Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Among its heterogeneous subtypes, luminal androgen receptor-positive (LAR) TNBC is driven by androgen signaling and presents limited treatment options. We previously identified dehydrogenase/reductase SDR family member 11 (DHRS11) as a novel enzyme involved in androgen biosynthesis, and demonstrated that Kobochromone A (KC-A), a polyphenol isolated from Carex kobomugi, inhibited androgen-driven proliferation in LAR TNBC cells via DHRS11 inhibition and AR downregulation. In this study, we synthesized 23 structural derivatives of KC-A and identified WH23 as the most potent DHRS11 inhibitor (IC50 = 37 nM). Molecular docking and MM-PBSA analysis revealed that the 2'-hydroxy group of WH23 forms a hydrogen bond with His210 of DHRS11, which was validated by site-directed mutagenesis. WH23 suppressed AR mRNA and protein expression, reduced 11-ketodihydrotestosterone (11KDHT)-induced c-Myc expression, and inhibited proliferation of MDA-MB-453 cells. Additionally, WH23 inhibited PI3K/AKT signaling, reducing phosphorylation of PDK1, AKT, mTOR, and ERK. Capivasertib (Cap), a clinically approved pan-AKT inhibitor, induced DHRS11 expression in MDA-MB-453 cells. Although Cap and WH23 did not show synergistic cytotoxicity in parental cells, Cap-resistant (Cap-R) cells, which exhibited elevated DHRS11 and c-Myc expression, showed significant sensitivity to the combination. In Cap-R cells, the combination of Cap and WH23 significantly induced apoptosis, demonstrating a synergistic anticancer effect. These findings establish WH23 as a dual-acting compound targeting both androgen biosynthesis and AR signaling, with potential to overcome AKT inhibitor resistance in LAR TNBC.

Nuclear factor erythroid-derived 2 like 1 (NFE2L1) is reported to be embedded in the endoplasmic reticulum (ER) membrane and subsequently undergo N-glycosylation at several asparagine residues as well as other ER-resident factors including cAMP response element binding protein 3 (CREB3)/ATF6 family members. In this study, we investigated the regulation of NFE2L1 protein expression by treating wild-type HEK293 cells and HEK293 cells deficient in selected ER-associated degradation (ERAD) factors with various reagents. NFE2L1 protein expression in wild-type HEK293 cells was negligible, but MG132/bortezomib treatment induced Endo H-resistant two bands. Suppressor/enhancer of lin-12-like (SEL1L)/hydroxymethylglutaryl-CoA (HMG-CoA) reductase degradation 1 (Hrd1) loss increased NFE2L1 protein expression without any stimuli. In these deficient cells, the band shift of NFE2L1 by MG132 was mostly suppressed. Treatment with the valosin containing protein (VCP) inhibitor CB-5083 increased NFE2L1 expression, but deficiencies in other ERAD-associated factors (ER degradation-enhancing α-mannosidase-like protein 2 (EDEM2), thioredoxin domain-containing protein 11 (TXNDC11), gp78, ring finger protein 5 (RNF5), ring finger protein 185 (RNF185), and USP19) did not affect its expression. Comparing the stability of the two intrinsic NFE2L1, which increases with proteasome inhibition, the higher molecular weight form corresponding to full-length form, was more unstable. Therefore, we constructed NFE2L1 genes with mutations in the site where NFE2L1 is cleaved by DDI2 and in the four asparagine residues where N-glycosylation occurs, and found that the high molecular weight form, especially a hypoglycosylated mutant, tended to be more unstable. Taken together, this study using several ERAD disordered models shows that the regulation of NFE2L1 is different in some ways from the regulation of CREB3/ATF6 family, and these findings implicate the diversity of N-glycosylated protein regulation in the ER.

