Misbahuddin Rafeeq

King Abdulaziz University · Department of Pharmacology

Lung cancer, a relentless and challenging disease, demands unwavering attention in drug design research. Single-target drugs have yielded limited success, unable to effectively address this malignancy’s profound heterogeneity and often developed resistance. Consequently, the clarion call for lung cancer drug design echoes louder than ever, and mult...

English: Computational biology has changed the way healthcare systems and biomedical engineering work. Nature-inspired intelligent computing (NIIC) approaches to predict potential biomarkers and drug targets could be an amazing bridge between biology/nature and today's advanced and sophisticated fields such as artificial intelligence, deep learnin...

English: Nature-inspired computational methods (NIC) have been effectively used to study pharmaceutical components and compounds. NIC involves problem-solving methods based on abstractions of natural processes that offer new ways to understand, model, and analyze natural complexity. These algorithms mimic biological systems to create new computatio...

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms,...

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms,...

Cervical Cancer (CC) is one of the most common types of cancer in women worldwide, with a significant number of deaths reported yearly. Despite the various treatment options available, the high mortality rate associated with CC highlights the need to develop new and effective therapeutic agents. In this study, we have screened the complete prepared...

Mixed lineage kinases (MLK) have emerged as potential therapeutic targets for the treatment of cancer, as they are often overexpressed or dysregulated in cancer cells, leading to aberrant signaling pathways that promote cancer cell proliferation, survival, and metastasis. Targeting MLK using small molecule inhibitors represents a promising therapeu...

Japanese encephalitis (JE) is a single-stranded, mosquito-borne, positive-sense RNA flavivirus that causes one of the most severe encephalitides. There are treatments available for those who contact this illness; however, there are no known cures. This disease has a 30% fatality rate, and of the people who survive, 30–50% develops neurologic and ps...

Bardet–Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod–cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity....

Cardiovascular diseases (CVDs) are the leading cause of death and morbidity globally. The renin-angiotensin system is an important regulatory system for maintaining cardiovascular and renal function. Therefore, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have emerged as first-line treatments for conditions such as hyp...

Kaposi’s sarcoma associated herpesvirus (KSHV) is causative agent of Kaposi’s sarcoma, Multicentric Castleman Disease and Pleural effusion lymphoma. KSHV-encoded ORF17 encodes a protease which cleaves -Ala-Ala-, -Ala-Ser- or -Ala-Thr-bonds. The protease plays an important role in assembly and maturation of new infective virions. In the present stud...

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, he...

Gymnema sylvestre (GS) is a perennial woody vine native to tropical Asia, China, the Arabian Peninsula, Africa and Australia. GS has been used as a medicinal plant with potential anti-microbial, anti-inflammatory and anti-oxidant properties. This study was conceptualized to evaluate the cytotoxicity potential of Gymnema sylvestre saponin rich fract...

Neurodegenerative disorders such as Alzheimer’s disease (AD), Glioblastoma multiforme (GBM), Amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD) are some of the most prevalent neurodegenerative disorders in humans. Even after a variety of advanced therapies, prognosis of all these disorders is not favorable, with survival rates of 14–...

Computational biology has changed how healthcare systems and biomedical engineering work. Nature-inspired intelligent computing (NIIC) approaches in predicting potential biomarkers and drug targets could be an astonishing bridge between biology/nature with today’s advanced and sophisticated areas like artificial intelligence, deep learning, compute...

The Nature-inspired computing (NIC) techniques have been effectively applied to research pharmaceutical components and compounds. NIC includes problem-solving methods based on abstractions of natural processes and provides new ways to understand, model, and analyse natural complexity. These algorithms mimic biological systems to create new computat...

The pandemic that started in 2020 left us with so much information about viruses and respiratory diseases, and the cause behind it was severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The world is still recovering, which costs so many economic and other indirect disasters; despite that, no medications are available on the market. Altho...

