Cellular and Molecular Biology

Diversity and biological functions of fungal secondary metabolites: Biocontrol agents for sustainable agriculture. A review

Zhou Jinna — 2025-05-26

Fungi produce a wide variety of secondary metabolites, including mycotoxins, antibiotics, and bioactive compounds, which have significant implications for human health and agriculture. These metabolites are synthesized through specialized biosynthetic pathways, which are often organized into gene clusters. Terpenoids, polyketides, non-ribosomal peptides, and hybrid compounds are primary categories of secondary metabolites, each with distinct biological roles. For example, terpenoids, such as deoxynivalenol and helvolic acid, polyketides, such as aflatoxins and lovastatin, and non-ribosomal peptides, such as penicillin G, have diverse applications, including as pharmaceuticals and biocontrol agents. Fungal metabolites also play a crucial role in microbial communication and agricultural pest control. Volatile metabolites released by fungi, including Fusarium and Trichoderma species, can inhibit plant pathogens and promote plant growth, thereby offering potential biocontrol strategies. Furthermore, entomopathogenic fungi produce secondary metabolites with insecticidal properties that facilitate their pathogenicity, including enzymes, toxins, and bioactive compounds. These metabolites have emerged as potential alternatives to synthetic insecticides in sustainable agricultural practices. A growing understanding of fungal secondary metabolites and their applications can contribute to advancements in pharmaceuticals, agriculture, and pest management.

The role of genetic and hormonal factors in shaping exercise responses and performance in children: a comprehensive review

Gholamreza Zourmand — 2025-05-26

This review aims to explore the role of genetic and hormonal factors in shaping exercise responses and performance in children, providing insights into their implications for training and talent identification. A comprehensive narrative review of the literature was conducted, analyzing studies published between 2014 and 2024. The review focused on genetic predispositions, key hormones regulating exercise performance, and their combined influence on physical development in children. Data were collected from peer-reviewed journals and analyzed using a descriptive approach to identify patterns and practical applications in pediatric exercise science. The review highlights that genetic factors play a foundational role in determining physical attributes such as muscle composition, aerobic capacity, and metabolic efficiency. Key genes, including ACTN3 and ACE, have been linked to variations in strength, endurance, and recovery potential. Hormonal factors, particularly growth hormone, insulin-like growth factor-1, testosterone, and cortisol, dynamically influence exercise adaptation, with significant changes occurring during developmental stages. The interaction between genetic and hormonal influences suggests that personalized training approaches can optimize performance while considering developmental stages and environmental factors. Ethical considerations surrounding genetic testing for talent identification remain a critical concern, emphasizing the need for responsible and evidence-based application in pediatric sports programs. Therefore, it is crucial to understand the relationship between genetic and hormonal factors for designing individualized exercise programs that enhance athletic potential while ensuring long-term health and well-being. Future research should focus on integrating genetic and hormonal insights with environmental and behavioral factors to develop holistic training strategies for children.

COVID-19 clinical outcomes and N-acetylcysteine (CoViNAC study): a GRADE compliant meta-analysis of randomized controlled trials with molecular docking and dynamics simulation studies with Mpro of SARS-CoV-2

Seshadri Reddy Varikasuvu — 2025-05-26

N-acetylcysteine (NAC) has been proposed as an adjuvant therapy for COVID-19, but evidence from randomized controlled trials (RCTs) remains inconclusive. This systematic review and meta-analysis evaluated NAC’s efficacy in improving mortality and recovery/discharge rates. Additionally, molecular docking and molecular dynamics simulation (MDMS) studies were conducted to assess NAC’s interaction with the SARS-CoV-2 main protease (Mpro), a key enzyme for viral replication. A systematic search identified 12 RCTs, with 11 trials (1125 patients) included in the mortality analysis. NAC significantly reduced mortality (RR=0.59, 95% CI 0.39–0.88, p=0.01; I²=62%), indicating a 41% decreased risk of death. Six RCTs (656 patients) showed improved recovery/discharge rates (RR=1.09, 95% CI 1.03–1.14, p=0.003; I²=0%). MDMS studies demonstrated stable NAC binding at the Mpro catalytic site, interacting with His41 and Cys145, crucial for enzymatic activity. These findings suggest NAC significantly improves clinical outcomes in COVID-19 and may inhibit viral replication by targeting Mpro. This integrated evidence substantiates NAC’s potential as a critical adjuvant therapy.

