Rashid Waseem

Mitochondria are implicated in a wide range of functions apart from ATP generation, and, therefore, constitute one of the most important organelles of cell. Since healthy mitochondria are essential for proper cellular functioning and survival, mitochondrial dysfunction may lead to various pathologies. Mitochondria are considered a novel and promising therapeutic target for the diagnosis, treatment, and prevention of various human diseases including metabolic disorders, cancer, and neurodegenerative diseases. For mitochondria-targeted therapy, there is a need to develop an effective drug delivery approach, owing to the mitochondrial special bilayer structure through which therapeutic molecules undergo multiple difficulties in reaching the core. In recent years, various nanoformulations have been designed such as polymeric nanoparticles, liposomes, inorganic nanoparticles conjugate with mitochondriotropic moieties such as mitochondria-penetrating peptides (MPPs), triphenylphosphonium (TPP), dequalinium (DQA), and mitochondrial protein import machinery for overcoming barriers involved in targeting mitochondria. The current approaches used for mitochondria-targeted drug delivery have provided promising ways to overcome the challenges associated with targeted-drug delivery. Herein, we review the research from past years to the current scenario that has identified mitochondrial dysfunction as a major contributor to the pathophysiology of various diseases. Furthermore, we discuss the recent advancements in mitochondria-targeted drug delivery strategies for the pathologies associated with mitochondrial dysfunction.

The prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, there is a need to develop an effective carrier system for the delivery of drugs to combat such diseases. In recent years, various biological macromolecules, including proteins, have been used as carriers for drug delivery. Irisin is a beneficial hormone in such diseases, including AD and related pathologies. Herein, the interaction mechanism of irisin with AD drugs such as memantine, galantamine, and fluoxetine is investigated. Fluorescence studies revealed that the above drugs bind to irisin with significant affinity, with fluoxetine having the highest binding affinity. Isothermal titration calorimetry (ITC) complemented the spontaneous binding of these drugs with irisin, delineating various associated thermodynamic and binding parameters. Molecular docking further validated the fluorescence and ITC results and unfolded the mechanism that hydrogen bonding governs the binding of fluoxetine to irisin with a significant binding score, i.e., −6.3 kcal/mol. We believe that these findings provide a promising solution to fight against AD as well as a platform for further research to utilize irisin in the drug-delivery system for an effective therapeutic strategy.

Aim: Expression of EGFP was investigated to ascertain the strength and specificity of CMV, U6 and hepatitis B virus (HBV) core promoters in hepatic and non-hepatic cells. Materials and methods: pSi...

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (K = 0.8 × 10⁷ M⁻¹), subsequently inhibiting its activity (IC₅₀ = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.

Employee engagement play a key role for the success of any organization because they provides the highest employee satisfaction , lower employee turnover rate , greater employee loyalty, better customer service, higher sales and higher profitability. The aim of this study is to examine the impact of reward and recognition and perceived supervisor support on employee engagement. The method used in research is quantities descriptive. We used questionnaire to collect data. The population in this study consisted of employees of Muslim Commercial Bank & National Bank of Pakistan. Data were collected in Multan from 108 employees but unfortunately 08 questionnaire data rejected because the data was not proper fill. The data were analyzed using through statically package for social science (SPSS Version 21).The results show that reward & recognition and supervisor support can engage employees for better performance. Hence; employee’s engagement can improve through the reward and recognition and supervisor support.

Commercial banks play an important role for the purpose of sustainable economic development in a country. This paper main theme to presents the comparison of financial performance between private commercial banks in Pakistan during the period of 2015–2019 by using the method of ratio analysis and some other financial indicators. Fourteen Commercial banks out of fifteen banks are selected for comparison of financial analysis. Due to the unavailability of data, the remaining one bank is not chosen for study because, yet they did not publish their final report in 2019. The data of ratio analysis was captured by using the final report of commercial banks, which are available on the bank's official websites. This study provides information about the different ratios which directly impact on bank performance.