Cerebellar ataxias (CAs) comprise a rare group of neurological disorders characterized by extensive phenotypic and genetic heterogeneity. In the last several years, our understanding of the CA etiology has increased significantly and resulted in the discoveries of numerous ataxia-associated genes. Herein, we describe a single affected individual fr...

Breast cancer (BC) is linked to estrogen receptor alpha (ER-α) positive. Tamoxifen and other estrogen selective modulators have proven to be beneficial in slowing the progression of ER-α BC. However, tamoxifen resistance emerges as a result of long-term treatment and cancer development. Therefore, it is of interest to document data on the molecular...

The association of COVID-19 with neurological complications is a well-known fact, and researchers are endeavoring to investigate the mechanistic perspectives behind it. SARS-CoV-2 can bind to Toll-like receptor 4 (TLR-4) that would eventually lead to α-synuclein aggregation in neurons and stimulation of neurodegeneration pathways. Olive leaves have...

Hearing impairment (HI) is a heterogeneous condition that affects many individuals globally with different age groups. HI is a genetically and phenotypically heterogeneous disorder. Over the last several years, many genes/loci causing rare autosomal recessive and domi�nant forms of hearing impairments have been identified, involved in various aspec...

Hearing impairment (HI) is a heterogeneous condition that affects many individuals globally with different age groups. HI is a genetically and phenotypically heterogeneous disorder. Over the last several years, many genes/loci causing rare autosomal recessive and dominant forms of hearing impairments have been identified, involved in various aspect...

It is well-acknowledged that ‘combination therapy’ of antibiotics is indispensable for the treatment of patients suffering from serious bacterial infections. Therefore, it is of interest to collect data from the in vitro tests using ‘rifampicin-cefotaxime’ and ‘rifampicin-tetracycline’ combination regimens against multi drug resistant Escherichia c...

Brain-derived neurotrophic factor (BDNF) involving tropomyosin kinase B and low affinity p75 neurotropin receptors is the most abundant and researched neurotropins in mammal’s brain. It is one of the potential targets for therapeutics in Alzheimer’s disease (AD) owing to its key role in synaptic plasticity. Low levels of BDNF are implicated in the...

Intellectual disability (ID) has become very common and is an extremely heterogeneous disorder, where the patients face many challenges with deficits in intellectual functioning and adaptive behaviors. A single affected family revealed severe disease phenotypes such as ID, developmental delay, dysmorphic facial features, postaxial polydactyly type...

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is one of the rapid spreading coronaviruses that belongs to the Coronaviridae family. The rapidly evolving nature of SARS-CoV-2 results in a variety of variants with a capability of evasion to existing therapeutics and vaccines. So, there is an imperative need to discover potent drugs tha...

The negative effects of leishmanicidal medications are numerous, and drug resistance to all of them has been observed. As a result, new medication development and the identification of novel therapeutic targets are critical. Leishmania major trypanothione reductase (Lm-TR), a NADPH-dependent flavoprotein oxidoreductase critical for thiol metabolism...

Abstract: Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, int...

Objective To investigate the effect of sequential Helicobacter pylori eradication therapy on serum osteoprotegerin levels in patients with H. pylori infection and co-existing inflammatory bowel disease (IBD). Methods Three groups of patients were involved in this observational cross-sectional study: IBD (n = 83), H. pylori infection (HP, n = 68),...

Purpose Oxidative stress is involved in pathogenesis of chronic viral hepatitis. Glutamine is an antioxidant, but there is a controversy about its risk-benefits. Nitrotyrosine is an oxidative stress marker. This observational cross-sectional study was designed to compare blood levels of glutamine and nitrotyrosine in treated versus untreated chroni...

Abstract: Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the surviv...

Background: Genetic disorders such as diabetes have severe implications on human health. Mutation or aberrant activity of different proteins are associated with diabetes. The hyperactivation of the peptidase function of dipeptidyl peptidase-4 (DPP4) strongly correlates with the elevated level of blood glucose in diabetic patients. Aim: Preventing t...