Nano-encapsulated Ajwain essential oil elicits resistance against early blight in tomatoes (Solanum lycopersicum L.)

Mahin Izadi — 2025-05-26

Early blight, caused by Alternaria alternata, poses a significant threat to tomato production worldwide. This study investigates the potential of nano-encapsulated ajwain (Trachyspermum copticum) essential oil, delivered via chitosan nanoparticles, to induce systemic resistance in tomato plants against early blight. Oxidative stress, measured by malondialdehyde content, was significantly reduced in plants treated with nano-encapsulated Ajwain essential oil compared to controls. Furthermore, the activity of antioxidant enzymes (SOD, CAT, and POD) was significantly elevated in treated plants, indicating an enhanced defense response. The nano-encapsulated essential oil demonstrated superior efficacy in controlling early blight symptoms. These results suggest that chitosan nanoparticle-mediated delivery of ajwain essential oil is a promising, environmentally friendly strategy for enhancing tomato resistance to early blight.

The cytotoxic effect of quercetin-induced apoptosis on lung metastatic cells from giant cell tumor of bone

Aarón Ernesto Marure-Rojano — 2025-05-26

The pulmonary parenchyma is the primary site of metastasis for giant cell tumor (GCT) of bone, a benign yet aggressive musculoskeletal tumor. Current treatments, including surgery and antibody therapy, are only partially effective and often lead to significant side effects. This study aimed to evaluate the apoptotic activity of quercetin, a naturally occurring flavonoid with anticancer properties, on metastatic GCT lung cells (TIB-223). The immunophenotype of the TIB-223 cell line was characterized using flow cytometry, revealing positivity for CD166 and CD47 markers and negativity for CD34, CD73, CD117, CD45, and fibroblast markers. The IC50 of quercetin was determined at 91.1 µM through MTT assays, demonstrating its cytotoxic effect in a dose-dependent manner. Apoptosis was confirmed via flow cytometry and Western blotting, showing increased caspase-3 expression after 24 hours of treatment. These findings indicate that quercetin induces apoptosis in metastatic GCT cells and could serve as a basis for developing phytopharmaceutical therapies targeting this pathology.

ESTs identification and construction of normalized cDNA libraries of Miscanthus lutarioriparius across combinations of salt and drought stresses

Jianfeng Liao — 2025-05-26

Miscanthus lutarioriparius is a perennial C₄ herb with high biomass production and is widely utilized as a non-food biobased material for bioproduction. This study successfully constructed two high-quality full-length normalized cDNA libraries from distinct salt-tolerant accessions of M. lutarioriparius under salt, drought, and combined salt-drought stress conditions. The study identified 420 high-quality Expressed Sequence Tags (ESTs) primarily associated with signal transduction mechanisms, post-translational modifications, energy production and transformation, as well as the synthesis, transport, and metabolism of amino acids, carbohydrates, and secondary metabolites. A total of 1370 Gene Ontology (GO) terms were obtained from two accessions, mainly related to cellular process, metabolic process, response to stimulus, biological regulation, biological regulation, cellular anatomical entity, binding, and catalytic activity. Five GO terms from the Biological Process Ontology consistently exhibited high P-values in both accessions, primarily associated with responses to exogenous substances and metabolic processes. The significant enrichment of genes associated with cellular components such as the chloroplast matrix, cytoplasm, and plastid matrix from the Cellular Component Ontology may explain the salt-drought tolerance mechanism of Miscanthus. This study is expected to deepen our understanding of the functional genes in Miscanthus plants and may provide a reference for screening salt and drought-resistance genes.

