D. U. Ozsahin
35222353000
Publications - 17
Bacterial infections and antimicrobial resistance patterns: a comprehensive analysis of health dynamics across regions in Pakistan (2013-2023)
Publication Name: Brazilian Journal of Biology
Publication Date: 2025-01-01
Volume: 85
Issue: Unknown
Page Range: Unknown
Description:
Antimicrobial resistance (AMR) is a significant public health concern globally, and Pakistan is no exception. The misuse and overuse of antibiotics, inadequate regulation of their sale, and a lack of awareness contribute to the rising levels of AMR in the country. study presents a detailed analysis of blood and urine samples collected in Pakistan over various periods, focusing on pathogen prevalence, gender distribution, and age-wise patterns. From January 2013 to 2017, the North region exclusively contributed to the blood sample dataset, with Salmonella emerging as the primary pathogen, particularly affecting infants and neonates. Subsequently, from January 2017 to December 2020, a significant dataset emerged from the North and Punjab regions, with Salmonella and E.coli prevalent across all age groups, notably impacting adults and infants. In the period from January 2021 to the present, blood samples predominantly originated from the North and Punjab regions, with Salmonella and E.coli remaining significant pathogens, affecting adults and the elderly. Regarding urine samples, from January 2013 to December 2017, E.coli was the dominant pathogen, with females showing a higher susceptibility to urinary tract infections (UTIs), particularly among the elderly. Similarly, from January 2017 to December 2020, E.coli remained predominant, with UTIs more prevalent in females and the elderly. In the most recent period, the North region significantly contributed to UTI cases, with E.coli remaining predominant and females exhibiting a higher susceptibility, especially among the elderly. This comprehensive analysis provides crucial insights into the epidemiology of blood and urinary tract infections in Pakistan, informing public health strategies and interventions aimed at addressing these health challenges.
Open Access: Yes
Lymphopenia as a diagnostic biomarker in clinical COVID-19: insights from a comprehensive study on SARS-CoV-2 variants
Publication Name: Brazilian Journal of Biology
Publication Date: 2025-01-01
Volume: 85
Issue: Unknown
Page Range: Unknown
Description:
The enduring SARS-CoV-2 pandemic necessitates robust tools for severity assessment. This study, conducted at Islamabad Diagnostic Center across Pakistan from January 2021 to August 2022, aimed to investigate hematological abnormalities among suspected SARS-CoV-2 subjects. Initial enrollment included 130,347 cases, with 53,078 confirmed positive and 77,269 negative. An additional 11,786 samples expanded the dataset to 142,133. The Omicron and Centaurus variants, in confirmed positive patients, exhibited a slightly higher frequency of hematological abnormalities (30.42%) than negative participants (27.01%). Notably, lymphocyte count reduction (40.95%) suggested its potential as an alternative diagnostic parameter for clinical COVID-19. Decreased levels of NA (37.99%), HGB (26.17%), MCV (20.60%), PLT (6.15%), and ALB (2.28%) were observed. Abnormally elevated NEU, CR, MONO, RBCs, WBC, and EOS levels affected 26.00%, 24.28%, 30.79%, 22.02%, 6.28%, and 5.53% of subjects, respectively. Comparatively, positive patients exhibited higher abnormal blood parameters—LYMP count (57.40%), NEU count (46.08%), EOS count (62.48%), MONO count (31.61%), RBC count (30.32%), ALC count (43.60%), CR count (30.91%), NA count (40.53%), CRP count (68.46%), and DD (63.08%) than negative counterparts. The study underscores lymphocytopenia’s potential as a cost-effective, early diagnostic biomarker for clinical COVID-19, preceding real-time PCR diagnosis. This supports its consideration in resource-limited settings for strategic screening and policy-making in the ongoing SARS-CoV-2 battle.
Open Access: Yes
Estimating high mobility group box protein 1 (HMGB1) single nucleotide polymorphisms among hepatitis B virus infected patients of Pakistan origin
Publication Name: Brazilian Journal of Biology
Publication Date: 2025-01-01
Volume: 85
Issue: Unknown
Page Range: Unknown
Description:
HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which induces fibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our results showed significant correlation of HMGB1 polymorphism with HBV infection in the selected Pakistani population.
