Current Pharmaceutical Design - Volume 25, Issue 38, 2019

Platelets are typically recognized for their roles in the maintenance of hemostasis and vascular wall repair to reduce blood loss. Beyond hemostasis, platelets also play a critical role in pathophysiological conditions like atherosclerosis, stroke, thrombosis, and infections. During infection, platelets interact directly and indirectly with bacteria through a wide range of cellular and molecular mechanisms. Platelet surface receptors such as GPIbα, FcγRIIA, GPIIbIIIa, and TLRs, etc. facilitate direct interaction with bacterial cells. Besides, the indirect interaction between platelet and bacteria involves host plasma proteins such as von Willebrand Factor (vWF), fibronectin, IgG, and fibrinogen. Bacterial cells induce platelet activation, aggregation, and thrombus formation in the microvasculature. The activated platelets induce the Neutrophil Extracellular Traps (NETs) formation, which further contribute to thrombosis. Thus, platelets are extensively anticipated as vital immune modulator cells during infection, which may further lead to cardiovascular complications. In this review, we cover the interaction mechanisms between platelets and bacteria that may lead to the development of thrombotic disorders. Platelet receptors and other host molecules involved in such interactions can be used to develop new therapeutic strategies to combat against infection-induced cardiovascular complications. In addition, we highlight other receptor and enzyme targets that may further reduce infection-induced platelet activation and various pathological conditions.

Fish oil is an abundant source of omega-3 (n-3 or ω-3) polyunsaturated fatty acids (PUFAs) and contains Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). PUFAs are very effective in preventing/ inhibiting cardiovascular incidents, particularly in individuals with high cardiovascular risk/accidents. In this review, composition, extraction of fish oil and its favorable/beneficial effects in Cardiovascular Diseases (CVDs) and molecular mechanism for its treatment/reduction have been discussed. Moreover, the application of fish oil for preventive/protective and remedial/curative properties in nutritive and health benefits has been summarized. All these aspects further search the opportunities/hope and scope with its expected opening and anticipations/ possibilities to provide additional therapeutic substitutes for the reduction of CVDs and registration of new drugs.

Cardiovascular diseases (CVDs) are the leading cause of premature death and disability in humans and their incidence is on the rise globally. Given their substantial contribution towards the escalating costs of health care, CVDs also generate a high socio-economic burden in the general population. The underlying pathogenesis and progression associated with nearly all CVDs are predominantly of atherosclerotic origin that leads to the development of coronary artery disease, cerebrovascular disease, venous thromboembolism and, peripheral vascular disease, subsequently causing myocardial infarction, cardiac arrhythmias or stroke. The aetiological risk factors leading to the onset of CVDs are well recognized and include hyperlipidaemia, hypertension, diabetes, obesity, smoking and, lack of physical activity. They collectively represent more than 90% of the CVD risks in all epidemiological studies. Despite high fatality rate of CVDs, the identification and careful prevention of the underlying risk factors can significantly reduce the global epidemic of CVDs. Beside making favorable lifestyle modifications, primary regimes for the prevention and treatment of CVDs include lipid-lowering drugs, antihypertensives, antiplatelet and anticoagulation therapies. Despite their effectiveness, significant gaps in the treatment of CVDs remain. In this review, we discuss the epidemiology and pathology of the major CVDs that are prevalent globally. We also determine the contribution of well-recognized risk factors towards the development of CVDs and the prevention strategies. In the end, therapies for the control and treatment of CVDs are discussed.

Background: Colorectal cancer (CRC) is one of the most common types of cancer and is associated with an increasing rate of mortality. Transforming Growth Factor-Beta (TGF-β) is often upregulated in CRC, and appears to play an important role in regulating cell proliferation, migration, immune surveillance, apoptosis, cell differentiation, drug-resistance and many cellular processes that may be involved in CRC, and therefore underscores its potential value as a therapeutic target in the treatment of CRC. An increased expression of the TGF- β pathway has been associated with poor prognosis in several cancer types, including CRC. Methods: Here, we describe the critical role of the TGF-β pathway in CRC as well as the preclinical and clinical investigations on TGF-β inhibitors, with particular emphasis on recent findings with small-molecule inhibitors in CRC. Several TGF-β inhibitors (e.g., Trabedersen, Galunisertib, Gradalis, PF-03446962, NIS793) have been generated over the past decade for targeting this pathway. Results: There is accumulating evidence of the therapeutic potential of this and other TGF-β inhibitors for the treatment of other malignancies. These inhibitors might be used in combination with chemotherapy as well as with other biological agents, in order to overcome different resistance mechanisms. However, further studies are needed to identify determinants of the activity of TGF-β inhibitors, through the analysis of genetic and environmental alterations affecting TGF-β and parallel pro-cancer pathways. Conclusion: These studies will be critical to improving the efficacy and selectivity of current and future anticancer strategies targeting TGF-β.

