Abstract:Transglutaminase 2 (TG2) is a widely distributed enzyme with multiple functions, including calcium-dependent protein cross-linking, signal transduction, extracellular matrix stabilization, autophagy, and immune regulation. Although TG2 has been extensively studied in human and murine models, its specific functions in camelids remain poorly elucidated. This review, driven by a hypothesis, integrates established knowledge of TG2 with the unique physiological characteristics of Camelus dromedarius and Camelus bactrianus, such as their ability to tolerate high temperatures, resist dehydration, maintain erythrocyte integrity, and adapt immunologically. The review explores potential roles for TG2 in processes including erythrocyte oxygen transport, cellular protein homeostasis, heat shock responses, and various aspects of cardiovascular, renal, hepatic, immune, and reproductive biology. Furthermore, the review considers the possibility that TG2 dysregulation may contribute to camelid health issues, particularly hepatic and renal fibrosis, parasite-associated inflammation, and metabolic disorders—conditions that bear significant similarities to bovine health problems such as liver fluke disease and heat stress. The review highlights areas where evidence is extrapolated from other mammals and outlines research priorities, including TGM2 sequence analysis, tissue expression profiling, activity-based proteomics, and validation of TG2-related biomarkers. By proposing TG2 as a potential, rather than confirmed, mediator of camelid adaptation, this review offers a careful conceptual framework for future comparative and veterinary research pertinent to both camelid and bovine health.
Abstract:Cognitive decline complicates a wide range of neurological conditions, from Alzheimer’s disease and stroke to epilepsy and traumatic brain injury. Yet, we still lack robust pharmacological options that can modify the underlying disease rather than just treat symptoms. Because these disorders share several core mechanisms—including neuroinflammation, disrupted metal homeostasis, oxidative stress, and blood-brain barrier breakdown—there is a strong translational case for drugs that can simultaneously target multiple mechanisms. Disulfiram, an aldehyde dehydrogenase inhibitor approved for alcohol use disorder, has recently garnered interest as a repurposing candidate due to its pharmacological effects extending beyond alcohol aversion. This review synthesizes the mechanistic and preclinical evidence supporting disulfiram as a potential neuroprotective strategy for cognitive impairment. The central premise is that disulfiram and its metabolite diethyldithiocarbamate engage several disease-relevant pathways: enhancement of ADAM10-dependent non-amyloidogenic amyloid precursor protein processing, inhibition of gasdermin D pore formation and NLRP3 inflammasome activation, modulation of copper homeostasis and ferredoxin 1-associated cuproptosis signaling, and preservation of blood-brain barrier integrity. Evidence from models of Alzheimer’s disease, epilepsy, cerebral ischemia/reperfusion injury, intracranial hemorrhage, and ethanol-related neurotoxicity indicates that disulfiram can attenuate neuropathological injury and, in selected models, improve learning, memory, or behavioral outcomes. Nonetheless, the current evidence remains predominantly preclinical, heterogeneous, and limited by uncertainty regarding brain exposure, dosing, formulation, long-term safety, and patient selection. Clinical translation will necessitate biomarker-informed trials, careful management of hepatic, neurological, psychiatric, and alcohol-related risks, and a clear distinction between neuroprotection and demonstrated cognitive benefit. Overall, disulfiram represents a timely example of mechanism-led neuropharmacological repurposing, yet its role in cognitive disorders should be considered a testable therapeutic hypothesis rather than an established intervention.
Abstract:Background: Ischemic stroke is a major cause of mortality and long-term disability worldwide. Oxidative stress and inflammation play central roles in the pathogenesis of cerebral ischemia–reperfusion injury, highlighting the need for effective neuroprotective strategies.\nObjective: To evaluate and compare the neuroprotective effects of β-glucan, nerinetide, and fluvastatin, and to assess their dose-dependent efficacy in an experimental model of cerebral ischemia–reperfusion injury.\nMethods: Adult rats were randomly assigned to normal control, sham-operated, ischemia–reperfusion untreated, and treatment groups receiving β-glucan, nerinetide, or fluvastatin at low and high doses (six rats per group). Cerebral ischemia–reperfusion injury was induced experimentally. Oxidative stress markers, including glutathione peroxidase, superoxide dismutase, and reactive oxygen species, were measured in brain sample. Data were expressed as mean ± standard deviation. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s post hoc test, while dose-dependent effects were evaluated using Welch’s independent samples t-test. A p-value less than 0.05 was considered statistically significant.\nResults: Ischemia–reperfusion injury significantly increased oxidative stress, as evidenced by elevated reactive oxygen species levels and reduced antioxidant enzyme activities. Treatment with β-glucan, nerinetide, and fluvastatin significantly attenuated oxidative stress compared with the untreated group. High-dose regimens generally produced greater improvements in oxidative stress markers than low-dose regimens, indicating a dose-dependent effect. Among the tested agents, nerinetide and fluvastatin demonstrated comparatively stronger antioxidant effects.\nConclusion: β-Glucan, nerinetide, and fluvastatin exert significant neuroprotective effects against ischemia–reperfusion-induced oxidative damage, with evidence of dose-dependent efficacy. These findings support their potential as therapeutic candidates for mitigating oxidative stress in ischemic stroke.