Open Access: Yes
Seroprevalence of hepatitis B and hepatitis C viral infections among refugees in Muzaffarabad, Pakistan
Publication Name: BMC Infectious Diseases
Publication Date: 2025-12-01
Volume: 25
Issue: 1
Page Range: Unknown
Description:
Background: Hepatitis B (HB) and Hepatitis C (HC) viral infections, with 328 million cases globally, represent a significant disease burden. Currently, Pakistan has 3.88 million HB and 9.31 million HC cases. High-risk populations like refugees are disproportionately affected by these infections. The objectives of this study were to determine the seroprevalence of hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) among Kashmiri refugees in Muzaffarabad, Pakistan, and to identify the key demographic and educational risk factors associated with the seroprevalence in this population. Methods: A cross-sectional study was conducted across eight refugee camps in the Muzaffarabad division, Pakistan. A six-membered team visited each camp to collect blood samples through venipuncture. The seroprevalence of HBsAg and anti-HCV was determined using rapid immunochromatographic test (ICT) kits. Results: A total of 550 sera samples were collected from the refugee population in Muzaffarabad. The overall seroprevalence was 5.82% (32/550) for HBsAg and 4.73% (26/550) for anti-HCV. A higher seroprevalence of HBsAg and anti-HCV was recorded among females 6.12% (15/245), and 6.53% (16/245), respectively, compared to males 5.75% (17/305), and 3.28% (10/305), respectively. A marked increase in seroprevalence of HBsAg and anti-HCV was noted with an increase in age: 1–10 (2.44%) and (2.44%), 41–50 (8.20%) and (6.56%), and 51–60 (8.93%) and (8.93%), respectively. Chi-square test revealed a statistically significant association between age and seroprevalence of HBsAg χ² (degrees of freedom (df):6, N = 550) = 27.22, p = 0.000, and HC χ² (df:6, N = 550) = 15.23, p = 0.019.The level of education impacted the seroprevalence of HBsAg and anti-HCV, resulting in a higher seroprevalence of HBsAg (6.9%) and anti-HCV (5.4%) among uneducated individuals compared to educated individuals (4.71%) and (3.99%), respectively. Conclusion: The seroprevalence of HBsAg and anti-HCV is high among the refugee population of Muzaffarabad, Pakistan. There is a need for the implementation of a robust vaccination program for HB as well as the establishing a hepatitis micro-elimination program among the Kashmiri refugee population of Muzaffarabad, Pakistan.
Open Access: Yes
An exploratory binding study of molnupiravir efficacy against emerging Omicron SARS-CoV-2 variants
Publication Name: Scientific Reports
Publication Date: 2025-12-01
Volume: 15
Issue: 1
Page Range: Unknown
Description:
SARS-CoV-2 (severe acute respiratory syndrome causing coronavirus 2) caused an epidemic that swept the globe and resulted in large number of casualties. It is still sporadically causing cases and has a long-term impact on the health of once infected individuals. Molnupiravir binds RNA dependent RNA polymerase (RdRp) of SARS-CoV-2 as well as spike protein. In this study, we assessed the mutated spike protein of BA.5 variant and BQ.1.1 subvariant of COVID-19 and tested their binding with it. Multiple sequence and structural alignment of homologous structures revealed highly conserved amino acid residues at the active site of the domain. The molecular docking of Molnupiravir with the active site of the domain, comprised conserved motifs (motif A-G), and exhibited considerable binding affinity against variant and subvariant protein targets. Molnupiravir exhibited stability in its interactions with the Omicron and BQ.1.1 spike proteins, preserving constant engagement within the active site. The protein and Ligand reached An equilibrium with An RMSD of 10.46 Å after 100 nanoseconds, whereas the Ligand measured 8.0 Å. Fluctuations were noted between 40 And 75 nanoseconds, stabilizing from 80 to 100 ns. In simulations including the BQ.1.1 subvariant, the RMSD values demonstrated considerable stability, exhibiting Little variations. The ligand demonstrated flexibility, altering its binding orientation over time, resulting in An average RMSD of 18.72 Å. Herein, investigation of molecular dynamics trajectories elucidated the conformational stability of Molnupiravir, emphasizing its interactions with active residues and the hydrogen bond acceptor and donor environments. The results highlighted the crucial function of protein loops in offering flexibility and enabling ligand binding within the active site. It is concluded that Molnupiravir has the potential to function as an inhibitor of both omicron and its subvariant BQ.1.1.