Any kind of injury may lead to wound formation. As per World Health Organization Report, “more than 5 million people die each year due to injuries. This accounts for 9% of the world’s population death, nearly 1.7 times the number of fatalities that result from HIV/AIDS, tuberculosis and malaria combined. In addition, ten million people suffer from non-fatal injuries which require treatment”. This scenario leads to increased health and economic burden worldwide. Rapid wound healing is exigent subject-field in the health care system. It is imperative to be updated on wound care strategies as impaired wound healing may lead to chronic, non-healing wounds and thus further contributes to the national burden. This article is a comprehensive review of wound care strategies. The first and second part of this review article focuses on the understanding of wound, its types and human body’s healing mechanism. Wound healing is natural, highly coordinated process that starts on its own, immediately after the injury. However, individual health condition influences the healing process. Discussion of factors affecting wound healing has also been included. Next part includes the detailed review of diverse wound healing strategies that have already been developed for different types of wound. A detailed description of various polymers that may be used has been discussed. Amongst drug delivery systems, oligomers, dendrimers, films, gels, different nano-formulations, like nanocomposites, nanofibers, nanoemulsions and nanoparticles are discussed. Emphasis on bandages has been made in this article.

Background: Biological sensors revolutionize the method of diagnoses of diseases from early to final stages using the biomarkers present in the body. Biosensors are advantageous due to the involvement of minimal sample collection with improved specificity and sensitivity for the detection of biomarkers. Methods: Conventional biopsies restrict problems like patient non-compliance, cross-infection and high cost and to overcome these issues biological samples like saliva, sweat, urine, tears and sputum progress into clinical and diagnostic research for the development of non-invasive biosensors. This article covers various non-invasive measurements of biological samples, optical-based, mass-based, wearable and smartphone-based biosensors for the detection of cancer. Results: The demand for non-invasive, rapid and economic analysis techniques escalated due to the modernization of the introduction of self-diagnostics and miniature forms of devices. Biosensors have high sensitivity and specificity for whole cells, microorganisms, enzymes, antibodies, and genetic materials. Conclusion: Biosensors provide a reliable early diagnosis of cancer, which results in faster therapeutic outcomes with in-depth fundamental understanding of the disease progression.

Background: Skin and soft tissue infections involve microbial invasion of the skin and underlying soft tissues. To overcome this problem, nanocomposites were obtained using gelatin as a biopolymer scaffold and silver nanoparticles as a wide spectrum antimicrobial agent. Water and glycerol have been used as solvents for the gelatin hydrogel synthesis. This mixture led to a stable and homogeneous biomaterial with improved mechanical properties. Methods: Silver nanoparticles were characterized using SEM, EDS and TEM. Moreover, the AgNp/gelatin nanocomposite obtained using these nanoparticles was characterized using SEM and FTIR. Moreover, mechanical and swelling properties were studied. Results: The storage modulus was 3000 Pa for gelatin hydrogels and reached 5800 Pa for AgNp/gelatin nanocomposite. Silver nanoparticles have been studied as an alternative to antibiotics. Importantly, the rate of silver release was modulated as a function of the temperature of the nanocomposite. Thus, the silver release from the nanocomposites at 24 °C and 38 °C was analyzed by atomic absorption spectroscopy. The silver release reached 25% after 24 h at 24 °C, while a 75% release was achieved at 38°C in the same period, showing the material thermoresponsive behavior. AgNp/gelatin nanocomposite showed a deleterious effect over 99.99% of Pseudomonas aeruginosa and Staphylococcus aureus, leading to a material with antimicrobial properties. Conclusion: AgNp/gelatin nanocomposite with improved mechanical properties and silver nanoparticles as a source of silver ions has been synthesized. The properties of the nanocomposite with controlled silver delivery result in a more efficient topical pharmaceutical form for wound healing applications.