Study of carbohydrate, bioactive compounds, antioxidants, vitamin C, and mineral content at the ripening stage of grapes, rambutan, and pineapple

Abu Bakar Mohammad Sharif Hossain — 2025-05-26

The experiment was carried out to investigate the carbohydrate content as represented by glucose, fructose and sucrose, total soluble solids, carotenoid, flavonoid, antioxidant, phenolic content, pH, and minerals as micro-macro nutrient content in grapes, rambutan, and pineapple. A total of 50 fruits were collected for rambutan, five fruits from pineapple, and five bunches were collected for grapes in Experiment 1: Glucose content was higher in rambutan and pineapple than in grapes. The higher fructose content was found in rambutan than in grapes and pineapple. The highest sucrose was observed in rambutan. The highest total soluble solid (TSS) content was found in rambutan. Vitamin C and fiber content exhibited the highest value in pineapple. However, carotenoid was higher in grapes and pineapple than in rambutan. The maximum flavonoid was found in rambutan. In addition, total antioxidant and phenolic content were higher in pineapple and rambutan than in grapes. Potassium content was higher in grapes and pineapple compared to the rambutan, whereas phosphorus content was the highest in pineapple, and calcium content was the highest in rambutan. Mn, Fe, and Zn were found in higher amounts in rambutan than in pineapple and grapes. In Experiment 2: glucose, sucrose, and vitamin C decreased while fructose, TSS, pH, and biomass increased. In addition, moisture decreased with the increase of total antioxidant capacity (TAC) in grapes, rambutan and pineapple. Carotenoid content was highest in grapes, flavonoid was highest in rambutan and total phenol was highest in pineapple. Therefore, it can be concluded that grapes showed better mineral content, rambutan exhibited the highest sugar and flavonoid content, and pineapple showed the highest bioactive compounds.

Seroprevalence of specific antibodies to Treponema pallidum in blood donors with DNA confirmation of seropositivity

Haween T. Nanakaly — 2025-01-28

The rising global incidence of syphilis underscores the risk of transmission through blood transfusions. Treponema pallidum, the pathogen responsible for syphilis, represents a major public health challenge. Accurate detection is essential for controlling the disease, particularly in asymptomatic blood donors. This study aimed to evaluate the seroprevalence of specific antibodies against T. pallidum in blood donors, confirmed by DNA testing for seropositivity. The goal was to enhance our understanding of syphilis exposure and improve the safety of blood donations. A total of 1,260 HIV, HCV, and HBsAg-negative blood donors were screened for T. pallidum-specific antibodies using enzyme-linked immunosorbent assay (ELISA). Initially, reactive samples were re-evaluated, and those repeatedly reactive were classified as seropositive for syphilis. ELISA-positive samples were further tested for T. pallidum DNA using real-time polymerase chain reaction (RT-PCR). Data analysis was done using SPSS with a level of significance p< 0.05 Of 1,260 blood donors, the seroprevalence of anti-T. pallidum antibodies was 0.158%, with both positive cases confirmed by PCR. The prevalence was 0.2% in males and 0.00% in females, with no significant gender differences (P > 0.05). The highest prevalence was in the 31-40 age group (0.5%), but this was not statistically significant (P > 0.05). There were no significant differences by donation type or marital status. Significant associations were observed with educational level (P < 0.05), with higher prevalence among high school graduates Our results confirm syphilis in Iraqi blood donors, highlighting the need for routine T. pallidum ELISA screening at transfusion centers. Positive cases should be discarded and affected donors treated. ELISA is an effective primary screening method, consistent with WHO guidelines for low-prevalence settings, and is essential for preventing transfusion transmission.