Open Access: Yes
Genetics of diabetes and its complications: a comprehensive review
Publication Name: Diabetology and Metabolic Syndrome
Publication Date: 2025-01-01
Volume: 17
Issue: 1
Page Range: Unknown
Description:
Background Diabetes mellitus (DM) affects hundreds of millions of people worldwide. Genetic research plays a cru-cial role in managing diabetes by providing valuable insights into genetic predispositions, facilitating early diagno-sis, and enabling personalized treatment strategies. Identification of important genetic markers has paved the way for the creation of targeted therapies, enhancing treatment outcomes and promoting preventive care for both type 1 diabetes mellitus ( T1DM) and type 2 diabetes mellitus ( T2DM). The aim of this study is to explore the role of different genes in the development of DM and its related complications. Methodology A comprehensive literature search was conducted from October 27 to November 14, 2024, to enlist articles related to genes involved in development of DM and its complications in search engines including PubMed, Medline, Google Scholar, and Scopus. We included original articles, case–control studies, cohort studies, review arti-cles, systematic review, and meta-analysis published between January 1, 2014, and November 14, 2024 in our study. Results In T1DM; research has historically concentrated on the role of HLA class II genes. However, recent studies have brought attention to the role of HLA class I genes in the disease’s development, suggesting a broader role of genetics than previously understood. CTLA4, IL2RA, and PTPN22, genes were also significantly linked to T1DM. In T2DM; TCF7L2 was found to be the most potent gene for its development among others genes such as LCAT, APOE, FTO. For gesta-tional diabetes mellitus (GDM), MTNR1B, CDKAL1, and IRS1 genes played an important role. Conclusion Genetics played an important role in the understanding of DM. Researchers have identified new genetic loci that can serve as diagnostic markers for DM and its associated compilations such as diabetic kidney disease (DKD), diabetic neuropathy (DN), diabetic retinopathy (DR) and cardiovascular diseases (CVDs). TCF7L2 and HLA class II are the strongest risk factors for T2DM and T1DM, respectively. Understanding the genetics of DM and its complications is essential for improving early detection, enhancing treatment outcomes, and developing targeted therapies for DM patients.
Open Access: Yes
A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence
Publication Name: Journal of Health Population and Nutrition
Publication Date: 2025-12-01
Volume: 44
Issue: 1
Page Range: Unknown
Description:
Background: Hypertension (HTN) impacts approximately 1.28 billion individuals globally and poses a great burden of disease. The objectives of this study are to explore the role of genetics, epigenetics, microbiome, and artificial intelligence (AI) in the management of HTN. A thorough literature search was conducted across various databases including PubMed, Google Scholar, Web of Science (WoS), and Medline to retrieve articles related to the role of genetics, epigenetics, microbiome, and AI in the precision medicine of HTN. Genes—including ACE, NOS3, ADD1, CYP11B2, NPPA, and NPPB—have a profound impact on blood pressure (BP) regulation in our body and polymorphism in these key genes can lead to HTN. Up or down-regulation of genes by epigenetic factors such as miRNA-155, miRNA-210, and miRNA-122 can significantly contribute to the development of HTN. These genetic and epigenetic factors can also be used as specific targets for gene editing and gene therapy for long-term management of HTN. However, the implementation of these techniques has not been possible in clinical settings due to lack of human studies and safety concerns related to unpredictable DNA alterations, nucleotide deletions, and loss of allele-specific chromosomes. Modulation of gut microbiome through oral supplements, fecal microbiota transplant (FMT), and dietary interventions has emerged as one the most effective and safe techniques for managing HTN in human models. AI-based cutting-edge models have helped curate personalized diet plans based on an individual’s unique microbiome, genomic information, and physiological conditions leading to a reduction in BMI, fat, BP, and heart rate while improving overall cardiac health and gut microbial diversity. Despite the significant advantages offered by AI-based medicine, ethical concerns—related to data privacy, bias, and discrimination—and ineffective models have led to limited integration of AI in precision medicine of HTN. The integration of genetics, epigenetics, microbiome, and AI-based models can play a key role in improving the current landscape of precision medicine of HTN. These cutting-edge techniques can lead to a shift from the current one-size-fits all approach to more personalized treatment plan however further research in human models is needed to determine the safety and true efficacy of these techniques. Additionally, new AI-models need to be developed that address ethical concerns and are effective in real-world clinical settings.