Background: At least 500 genetic polymorphisms associated with the CYP2C19 and CYP2C18 enzymes have been identified, yet few polymorphisms have been measured in the Saudi population. Therefore, this study was aimed at determining the frequencies of numerous unmeasured CYP2CJ9 and CYP2CJ8 genetic variations, and their clinical and pharmacological implications, in KSA. Research design and methods: A multicenter crosssectional study was conducted to determine the frequency of 141 CYP2C19 and CYP2C18 genetic variants. Blood samples from 374 Saudi adults were genotyped. GenomeStudio software was used for genotype calling for all samples. Bioinformatics analyses were performed for variant annotation. We excluded the rs4244285 variant since our main objective was to determine the frequency of numerous unmeasured or poorly documented CYP2C19 and CYP2C18 genetic variants in KSA. Including rs12769205 mitigated the haplotype analysis concern. Both rs4244285 and rs12769205 are CYP2C19*2 key variations linked to loss of function. Results: Of the 141 variants associated with the CYP2C19 and CYP2C18 genes measured in 374 participants, 53 were detected, and the other 88 were not detected. Five detected variants had high frequencies: rs7067866, rs7916649, rs4917623, rs12248560, and rs11188072. Several detected variants were associated with clinical effects and appeared to influence drug metabolism. Conclusions: This study investigated the presence of many previously undescribed CYP2C19 and CYP2C18 genetic variants in the Middle Eastern population. Tens of previously unmeasured CYP2C19 and CYP2C18 variants were identified in the Saudi population. Our findings have potential to contribute to pharmacogenomics and personalized medicine, and to support clinical decision-making.

α-aminophosphonate and its derivatives have attracted significant attention, due to its numerous biological activities. A one-pot Kabachnik-Fields reaction involving three components 1,3-diaryl pyrazole derivatives 1, various aromatic aldehydes, and triethylphosphite in CH2Cl2 with lithium perchlorate acting as a Lewis acid catalyst was used to create α-aminophosphonates based on pyrazole skeletons. A variety of physical, spectroscopic, and analytical data were used to validate each newly synthesized molecule. The in-silico target prediction using artificial intelligence and a database of Swiss Target Prediction for the designed α-aminophosphonates 3a–h exhibited that these derivatives may exert their activity with more than one target. Structure–activity relationship studies have revealed that variations aryl aldehyde, N1-aryl and C3-pyrazole aryl substituents modulate biological profiles, including antioxidant, anti-inflammatory, anti-proliferative activities. Based on antioxidant investigation, compound 3g showed strong scavenging activity for DPPH and ABTS+ radicals compared to L-ascorbic acid. For inhibition of protein denaturation, compound 3g recorded the highest anti-inflammatory impact followed by compound 3f, which had a moderate in comparison to aspirin. Moreover, anticancer activity demonstrated that compound 3g displayed the most potent anticancer activity against the MCF-7 and HepG-2 cell lines when compared to Doxorubicin. Finally, a molecular docking simulation of the promising derivative 3g was conducted within the active sites of VEGFR-2 (PDB: 4ASD) and EGFR-Tk (PDB: 1M17). Compounds show a favorable binding affinity, characterized by multiple types of interactions within the binding pocket. These findings suggest that compound 3 g may exhibit antiproliferative activity through mechanisms involving VEGFR-2 and EGFR-Tk.