Optimizing Se- methylselenocysteine concentration to enhance glutathione peroxidase 1 expression and mitigate oxidative stress in senescent human fibroblast

Hazem K Ghneim — 2025-05-26

Glutathione peroxidase 1 (GPx1) activity, gene expression, and several oxidative stress (OS) marker levels were investigated in the senescent passage (P) 20, 25, and 30 fibroblasts cultured in media supplemented with increasing Se-Methylselenocysteine (MSC) increments. While GPx1 activity slightly increased in cells grown in standard culture medium (CM1) compared to primary P5 cells, the enzyme exhibited significant MSC-dose-dependent elevations in cells cultured in MSC-supplemented media (CM3-CM6) compared to CM1 (p<0.001). GPx1 activity in CM5-incubated P30, P25, and P20 cells equaled 5.99±0.62, 4.72±0.48, and 4.06±0.36 µmoles/min/mg protein respectively (p<0.001), with percentage increases of 250% in P30 cells compared to 190% in P20 cells when cultured with CM1. Similarly, GPx1 expression was markedly upregulated in CM2, CM4, and CM6-incubated cells compared to primary P5 cells (p<0.001), with fold change values of 1.51±0.12, 1.99±0.16, and 2.31±0.19 in P20 cells. Percentage upregulations were 50.0±3.68%, 89.5±7.11%, and 126.5±9.74% in CM2, CM4, and CM6-incubated P20 cells respectively, and reached 248.0±18.6% in P30 cells at the highest MSC concentration. Concurrently, OS marker levels were substantially higher in CM1-cultured P25 and P30 senescent cells compared to primary P5 cells (p<0.001). Furthermore, hydrogen peroxide levels were significantly reduced in CM3-incubated cells compared to CM1 (p<0.01), reaching the lowest values in CM6 (p<0.001), with reductions of approximately 11.5%, 40%, 57%, and 58% in P30 CM3, CM4, CM5, and CM6-incubated cells respectively. MSC-Km values for GPx1 were 0.87, 1.13, and 1.92 µM in P20, P25, and P30 cells, respectively, with corresponding Vmax values of 4.59, 5.68, and 7.94 µmole/min/mg protein. These findings suggest that senescent cells utilize higher amounts of MSC to upregulate GPx1 expression and maximize its activity, supporting using Se supplements to combat OS.

Development and in vitro evaluation of mefenamic acid orodispersible tablets prepared by direct compression

Muhammad Adnan — 2025-05-26

Mefenamic acid functions as a nonsteroidal anti-inflammatory drug (NSAID) of the fenamate class, which treats pain and inflammation by inhibiting cyclooxygenase (COX-1 and COX-2) enzymes to decrease prostaglandin production. Mefenamic acid has strong therapeutic properties that help to treat arthritis and dysmenorrhea. The rapid dissolution of orodispersible tablets (ODTs) makes them an effective treatment option for patients with dysphagia. This study developed and evaluated mefenamic acid ODTs through direct compression while adding super-disintegrants, including croscarmellose sodium, crospovidone, and sodium starch glycolate, to improve drug release and disintegration speed. Pre-formulation analysis through FTIR spectroscopy showed that the drug and excipients maintained compatibility without detectable interactions. Product quality assessment included tests for hardness and weight variation, friability and disintegration time, dissolution studies, and stability testing. The performance of the formulation was evaluated through supplementary tests that measured the moisture uptake, wetting time, and water absorption ratio. The zero-order model provided the most accurate explanation of drug release kinetics among the model-dependent approaches, which included the zero-order, first-order, Higuchi, and Hixson-Crowell models. The combination of 7% croscarmellose sodium in formulation F1 produced the best results by enabling quick dissolution while maintaining the optimal disintegration time and improving drug absorption and patient compliance. Stability tests showed that the formulation structure remained consistent during the entire testing period, thus proving its durability. The direct compression method was effective for manufacturing stable mefenamic acid ODTs according to this research. This research demonstrates how super-disintegrants boost formulation performance, establishing ODTs as a promising drug delivery system for better therapeutic results and patient medication compliance.

