Search Results (135)

Castrate-resistant prostate cancer (PCa) is a critical situation in which many patients will relapse. Hormonal androgen deprivation therapy (HADT) is the gold standard of care when a patient relapses, following primary surgical or radiation therapy. Usually, the benefits from HADT are poor and recurrent disease after HADT treatment is termed castrate-resistant prostate cancer (CRPC), which is in most cases fatal. The therapeutic regimens for CRPC include chemotherapy with docetaxel, immunotherapy agent sipuleucel-T, the taxane cabazitaxel, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide. Thus, it is imperative to study the inherent property of prostate cancer cells, to resist therapy and reconsider the therapeutic protocols (continuous v’s intermittent). We make use of a hybrid mathematical model which consists of an extension of a very potent ordinary differential equation (ODE) Baez–Kuang model, combined with two Game Theory components: the Minority Game for adaptive behavior and the Axelrod model for heterogeneity behavior. Our study suggests that increasing tumor adaptability, through Minority Game dynamics, improves short-term prostatic-specific antigen (PSA) control and stabilizes therapy cycles. However, this comes at the cost of driving the tumor to a homogeneous, androgen-independent (AI) state, which is therapy-resistant. Conversely, maintaining heterogeneity, via Axelrod dynamics, sustains a mixed population, with androgen-dependent (AD) cells persisting longer and potentially delaying resistance emergence. Full article

The recovery and cryopreservation of epididymal spermatozoa enable genetic preservation in male dogs that die unexpectedly or require castration; however, sperm collection is typically performed immediately after surgery, and artificial insemination is often surgical. This study aimed to evaluate whether epididymides stored at 4–5 °C for 24 h prior to sperm recovery retain fertilizing capacity after cryopreservation and whether pregnancy can be achieved using endoscopically guided transcervical intrauterine insemination. Testes and epididymides from an eight-month-old German Shepherd dog were stored in physiological saline at 4–5 °C for 24 h following castration. Spermatozoa were recovered from the cauda epididymis using single-incision aspiration, evaluated, frozen according to the Uppsala method, and stored in liquid nitrogen for two months. After thawing, 62 × 10⁶ progressive motile spermatozoa were inseminated once into a bitch in heat using transcervical endoscopic guidance. Pregnancy was confirmed by ultrasonography, and nine healthy puppies were delivered at term. These findings demonstrate that 24 h refrigerated storage of the epididymis does not impair post-thaw fertilizing ability and that non-surgical transcervical intrauterine insemination represents an effective alternative to surgical techniques for the use of frozen–thawed epididymal semen in dogs. Full article

Gonad loss triggers severe endocrine disorders and altered energy metabolism, yet the precise mechanisms remain poorly understood. In swine production, surgical castration is widely performed to eliminate boar taint and aggressive behavior, but it impairs feed efficiency, increases fat deposition, and raises animal welfare issues. Castration reduces testosterone and estrogen levels, leading to elevated gonadotropin-releasing hormone (GnRH) and its downstream follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Traditionally viewed as a reproductive hormone, FSH has recently emerged as a critical regulator of peripheral metabolism. Based on these findings, we designed and developed a novel FSH vaccine comprising an FSHβ13AA-tandem-ovalbumin conjugate, which has been demonstrated to effectively regulate growth and metabolism in castrated boars. In conclusion, this review underscores the previously underrecognized metabolic functions of follicle-stimulating hormone (FSH) and proposes a novel immunomodulatory strategy targeting FSH for fine-tuning organ function and energy metabolism. This approach shows considerable potential for advancing sustainable, welfare-oriented swine production. Full article