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The objective of this research was to investigate the impacts of supplementing both unenriched and enriched live Artemia salina with Chlorella vulgaris and Dunaliella salina in goldfish (Carassius auratus) diets on various parameters, including growth performance, feed utilisation, blood parameters, immunity, histology, and β-carotene levels. The experiment was conducted for 90 days, and all groups of goldfish (initial weight = 2.51 ± 0.01 g/fish, N = 180) received commercial diet supplements (unenriched Artemia (UE), Chlorella-enriched Artemia (CE), Dunaliella-enriched Artemia (DE), and Artemia enriched with both Chlorella and Dunaliella (CDE)). Compared to other fish groups, goldfish given CDE had better final weight, weight gain, average daily gain, specific growth rate, relative growth rate, final length, and length gain, and a lower feed conversion ratio. CDE had the best hematological, antioxidant, and immunity parameters (Immunoglobulin M levels, lysozyme activity, phagocytic activity, and phagocytic index). In addition, goldfish given CDE had the greatest β-carotene content at 8.90 ± 0.4 mg/100 g. Goldfish given enriched Artemia, specifically CDE, exhibited increased intestinal villus length, width, and goblet cells, as determined by histomorphometric analysis (p < 0.05). Additionally, upregulation of MCH, MCH-R, POMC, IGF-1, and TNF-α genes was observed in CDE. In conclusion, supplementing goldfish diets with CDE has several advantages, including improved growth performance, blood parameters, immunity, histology, β-carotene levels, and gene expression related to growth and immunity. The study's results indicate that Artemia enhanced with Chlorella and Dunaliella can improve the health, growth performance, and development of goldfish in aquaculture.

Objective: This bibliometric study aimed to analyze the global research trends, collaborations, and advancements in enfuvirtide, the first HIV fusion inhibitor, from 2002 to 2025, mapping its scientific evolution and identifying future research directions. Methods: Data were extracted from the Scopus database in April 2025, covering English-language studies on enfuvirtide. Bibliometric tools, including VOSviewer and Bibliometrix in R, were employed to analyze publication trends, author impact, institutional contributions, keyword co-occurrences, and international collaborations. Nonresearch documents were excluded to ensure analytical precision. Results: The analysis included 260 records, revealing a peak in research output in 2008 (32 articles), followed by a decline post-2012 to one to three articles annually by 2025. The key research themes and clusters in enfuvirtide studies include clinical applications, molecular mechanisms, therapeutic combinations, resistance patterns, and patient outcomes. The dominant themes revolved around enfuvirtide’s role as an HIV fusion inhibitor, its efficacy in antiretroviral therapy, and its structural interaction with gp41. Emerging topics included its use in specialized populations, for example, pregnancy and novel delivery systems. Thematic clusters highlighted its clinical trial history, pharmacokinetics, and injection-related challenges, alongside investigations into resistance mutations and viral adaptation. Conclusions: Enfuvirtide research peaked shortly after its FDA approval in 2003 but declined due to practical challenges such as administration barriers and the emergence of newer antiretroviral therapies. Future research should explore novel delivery systems, combination therapies, and applications in specialized populations to revitalize its role in HIV treatment.

Enrofloxacin is widely used in veterinary medicine, yet no comprehensive work has examined how global research and collaboration have evolved since its introduction in the late 1980s. Knowledge of these trends is essential to supporting the responsible use of antibiotics and to overcoming antimicrobial resistance. The study comprised 1658 articles from the Scopus database published between 1988 and August 2025. The Bibliometrix R package and VOSviewer software were used to conduct bibliometric analyses, including citation analysis, co-authorship mapping, keyword co-occurrence networks, thematic mapping, and trend detection. Using these analytical approaches, results showed that annual publication output peaked in 2024. Furthermore, thematic evolution analysis indicated a shift from early pharmacological research to environmental remediation and antimicrobial resistance studies. Research themes shifted from early pharmacological studies to analytical chemistry and residue detection, and ultimately to environmental remediation technologies, including photocatalytic degradation, biochar adsorption, and advanced oxidation processes (2016-present). The most cited articles on enrofloxacin focused on bioaccumulation, phototoxicity, photodegradation, and ecotoxicological investigations. Studies on enrofloxacin have shifted from basic pharmacology to environmental and resistance issues. Based on these trends, the findings highlight the growing need for interdisciplinary and translational research. Interdisciplinary solutions to the interrelated issues of food security, antimicrobial resistance, and environmental sustainability that enrofloxacin research ultimately serves are required.