Background: Polydactyly is a prevalent digit abnormality characterized by having extra digits/toes. Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: GLI3, GLI1, ZRS regulating LMBR1, IQCE, ZNF141, PITX1, MIPOL1, FAM92A, STKLD1, KIAA0825, and DACH1. Method: A single affected family member (IV-4) was subjected t...

The COVID-19 pandemic caused by highly-infectious virus namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in infection of millions of individuals and deaths across the world. The need of an hour is to find the innovative solution for diagnosis, prevention, and cure of the COVID-19disease. Nanotechnology is emerging as...

Atherosclerosis is one of the leading causes of mortality and morbidity worldwide. Chemokines and their receptors are implicated in the pathogenesis of atherosclerosis. CXCL12 is a member of the chemokine family exerting a myriad role in atherosclerosis through its classical CXCR4 and atypical ACKR3 (CXCR7) receptors. The modulatory and regulatory...

The term autosomal recessive congenital ichthyosis (ARCI) is the subgroup of ichthyosis, which describes a highly heterogeneous group of genetic disorders of the skin characterized by cornification and defective keratinocytes differentiation associated with mutations in at least 14 genes including PNPLA1 . To study the molecular basis of the Pakist...

Background Phosphoglycerate mutase (PGAM) deficiency is associated with a rare glycogen storage disease (glycogenosis type X) in humans caused by pathogenic variants in the PGAM2 gene. Several genes causing autosomal forms of glycogen storage disease (GSD) have been identified, involved in various forms of neuromuscular anomalies. Methods Targeted...

Aromatase plays a significant role in the progression of estrogen receptor-positive (ER-positive) breast cancer. The adverse side effects of currently used aromatase inhibitors (AIs) necessitate the development of new AIs that are more active, selective, and less toxic. This study used a computational approach to screen 503 natural compounds ZINC d...

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology...

An amendment to this paper has been published and can be accessed via the original article.

Background Ulcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory...

Background and Objective: The use of plasma calprotectin; a protein mainly expressed in neutrophils; as a diagnostic and/or prognostic marker in type 2 diabetic patients is still controversial. Being a non-invasive test, this study was designed to detect if urinary calprotectin could be used to differentiate between treated-controlled and treated-u...

Effect of low and high dose of losartan and candesartan (ARBs) was evaluated on murine model of low grade renal dysfunction.

Background: One of the loop diuretics, furosemide, was found useful in bronchial asthma. It enhanced anti-asthmatic effects of albuterol. The underlying mechanism is still unclear. Objective: This study was planned to investigate whether the enhancing effect of furosemide for albuterol in ovalbumin-induced asthmatic BALB/c mice is diuretic-relat...

Approximately 20%–30% of schizophrenia patients are resistant to current standard pharmacotherapies. Recent schizophrenia research aims to identify specific pathophysiological abnormalities and novel targets in the disease, with the goals of identifying at-risk individuals, facilitating diagnosis, prompting early and personalized interventions, and...

Purpose: To evaluate the prescription patterns of anti-diabetic drugs in a government hospital in Saudi Arabia. Methods: Retrospective prescription information and medical records of patients who visited outpatient clinics during the last one year were used. The prescriptions were grouped into three: appropriate, partially appropriate and inappropr...

Aim: Genetic variants contribute to statins' therapeutic variability. SREBF-SCAP pathway is a key player in lipid homeostasis. Hence, effect of SREBF-SCAP polymorphisms on therapeutic response was studied. Patients & methods: Metabolic syndrome patients of either sex were prescribed rosuvastatin 10 mg for 24 weeks. Clinical, anthropometric and l...

Investigation of altered therapeutic response due to genetic variability

Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice. Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated groups. The following trea...

