The phylum Apicomplexa encompasses a diverse group of protozoan parasites of profound medical and veterinary importance, among which the genera Plasmodium and Babesia stand out because of their shared pathological niche within host erythrocytes. While Plasmodium spp., transmitted by anopheline mosquitoes, are the causative agents of human and zoonotic malaria, Babesia spp., transmitted by ixodid ticks, cause babesiosis, a burgeoning zoonosis and a significant cause of economic loss in the livestock industry. Globally, babesiosis is an emerging threat, with Babesia microti being the primary cause of human babesiosis in the USA and Europe, transmitted by Ixodes scapularis ticks. Although their life cycles diverge critically, most notably in the presence of an exo-erythrocytic hepatic stage in Plasmodium and its absence in Babesia, both parasites share a core pathogenic strategy. They invade, replicate within, and lyse red blood cells, leading to the clinical manifestations of haemolytic anaemia and fever. This review undertakes a comprehensive comparative analysis of Plasmodium and Babesia, leveraging the vast body of research on the former to illuminate the biology and vulnerabilities of the latter. We systematically dissected their parallel life cycles in both vertebrate and invertebrate hosts, elucidating the molecular mechanisms underlying their distinct developmental pathways and transmission strategies. A central focus is placed on the conserved machinery of erythrocyte invasion, a multi-step process mediated by an apical complex of secretory organelles (micronemes and rhoptries) and specific ligand-receptor interactions, which presents a prime target for intervention. Beyond cellular invasion, we delve into the shared metabolic architecture that constitutes the foundation for cross-species drug discovery. We critically evaluated high-value conserved targets, such as the mitochondrial cytochrome bc₁ complex, proteasomal protein degradation system, unique apicoplast organelle with its prokaryotic pathways, essential kinases, and folate biosynthesis pathway, dihydroorotate dehydrogenase (DHODH), ATP4, falcipain proteases, and the heme detoxification pathway. For each target, we discuss the mechanism of action of existing and experimental inhibitors, the evidence for their efficacy across both genera, and the emerging challenge of drug resistance. Ultimately, this synthesis argues that the deep evolutionary relationship between Plasmodium and Babesia has resulted in a core set of indispensable biological processes that are susceptible to parallel therapeutic interventions. By mapping the shared vulnerabilities within their erythrocytic pathogenesis, this review will be useful in designing novel, broad-spectrum antiprotozoal agents and strategic drug repurposing efforts, thereby advancing the fight against both malaria and babesiosis.

HER2-overexpressing (3+) breast cancer exhibits distinct clinicopathological characteristics compared to HER2 1+ and 2+ tumors; however, differences in their molecular features remain poorly defined. This study aimed to investigate clinicopathologic and somatic alterations in breast tumors stratified by HER2 status. Ninety breast cancer patients were stratified by HER2 expression (1+, 2+, 3+) using immunohistochemistry and confirmed by FISH. For each patient, paired diagnostic biopsies and post-neoadjuvant chemotherapy (NACT) residual tumors were analyzed. Targeted next-generation sequencing (NGS) was performed on 34 paired samples, and shortlisted variants were validated by digital droplet PCR (ddPCR) in 90 cases. Among the 90 paired samples, 40 were HER2-high, and 50 were HER2-low/TNBC. HER2-high tumors presented with a larger mean size (3.34 cm vs. 2.29 cm) but lower lymph-node metastasis (40

Tropical theileriosis, caused by the protozoan parasite Theileria annulata, is an economically significant constraint to cattle production, with disease control increasingly compromised by emerging resistance to the primary chemotherapeutic agent, buparvaquone. This study aimed to screen candidate compounds for in vitro anti-theilerial activity and host cell safety. Four compounds — hesperidin methyl chalcone (HMC), p-coumaric acid, dodecyl trimethylammonium bromide (DDTAB), and diclofop-methyl — were evaluated for anti-theilerial activity using a resazurin-based viability assay on a T. annulata-infected bovine lymphocyte cell line. Host cell safety was assessed via cytotoxicity assays on bovine peripheral blood mononuclear cells and haemolytic assays on bovine erythrocytes. DDTAB, a cationic surfactant, showed the strongest concentration-dependent inhibition among the four (IC₅₀ = 1125.4 μM), while the remaining compounds were substantially weaker (IC₅₀ 3048.2 – 5771.7 μM). All compounds, including DDTAB, showed low host cell toxicity (<19

