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Wound healing is an essential biological process which involves tissue repair and recovery and includes the action of a complex system of blood cells, cytokines, and growth factors. It is a process attended by integrated cellular and biochemical events and characterized by four phases: haemostasis, inflammation, proliferation, and remodelling. Medicinal plants which have healing applications, continue to play a central role in the healthcare system of a large proportion of the world's population. Numerous studies have shown that several Australian plant species used medicinally, contain biologically active extracts and compounds which have enormous potential for the treatment and management of a wound. Medicinal plants contain a wide range of chemical compounds as the unique flora of Australia offers an array of diverse bioactives, which elicit antibacterial, antioxidant, anti-inflammatory and wound healing abilities. Such properties are not limited to the edible sections of plants as the roots, bark, sap, leaves and seeds from a vast array of plants have demonstrated similar effects. In this review article, various Australian native plants which are scientifically proven to have antibacterial and anti-inflammatory properties that support wound healing, are discussed. This review also briefly discusses the general wound healing process, wound-colonizing bacteria, factors that affect wound healing, and costs involved in the treatment and management of chronic wounds. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the greatest challenges facing the world today. In the United States alone, it is responsible for the death of more than 20,000 people each year. DNA gyrase, a well-validated drug target, is involved in bacterial DNA replication, repair and decatenation. Currently, the fluoroquinolone class of antibacterials act via inhibition of the DNA gyrase enzyme. However, their efficacy is hindered by the increasing incidence of antimicrobial resistance. Therefore, in this review, we provide an account regarding the structure of DNA gyrase and quinoline and non-quinolone inhibitors published within the last five years (2015–2019). Further, we also discuss molecular interactions and structure-activity relationship studies of the published inhibitors. Image 1 • A brief overview of the DNA gyrase structure is provided. • Mechanism of interaction of DNA gyrase in DNA supercoiling has been discussed. • DNA gyrase inhibitors reported in the last five years are reviewed. • DNA gyrase inhibitors under clinical development are provided. [ABSTRACT FROM AUTHOR]

• Erigeron bonariensis (EB) or Conyza bonariensis is an endangered species of South Africa. • EB contains quercetin, naringenin, stigmasterol, apigenin, baicalein, rutin, luteolin and caffeic acid. • An RP- HPLC method was developed to identify and estimate quercetin in EB extract. • The method was validated as per ICHQ2 R1 guidelines. • Developed RP-HPLC method was found linear, accurate, precise and reproducible. Erigeron bonariensis Linn (EB) is a species of Erigeron , belonging to Asteraceae. It found throughout the tropics and subtropics as a pioneer plant ; its precise origin is unknown, but most likely it stems from Central America or South America. It has become naturalized in many other regions, including North America , Europe and Australia. In South Africa, this plant is well known as Conyza bonariensis and listed under "Red List of South African Plants". Its extract contains many bioactives such as quercetin, naringenin, stigmasterol, apigenin, baicalein, rutin, luteolin and caffeic acid. These have good therapeutic potential. Among them, quercetin (QUE) is widely found in EB's extract. In this current research, QUE was successfully detected in EB extract utilising a gradient reverse phase high performance liquid chromatography (RP- HPLC) method. The method was developed and validated using a C18 column (250 mm length x 4.5 mm internal diameter). The mobile phase used was methanol and water. A flow rate of 1 mL/min was used during the elution. Initially the water-to-methanol ratio at 75:25 v/v (water: methanol) for 3 min, then at 50:50 v/v (water: methanol) for 3–7 min, then at 50:50 v/v (water: methanol) for 10–15 min, and lastly at 10:90 v/v (water: methanol) for 20 min, to achieve the best elution. The developed analytical technique was validated in terms of linearity, LOD, LOQ, recovery, precision, and specificity using ICH Q2 R1 guidelines. The amount of QUE in EB was determined and reported by us for the first time. The extraction was carried out using 970 g of whole plant powder, was macerated in 4 L of hydroethanol (50: 50 v/v) and was concentrated under vacuum. The percentage yield was found to be 5.5% w/w (2.75 g/55 g of EB extract) and HPLC method was developed using sample concentration of 60 mg/100 mL (600 µg/mL) in methanol and retention time (RT) of the standard and QUE in extract was found to be 15.3 and 15.7 min, respectively. The linearity, correlation coefficient, limit of detection (LOD), limit of quantification (LOQ), and RSD were found to be 200–1000 µg/mL, 0.9991, 35.66 µg/mL, 108.18 µg/mL, and smaller than 1 % respectively indicating the developed method was precise. Hence the current research laid a platform to identify the important drug leads like QUE (1% w/w) and further research targeting the phytochemical and biological exploration is in progress. The current analytical investigation was successful in phytochemical fingerprint and quantification of QUE in EB. [ABSTRACT FROM AUTHOR]