Background: Bronchial asthma is a social and economic healthcare burden. Drug utilization studies are important tools to assess current prescription practices against standard guidelines and help in rationalizing the management. Materials and methods: This retrospective cross-sectional study was designed to evaluate the pattern of drug utilizati...

Objectives Study of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use. Methods Extensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics. Key findingsCystic fibrosis is an autosomal recessi...

Airway remodeling in bronchial asthma is resistant to current treatments. Inflammatory mediators and matrix metalloproteinase-9 (MMP-9) is involved in pathogenesis of airway inflammation and remodeling and thus their inhibition could be beneficial in this respect. In a recently-published work, we concluded that co-inhalation of roflumilast+fluticas...

Diabetes is a metabolic disease; it results due to lack of insulin production, insulin action or both. It became epidemic in all over the world. Glycation of proteins is a major contributor to development of diabetes mellitus. HSA is the abundant protein in human blood; it is highly prone to glycation by the reducing sugars in-vitro and in-vivo in...

Roflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory ce...

Aim: Statins treat dyslipidemia associated with metabolic syndrome. Genetic factors contribute to variable response. Sterol regulatory element-binding factors cleavage-activating protein (SCAP) pathway regulates lipid homeostasis, so effect of SNP in SCAP gene on rosuvastatin response was studied. Materials & methods: Metabolic syndrome patients...

There is widespread consumption of energy drinks especially by young population. Aggressive marketing in the name of performance improvement is directed towards young adults. Most consumers don't know about the largely unregulated constituents. High levels of caffeine and sugar often lead to adverse effects. This study was conducted among universit...

Context: Metabolic syndrome (MS) is a constellation of metabolic irregularities consisting of dyslipidemia, hypertension, hyperglycemia, chronic inflammatory, and hypercoagulable state predisposing to diabetes and cardiovascular events. Statins are first-line drugs to treat the associated atherogenic dyslipidemia. Aim: Effect of rosuvastatin on...

Exercise physiology has become an increasingly important topic for research and discussion. Physical inactivity and sedentary lifestyles is linked to various chronic and metabolic diseases. Exercise has shown to increase muscular strength, decrease blood pressure, increase oxygen consumption and improve the cardiovascular / cardio-respiratory funct...

Free radicals and reactive oxygen species are electrically charged molecules produced spontaneously during normal metabolic processes. They attack and damage the lipids, proteins, nucleic acids and other biologically important molecules. They are neutralized by antioxidant defence systems. Disturbance of oxidant-antioxidant equilibrium and exposure...

Intercellular communication plays a pivotal role in various physiological functions. This is mainly done through gap junctions and trans-membrane channels. The structural proteins forming these channels are different in vertebrates and invertebrates namely connexins and innexins respectively. Recently, a new class of proteins playing a crucial role...

Metabolic syndrome predisposes to diabetes and atherosclerotic vascular disease. Statins reduce cardiovascular events, so all metabolic syndrome patients should be evaluated for dyslipidemia. Many patients fail to achieve lipid goals with statin monotherapy. Co-administration of ezetimibe (EZE) and atorvastatin (ATV) may enable more patients to ach...

Free radicals are electrically charged molecules that are produced during the course of normal metabolism. They spontaneously attack lipids, proteins, nucleic acids and other biologically important molecules. Polyunsaturated lipids are particularly sensitive to their attack. Free radicals and oxidative stress have been reported to be involved in ti...

Human subjects’ participation in medical research has often raised ethical concerns. After Nazi exploitation; various Guidelines & Declarations were prepared, but still unethical behaviour of healthcare practitioners is being reported. After graduation and entering into practical field; sudden exposure to challenges makes it difficult to take decis...

According to WHO, Pharmacovigilance activities are done to monitor detection, assessment, understanding and prevention of any obnoxious adverse reactions to drugs at therapeutic concentration on animal and human beings. However, there is also a growing focus among scientists and environmentalists about the impact of drugs on environment and surroun...