Ex vivo biomechanical investigations of combined extra- and intracapsular stabilization in canines with cranial cruciate ligament deficiency.

Intracapsular reconstruction (ICR) has long been recommended as a treatment for cranial cruciate ligament deficiency (CCLD) in dogs, but it has fallen out of favor due to its inferior long-term functional outcomes. These outcomes may be attributed to the poor stiffness and strength of the graft in the early period before ligamentization is completed. Additional placement of extracapsular sutures to mechanically protect the graft during the ligamentization process may be a viable method to address this problem. However, the biomechanical effect of this combined surgical approach remains unknown. This study aimed to evaluate the 3D kinematics of the CCLD stifle in dogs in response to ICR and combined extra- and intracapsular reconstruction (CEICR). Twelve hindlimbs were collected from nine cadavers of mature dogs. The limbs were tested using a custom-made testing apparatus that reproduces their sagittal plane kinematics during the stance phase. Four statuses of stifle joints were tested, namely, (a) cranial cruciate ligament (CCL) intact; (b) CCLD; (c) CCLD stifle stabilized by CEICR; and (d) CCLD stifle stabilized by ICR only. Three-dimensional stifle kinematics at the 5 instances of the stance phase were measured with an optoelectronic system. The results showed that ICR marginally corrects the increased adduction, internal rotation, and caudodistal stifle joint center displacement that occur as a result of CCLD. CEICR led to better restoration of the stifle kinematics, especially with respect to the internal rotation and cranial translation stabilities. Furthermore, CEICR only resulted in minor excessive restraints on other motion components. The findings indicated that the additional lateral fabellotibial suture offers immediate stability to the stifle, consequently lowering the risk of graft over-elongation in the short term postoperatively. Considering the propensity for the extracapsular suture to degrade over time, further in vivo studies are warranted to explore the long-term effects of the CEICR procedure.

Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis.

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects.

Estimation of footprints of the canine stifle ligaments using deformable shape templates of bones.

Knowledge regarding the ligament footprints in the canine stifle is essential for biomechanical modeling of the joint and patient-specific surgical planning for anatomical ligament reconstruction. The present study aimed to establish and evaluate deformable shape templates (DSTs) of the femur and tibia with footprints of the cruciate and collateral ligaments embedded for the noninvasive estimation of ligament footprint positions. To this end, a data set of computed tomography (CT)-derived surface models of the femur and tibia were established and used to build statistical shape models (SSMs). The contours of the stifle ligaments were obtained from CT scans of 27 hindlimb specimens with radio-opaque markings on the ligament footprints. The DST, constructed by embedding averaged footprint contours into the SSM, was used to estimate subject-specific ligament footprints in a leave-one-out cross-validation framework. The DST predictions were compared with those derived from radio-opaque-marked footprints. The results showed that the averaged Euclidean distances between the estimated and reference footprint centroids were less than 1.2 mm for the cruciate ligaments and 2.0 mm for the collateral ligaments. The DST appeared to provide a feasible alternative approach for noninvasively estimating the footprints of the stifle ligaments in vivo.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx.

Introduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology. Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks. Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte. Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.

Ex vivo biomechanical evaluation of extracapsular stabilization with quasi-isometric points in canine cranial cruciate ligament-deficient stifles.

BACKGROUND: Cranial cruciate ligament (CCL) disease is one of the most common causes of lameness in dogs. The extracapsular stabilization (ECS) utilizing bone anchors and monofilament nylon leader was an alternative treatment for CCL-deficient (CCLD) dogs. However, the biomechanical response of the canine stifle to such a surgical repair strategy in conjunction with the use of recently reported quasi-isometric anchoring points remains unclear. The objectives of the study were to evaluate the mobility and stability of CCL-intact, CCLD, and CCLD stifles repaired with ECS at two different pairs of quasi-isometric points (quasi-IPs). METHODS: Twelve stifle specimens from 7 dogs underwent mobility and stability tests under 4 different conditions, namely, CCL-intact, CCLD, and ECS-repaired at 2 different pairs of quasi-IPs (referred to as ECS-IP1 and ECS-IP2). The mobility tests evaluated 6 degrees-of-freedom stifle kinematics during flexion and extension. The stability tests involved cranial drawer and tibial internal rotation (IR) tests at various stifle opening angles and quantifying the cranial tibial translation (CTT) and tibial IR angles under constantly applied loadings. RESULTS: The ECS repaired at quasi-IPs was shown to restore cranial instability of the stifles with averaged CTT magnitudes < 1.4 mm. During the tibial IR test, the ECS treatments resulted in significantly less tibial IR compared to those in intact CCL stifles. The mobility tests showed similar results. CONCLUSION: The 2 chosen pairs of quasi-IPs were shown to effectively correct the excessive CTT caused by CCLD stifles, whereas the excessive tibial external rotation in comparison to those of intact stifles should be considered for its subsequent influence on joint alignment and the contact pressure applied to the stifle joint.

Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

The Effects of Bacillus licheniformis-Fermented Products on the Microbiota and Clinical Presentation of Cats with Chronic Diarrhea.

Bacillus licheniformis-fermented products (BLFP) are probiotics with antibacterial, antiviral, and anti-inflammatory properties that can improve growth performance. This study aimed to compare the fecal microbiota of diarrheal cats with chronic diarrhea (n = 8) with that of healthy cats (n = 4) from the same household using next-generation sequencing, and evaluate the effectiveness of oral administration of BLFP in relieving clinical signs and altering the intestinal microbiota in diarrheal cats. Six out of eight diarrheal cats showed clinical improvement after BLFP administration for 7 days, and the stool condition of the other two was normal. A higher Firmicutes/Bacteroidetes ratio was noted in the feces of diarrheal cats without clinical improvement as compared with those in the healthy cats and in the diarrheal cats with clinical improvement after receiving BLFP. The phylum Bacteroidetes and class Bacteroidia decreased significantly in diarrheal cats regardless of BLFP administration. Blautia spp., Ruminococcus torques, and Ruminococcus gnavus, which belong to the Clostridium cluster XIVa and have been reported as beneficial to intestinal health, increased significantly in feces after treatment. Furthermore, Clostridium perfringens also significantly decreased in diarrheal cats after BLFP administration. Overall, BLFP could be a potential probiotic to relieve gastrointestinal symptoms and improve fecal microbiota in cats with chronic diarrhea.

Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca.

BACKGROUND: Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS. RESULTS: The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician. CONCLUSION: To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.

Oxidative Stress-Induced Alterations of Cellular Localization and Expression of Aquaporin 1 Lead to Defected Water Transport upon Peritoneal Fibrosis.

Being one of the renal replacement therapies, peritoneal dialysis (PD) maintains around 15% of end-stage kidney disease patients' lives; however, complications such as peritoneal fibrosis and ultrafiltration failure during long-term PD compromise its application. Previously, we established a sodium hypochlorite (NaClO)-induced peritoneal fibrosis porcine model, which helped to bridge the rodent model toward pre-clinical human peritoneal fibrosis research. In this study, the peritoneal equilibration test (PET) was established to evaluate instant functional changes in the peritoneum in the pig model. Similar to observations from long-term PD patients, increasing small solutes transport and loss of sodium sieving were observed. Mechanistic investigation from both in vivo and in vitro data suggested that disruption of cytoskeleton induced by excessive reactive oxygen species defected intracellular transport of aquaporin 1, this likely resulted in the disappearance of sodium sieving upon PET. Functional interference of aquaporin 1 on free water transport would result in PD failure in patients.

In vivo three-dimensional isometry analysis of suture attachment sites for extracapsular suture stabilization of the canine stifle.

BACKGROUND: The study aimed to perform isometry analysis of a selection of suture attachment points for extracapsular stabilization with three-dimensional (3D) measurements and normal gait kinematics of the stifle joint. METHODS: Thirteen client-owned dogs were recruited. Fluoroscopic images of the stifle during treadmill walking and computed tomography of the same joint were acquired. Stifle kinematics were reconstructed using 3D model-based fluoroscopic analysis. Variability of the distance between the femoral and tibial attachment sites across gait cycles was evaluated. The maximum length variation (MLV) and maximum length percent variation (MLPV) were quantified and used to determine the level of isometry of the attachment site combinations. RESULTS: A selection of combinations with lower mean MLV (<2.5 mm) or MLPV (<8%) was identified from 315 combinations, and all the combinations involved femoral attachment sites near the distal pole of the lateral fabella. The combinations also involving tibial attachment sites near the proximal tibial crest showed improved isometry, with an MLPV < 6%. CONCLUSION: Combinations using attachment sites around the distal pole of the lateral fabella and proximal tibial crest or caudal to the long digit extensor groove appeared to have improved isometry.