BACKGROUND:We previously established HEK293 cells deficient in SEL1L, a key component of endoplasmic reticulum-associated protein degradation (ERAD), and attempted to identify factors affected by ERAD dysfunction through comprehensive MS analysis. Among the factors increased by SEL1L-deficiency, lysyl oxidase (LOX) which plays a role in extracellular matrix cross-linking was involved. METHODS AND RESULTS:To elucidate the regulatory mechanisms of LOX mRNA and protein, we applied several ERAD-deficient cells and drug treatments. In SEL1L-deficient cells, LOX mRNA expression levels were observed to increase approximately twofold, and the increase in high molecular weight preproLOX protein was more remarkable in each SEL1L deletion. SEL1L-deficiency also slightly increased the amount of secreted LOX protein cleaved by proteases. Increased proproLOX was also observed in cells lacking Hrd1 that associates with SEL1L. Interestingly, LOX protein was hardly increased in cells deficient for EDEM2 and TXNDC11, which are involved in mannose trimming of N-glycosylated proteins. Since ERAD failure may induce sustained ER stress, we examined the effects of three ER stress inducers on LOX expression. Changes in LOX mRNA following 6-h treatment with each reagent was negligible compared to the major ER stress-inducible mRNA. In contrast, long-term treatment with thapsigargin and tunicamycin increased intracellular LOX protein, but significantly decreased secreted LOX protein. Finally, we examined the effects of proteasome and lysosome inhibitors on LOX expression and, unexpectedly, each reagent hardly increased LOX mRNA or protein levels. CONCLUSIONS:These results suggest that expression of intrinsic LOX protein is regulated by SEL1L and Hrd1 in a ubiquitin-proteasome-independent manner.

Foot-and-mouth disease (FMD) is a highly contagious transboundary viral disease causing significant economic losses in livestock. This study investigated the serotype distribution and molecular epidemiology of FMD viruses (FMDV) circulating in Sudan between 2019 and 2022. A total of 51 epithelial tissue samples were collected from outbreaks in Khartoum, Blue Nile and Northern States. Samples were analyzed via virus isolation in bovine thyroid cell culture (BTY), antigen detection ELISA, and real-time reverse transcription PCR (rRT-PCR). Antigen detection ELISA successfully typed 13 of 51 (25.5%) epithelial tissue samples, of which 10 were identified as serotype A and 3 as serotype O. In contrast, rRT-PCR detected FMDV RNA in 33 of the 35 samples (94.3%) that were suitable for molecular analysis, showing the superior diagnostic sensitivity of this molecular method. FMDV positive samples were further characterized by sequencing the VP1-coding region. These data demonstrated the presence of two serotypes (A and O), while SAT serotypes were not detected during the study period. Serotype A was detected in outbreaks during 2019, 2021 and 2022, while serotype O predominated in 2020. Phylogenetic analysis of VP1-coding sequences showed that serotype A sequences clustered within the A/AFRICA topotype, lineage G-IV and were closely related to strains from Egypt and Ethiopia. Serotype O sequences were clustered within the EAST AFRICA-3 (EA-3) topotype and showed ≥ 96% identity with the Egyptian isolates. VP1 analysis revealed conserved functional motifs alongside variability within the immunodominant antigenic region, suggestive of ongoing viral evolution with potential implications for vaccine effectiveness. These results suggested the persistent circulation of FMDV serotypes A and O in Sudan with close genetic relationships to viruses recovered from neighboring countries. These findings suggested the transboundary transmission of FMDVs and a role for cross-border livestock movements in virus dissemination. Continuous molecular surveillance and regional cooperation are essential to improve vaccine matching and strengthen FMD control strategies in endemic regions.