A 10-year-old castrated male Chihuahua weighing 3.06 kg was presented with a chronic, progressively worsening cough of five months’ duration. Diagnostic imaging, including thoracic radiography and computed tomography, identified a well-defined cranial mediastinal mass consistent with a thymic tumor. Surgical excision was performed via median sternotomy with complete thymectomy. Following tumor removal, sternal closure was achieved using a non-absorbable ultra-high-molecular-weight polyethylene (UHMWPE) suture material (FiberWire^®, Arthrex, Naples, FL, USA). Histopathological examination confirmed the diagnosis of an epithelial-predominant thymoma with narrow but complete surgical margins. Postoperative recovery was uneventful, and the dog was discharged three days after surgery. Clinical signs, including coughing, progressively improved during follow-up. Radiographic evaluation performed up to postoperative day 57 demonstrated stable sternal alignment without evidence of dehiscence, implant-related complications, or disease recurrence. This report describes the first clinical case of FiberWire use for median sternotomy closure following thymectomy in a dog. The favorable clinical and radiographic outcomes observed during postoperative follow-up suggest that FiberWire may represent a viable alternative to traditional stainless-steel wire for sternal fixation in canine thoracic surgery. Full article

Castration is widely used in goat production to improve meat quality and manage reproduction, yet conventional surgical methods raise significant animal welfare concerns. Immunocastration targeting gonadotropin-releasing hormone (GnRH) offers a promising, welfare-friendly alternative, but its efficacy in slow-growing indigenous breeds remains poorly defined. In this study, we developed a novel tandem-repeat GnRH(30) recombinant vaccine and evaluated its effects on growth performance, reproductive function, and meat quality in male Leizhou goats. Eighteen six-month-old bucks were assigned to an immunocastration group (IM), surgical castration group (SC), or intact control group (IC). Vaccinated goats produced sustained anti-GnRH antibodies and exhibited significantly suppressed testosterone levels comparable to surgical castrates. Immunocastration induced marked testicular atrophy, disrupted spermatogenesis, reduced semen volume and sperm motility, and increased sperm abnormalities. Importantly, early growth performance and final body weight were not significantly affected. Compared with intact males, both IM and SC goats showed improved meat quality traits, including reduced drip loss and shear force, accompanied by increased intermuscular fat deposition, with overall patterns in the IM group closely resembling those of surgical castration. Overall, these findings indicate that the GnRH(30) vaccine can effectively suppress spermatogenesis and improve meat quality without affecting growth, providing an effective technical approach for castration management in indigenous goats. Full article

Background and Objectives: Prostate cancer exhibits substantial biological heterogeneity. Although several biomarkers reflecting aggressive tumor behavior have been identified, molecular indicators related to biological adaptation to androgen deprivation remain limited. This study aimed to comparatively evaluate ISM-1 and B7-H3 expression in localized prostate cancer (LPC) and the pre-CRPC group (pre-treatment diagnostic biopsy tissue from patients who subsequently developed CRPC), and to investigate their clinicopathological associations in the pre-CRPC group. Materials and Methods: This retrospective study included 30 surgically treated LPC cases and 32 pre-CRPC cases with available prostate tissue samples obtained prior to the development of castration resistance. ISM-1 and B7-H3 expression levels were evaluated immunohistochemically using the H-score method (intensity 0–3 × proportion score 0–3 [0%, 1–19%, 20–50%, >50%]). Expression patterns were compared between LPC and pre-CRPC groups. Within the pre-CRPC group, associations with clinicopathological parameters were evaluated using H-scores as continuous variables, and time to castration resistance was analyzed using Cox regression. Results: ISM-1 expression was generally low in LPC cases, with a median H-score of 0, whereas pre-CRPC biopsy tissues demonstrated a marked increase in ISM-1 expression. B7-H3 expression was higher and more homogeneous in the pre-CRPC group compared with LPC. In the pre-CRPC group, ISM-1 and B7-H3 H-scores showed a strong positive correlation. No statistically significant associations were identified between ISM-1 or B7-H3 expression levels and most conventional clinicopathological parameters; however, both markers differed significantly across Grade Groups. Neither marker showed a statistically significant association with time to castration resistance, although ISM-1 demonstrated a non-significant trend toward a longer time to resistance. Conclusions: ISM-1 and B7-H3 exhibit distinct expression patterns across different stages of prostate cancer but show associated expression profiles in the pre-CRPC group. While B7-H3 appears to reflect aggressive tumor biology, the independent expression pattern of ISM-1 and its non-significant trend toward a longer time to resistance suggest a potential role in the clinical trajectory toward castration resistance. Combined assessment of ISM-1 and B7-H3 may contribute to a better understanding of tumor biology in patients who subsequently develop CRPC. These findings are descriptive and hypothesis-generating. Full article