Evaluation of and the prognostic factors for cats with big kidney-little kidney syndrome.

BACKGROUND: The term big kidney-little kidney syndrome in cats has been used for many years, but the definitions are not consistent and relevant research is limited. OBJECTIVE: To determine the factors that differ between normal and BKLK cats, as well as to develop models for predicting the 30-day survival of cats with ureteral obstruction (UO). ANIMALS: Sixteen healthy cats and 64 cats with BKLK. METHODS: Retrospective study. To define BKLK by reference to data from clinically healthy cats. The demographic and clinicopathological data among groups were statistically analyzed. RESULTS: Big kidney-little kidney syndrome cats had higher blood urea nitrogen (BUN) (median [interquartile range] 69 [28-162] vs 21 [19-24] mg/dL, P < .001), creatinine (5.6 [1.9-13.3] vs 1.3 [1.05-1.40] mg/dL, P < .001), and white blood cells (10 800 [7700-17 500] vs 6500 [4875-9350] /µL, P < .001) and lower hematocrit (32.8 [27.1-38.4] vs 39.1 [38.1-40.4]%, P < .001), urine specific gravity (1.011 [1.009-1.016] vs 1.049 [1.044-1.057], P < .001) and pH (5.88 [5.49-6.44] vs 6.68 [6.00-7.18], P = .001) compared to the control cats. A lower body temperature (BT; 38.1 [37.9-38.2] vs 38.7 [38.3-39.2]°C, P = .009), higher BUN (189 [150-252] vs 91 [36-170] mg/dL, P = .04), and creatinine (15.4 [13.3-17.4] vs 9.0 [3.1-14.2] mg/dL, P = .03) were found among the UO cats that were not 30-day survivors. A combination of BUN, phosphorus, and BT can predict 30-day survival among UO cats with an area under receiver operating characteristic curve of 0.863. (P = .01). CONCLUSION: An increase in the length difference between kidneys can indicate UO, but cannot predict outcome for BKLK cats.

A real-time camera-based adaptive breathing monitoring system.

Breathing is one of the vital signs used to assess the physical health of a subject. Non-contact-based measurements of both breathing rate and changes in breathing rate help monitor health condition of subjects more flexibly. In this paper, we present an improved real-time camera-based adaptive breathing monitoring system, which includes real time (1) adaptive breathing motion detection, (2) adaptive region of interest detection to eliminate environmental noise, (3) breathing and body movement classification, (4) respiration rate estimation, (5) monitor change in respiration rate to examine overall health of an individual, and (6) online adaptation to lighting. The proposed system does not pose any positional and postural constraint. For evaluation, 30 videos of 15 animals are tested with drugs to simulate various medical conditions and breathing patterns, and the results from the proposed system are compared with the outputs of an existing FDA-approved invasive medical system for patient monitoring. The results show that the proposed method performs significantly correlated RR results to the reference medical device with the correlation coefficient equal to 0.92 and p-value less than 0.001, and more importantly the proposed video-based method is demonstrated to produce alarms 10 to 20 s earlier than the benchmark medical device. Graphical abstract The proposed system flowchart to extract the respiratory pattern from video.

Hypochlorite-induced porcine model of peritoneal fibrosis through the activation of IL1ß-CX3CL1-TGFß1 signal axis.

Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15-30 mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1ß, CX3CL1 and TGFß on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models.

Description of soft tissue artifacts and related consequences on hindlimb kinematics during canine gait.