Open Access: Yes
Bridging the gap between point-of-care and laboratory standards: comparative evaluation of MedSenso and DSA glucometers against Cobas analyzers for accurate diabetes monitoring
Publication Name: Brazilian Journal of Biology
Publication Date: 2025-01-01
Volume: 85
Issue: Unknown
Page Range: Unknown
Description:
Diabetes mellitus remains a major global health burden, with effective management relying heavily on accurate blood glucose monitoring. Personal glucometers are widely used for daily self-checks, yet their performance must be rigorously validated against laboratory standards to ensure reliability. This study undertook a diagnostic evaluation of three glucometers, DSA, MedSenso, and the laboratory-based Cobas systems (C503 and Pro analyzers), to assess their precision and clinical applicability. In a cross-sectional design, 150 clinical samples from diabetic patients were analyzed using the DSA glucometer and Cobas C503, while an additional 200 diabetic blood samples were tested to compare MedSenso with the Cobas Pro analyzer. Ethical approval was obtained, and diagnostic parameters including sensitivity, specificity, correlation, and difference percentages were evaluated against the respective Cobas gold-standard systems. Results revealed nuanced but clinically meaningful findings. For the DSA glucometer, correlation with Cobas C503 ranged from 87.9% to 100%, with differences varying between 0.0% and 32.3%. Although entries with perfect correlation (100%) and no difference (0.0%) indicated excellent agreement, instances of high correlation coupled with significant differences highlighted systematic biases, particularly consistent over- or underestimation by the DSA device. Such discrepancies underscore the need for device-specific awareness to avoid misinformed clinical decisions. In contrast, the MedSenso glucometer demonstrated excellent agreement with Cobas Pro, showing a correlation coefficient of 0.984 and near-identical glucose results across tested samples. Its ease of use and rapid reporting make MedSenso especially promising for clinical settings where fast decision-making is essential. Collectively, the study underscores the complexity of glucose measurement in diabetes care. While the DSA glucometer requires cautious interpretation due to systematic biases, MedSenso emerges as a trustworthy and practical alternative for both clinical and routine use. These findings highlight the importance of balancing correlation strength and difference analysis in device selection, reinforcing the need for continuous validation against laboratory standards to ensure accurate and dependable diabetes management.
Open Access: Yes
Stability analysis of a fractional prey–predator model with Holling type III functional response and disease in both populations
Publication Name: Network Modeling Analysis in Health Informatics and Bioinformatics
Publication Date: 2026-12-01
Volume: 15
Issue: 1
Page Range: Unknown
Description:
This paper develops and analyzes a fractional-order predator–prey model with Holling type III functional response, incorporating the transmission of a contagious disease between both populations. We first establish the existence, uniqueness, non-negativity, and boundedness of solutions for the fractional-order system. The local stability of the model’s equilibrium points is examined, and the global stability is rigorously proved using a suitable Lyapunov function. We also investigate the effects of disease transmission on the predator–prey dynamics by identifying multiple equilibria, threshold parameters, and stability conditions. In particular, we analyze the existence of Hopf bifurcation at the endemic equilibrium point through bifurcation analysis, revealing the possible emergence of periodic oscillations. Analytical results are complemented by numerical simulations, highlighting the importance of incorporating both Holling type III predation and disease transmission when assessing prey–predator coexistence.