Association of cytomegalovirus and high-risk human papillomavirus with breast cancer progression

Hala Mohammed Majeed — 2025-05-26

In Iraq, breast cancer is the most prevalent malignancy among women, prompting increased research in the last decade. This retrospective study aimed to determine the role of human papillomavirus (HPV) and cytomegalovirus (CMV) in breast tumors. The study included 140 formalin-fixed, paraffin-embedded breast tissue samples from 100 patients with breast tumors and 20 normal breast tissue samples as controls. Patients ranged in age from 16 to 72 years. In situ hybridization was performed on samples collected from hospitals and private laboratories in Kirkuk and Tikrit between January 15 and December 15, 2022. CMV was detected in 25% (25/100) of breast cancer tissues, while HPV was found in 45% (45/100), compared to the control group, which tested negative for both viruses. Among HPV-positive cases, HPV genotype 31 was the most prevalent (58.33%), followed by HPV16 and HPV18 (20.8% each). These findings suggest that HPV, particularly genotype 31, and CMV may play a role in breast cancer development in the Iraqi population.

Antimicrobial and therapeutic properties of bacteriocins from Lactobacillus casei isolated from goat milk

Jumaila Koori Parambil — 2025-05-26

Lactic acid bacteria (LAB) bacteriocins are renowned for their broad spectrum of antimicrobial activity. These organisms are generally recognized as safe and are predominantly utilized in food preservation, effectively suppressing harmful bacteria. The present study aims to isolate LAB from goat milk, purify bacteriocins and analyze its therapeutic applications. Of the 26 isolates, isolate GO3 showing enhanced antimicrobial activity against food-borne pathogens was identified using 16s rRNA sequencing. The organism was identified as Lactobacillus casei GO3 with 100% similar to Lactobacillus casei strain NR115322.1. Cystathionine gamma-synthase gene (MetB) with high homology to Lacticaseibacillus casei strain MetB gene was detected in the isolate GO3. The partially purified bacteriocin from Lactobacillus casei GO3 demonstrated a broad spectrum of antibacterial activity, achieving 76.4% inhibition against Gram-positive B. subtilis and 46.2% against Gram-negative Salmonella typhi and antifungal activity, with maximum against Phytophthora infestans (47.7%) and a minimum against Fusarium oxysporum (42.2%). In addition to its antimicrobial activities, the bacteriocin demonstrated significant anti-inflammatory, α-amylase inhibition, antioxidant and anticancer activity. Further studies are required to analyze its mechanism of action and potential therapeutic applications in real-world scenarios.

Urotensin-II receptor contributes to the pro-inflammatory TLR4/MyD88/NF-κB/iNOS/NO pathway-mediated cardiovascular response to systemic lipopolysaccharide challenge in a septic shock model in rats

Muhammed Ahmed-Reda Elosman — 2025-05-26

Urotensin (U)-II through the U-II receptor (UT) (the orphan G protein-coupled receptor; GPR14) plays an important role in the pathogenesis of many cardiovascular and renal diseases characterized by increased production of vasodilatory and pro-inflammatory mediators. This study tested the hypothesis of whether UT contributes to the pro-inflammatory TLR4/MyD88/NF-kB/iNOS/NO pathway-mediated changes in the cardiovascular response to systemic lipopolysaccharide (LPS) challenge in a rat model of septic shock. SB-710411, a UT antagonist, was used to test this hypothesis. Rats were injected with SB-710411 1 hour following an injection of saline or LPS. A tail-cuff device was used to record the mean arterial pressure and heart rate values of rats. Serum U-II and nitrite levels and U-II, GPR14, TLR4, MyD88, NF-kB, IL-1β, and iNOS mRNA expression in the cardiovascular and renal tissues were measured. Mean arterial pressure was reduced and heart rate was increased at 4 hours following LPS injection. In addition to the levels of U-II and nitrite in the sera of rats injected with LPS, the expression of U-II, GPR14, TLR4, MyD88, NF-kB, IL-1β, and iNOS was increased in the cardiovascular and renal tissues. SB-710411 at 0.01 mg/kg dose ameliorated the changes induced by LPS, excepting the increased serum nitrite level. These findings suggest that UT contributes to hypotension and tachycardia mediated by the TLR4/MyD88/NF-kB/iNOS/NO pathway, accompanied by an increase in pro-inflammatory cytokine expression in tissues related to the cardiovascular and renal systems, in response to systemic LPS challenge in rats.