BACKGROUND: Soft tissue artifacts (STAs) are a source of error in marker-based gait analysis in dogs. While some studies have revealed the existence of STAs in the canine hindlimb, STAs and their influence on kinematic gait analysis remain unclear. METHODS: Thirteen healthy Taiwan dogs affixed with twenty skin markers on the thigh and crus were recruited. Soft tissue artifacts and their influence on the determination of segment poses and stifle angles were assessed by simultaneously measuring marker trajectories and kinematics of the underlying bones via a model-based fluoroscopic analysis method. RESULTS: Markers on the thigh showed higher STAs than those on the crus, with root-mean-square amplitudes up to 15.5 mm. None of the tested marker clusters were able to accurately reproduce the skeletal poses, in which the maximum root-mean-square deviations ranged from 3.4° to 8.1°. The use of markers resulted in overestimated stifle flexion during 40-60% of the gait cycle and underestimated stifle flexion during 80-90% of the gait cycle. CONCLUSIONS: Considerable magnitudes and effects of STAs on the marker-based 3D gait analysis of dogs were demonstrated. The results indicate that the development of error-compensation techniques based on knowledge regarding STAs is warranted for more accurate gait analysis.

Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes.

BACKGROUND: The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate. RESULTS: Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate. CONCLUSIONS: This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment.

Evaluation of a multibody kinematics optimization method for three-dimensional canine pelvic limb gait analysis.

BACKGROUND: Skin marker-based three-dimensional kinematic gait analysis were commonly used to assess the functional performance and movement biomechanics of the pelvic limb in dogs. Unfortunately, soft tissue artefact would compromise the accuracy of the reproduced pelvic limb kinematics. Multibody kinematics optimization framework was often employed to compensate the soft tissue artefact for a more accurate description of human joint kinematics, but its performance on the determination of canine pelvic limb skeletal kinematics has never been evaluated. This study aimed to evaluate a multibody kinematics optimization framework used for the determination of canine pelvic limb kinematics during gait by comparing its results to those obtained using computed tomography model-based fluoroscopy analysis. RESULTS: Eight clinically normal dogs were enrolled in the study. Fluoroscopy videos of the stifle joint and skin marker trajectories were acquired when the dogs walked on a treadmill. The pelvic limb kinematics were reconstructed through marker-based multibody kinematics optimization and single-body optimization. The reference kinematics data were derived via a model-based fluoroscopy analysis. The use of multibody kinematics optimization yielded a significantly more accurate estimation of flexion/extension of the hip and stifle joints than the use of single-body optimization. The accuracy of the joint model parameters and the weightings to individual markers both influenced the soft tissue artefact compensation capability. CONCLUSIONS: Multibody kinematics optimization designated for soft tissue artefact compensation was established and evaluated for its performance on canine gait analysis, which provided a further step in more accurately describing sagittal plane kinematics of the hip and stifle joints.

Effects of soft tissue artefacts on computed segmental and stifle kinematics in canine motion analysis.

Skin marker-based motion analysis has been widely used to evaluate the functional performance of canine gait and posture. However, the interference of soft tissues between markers and the underlying bones (soft tissue artefacts, STAs) may lead to errors in kinematics measurements. Currently, no optimal marker attachment sites and cluster compositions are recommended for canine gait analysis. The current study aims to evaluate cluster-level STAs and the effects of cluster compositions on the computed stifle kinematics. Ten mixed-breed healthy dogs affixed with 19 retroreflective markers on the thigh and shank were enrolled. During isolated stifle passive extension, the marker trajectories were acquired with a motion capture system, and the skeletal poses were determined by integrating fluoroscopic and CT images of the bones. The cluster-level STAs were assessed, and clusters were paired to calculate the stifle kinematics. A selection of cluster compositions was useful for deriving accurate sagittal and frontal plane stifle kinematics with flexion angles below 50 per cent of the range of motion. The findings contribute to improved knowledge of canine STAs and their influence on motion measurements. The marker composition with the smallest error in describing joint kinematics is recommended for future applications and study in dogs during dynamic gait assessment.

Evaluation of antiviral activity of Bacillus licheniformis-fermented products against porcine epidemic diarrhea virus.