Abstract:Cancer during pregnancy is increasingly common, leading to greater use of systemic antineoplastic therapy during gestation. Although chemotherapy administered during the second and third trimesters is generally considered relatively safe with respect to major congenital malformations, its long-term effects on offspring neurodevelopment remain incompletely characterized. Epidemiological evidence largely demonstrates preserved global intelligence in exposed children; however, subtle impairments in higher-order cognitive domains, including executive function, working memory, and visuospatial processing, have been reported, with treatment-related iatrogenic prematurity being a key confounding factor in neurodevelopmental outcomes in this population. From a neuropharmacological perspective, fetal central nervous system vulnerability may arise from transplacental drug transfer, developmental immaturity of the fetal blood–brain barrier, direct cytotoxicity to neural stem and progenitor cells, chemotherapy-induced neuroinflammation and oxidative stress, and disruption of oligodendrocyte maturation and myelination. Recent genomic studies have revealed persistent somatic mutational signatures in fetal hematopoietic stem cells following in utero exposure to platinum-based chemotherapy. Individual susceptibility may be influenced by pharmacogenetic polymorphisms in genes involved in neuronal repair and synaptic plasticity, such as APOE and BDNF, and by chemotherapy-induced epigenetic reprogramming. Collectively, these findings highlight the need for prospective longitudinal surveillance and the development of targeted neuroprotective strategies for children exposed to chemotherapy in utero.
Abstract:Tirzepatide (TZP) has emerged as a significant therapeutic agent for the management of obesity and type 2 diabetes mellitus (T2DM). In response to meals, TZP enhances insulin secretion by leveraging the incretin effect of GLP-1 and GIP. This review elucidates the mechanism of action of TZP in regulating weight and blood glucose levels. Additionally, the review explores other medical applications of TZP. Moreover, the potential application of TZP in neurodegenerative disorders is also considered. However, this review addresses ongoing debates about the long-term safety and metabolic effects of TZP, particularly regarding GIP stimulation, which may lead to adverse outcomes such as fat redistribution and lipogenesis. Recent cardiovascular outcome data have established its non-inferiority to other GLP-1 agonists, although discussions persist regarding the precise role of GIP agonism and long-term cost-effectiveness. The review underscores the necessity for a balanced approach that integrates scientific accuracy with ethical responsibility when considering TZP for metabolic disorders. The review highlights the importance of ongoing research to fully understand the benefits and risks of TZP, ultimately aiming to improve patient outcomes in the management of obesity and T2DM. This comprehensive analysis serves as a foundation for future studies and clinical applications of TZP in metabolic health.
Abstract:The thyroid axis is a master regulator of metabolism, development, and homeostasis in mammals. However, the diversity of endocrine strategies employed by species adapted to extreme environments remains incompletely understood. Camelids, particularly the dromedary camel (Camelus dromedarius), represent an exemplary model of physiological resilience, thriving in arid deserts characterized by thermal extremes, water scarcity, and poor-quality forage. In stark contrast, human thyroid physiology is calibrated for metabolic stability within a comparatively narrow homeostatic range. This review synthesizes the current state of knowledge on the comparative thyroid endocrinology of camels and humans. We examine species-specific differences in the anatomical organization of the thyroid gland, the regulation of the hypothalamic–pituitary–thyroid (HPT) axis, and the peripheral metabolism of thyroid hormones. A central theme is the camel’s remarkable endocrine plasticity, characterized by a controlled, reversible downregulation of thyroid function in response to environmental stress. This includes a significant reduction in circulating triiodothyronine (T3) levels during dehydration and heat exposure, which lowers metabolic rate, conserves body water, and minimizes endogenous heat production. This adaptive hypometabolic state contrasts sharply with the pathophysiology of non-thyroidal illness syndrome (NTIS) in humans, where similar hormonal profiles are associated with critical illness and poor prognosis. We discuss the controversies and knowledge gaps in the field, such as the precise molecular mechanisms governing deiodinase enzyme activity in camels and the interplay between the thyroid and other endocrine axes in coordinating desert adaptation. By juxtaposing the divergent thyroid strategies of these two species, this review provides critical insights for veterinary diagnostics and management of camelids and offers a unique translational perspective on metabolic resilience, stress endocrinology, and the evolution of homeostatic control systems.