Equine surra, caused by Trypanosoma evansi, is an important haemoprotozoan disease of working equids. This prospective descriptive pilot field study evaluated short-term changes after quinapyramine treatment and monitored T. evansi DNA detection during follow-up. Twelve indigenous horses from Ghazipur district, Uttar Pradesh, India, were included. Six naturally infected PCR-positive horses received a commercial quinapyramine preparation at 5.0 mg/kg body weight by subcutaneous injection, and six PCR-negative horses served as contemporaneous comparison animals. Blood collected on Days 0, 3, 7, 14, and 21 was examined by the microhaematocrit centrifugation technique, Giemsa-stained blood-smear examination, conventional PCR targeting a 196-bp invariable surface glycoprotein sequence, and indirect antibody ELISA. No parasites were detected microscopically in treated horses from Day 3 onward. PCR-negative status was recorded in 2/6 horses on Day 3, 4/6 on Day 7, and 3/6 on Days 14 and 21. The greatest observed PCR-negative proportion was therefore 66.7% on Day 7, followed by 50.0% on Days 14 and 21. The recorded group-level antibody relative percentage positivity increased from 75 on Day 0 to 90 and 91 on Days 3 and 7, respectively, and declined to 50 and 51 on Days 14 and 21. The findings indicate rapid suppression of microscopically detectable parasitaemia but incomplete and non-sustained PCR-negative conversion in some horses during the 21-day follow-up. Conventional PCR provided additional post-treatment information beyond microscopy, whereas antibody ELISA reflected continuing antibody reactivity rather than immediate parasitological cure. Larger controlled studies with longer follow-up and quantitative molecular testing are required to define treatment effectiveness more precisely.

Selective Intra-arterial Therapy (SIRT) using 90Y-spheres is a well-established treatment for hepatocellular carcinoma (HCC), but its high cost creates an economic barrier. We present the utility, preliminary therapeutic efficacy, and safety of 188Re-microspheres SIRT plus sorafenib in prospective interventional study. Sixty patients with Barcelona Clinic Liver Cancer (BCLC) B/C HCC underwent 188Re-SIRT with 3678 ± 1214 MBq (100 ± 33 mCi) 188Re-microspheres in combination with sorafenib. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. Prognostic value of FDG PET/Triple-phase CT (TPCT) was analyzed, comparing modified response evaluation criteria in solid tumors (mRECIST) with positron emission tomograph response criteria in solid tumors (PERCIST) criteria. Cox proportional hazards and Kaplan–Meier analyses were performed to identify prognostic factors affecting preliminary treatment efficacy and survival. Single-point dosimetry was performed using Qthera.AI software. The median OS was 11 months. Qthera.AI estimated mean time integrated activity coefficient for 188Re-microspheres was 27.0 ± 17.7 h. The mean absorbed doses to tumor, healthy liver, lungs, and spleen were 92.4 Gy, 7.0 Gy, 3.4 Gy, and 21.9 Gy, respectively. Both mRECIST and PERCIST showed comparable median PFS (3.0 months; p=1.000) and extra-hepatic PFS (3.0 months; 0.317), while PERCIST indicated a higher median hepatic PFS (6.0 vs. 3.0 months; 0.655). mRECIST and PERCIST classified 45.0

Background: Six representative ITS1-PCR amplified products were used for the amplifications of conserved regions of 18S and 5.8S rDNA to amplify Internal Transcribed Spacer1 (ITS1) gene of 540 bp of Typanosoma evansi isolates in equine from three agroclimatic zones of Eastern Uttar Pradesh, India. Methods: Multiple sequence alignment was done by MAFFT online multiple sequence alignment tools by selecting the necessary parameters. The phylogenetic study of ITS1 gene revealed all the three isolates (T. evansi horse India Uttar Pradesh-North Eastern Plane Zone, T. evansi mule India Uttar Pradesh-Eastern Plane Zone and T. evansi horse India Uttar Pradesh-Vindhyan Zone) of T. evansi were clustered in single group. Result: Multiple alignment of nucleotide sequence of ITS1 genes showed that T. evansi isolates from Eastern region of Uttar Pradesh, Indian had > 99% nucleotide homology with isolates of camel Iran (KX898420), camel Egypt (MW603779.1) and buffalo China (FJ712715.1).