Bacillus licheniformis (B. licheniformis) is commonly used as probiotic and its secondary metabolites are attractive anti-microbial candidate. In the present study, we aimed to evaluate the antiviral activity of crude extracts from B. licheniformis against porcine epidemic diarrhea virus (PEDV), a highly contagious enveloped porcine virus that has caused great economic loss in pigs. In vivo, PEDV-infected piglets supplemented with air-dried solid state fermentative cultivate containing B. licheniformis-fermented products (BLFP) showed milder clinical symptoms and decreased viral shedding. Importantly, no significant systemic pathological lesions and no reduction in average daily gain were noted in pigs supplemented with the BLFP, which suggests that it is safe for use in pigs. In vitro experiments revealed that while B. licheniformis crude extracts exhibited no toxicity in Vero cells, co-cultivation of B. licheniformis crude extracts with PEDV significantly reduced viral infection and replication. Summarized current results suggest that the B. licheniformis-fermented products could be a novel candidate food additive for reducing the impact of PED on the swine industry.

Role of nuclear factor-kappa B in feline injection site sarcoma.

BACKGROUND: Chronic inflammation has been implicated in sarcomagenesis. Among various factors, activation of nuclear factor-kappa B (NF-κB) signaling pathway has been documented being able to target genes associated with tumor progression and up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. Feline injection sites sarcomas (FISS) are malignant entities derived from the mesenchymal origin. The disease has been considered to be associated with vaccine adjuvant, aluminum, which serves as a stimulus continuously inducing overzealous inflammatory and immunologic reactions. To understand the contribution of NF-κB in FISS, detection of activated NF-κB in paraffin-embedded specimens, in vitro establishment of primary cells derived from FISS, and evaluation of the effects of the NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on primary tumor cells were conducted. RESULTS: In this study, nuclear expression of NF-κB p65 was detected in 83.3% of FISS cases and not correlated with tumor grading, sex, and age. Primary cells derived from FISS in three cats exhibiting same immunohistochemical characteristics as their original tumor were successfully established. The NF-κB inhibitor, DHMEQ, was able to prevent nuclear translocation of NF-κB p65, inhibit cell proliferation, migration, and colonization in dosage-dependent manners, and induce cell apoptosis in these primary FISS cells. CONCLUSIONS: High expression rate of nuclear NF-κB p65 in FISS cases and dose-dependent inhibitory effects on the growth of FISS primary cells treated with NF-κB inhibitor suggested that NF-κB might be a potential molecular therapeutic target for FISS.

Dietary wild bitter gourd displays selective androgen receptor modulator like activity and improves the muscle decline of orchidectomized mice.

Loss of skeletal muscle mass and strength is often associated with disability and poor quality of life. Selective Androgen Receptor Modulators (SARMs) are under development as potential treatment. This study aims at examining the potential of wild bitter gourd (BG) as a SARM and its effects on the muscle decline induced by orchiectomy. In the cell-based androgen receptor (AR) transactivation assay, the BGP extract showed weak agonistic and antagonistic activities, resembling those of some SARMs. Male C57BL/6J mice were sham-operated (Sham group) or castrated (Cast groups) and fed a modified AIN-93G high sucrose diet supplemented without (Cast group) or with 5% lyophilized BG powder (Cast + BGP) or with testosterone propionate (7 mg TP per kg diet, Cast + TP) for 23 weeks. In contrast to the Cast + TP group, the BGP supplementation did not affect the serum testosterone concentration, and prostate and seminal vesicle mass. Both TP and BGP supplementation increased the weight of androgen responsive muscles, bulbocavernosus (BC) and levator ani (LA) (p < 0.05). The grip strength and the performance on a rotarod of the Cast + BGP group were comparable to those of the Cast + TP group (p > 0.05). The number of succinate dehydrogenase (SDH)-positive fibers of the Cast + BGP group was not significantly different from that of the Sham and Cast + TP groups (p > 0.05). The BGP supplementation up-regulated the Pgc1α, Ucp2 or Ucp3 gene expressions in skeletal muscles of castrated mice (p < 0.05). BGP showed some characteristics of the SARM and might improve skeletal muscle function through the up-regulation of mitochondrial biogenic genes and oxidative capacity, and ameliorated the castration-induced decline of skeletal muscle function in mice.