Search

Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions.

Increased inflammasome responses are strongly implicated in inflammatory diseases; however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of nucleotide-binding oligomerization domain-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) and absent in melanoma-2 (AIM2) inflammasomes in cigarette smoke-induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). We targeted NLRP3 with the inhibitor MCC950 given prophylactically or therapeutically and examined Aim2-/- mice in cigarette smoke-induced experimental COPD. MCC950 treatment had minimal effects on disease development and/or progression. Aim2-/- mice had increased airway neutrophils with decreased caspase-1 levels, independent of changes in lung neutrophil chemokines. Suppressing neutrophils with anti-Ly6G in experimental COPD in wild-type mice reduced neutrophils in bone marrow, blood and lung. By contrast, anti-Ly6G treatment in Aim2-/- mice with experimental COPD had no effect on neutrophils in bone marrow, partially reduced neutrophils in the blood and had no effect on neutrophils or neutrophil caspase-1 levels in the lungs. These findings identify that following cigarette smoke exposure, Aim2 is important for anti-Ly6G-mediated depletion of neutrophils, suppression of neutrophil recruitment and mediates activation of caspase-1 in neutrophils.

Laccases are green catalysts widely employed in various industrial, environmental, clinical and biotechnological applications. This study was aimed to develop the cost effective and efficient process for high level of fungal laccase production from crude glycerol. Initially, laccase gene (lac1) of Trametes cinnabarina was chemically synthesized, and integrated into Pichia pastoris strains (BG10, 11 and 16) by using pD915 vector which can facilitate the constitutive secretory expression of laccase (lac1). Among the recombinant P. pastoris strains developed, st.BG10 (wild type) was supported the high level of laccase production (2851 ± 72 U/l) from pure glycerol based media. While replacing the pure glycerol by crude glycerol (60%), the media supported the cellular growth of st.BG10 (lac1), and produced 2343 ± 60 U/l of laccase after 48 h. The free cell biomass of st.BG10 (lac1) was recycled for 6times and produced > 8800U of laccase by using pure/crude glycerol media. Simultaneously, different matrices (agar–agar, calcium alginate, and polyacrylamide-gel) were tested to immobilize the st.BG10 (lac1) for laccase production, in which 6% calcium alginate immobilized cells to the bead size of 2.98 ± 0.07 mm were found to be stable, and recycled for 18 batches with 27,681–33926 U of laccase production from pure/crude glycerol based media. These findings would significantly assist to develop cost effective bioprocess for laccase production from crude glycerol (a waste product of biodiesel industry), and this is the first report on fungal laccase production by recyclable recombinant yeast using crude glycerol as substrate. Graphical Abstract: [Figure not available: see fulltext.]

Purpose: This study was aimed to assess knowledge regarding RLS among medical teachers and medical students. Method: ‘Knowledge about RLS (K-RLS)’ questionnaire was developed, validated and used to assess knowledge of study participants about RLS. It was applied to 50 medical teachers likely to get patients with RLS in addition to 324 undergraduate medical students. Results: Individual item validation ranged between 0.8 and 1. Average scale CVI (S-CVI/Ave) was 0.95 for the whole questionnaire and universal agreement (S-CVI/UA) scores for whole of the questionnaire was 0.75. K-RLS had good internal consistency (Cronbach’s alpha = 0.89). Results showed that knowledge regarding RLS was poor among students as well as medical teachers. Conclusion: K-RLS is a reliable tool to assess knowledge about RLS among health care professionals. Knowledge about RLS is poor among medical students as well as teachers.

The vagina is an essential part of the female reproductive system and offers many potential benefits over conventional drug delivery including a large surface area for drug absorption, relatively low enzymatic activity, avoids first-pass effects, and ease of administration. The vaginal mucosal cavity is an effective route for administering therapeutic agents that are intended both for local and systemic administration. The present review provides a comprehensive overview of recent trends and developments in vaginal drug delivery. Marketed formulations and products under clinical study are also reviewed. Various novel vaginal delivery systems have been studied in recent years as an effective tool for delivering a range of therapeutic agents to the vagina. These systems offer numerous benefits, including sustained delivery, improved bioavailability, effective permeation, and higher efficacy. The recent focus of the scientific community is on the development of safe and efficient drug delivery systems such as nanoparticles, microparticles, vesicular systems, vaginal rings, microneedles, etc. for vaginal application. Various factors such as the physicochemical properties of the drugs, the volume and composition of the vaginal fluid, the pH of the vaginal fluid, the thickness of the vaginal epithelium, and the influence of sexual intercourse may influence the release of drugs from the delivery system and subsequent absorption from the vaginal route. To date, only limited number of in vivo studies on novel vaginal DDS have been reported. Additionally, drug release kinetics under varying vaginal environments is also not well understood. More research is needed to ensure the suitability, biocompatibility, and therapeutic effectiveness of novel DDS for vaginal delivery. Although numerous strategies and interventions have been developed, clinical translation of these systems remains a challenge. The toxicity of the carrier system is also an important consideration for future