Cardiotoxicity and impairment of cardiac function are mostly diagnosed by echocardiography and based on objective metrics of cardiac function. The aim of the present study is to investigate the effect of azithromycin on the echocardiographic characteristics in healthy donkeys. Ten healthy donkeys were enrolled in a prospective crossover study. The study included two groups: (1) a placebo (normal saline, NaCl 0.9%), and (2) azithromycin (at a dose of 5 mg/kg body weight). A 2.0-3.9 MHz phased-array transducer was used for echocardiographic examination. Echocardiographic examinations were performed for donkeys before treatment (T0) and at 15, 30, 60, 90, 120, 180, and 240 min after azithromycin administration. In the azithromycin group compared to Placebo, the drug induced a significant increase in interventricular septal thickness in end-diastole (IVSTd) and interventricular septal thickness in end-systole (IVSTs) (P < 0.05), but it induced a significant decrease in left ventricular internal diameter (LVID) at end diastole (LVIDd) and at end systole (LVIDs) (P < 0.01). There was also a significant (P < 0.05) decrease in left ventricular posterior wall thickness at the end of diastole (LVPWd) and at the end of systole (LVPWs) compared with placebo. Left ventricular volume increased significantly (P < 0.05) at the end diastole (EDV), and at the end systole (ESV). Fractional shortening (FS%) decreased significantly (P < 0.05) in donkeys receiving azithromycin compared to placebo. In conclusion, azithromycin in healthy donkeys induces transient and mild effects on echocardiographic parameters with fewer overt clinical signs. Further studies are needed to evaluate the efficacy of this drug, specifically in equines with underlying cardiac disease.

Objectives: To explore the citation impact, journals, international collaborations, trends of research topics and gain more visibility for the Saudi contribution to the global scientific landscape. Methods: This bibliometric study analyzes the top 100 cited publications affiliated with Saudi Arabia in Scopus, from inception to January 2026. The extracted bibliometric indicators include total citation metrics, sources, collaboration maps, and co-occurrence networks of keywords and collaborations. Results: The results indicate a strong predominance for medicine and health sciences as the subjects of the most prolific and significant number of citations. A substantial proportion of the most cited papers originates from major global health projects, in particular the Global Burden of Disease (GBD) consortium, which focuses on mortality, morbidity, and epidemiological metrics. Clinical and public health fields are highly represented, including obesity and cardiovascular risk, disease burden, and population health metrics. The most frequent journals include the leading medical journals in the field, namely The Lancet, Nature, Science and the New England Journal of Medicine. Keyword analysis confirms the dominance of medical themes; the most prominent keywords included epidemiology, risk factors, and global health indicators. Within the biomedical predominance, bioinformatics tools such as MEGA software contribute to the citation impact. Conclusions: Saudi Arabia's citation impact is predominantly driven by international consortia participation and bioinformatics tool development, highlighting the opportunities for strengthening independent and nationally led research programs of global significance.

The proliferative capacity and drug resistance of cancer cells are thought to be related to adaptations to the low nutrient and hypoxic conditions known as the tumor microenvironment. This adaptation is suggested to involve the unfolded protein response (UPR) triggered by the endoplasmic reticulum (ER) stress. Therefore, the ER stress induced under these conditions is considered one of the attractive targets for antitumor drug development. In this study, we designed and synthesized decenoic acid derivatives and found two compounds, 13-Chloro-6-(4-fluorophenoxy)tridec-6-en-8-yn-1-ol (Cpd6) and 13-Chloro-6-(4-methoxyphenoxy)tridec-6-en-8-yn-1-ol (Cpd2) showed cytotoxicity against human glioma cell-line, T98G, under the serum- and glucose-deprived condition. These two compounds exerted inhibitory effects on several ER and Golgi stress responses triggered under this low-nutrient condition. Furthermore, Cpd6 profoundly downregulated the expression of c-Myc protein, a well-known oncogenic factor, in T98G cells. This study is expected to contribute to the development of fatty acid-derived antitumor compounds targeting the ER and Golgi stress responses.