Ureterolithiasis is a common cause of ureteral obstruction in dogs, often leading to kidney injury. Medical expulsive therapy (MET) using α-adrenergic antagonists has been proposed as a nonsurgical treatment option in selected cases and is thought to facilitate ureteral stone passage by reducing ureteral smooth muscle tone. A 9-year-old castrated male Chihuahua weighing 1.78 kg was presented with anorexia. Physical examination revealed 7% dehydration and pale mucous membranes. Serum biochemistry demonstrated severe azotemia, with markedly elevated symmetric dimethylarginine (>100 μg/dL; reference interval [RI], 0–14 μg/dL), blood urea nitrogen (157.9 mg/dL; RI, 7–25 mg/dL), and creatinine (2.2 mg/dL; RI, 0.5–1.5 mg/dL). On day 4 of hospitalization, ultrasonography revealed dilation of the renal pelvis (16.1 mm), ureteral distention (3.74 mm), and multiple ureteroliths (maximum diameter, 3.31 mm) at the ureterovesical junction. Antegrade pyelography confirmed a right ureteral obstruction. As the owner declined surgical intervention, MET including tamsulosin, was initiated with close clinical monitoring. After 3 days, improvement in azotemia and resolution of ureteral obstruction were observed. Although concurrent medical treatments were administered, this case provides clinical insight into the potential role of tamsulosin as part of medical management of obstructive ureterolithiasis in a dog with small distal ureteral stones. Full article

Dog overpopulation poses serious challenges to public health, animal welfare, and environmental sustainability. While surgical castration remains the most commonly used method for controlling reproduction in dogs, it carries risks and limitations, including surgical complications and long-term behavioral or physiological side effects. This review examines the potential of immunocastration—vaccination targeting gonadotropin-releasing hormone (GnRH)—as an alternative approach. Immunocastration has been shown to suppress reproductive hormones, reduce gonadal function, and decrease behaviors such as roaming, aggression, and sexual mounting in dogs. The review also includes evidence from other species (e.g., pigs, cattle, and horses) to contextualize effectiveness and welfare implications. While behavioral effects are more variable and less frequently studied than physiological outcomes, recent findings suggest immunocastration may have fewer negative emotional side effects (e.g., anxiety and stress-related behaviors) than surgical sterilization. The review highlights the mechanisms, applications, and behavioral outcomes of immunocastration, including its reversibility, cost-effectiveness, and suitability for mass implementation. Overall, immunocastration offers a promising addition to dog population management strategies, particularly in regions with limited surgical infrastructure. Future research should focus on standardizing vaccine protocols and assessing long-term behavioral and welfare outcomes in diverse dog populations. Full article