Abstract:Background: Sequential doxorubicin/cyclophosphamide (AC) followed by paclitaxel is a commonly used chemotherapy regimen in breast cancer and is associated with cumulative systemic toxicity. Routine laboratory biomarkers may provide an accessible means of tracking hematologic, hepatic, and electrolyte changes during treatment.\nObjective: To quantitatively characterize cumulative and phase-specific changes in a broad panel of routine laboratory biomarkers during sequential AC followed by paclitaxel chemotherapy.\nMethods: A retrospective longitudinal study was conducted in 29 female breast cancer patients treated with four cycles of AC followed by four cycles of paclitaxel, yielding eight sequential treatment time points. After data cleaning, linear mixed models were used to evaluate overall biomarker trajectories across all time points and the effects of treatment phase, cycle within phase, and their interaction on 25 hematologic, hepatic, and electrolyte parameters. P-values were adjusted using the Benjamini-Hochberg false discovery rate method.\nResults: Significant progressive changes were observed across the 8-cycle treatment course. Hematologic indices showed sustained declines in RBC count, hemoglobin, and hematocrit (all overall trend FDR p<0.001), with hemoglobin declining from 12.75 ± 1.20 g/dL at AC Cycle 1 to 11.21 ± 1.13 g/dL at Paclitaxel Cycle 4. Significant phase-by-cycle interactions for hemoglobin (FDR p=0.005) and hematocrit (FDR p<0.001) indicated a steeper decline during the AC phase with relative stabilization during paclitaxel. MCH, MCHC, and RDW increased progressively (all overall trend FDR p<0.001), suggesting evolving erythropoietic stress. MPV declined significantly over the treatment course (FDR p<0.001). Among hepatic markers, GGT showed significant phase, cycle, and phase-by-cycle effects (all FDR p≤0.002), indicating a distinct phase-dependent trajectory. Electrolyte changes included a significant overall decline in potassium (FDR p=0.005) and a significant phase-by-cycle interaction for calcium (FDR p=0.026).\nConclusion: Sequential AC followed by paclitaxel chemotherapy is associated with cumulative, progressive, and phase-specific alterations in routine hematologic, hepatic, and electrolyte biomarkers. The observed trajectories of hemoglobin, RDW, GGT, potassium, and calcium suggest that routinely collected laboratory parameters may help characterize the systemic toxicity profile of this regimen and may serve as practical candidates for future prospective validation studies.
Abstract:Open feedlots expose heifers to radiant load before summer peaks. We compared three shade geometries paired with elevated bedding pads in a replicated pen trial. Respiration rate, rectal temperature at peak solar angle, and daily gain were recorded for twenty-eight days. East-west oriented shade with side baffles lowered black-globe-adjusted heat indices more than simple roof extensions. Average daily gain improved modestly with fewer panting hours. Costing notes help producers prioritize retrofit sequences when steel prices fluctuate.
Abstract:Dual-purpose farms balance milk and calf sales under rainfall uncertainty. We modeled split-calving calendars against historical forage gaps and milk price seasonality for sixty-five households. Partial budgeting included labor for extra heatsynch visits and calf mortality risk. Farms that shifted twenty percent of calvings to the short rainy window improved cash flow stability without large herd expansion. Sensitivity analysis showed benefits hinge on access to conserved forage and timely artificial insemination services rather than genetics alone.
Abstract:Automated body condition scoring often fails under mixed natural and fluorescent lighting. We trained a compact model on hip and pin bone landmarks from phone video collected on eight farms. Augmentations simulated glare, shadows, and partial occlusion from headlocks. Compared with technician scores, the model achieved acceptable agreement on a five-point scale after farmer-guided recalibration each lactation stage. Deployment used on-device inference to limit data costs. Practical guidance covers camera height, lane markings, and when to reshoot clips after facility changes.