An intravenous drug called sugammadex is used to counteract the adverse reactions of the relaxation medications rocuronium and vecuronium, which are given during operations to provide full anesthesia. The principal objective of the presented study is developing and validating a complete, innovative, fast, isocratic, and green shelf life liquid chromatography methodology, Sugammadex sodium levels in injectable therapies can now be measured. A number of tests were performed on sugammadex sodium in accordance with ICH guidelines. Sugammadex sodium and its related degradants were effectively separated via isocratic separation. At ambient conditions, the Zorbax SB ODS stationary phase was used to quantify and validate the drug substance. The isocratic mobile phase runs at a flow rate of 1.0 mL/min. It includes the eluting phase that comprises of 7 mL/L aqueous solution of triethylamine adjusted at pH 3.0 with phosphoric acid: ethanol (750:250) (V:V). The positive environmental impacts of the LC technique are demonstrated by the combined AES grade of 87, CACI rating of 78, AGSA rating of 75, MoGAPI rating of 80, BAGI rating of 82.5, and final whiteness rating of 96.7.

Heat stress (HS) is one of the many challenges facing the poultry industry. Many effective strategies reduce the harmful effects of HS on birds, the most important of which are feed additives due to their many beneficial properties. The present study investigated the effects of dietary supplementation with antibacterial peptides (melittin [MEL]) and turmeric essential oil on growth performance, cecum microbial content, immunity, and gene expression in heat-stressed broilers. The first experiment, a completely randomized design, used three levels of MEL (50, 100, and 150 mg kg -1), with five replicates of 10 chicks each. In the second experiment, a total of 600 one-day-old chicks were completely randomly distributed into five experimental groups. The five experimental groups included the following: the first group was fed a basal diet without feed additives or exposed to HS (the control group), the second group was fed a basal diet and exposed to HS without feed additives (COHS), while the other groups were exposed to HS and adding turmeric essential oil (TEO, 200 mg kg-1), melittin (MEL, 150 mg kg-1), and their mixture (MTC). Results of the first experiment indicated that body weight gain (1 to 28 days) increased linearly, while the feed conversion ratio decreased linearly (P < 0.05) with increasing MEL supplementation. In the second experiment, results indicated that dietary supplementation with MTC improved broilers' growth performance through lowering the feed conversion ratio and raising the body weight gain, and crude protein digestibility (P < 0.05). It also enhanced carcass characteristics (P < 0.05) by increasing carcass yield, breast meat, and thigh meat, while decreasing abdominal fat. Supplementing MTC boosted the immuno-antioxidant status by increasing IgA, IL-10, and superoxide dismutase levels (P < 0.05) and decreasing IL-6 and MDA levels. Additionally, MTC maintained intestinal integrity by increasing intestinal ZO-1 and MUC-2 gene expression (P < 0.05) and increasing Lactobacillus count. In conclusion, adding MTC mitigated the negative effects of HS by boosting growth performance and immune-antioxidant status, modifying intestinal microbiota, and up-regulating ZO-1 and MUC-2 gene expression in broiler chickens.

Background:At least 500 genetic polymorphisms associated with the CYP2C19 and CYP2C18 enzymes have been identified, yet few polymorphisms have been measured in the Saudi population. Therefore, this study was aimed at determining the frequencies of numerous unmeasured CYP2C19 and CYP2C18 genetic variations, and their clinical and pharmacological implications, in KSA. Research design and methods:A multicenter cross-sectional study was conducted to determine the frequency of 141 CYP2C19 and CYP2C18 genetic variants. Blood samples from 374 Saudi adults were genotyped. GenomeStudio software was used for genotype calling for all samples. Bioinformatics analyses were performed for variant annotation. We excluded the rs4244285 variant since our main objective was to determine the frequency of numerous unmeasured or poorly documented CYP2C19 and CYP2C18 genetic variants in KSA. Including rs12769205 mitigated the haplotype analysis concern. Both rs4244285 and rs12769205 are CYP2C19∗2 key variations linked to loss of function. Results:Of the 141 variants associated with the CYP2C19 and CYP2C18 genes measured in 374 participants, 53 were detected, and the other 88 were not detected. Five detected variants had high frequencies: rs7067866, rs7916649, rs4917623, rs12248560, and rs11188072. Several detected variants were associated with clinical effects and appeared to influence drug metabolism. Conclusions:This study investigated the presence of many previously undescribed CYP2C19 and CYP2C18 genetic variants in the Middle Eastern population. Tens of previously unmeasured CYP2C19 and CYP2C18 variants were identified in the Saudi population. Our findings have potential to contribute to pharmacogenomics and personalized medicine, and to support clinical decision-making.