Bovine tropical theileriosis, caused by Theileria annulata, is a significant economic burden in endemic regions. The limitations of current control measures necessitate the development of new therapeutic agents. This study evaluated the anti-Theileria potential and host cell safety of rutin, andrographolide, dodecyltrimethylammonium bromide (DTAB), and fusidic acid. Antiparasitic efficacy was assessed using a resazurin-based growth inhibition assay on T. annulata-infected bovine lymphocytes. Cytotoxicity and haemolytic activity were evaluated using healthy bovine peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs), respectively. All compounds exhibited concentration-dependent anti-theilerial activities. Andrographolide was the most potent (IC₅₀ = 542.89 µM), followed by fusidic acid (IC₅₀ = 573.64 µM) and DTAB (IC₅₀ = 633.98 µM), while rutin showed weak activity (IC₅₀ = 2748.04 µM). In the cytotoxicity assay, andrographolide was the least toxic to PBMCs (15.06

Cepharanthine, a bioactive alkaloid dervived from the plant Stephania cephalantha has recently gained significant attention for its promising therapeutic potential. In view of the increasing resistance and toxicity reports associated with current treatments for Trypanosoma evansi, the present study evaluated the anti-trypanosomal activity of different concentrations of Cepharanthine against T. evansi under both in vitro and in vivo conditions. Cepharanthine exhibited significant anti-trypanosomal activity, with an IC50 value of 1131 nM at 24 h. Additionally, high specific selectivity indices (SSI) of 78.84 on Vero cell line and 107.78 on equine PBMCs, indicates high safety profile. In the mice model, Cepharanthine cleared parasitemia within 10 days and extended survival period of infected mice by more than 30 days when administered at a dose of 12.5 mg/kg body weight, followed by additional dosages at 48- and 72-hour intervals. In transcript analysis, the upregulated mRNA expression of trypanothione reductase (2.15- fold, p < 0.05) and aurora kinase (1.27-folds, p < 0.05) suggested the disturbance in redox homeostasis and cell cycle regulation by Cepharanthine. On the other hand, trans-sialidase, oligopeptidase, arginine kinase, topoisomerase II, calcium ATPase 1 and ornithine decarboxylase remained unaffected after 24 h of exposure. Collectively, these findings indicate that Cepharanthine exert potent anti-T. evansi activity and may serve as safer alternative to existing conventional anti-trypanosomal drugs against T. evansi.

Graves’ disease (GD) is the most common cause of thyrotoxicosis among children, characterized by stimulating autoantibodies against the thyrotropin receptor. In the pediatric population, GD is often more aggressive than in adults, with spontaneous remission rates after standard antithyroid drug therapy rarely exceeding 30% after 2 years of treatment. Radioactive iodine (RAI) therapy offers a minimally invasive, definitive solution by inducing permanent thyroid ablation through beta-particle-mediated follicular destruction. This review explores the timing of definitive therapy, the radiobiological mechanisms of iodine-131, and the comparative efficacy of RAI versus total thyroidectomy. Drawing on the 2016 American Thyroid Association and 2022 European Thyroid Association consensus guidelines, the analysis emphasizes the shift toward high-dose ablative strategies to ensure treatment success and minimize the theoretical risks of sublethal radiation exposure. Long-term safety data regarding secondary malignancies, reproductive health, and orbitopathy are scrutinized through recent evidence, confirming the relative safety of RAI in children over 10 years of age.