Surgical castration, a common practice in animal husbandry, raises animal welfare concerns and adversely affects growth performance. Active immunization against gonadotropin-releasing hormone (GnRH) provides a non-surgical alternative. Both methods ultimately suppress sex hormone production, but their comparative effects on the gut microbiota, a crucial regulator of host health and metabolism, remain unclear. Here, 60 Sprague Dawley (SD) rats were randomly allocated into three groups—control (n = 20; 10 female and 10 male), surgical castration (n = 20; 10 female and 10 male), and GnRH immunocastration groups (n = 20; 10 female and 10 male)—at 4–5 weeks of age to comparatively investigate the impacts of surgical versus GnRH immunocastration on the gut microbiota. Our study demonstrated GnRH immunocastration significantly reduced gonadal weight, effectively suppressing gonadal development to a level comparable to surgical castration. However, the two methods induced distinct, sex-dependent shifts in the gut microbiota. Surgical castration reduced the gut microbial community diversity, whereas the community structure of GnRH immunocastrated rats more closely resembled that of the control group, indicating a milder impact on the microbial diversity and composition. Notably, GnRH immunocastration resulted in higher microbial alpha diversity than surgical castration in both female and male SD rats. Specific bacterial genera, such as Clostridia_UCG014, Lactobacillus, and Lachnospiraceae_UCG006, were similarly altered in both surgical castration and GnRH immunocastration female SD rats, while Intestinimonas and Erysipelatoclostridiaceae_UCG004 were concurrently changed in male SD rats. Conversely, Eubacterium_nodatum_group exhibited opposite responses, increasing with GnRH immunocastration but decreasing with surgical castration in male SD rats. Functional prediction revealed fundamental sex differences in microbial metabolic pathways. In females, nitrogen metabolism, glyoxylate/dicarboxylate metabolism, and mismatch repair were changed, while the pathways involved in siderophore biosynthesis, the citrate cycle (TCA cycle), genetic information processing, and amino acid metabolism were changed in male SD rats. In conclusion, GnRH immunocastration appears to be a less disruptive intervention, better preserving microbial diversity and inducing a unique functional profile. These findings highlighted the importance of considering the castration method’s impact on the gut microbial ecosystem in animal production and provided insights for developing humane and effective approaches to animal population control. Full article

Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204⁺ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3⁺ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusions: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies. Full article

Previous studies have demonstrated that follicle-stimulating hormone (FSH) plays a critical role in promoting adipogenesis. Surgical castration results in elevated FSH concentrations in pigs, and is accompanied by reduced feed efficiency. This study aimed to investigate the effects of a novel FSH vaccine comprising FSHβ13AA-tandem-ovalbumin conjugate on growth performance and meat quality in barrows. Twenty-four barrows with initial body weight of 32.54 ± 1.90 kg and 12-week age, were randomly assigned to three groups: Placebo-immunized, GnRH-immunized, and FSH-immunized. At three weeks after booster immunization, the FSH-immunized group exhibited significantly improved feed efficiency compared to GnRH-immunized barrows. Compared to the Placebo-immunized group, GnRH and FSH vaccination reduced average backfat thickness by 0.90% and 4.55%, abdominal fat weight by 3.49% and 10.56%, and abdominal fat percentage by 4.09% and 11.95%, respectively. Moreover, the FSH-immunized group showed a significant increase in liver weight relative to the Placebo-immunized group. In addition, compared with the control group, at slaughter FSH vaccination significantly increased muscle pH at 45 min, drip loss at 24 h, and shear force (p < 0.05). These results demonstrate that active immunization against FSH in barrows can enhance feed efficiency and reduce adiposity, as well as influence the meat quality. Full article

Elevated cholesterol levels play important mitogenic roles. Pseurotin A (PsA) is a fermentation product that has recently been reported as a dual inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion and protein-protein interaction (PPI) with the LDLR. PsA showed a high acute safety profile and therapeutic potential against metastatic castration-resistant prostate cancer (mCRPC). The study aims to uncover the chronic safety, distribution, and anti-mCRPC genomic and molecular mechanistic insights of PsA. A 90-day chronic safety assessment of PsA up to 80 mg/kg in Swiss albino mice showed no signs of hematological, biochemical, or major organ toxicity. PsA demonstrated rapid intravenous distribution and elimination in Swiss albino mice. PsA is biodistributed to multiple key organs but was not detected in the brain, indicating its inability to cross the blood-brain barrier. PsA effectively suppressed the recurrence of nude mice xenografted mCRPC, which was subjected to a neoadjuvant docetaxel and enzalutamide regimen, followed by surgical excision. Collected PsA and vehicle control-treated recurrent tumors were subjected to RNA-sequencing and pathway enrichment analysis (PEA) of differentially expressed genes (DEGs). PsA-treated tumors revealed multiple significantly enriched pathways associated with promoting tumor apoptosis and inhibiting both invasion and migration. The PPI network analyses for the downregulated DEGs displayed prominent networks of genes associated with the ubiquitin-proteasome system. Results provide comprehensive mechanistic and preclinical validations for PsA’s potential as a novel PC recurrence suppressive lead entity. Full article