Open Access: Yes
Exploring the hub gene CERS6 as a therapeutic target in type 1 diabetes through a bioinformatics and network analyst approach
Publication Name: Scientific Reports
Publication Date: 2026-12-01
Volume: 16
Issue: 1
Page Range: Unknown
Description:
Insulin-producing β-cells are destroyed in type 1 diabetes mellitus (T1DM), a chronic autoimmune disease that results in complete insulin insufficiency and metabolic dysfunction. According to a survival study that used p values, some hub genes are important for predicting and diagnosing illness. Scientists have inferred medicines to identify possible therapies that interact with the identified hub genes. The GSE10586 gene expression dataset from the Gene Expression Omnibus (GEO) was used for this investigation, which included 27 samples from 15 healthy controls and 12 diabetic patients. Normalization methods such as variance stabilization normalization (VSN) were used as part of the data pretreatment. A protein‒protein interaction (PPI) network was constructed, principal component analysis (PCA) was performed, heatmaps were created, and the Limma algorithm was used to analyze differential gene expression. Using DAVID v6.8 and KEGG pathway annotations, the functional enrichment of differentially expressed genes (DEGs) was evaluated. Furthermore, a computational study revealed CERS6 to be one of the potential hub genes. Four drugs, methotrexate, eliglustat, myriocin and statin, were the focus of further studies on the basis of predictions made via ChemSpider and PubChem database analysis. To determine the optimal binding positions of these drugs with CERS6, we used molecular docking techniques. The binding affinity of methotrexate was 8.48 kcal/mol, that of myriocin was 7.85 kcal/mol, that of eliglustat was − 6.62 kcal/mol, and that of serine was − 4.90 kcal/mol against the binding pocket’s active residues. To determine how consistently each drug interacted with the CERS6 protein over time, molecular dynamics (MD) simulations were run. Throughout the simulation intervals, both medications were confirmed to be stable, with minor alterations in the CERS6 protein loop region. Therefore, the investigation of structure-based drug design has potential for identifying specific therapeutic targets. Ten hub genes were identified via network analysis of differentially expressed genes. These hub genes could serve as novel targets for T1DM detection, prognosis, and targeting. CERS6 exhibited the highest degree of interaction. Methotrexate, eliglustat, myriocin and statins were identified as potential drugs for CERS6. Overall, these findings provide valuable insights that could pave the way for new experimental strategies in T1DM therapy.
Open Access: Yes
The Painlevé analysis and computational technique for new wave solutions with its numerical validation to the complex short pulse equation
Publication Name: Kuwait Journal of Science
Publication Date: 2026-04-01
Volume: 53
Issue: 2
Page Range: Unknown
Description:
This article aims to derive novel varieties of exact solitonic wave solutions to the complex short pulse equation using an effective technique known as the Riccati-Bernoulli sub-ODE method (RBSODM), which does not conform to the balance rule. For the first time, the resonance induced by the arbitrariness of the singular manifold is analyzed in the proposed model through the application of Painlevé analysis (PA). The complex short pulse (CSP) equation models the behaviour of ultra-short optical pulses in nonlinear media. It serves as a more accurate model than the non-linear Schrödinger equation when the pulse width approaches the optical cycle scale. The proposed model incorporates both dispersion and Kerr-type nonlinearity, capturing the essential features of femtosecond pulse dynamics. Diverse types of rogue wave soliton solutions have been extracted such as bright soliton, dark soliton, W-like soliton, M-like soliton, and higher-order breather soliton. Moreover, the numerical approximations for all obtained analytical traveling wave solutions have been implemented by using the Haar wavelet approach (HWA). A comparison between the obtained analytical and numerical solutions is presented. Two-dimensional and three-dimensional graphical simulations are generated using the Mathematica software. The graphical simulations demonstrates the novelty of the obtained results and facilitate the interpretation of the dynamical properties of the proposed model.