To evaluate the efficacy and safety of robotic-arm-assisted [18F]NaF-PET/CT-guided intra-articular block for lumbar facet joint (LFJ) or sacroiliac joint (SIJ) arthropathy. In this single-centre, non-randomized, prospective phase 2 clinical-trial, participants with chronic low back pain (CLBP) were recruited from August 2022 to June 2024. Participants having NaF-avid LFJ or SIJ on [18F]NaF-PET/CT underwent robotic-arm-assisted intra-articular block with steroids and local anaesthesia. Baseline, immediate post-procedural, and 3-month follow-up visual analog score (VAS), Low-Back Outcome Scale (LBOS), Oswestry Disability Index (ODI), and change in SUV values of target joints were documented. The primary end-point of the trial was ≥ 50

Visceral leishmaniasis is a neglected tropical disease. Drug resistance and toxicity are the critical issues with the currently available antileishmanial drugs. Therefore, research efforts are underway to identify and validate new drug targets specific to Leishmania parasite. The enzyme homoserine dehydrogenase (HSD) functions in the third step of aspartate pathway. The present study focuses on the biophysical and biochemical characterization of HSD enzyme from Leishmania donovani (LdHSD) which is unique to the parasite with no homologous enzyme in the host. LdHSD gene was cloned in pET28c(+) vector and transformed in E. coli BL21 (DE3) strain. LdHSD recombinant enzyme of molecular weight 46.6 kDa with 6X-His tag at the C-terminal end was expressed, purified by nickel affinity chromatography and confirmed by western blot analysis using anti-His antibody. Effect of pH, temperature, salts, metal ions and amino acids on the recombinant enzyme were evaluated. Kinetic parameters of LdHSD were evaluated for substrates L-homoserine and NADP+. Biophysical analysis revealed that the enzyme is rich in β-sheets. Thermal denaturation study revealed that the protein is stable up to 45 °C. Furthermore, comprehensive comparative sequence analysis and structural modeling revealed the structural and functionally important residues, which are involved in the catalytic mechanisms. The putative binding mode of the natural substrate L-homoserine into the active site of LdHSD was also elucidated. These findings provide a foundation for the development of selective, target-based inhibitors against the HSD enzyme of the parasite.

Introduction: Integrin antagonist complex (IAC), a novel alpha v beta 3 integrin antagonist peptidomimetic, has emerged as a promising agent for molecular imaging of tumor angiogenesis. This study evaluates the biodistribution and clinical efficacy of [Ga-68]Ga-DOTAGA-IAC PET/CT in detecting radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), comparing its diagnostic performance with [F-18]F-FDG PET/CT. Materials and Methods: In this prospective pilot study, RAIR-DTC patients underwent whole-body imaging with [F-18] F-FDG PET/CT, followed by [Ga-68]Ga-DOTAGA-IAC PET/CT. Biodistribution patterns of [Ga-68]Ga-DOTAGA-IAC were assessed. Lesions with abnormal, nonphysiologic tracer uptake (showing activity exceeding mediastinal blood pool) were considered positive for disease. Imaging findings were compared between the two modalities, and quantitative metrics, including SUVmax, metabolic tumor volume, and total lesion glycolysis, were analyzed statistically. Results: Among 30 patients with RAIR-DTC, [Ga-68]Ga-DOTAGA-IAC PET/CT revealed predominant physiological tracer uptake in the kidneys. [F-18]F-FDG PET/CT identified 97 lesions, predominantly nodal (73.2%), while [Ga-68]Ga-DOTAGA-IAC PET/CT detected 34 lesions, 50% of which were nodal. Few patients exhibited multiple lesions with varying uptake grades, with 20% showing coexisting higher-grade lesions (grade II or above) on [Ga-68]Ga-DOTAGA-IAC PET/CT. Conclusion: Angiogenesis imaging using [Ga-68]Ga-DOTAGA-IAC PET/CT demonstrates limited sensitivity for lesion detection in patients with RAIR-DTC compared with [F-18]F-FDG PET/CT. However, the potential of [Ga-68]Ga-DOTAGA-IAC as a diagnostic tool for other cancers has been used in other cancers with positive imaging characteristics warranting further exploration.