Surgical castration of male piglets is a common practice to prevent boar taint and reduce aggressive behaviour. However, it raises welfare concerns and alters carcass fat deposition. Immunocastration, a vaccine-based alternative targeting gonadotropin-releasing hormone (GnRH), mitigates these welfare issues. This study evaluated carcass traits and meat quality in surgically and immunocastrated pigs slaughtered at two weight classes (approximately 116 kg and 136 kg). We compared growth performance, carcass composition, fat quality, and key meat quality indicators among surgically castrated males, immunocastrated males, and immunocastrated females. Inclusion of uncastrated and immunocastrated females provides novel comparative data for mixed-sex production systems, where such information is scarce. This broader evaluation helps fill current gaps in knowledge about immunocastration effects in female pigs. Surgically castrated males showed higher backfat thickness and fat content, particularly at the heavier weight, while immunocastrated pigs exhibited intermediate traits. Ultimate pH, colour, marbling, water-holding capacity, and moisture loss varied with castration method, sex, and slaughter weight, though many differences were subtle. The findings confirm that immunocastration offers a favourable balance between animal welfare and production traits, producing pork quality comparable to surgical castration. These results provide valuable insights for optimizing pork production systems, balancing welfare, efficiency, and meat quality. Full article

This essay examines mass castration allegations within the North Indian guru movement Dera Sacha Sauda. Drawing on court records, public commentary, and prior fieldwork, it traces how surgical procedures served as a mechanism of enforced proximity and devotional binding. Castration here functions less as renunciation than as anatomical control within a system of engineered devotion that sutures followers into machinic forms of loyalty. The essay situates these acts within a broader politics of sacrificial excess, linking them to hijra initiation, Mughal-coded sovereignty, and strategies of masculine containment. What emerges is a devotional regime of irreversible subtraction and a sovereignty staged through ritual overreach. Full article

Use of sedation for disbudding is common practice in a number European countries, with United Kingdom (UK) practices adopting its use. This study assessed the effects of disbudding with and without xylazine sedation on growth rates and calf health on a UK calf rearing unit. Data was collected from 485 dairy crossed with beef breed calves between April and August 2024 from a single calf rearing unit in England. Calves were purchased from multiple farms across the UK and arrived on site at approximately 21 days of age. Calves were disbudded—and, in the case of male calves, surgically castrated—at approximately three weeks after arrival on farm. Pens of calves were assigned to undergo disbudding with (SED, n = 238) or without (CTL = 234) xylazine sedation at a dose of 0.2 mg/kg administered intramuscularly. Calves from both groups were provided with local anaesthetic (procaine hydrochloride) as a cornual nerve block and a non-steroidal anti-inflammatory drug (meloxicam). While other studies have demonstrated some behavioural and physiological indicators of pain to be reduced with sedation, this study found that calves in the SED group had a reduced daily liveweight gain (DLWG) of 0.14 kg/day in the short term (mean 20 days) following disbudding (p < 0.001), but there was no difference in growth rates in the medium-term (mean 43 days) post-disbudding (p = 0.30). Some of this difference could be explained by the slightly higher DLWG pre-disbudding in the CTR group, and it is likely that the physiological impacts of sedation accounted for the rest of this difference. This initial reduction in DLWG following disbudding with sedation should be considered by vets, especially on farms where growth rates may already be compromised. In the sedated calves, 19.3% exhibited either some movement or entry into sternal recumbency. Specifically, a light plane of sedation with calves entering sternal recumbency was associated with a reduction in DLWG of 0.89 kg/day compared to 0.98 kg/day for those that remained in lateral recumbency throughout (p = 0.008). The light plane of sedation may have created additional calf stress, impacted feeding behaviours, and impinged welfare, with further work needed to establish the reasons for insufficient sedation. There was no difference in the number of post-disbudding treatment outcomes between calves disbudded with and without sedation (p = 0.97). Full article