Summary: Background: Untreated Chlamydia trachomatis infections in women can result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), ultimately culminating in tubal occlusion and infertility. Whilst nucleic acid amplification tests can effectively diagnose uncomplicated lower genital tract (LGT) infections, they are not suitable for diagnosing upper genital tract (UGT) pathological sequelae. As a consequence, this study aimed to identify serological markers that can, with a high degree of sensitivity and specificity, discriminate between LGT infections and UGT pathology. Methods: Plasma was collected from 73 women with a history of LGT infection, UGT pathology due to C. trachomatis, or no serological evidence of C. trachomatis infection. Western blotting was used to analyze antibody reactivity against extracted chlamydial proteins. Sensitivity and specificity of differential markers were also calculated. Results: Four antigens (CT157, CT423, CT727 and CT396) were identified and found to be capable of discriminating between the infection and disease sequelae state. Sensitivity and specificity calculations showed that our assay for diagnosing LGT infection had a sensitivity of 75% and specificity of 76%, whilst the assay for identifying UGT pathology demonstrated 80% sensitivity and 86% specificity. Conclusions: The use of these assays could potentially facilitate earlier diagnoses in women suffering UGT pathology due to C. trachomatis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Growing popularity of DS for nutritional needs, driven by perceived safety. • Concerns about the deliberate adulteration of DS with synthetic medications. • Prevalence of a wide range of synthetic medicines in adulterated DS. • Spectroscopy, chromatography, and hyphenated techniques are used for detecting adulterants in DS. Dietary supplements (DS) are becoming more and more popular to meet nutritional demands for a variety of reasons, including the widespread belief of being safe. However, a current trend shows an upsurge in the deliberate adulteration of DS with synthetic medications, which has the potential to have major harmful side effects. It has been observed that DS adulteration includes a remarkable number of synthetic medicines and their analogues. This review discusses the various types of synthetic medications that were found to be contaminated in DS. The primary objective of this review is to highlight analytical techniques for identifying adulterants in DS. Different types of techniques like spectroscopy, chromatography and hyphenated techniques are used for the determination of different types of adulterants in DS. Other techniques like the immunoassay method, electrophoretic method and ion mobility spectrometry are also used in the determination of adulterants. [ABSTRACT FROM AUTHOR]

The well‐known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1‐, β2‐, and β3‐adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin‐converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1‐7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G‐protein‐coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G‐protein‐mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome‐wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator‐like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9). [ABSTRACT FROM AUTHOR]

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti‐inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post‐transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro‐inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases. [ABSTRACT FROM AUTHOR]

Objectives: Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre‐exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother‐to‐child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. Key findings: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non‐nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. Summary: Some of the most common pre‐exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non‐nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples. [ABSTRACT FROM AUTHOR]

Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014–2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies. Image 1 • Drug targets important for anti-dengue drug discovery have been briefly discussed. • Anti-dengue compounds reported in the last five years are discussed. • Anti-dengue activity of other classes of clinically approved drugs is provided. [ABSTRACT FROM AUTHOR]

Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases. • Oligonucleotides are polynucleic acids consists of five base pairs. • They act by altering gene expression of an affected individual. • In respiratory diseases they are emerging as a newer therapy. [ABSTRACT FROM AUTHOR]

Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase. • Macrophages are well-known immune cells present in the airways. • Macrophages essentially retain pulmonary homeostasis and anti-inflammatory function. • Macrophages present a therapeutic target for the treatment of respiratory diseases. • Novel drug delivery system are gaining attention to target airways macrophages. • Vesicular drug delivery provides improved patient compliance with lesser side effects. [ABSTRACT FROM AUTHOR]

Abstract Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic. Highlights • Oxidative stress level contributes to severity of chronic respiratory diseases. • Delivery of new antioxidant therapies via novel drug delivery is urgently needed. • Novel vesicular drug delivery systems are gaining attention in targeting oxidative stress. • Vesicular drug delivery provides improved patient compliance and fewer side effects. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Celastrol exhibits curative properties in the treatment of several diseases. • Celastrol modulates through a variety of molecular targets in the system. • Clinical trials have demonstrated therapeutic effectiveness of celastrol. • The therapeutic properties of celastrol circumvent its toxicological limitations. • Further studies are needed to establish safety, efficacy and dosage of celastrol. Abstract In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development. [ABSTRACT FROM AUTHOR]

Fisetin (FS) is a bioactive flavonoid obtained mostly from apple and strawberry and classified under the category of food supplements due to numerous pharmacological effects against various diseases through multiple mechanistic pathways. It acts as excellent neuroprotective, cardioprotective, anti-invasive, anti-tumorigenic, anti-angiogenic, anticancer, antidiabetics, antioxidant, anti-inflammatory agent. Despite having excellent safety and efficacy profile, FS is very less explored to clinical research either as food supplement or, as therapeutic agent due to its poor aqueous solubility, low bioavailability and reduced blood brain barrier permeability. Multiple mechanistic pathways through which FS elicits its pharmacological actions and the challenges associated with FS that compromises therapeutic efficacy are described in this article. The nanoformulations developed to enhance the bioavailability and therapeutic efficacy of FS are also covered with detailed description of research works carried by various researchers. These include nanoemulsions, liposomes, ethosomes, glycerosomes, polymeric micelles, self-nanoemulsifying drug delivery system and polymeric nanoparticles. Various patents pertaining to extraction/isolation, formula composition and therapeutic uses of FS as well as some clinical studies conducted using FS as active moiety are also enlisted. [Display omitted] • Fisetin works through multiple mechanisms for the treatment of various diseases. • Poor solubility and poor oral bioavailability of fisetin impediment its therapeutic efficacy. • NDDS play major role in overcoming bioavailability challenges associated with fisetin. • Research based reviews about therapeutic potential of fisetin and its NDDS are discussed. • Patents on pharmaceutical and non-pharmaceutical applications of fisetin are highlighted. [ABSTRACT FROM AUTHOR]

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections. [Display omitted] [ABSTRACT FROM AUTHOR]

The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases. Relevant published studies, literature and reports were searched from accessible electronic databases and related institutional databases. We used keywords, viz ; microbiome, microbiota, microbiome drug delivery and respiratory disease. Selected articles were carefully read through, clustered, segregated into subtopics and reviewed. The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage, bacteria-derived lipid vesicles and microbe-derived extracellular vesicles. This review highlights the relationships between microbiota and different types of respiratory diseases, the importance of microbiota towards human health and diseases, including the role of novel microbiome drug delivery systems in targeting various respiratory diseases. • Microbiome-based therapeutics deeply impact pharmaceutical and medical fields. • Engineered bacteriophage has potential antibiotic adjuvant activity. • Crosstalk between lung and gut microbiota influences immune response. • These bio-systems has potential to improve patient compliance and drug profile. [ABSTRACT FROM AUTHOR]