Open Access: Yes
Discovery of potential antiviral compounds and accelerating the therapeutic discovery against monkeypox virus
Publication Name: Scientific Reports
Publication Date: 2026-12-01
Volume: 16
Issue: 1
Page Range: Unknown
Description:
Monkeypox virus is a zoonotic virus of the genus Orthopox viruses. It can be transmitted through direct or indirect contact with animals or infected ones. Owing similarity of pathogenesis with smallpox, the same drugs can be used for both viruses, but they are not specific and only help to relieve the symptoms only. Therefore, the absence of antiviral treatment or licensed vaccine highlights an urgent need, especially due to its rapid prevalence. The study screened the library of compounds to retrieve drug-like molecules that can act against monkeypox virus. The highly virulent target gene B8R having uniport ID Q3I8J0 was chosen. Targeting B8R is substantial for global health and can align with SDG 3 and awareness of disease management. The B8R was modelled via Artificial intelligence (AI) AlphaFold method and then exposed to a library of compounds. Complementary interactions in the active site were shown by molecular docking. The Complex-1 had the greatest binding affinity (–8.4 kcal/mol), followed by Complex-2 (–8.1 kcal/mol) and Complex-3 (–7.7 kcal/mol). After 125 ns, Complex-1 reached equilibrium at 7.5 Å RMSD, according to MD simulations, exhibiting stable ligand retention and reliable interactions with crucial residues Gly135 and Lys136. Complex-3 shown intermediate protein stability (6 Å RMSD) but notable ligand fluctuation (48 Å RMSF), while Complex-2 displayed increased protein RMSD (8 Å RMSD) and delayed ligand stabilisation (16 Å RMSF). These results were corroborated by PCA analysis, which showed that Complex-1 exhibits coherent structural development whereas Complex-2 and Complex-3 show scattered and compact trajectories, respectively. Complex-1 promise for Mpox viral inhibition was highlighted by the fact that it was the most stable and dynamically favourable contender overall. The N-terminal follows the folding trend. The insilico analysis not only proposed a potent compound but also provides deep insight into the behavior of protein. The proposed potent compound against this zoonotic virus can be helpful to combat the monkeypox virus by subjecting it further towards experimental investigation.
Open Access: Yes
Langevin neutral impulsive fractional stochastic system along fractional Brownian motion-A controllability analysis
Publication Name: Journal of Low Frequency Noise Vibration and Active Control
Publication Date: 2026-01-01
Volume: Unknown
Issue: Unknown
Page Range: Unknown
Description:
The purpose of this work is to investigate the controllability of Langevin-type stochastic neutral impulsive integro-differential equations governed by the Caputo fractional derivative and driven by fractional Brownian motion, which arise naturally in systems exhibiting memory, impulsive effects, and stochastic disturbances. Using resolvent operators and fixed-point techniques, necessary and sufficient controllability conditions are established for the associated linear system, while the controllability of the nonlinear system is demonstrated via the Banach contraction principle. The theoretical results confirm that appropriate control functions can steer the system to a desired state within a finite time interval. Finally, illustrative numerical examples are provided to demonstrate the applicability and effectiveness of the obtained results, highlighting their relevance to practical stochastic control problems.