Large carnivore populations are declining worldwide due to anthropogenic causes such as habitat loss and human expansion into wild areas. Competition between large carnivores can exacerbate this decline. While brown hyena Parahyaena brunnea and spotted hyena Crocuta crocuta belong to the same family, they are rarely found in the same area or co-occur at low densities as spotted hyena are known to exclude brown hyena. In Central Tuli, Botswana, however, brown hyena and spotted hyena are both found at high densities. We undertook a camera trap survey in this area to estimate the densities of both species, and to examine temporal overlap and co-detection patterns of brown and spotted hyena. Estimated population densities based on spatial capture–recapture models were 10.5 ± 1.9/100 km2 for brown hyena and 14.9 ± 2.2/100 km2 for spotted hyena. These population densities are among the highest reported estimates in southern Africa. Strong temporal overlap was found between brown and spotted hyena, while there was no decrease in detection rate of brown hyena at camera sites where spotted hyena were also detected, which indicates that both hyena species did not tend to avoid encounters. Although both species compete for the same prey, we suggest as possible explanations that prey densities are high and that competition does not significantly negatively impact brown hyena, because brown hyena is a scavenger whereas spotted hyena scavenge and kill prey. With the found high densities of both carnivores, this study adds to the known variation in composition of existing large carnivore communities and suggests testable explanations for these densities.

This book examines numerous nanoparticle-based drug systems such as nanocrystals, dendrimers, polymeric micelles, protein-based, carbon nanotube, and liposomes that can offer advantages over traditional drug delivery systems such as ...

Cell Signaling pathways form an integral part of our existence, that allows the cells to comprehend a stimulus and respond back. Such reactions, to external cues from the environment, are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people who are asthmatic, 65 million who are suffering from COPD, 2.3 million who are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and nation annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

OBJECTIVE: The aim is to study the knowledge and attitude of medical undergraduate students regarding obstructive sleep apnea (OSA). MATERIALS AND METHODS: This cross-sectional study involved 324 medical undergraduate students in clinical semesters. Knowledge and attitude regarding adult OSA were assessed using the obstructive sleep apnea knowledge and attitude (OSAKA), and to evaluate the same about childhood OSA, OSAKA-KIDS was used. RESULTS: Results showed that the study population was not informed about OSA among adults as well as kids. Most of the participants could recognize that snoring was a common symptom of adult OSA but failed to identify the association between childhood OSA and hyperactivity. The participants had a good knowledge about the pathophysiology of OSA. More than 80% of students reported that OSA is an important disorder and that these patients should be identified. CONCLUSION: Medical undergraduates are poorly informed about OSA.

© Springer Nature Singapore Pte Ltd. 2020. Mycobacterium tuberculosis (Mtb), the causitive agent of Tuberculosis (TB) is the leading cause of infection. The infection is caused by aerosols and infects the alveolar macrophage. The lungs counteract against the infection by the antioxidant system in response to the oxidative stress (OS) caused. Mycobacteriumstimulates the lung macrophage to produce reactive oxygen species (ROS). Furthermore, the treatment involves long term multiple drug regimens resulting in poor patient compliance leading to multidrug resistance (MDR-TB). The different first-line and second-line antibiotics are administered in an inactive form which gets converted into the active form by the OS response system of the host and the Mtb. Mtb alters the redox balance via mycolic acid, NADH/NAD+ ratio, and antioxidant enzymes in response to stress. In the following chapter, we have discussed the role of oxidative stress in the host and the pathogen along with the immunological complexities and the genetic modifications resulting in multidrug-resistant tuberculosis. It also discusses the different strategies to target the Mtb infection.

Regardless of advances in detection and treatment, breast cancer is a major cause of women death and affecting about 1.5 million women all over the world. Since the last decade, genome wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute large family of non-coding RNAs which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus for more studies on the role of microRNAs in breast cancer.

© 2020 Wiley Periodicals, Inc. Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.