Identifying a novel class of lead compounds for monoacylglycerol lipase inhibition: an integrated computational study

Faizul Azam — 2025-05-26

Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol and other monoacylglycerols in the brain and peripheral tissues. Elevated MAGL levels in invasive malignancies promote tumor growth by releasing free fatty acids, making MAGL inhibition a potential strategy for treating cancer. In this study, a virtual screening workflow began with Pharmit web server, where a pharmacophore was generated based on the X-ray crystal structure of MAGL complexed with its inhibitor, (2-cyclohexyl-1,3-benzoxazol-6-yl){3-[4-(pyrimidin-2-yl)piperazin-1-yl]azetidin-1-yl}methanone. A total of 5.241 million molecules from the MolPort database were screened, utilizing its diverse and purchasable chemical space to enhance the likelihood of identifying novel MAGL inhibitors and facilitating experimental validation. After applying filters based on Lipinski's and Veber's rules, a maximum energy cutoff of -7.0 kcal/mol, and an RMSD of 2Å, 4027 hits were obtained. The compounds were then docked using Vina-GPU, and the top five hits, along with the co-crystal inhibitor, were further analyzed through DFT computations and molecular dynamics simulations. MMGBSA computations identified MolPort-007-806-063 as the most potent compound, with a binding energy of -59.9±0.23 kcal/mol. In comparison, the co-crystal inhibitor exhibited a binding energy of -56.26±0.22 kcal/mol, while the other compounds showed energies of -54.57±0.26 kcal/mol, -53.57±0.24 kcal/mol, -41.13±0.33 kcal/mol, and -36.23±0.36 kcal/mol. These compounds are promising MAGL inhibitor candidates for experimental validation through enzyme inhibition assays, cell-based activity assays, and crystallographic studies to confirm their predicted binding modes and potency.

Molecular Identification of erm A and erm B, erm C genes in methicillin-resistant Staphylococcus aureus isolates from burns Patients and their association with multidrug resistance

Sarmad Qassim Mohammad — 2025-05-26

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant hospital-acquired pathogen, particularly concerning in burn patients due to its multidrug resistance. This study aimed to assess the antibiotic sensitivity profile and identify the presence of erm genes (ermA, ermB, and ermC) associated with erythromycin resistance in MRSA isolates from burn patients. A total of 80 S. aureus isolates were collected from burn cases, with initial diagnoses performed using conventional culture and microscopic methods. MRSA isolates were confirmed using chromogenic agar media, and antibiotic susceptibility was determined via the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect the erm genes responsible for macrolide resistance. Among 80 samples, 40 were identified as S. aureus, of which 18 were confirmed as MRSA. PCR analysis revealed the prevalence of ermA, ermB, and ermC genes at rates of 12%, 33%, and 11%, respectively. All MRSA isolates exhibited multidrug resistance to antibiotics, highlighting the challenge of treating infections in burn patients. This study underscores the critical need for molecular characterization of MRSA strains to inform effective therapeutic strategies and control their spread in burn wards.

Synthesis, characterization and biological screening of N-heterocyclic carbene Ag(I) catalysts for aldehyde–amine–alkyne coupling reaction

Lamia Boubakri — 2025-05-26

N-heterocyclic carbenes (NHCs) are widely recognized for their applications in organometallic chemistry, catalysis, and pharmaceutical research due to their unique steric and electronic properties. In this study, we report the synthesis of six novel unsymmetrical N,N-disubstituted benzimidazolium salts (2a–f) and their corresponding silver-NHC complexes (3a–f). The structures of all compounds were characterized using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and elemental analysis. The biological potential of these compounds was evaluated through in vitro antimicrobial assays against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata. Additionally, anticancer activity was tested against A549, HCT116, and BEAS-2B cell lines, revealing promising results for some derivatives. Preliminary catalytic studies demonstrated the effectiveness of the silver-NHC complexes in A3-coupling reactions involving aldehydes, alkynes, and amines. These reactions yielded propargylamines with high conversion rates (up to 90%) using minimal catalyst amounts. This work highlights the dual utility of these compounds as both potent biological agents and efficient catalysts, paving the way for further exploration of their applications in medicinal chemistry and sustainable catalysis.