Open Access: Yes
A SPECTRAL COLLOCATION SCHEME WITH 2D ULTRASPHERICAL WAVELETS FOR FRACTIONAL NONLINEAR GAS DYNAMICS EQUATIONS UNDER CAPUTO–FABRIZIO DERIVATIVE
Publication Name: Fractals
Publication Date: 2026-01-01
Volume: Unknown
Issue: Unknown
Page Range: Unknown
Description:
Gas Dynamics Equations (GDEs) play a fundamental role in modeling fluid flows phenomena across a range of applications, from environmental systems to aerospace engineering. These equations mathematically represent the fundamental laws of mass, momentum and energy conservation. Modeling complex gas flows often requires advanced mathematical tools capable of capturing nonlocal and memory-dependent behavior. Therefore, this study explores the implementation of the Caputo–Fabrizio Fractional Derivative (CFFD) in the analysis of GDEs, highlighting its potential to accurately capture the behavior of complex fluid dynamics systems. A two-dimensional (2D) wavelet-based approach combined with suitable collocation grids is employed to approximate the solutions for spacetime Fractional Gas Dynamics Equations (FGDEs). The concept of the CFFD, with its nonsingular kernel, is integrated into the framework of GDEs, offering a more precise analytical perspective. By reformulating the FGDEs into a system of algebraic equations, the proposed approach enables efficient computation via iterative technique. The error analysis of the numerical results is presented through graphs and tables for three illustrative examples with varying fractional values, demonstrating a strong correlation between the analytical and approximated solutions. The performance of the scheme is evaluated using multiple error metrics, including minimum absolute error, L∞ error, L2 error, and LRMS errors. The absolute errors demonstrate the improvement in results of FGDEs as the wavelet basis increases. The results validate the reliability and ease of implementation of the suggested approach for solving the FGDEs. The study demonstrates the method’s reliability, and potential for solving a wide class of nonlinear fractional models governed by nonlocal dynamics.
Open Access: Yes
MEK1/2 Inhibitor (U0126) and PI3K Inhibitor (LY294002) Suppress Herpes Simplex Virus Type 1 Replication by Targeting MAPK/ERK1/2 and PI3K/AKT Signaling Pathways: Implications for Oral Health and Translational Control of Orolabial HSV-1 Infection
Publication Name: Iranian Journal of Pharmaceutical Research
Publication Date: 2025-01-01
Volume: 24
Issue: 1
Page Range: Unknown
Description:
Background: Current antivirals for orolabial Herpes simplex virus type 1 (HSV-1) often provide incomplete suppression and limited reactivation control, sustaining recurrent oral lesions and inflammation that compromise oral health. HSV-1 subverts host signaling networks to enhance its replication and trigger inflammation. Among these, the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways are hijacked to facilitate viral gene expression and cell survival. Objectives: In this study, we employed U0126 [a mitogen-activated protein kinase 1/2 (MEK1/2) inhibitor] and LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor] as targeted pharmacological tools to intercept HSV-1’s exploitation of host keratinocyte signaling. Methods: Human HaCaT keratinocytes were infected with HSV-1 and treated with U0126 or LY294002. Western blotting was used to assess phosphorylation of ERK1/2 and activation of protein kinase B (AKT). MTT assays were performed to evaluate cell viability. Real-time PCR was utilized to quantify viral transcripts (ICP0, ICP4, gB, and gC) and inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Confocal microscopy was employed to visualize the intracellular distribution of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), phosphorylated activation of protein kinase B (p-AKT), and HSV-1 glycoprotein D (gD). Viral titers were determined using plaque assays. Results: The HSV-1 infection induced a time-dependent increase in phosphorylation of ERK1/2 and AKT, with p-ERK1/2 peaking at 12 h and p-AKT increasing 2.5-fold by 24 h. Cell viability declined from 100% at baseline to 45% at 24-hours post-infection (hpi). Treatment with U0126 and LY294002 reduced p-ERK1/2 and p-AKT levels to 25% and 30% of infected controls, respectively, restoring viability to 82 - 86%. Both inhibitors markedly suppressed viral gene expression (ICP0, ICP4, gB, gC down by 60 - 80%) and inflammatory cytokines (IL-6 and TNF-α reduced by > 50%). Plaque assays showed a strong decline in infectious titers — from 175 plaques per well in untreated infection to 60 and 45 plaques after U0126 and LY294002, respectively. Confocal imaging further revealed diminished nuclear accumulation of p-ERK1/2 and p-AKT, indicating disruption of post-entry signaling critical for viral replication. Conclusions: Targeting host signaling bottlenecks with U0126 and LY294002 offers a dual-pronged antiviral strategy against HSV-1 by dismantling the ERK/AKT axis critical for replication and inflammatory amplification. These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.
