment of NF-ΚB inhibitor (JSH-23). Conclusion: The current results demonstrated KDM4A inhibition improves functional recovery in ischemic stroke by repressing NF-ΚB activation and subsequent neuroinflammation.

Aims: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. Materials & Methods: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Results: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. Conclusion: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.