This article presents my personal and scientific perspective as a pharmacologist and drug discovery specialist for camel research. My main aim over the last ten years was to provide a multidisciplinary contributions for the advancement of camel health through pharmacology, molecular modelling, bioinformatics, and veterinary medicine. Between 2014 and 2024, this research resulted in 54 publications across 26 journals with a strong international collaboration network involving 99 coauthors. The main areas of research were drug discovery for Middle East Respiratory Syndrome Coronavirus (MERS-CoV), pharmacokinetics of veterinary drugs in camels, bibliometric research on camel science around the globe, meta-analyses for the therapeutic applications of camel milk, camels as hosts for zoonotic diseases, trypanosomiasis as a neglected disease in camels, identification of antiparasitic molecules, molecular modeling of pathogen–host interactions including the understanding of camel-specific metabolic pathways. The use of a One Health strategy through these multidisciplinary contributions resulted in the discovery of new therapeutic options for camel diseases. The research also led to 15 patents in drug discovery, including United States patents targeting MERS-CoV fusion inhibition and broad-spectrum antitrypanosomal compounds relevant to camel health. These interdisciplinary studies combined with my experimental pharmacology findings represent an integrated effort in computational drug discovery, in vitro investigative pharmacology, and One Health approach applied to camel diseases that deserves a new therapeutic option. Personally, I am grateful for the opportunities I was blessed with through this journey and I look forward to further efforts and discoveries that will contribute effectively to camel health and welfare.

Camel nasal myiasis, caused by the larvae of Cephalopina titillator, poses significant health and economic burdens in tropical and subtropical regions. Ivermectin, a widely used antiparasitic, has shown promise, but its detailed tissue damaging effects and its mechanisms on this parasite remain underexplored. This study was aimed to elucidate the mechanism of action of Ivermectin against C. titillator larvae, the causative agent of camel nasal myiasis, by evaluating its histopathological and immunohistochemical effects on larval tissues, focusing on cellular structures, proliferative activity, and apoptosis. Larvae were collected from slaughtered camels in Al-Ahsa, Saudi Arabia, and exposed to Ivermectin (1 µg/ml) for 8 hours. Histopathological analysis assessed tissue damage in the cuticle, muscles, fat bodies, and gut. Immunohistochemistry was performed to detect Proliferating Cell Nuclear Antigen (PCNA) and caspase 3 expressions to evaluate cell proliferation and apoptosis, respectively. Control larvae received vehicle treatment. Ivermectin induced widespread damage across multiple larval strucutres. Structural barriers were compromised through cuticle thinning, locomotion was impaired by extensive muscle degeneration, and metabolic function was disrupted by fat body necrosis and lipid depletion. Digestive capacity was adversely affected by gut epithelial degeneration and brush border disruption. At the cellular level, ivermectin markedly suppressed PCNA expression in gut epithelium, indicating inhibition of tissue renewal, while strongly activating caspase-3-mediated apoptosis in the cuticle, fat body and gut. These combined effects suggest irreversible functional collapse rather than transient paralysis. Ivermectin impairs larval structural and cellular integrity, mobility, and metabolic functions while promoting apoptosis and inhibiting tissue repair. These findings clarify its larvicidal efficacy and support its use in managing C. titillator infestations in camels.