Open Access: Yes
DOI: 10.5812/ijpr-164639
Soluble factors from Aspergillus fumigatus promote NF-κB/AKT/ERK activation and pro-tumor phenotypes in lung cancer cells in vitro
Publication Name: Archives of Microbiology
Publication Date: 2026-06-01
Volume: 208
Issue: 6
Page Range: Unknown
Description:
Role of environmental fungi and Aspergillus fumigatus in respiratory diseases remains evident; however, its contribution to directly influencing lung cancer progression remains obscure. In this study, we investigated the effect of Aspergillus fumigatus extract (AFE) on the development of tumor-promoting characteristics in human lung cancer cell lines. The organism was distinguished based on Lactophenol Cotton Blue staining and further distinguished with protein expression patterns via SDS-PAGE and BCA analysis. A549 and H1299 lung adenocarcinoma human cell lines were challenged with AFE, and various cellular responses were monitored simultaneously for cell viability, proliferative activity, inflammatory gene expression, DNA damage expression, and migratory responses. AFE caused increased cell viability and exhibited cellular characteristics of highly proliferating cells with significant expression of Cyclin D1 and c-MYC. Highly inflammatory gene expression responses and protein expressions of AKT, ERK1/2, and NF-κB signaling pathways were noticed at both the gene and protein expression levels with NF-κB nuclear translocation verified with confocal microscopy studies. DNA damage expression markers like γ-H2AX, p-ATM, and p53 significantly contributed with observable genomic DNA cleavage. Additionally, AFE-exposed cells exhibited faster wound closure and expression of Epithelial-mesenchymal transition-associated factors contributing to cell migration and therapeutic efficacy of this combined approach needs further investigation and development into a targeting therapeutic agent against lung cancer.
Open Access: Yes
Acylglycerol Kinase 2-mediated Inhibition of Sirtuin 2 Restores AMPK/AKT/mTOR Signaling Balance in Podocytes: A Pharmacological Strategy for Diabetic Nephropathy
Publication Name: Iranian Journal of Pharmaceutical Research
Publication Date: 2026-12-01
Volume: 25
Issue: 1
Page Range: Unknown
Description:
Background: Diabetic nephropathy is a major cause of end-stage renal disease, driven in part by molecular dysfunctions in podocytes. Sirtuin 2 (Sirt2), a cytoplasmic NAD+-dependent deacetylase, has emerged as a potential regulator of key metabolic pathways, but its specific role in podocyte biology remains poorly defined. Objectives: This study aimed to investigate the function of Sirt2 in human podocytes (hPodo), delineate its interaction with histone deacetylase 6 (HDAC6), and evaluate the therapeutic potential of Sirt2 inhibition in restoring metabolic balance and protecting against diabetic nephropathy-associated podocyte stress. Methods: Comparative expression analysis was performed between hPodo and HEK293T kidney cells. Pharmacological inhibition of Sirt2 was carried out using acylglycerol kinase 2 (AGK2), alongside siRNA-mediated Sirt2 knockdown. AMPK/AKT/mTOR signaling activity was assessed by Western blotting and functional assays to determine metabolic and growth responses. Results: Human podocytes exhibited significantly elevated Sirt2 expression and high levels of HDAC6, forming a unique Sirt2–HDAC6 regulatory complex. Inhibition or silencing of Sirt2 induced robust AMPK activation while suppressing AKT/mTOR signaling. This signaling reprogramming restored energy sensing and attenuated hyperactive growth pathways, alleviating podocyte stress. Acylglycerol kinase 2 treatment reestablished metabolic homeostasis by disrupting Sirt2-mediated repression of AMPK. Conclusions: Sirtuin 2 inhibition, particularly through AGK2, emerges as a novel pharmacological strategy to protect podocytes, restore metabolic regulation, and potentially slow the progression of diabetic nephropathy. Significance Statement By inhibiting one of the important intracellular signaling pathways in human kidney cells, we could reduce the cellular stress that is commonly observed in diabetic kidney injury. This could serve as a drug target to slow the progression of kidney disease associated with diabetes mellitus.
Open Access: Yes
DOI: 10.5812/ijpr-165603
