Key points for translating wound regenerative agents from in vivo assays in mice to clinical validation.

Skin wound healing leads to the recovery of tissue structure and homeostasis after injury. Numerous factors can hamper wound healing and complete recovery of the harmed tissue, causing the formation of scars or chronic wounds. Therapeutic options to improve wound regeneration are limited, possibly due to failure during pre-clinical validation toward clinical trials. In this article, the authors aim to convey key points and provide recommendations for the development of regenerative agents that improve wound healing using mouse models.First, the authors highlight the differences in the wound healing processes of mice and humans. Later, the authors apply a quasi-systematic research approach based on a search algorithm of 32 terms that focuses on in vivomouse model assays of regenerative factors. The authors analyze the top 20 most cited articles of 2241 hits produced by Scopus. The authors focus the search on a period covering the last 10 years (January 2011 to October 2021). The authors synthesize information from the top 20 articles and present the most common type of mouse model used, mouse characteristics (strain, sex, age, weight), surgical wounding technique employed (size, location, equipment), agents tested, methods of wound monitoring, regeneration assessment and key points to consider for the translational potential of these agents. This knowledge will help the scientific community design better in vivo assays and translate their results to further research and clinical validation.

Filgrastim (r-met-hu G-CSF) enhances the efficiency of spermatogenesis in prepubertal Bos indicus bulls.

This study aimed to test the effects of the drug r-met-hu-G-CSF (filgrastim) on spermatogenic efficiency in prepubertal Brahman bulls. Twelve intact, healthy prepubertal bulls were administered 0, 1 (LD = low dose) or 4 (HD = high dose) µg/Kg r-met-hu-G-CSF (daily for 4 days), and haematological analysis was performed. Bulls were castrated (D0 or D60). BW (body weight) and SC (scrotal circumference) were recorded. Testis weight and volume were taken at castration with samples for testis histology and stereology: germ cell types, spermatids count and DSP (daily sperm production per gram)/g of testicular parenchyma. Testicular weight, volume, BW, SC and gonadosomatic index (GSI) were NS (LD-HD; p > .05). At D0 (age 11 months), the most advanced germ cell types (maGCt) ranged from intermediate spermatogonia to pachytene spermatocytes. After 2 months, control animals had round spermatids as maGCt, LD animals 75% round spermatids and 25% elongated spermatids, and HD animals round spermatids. Spermatids/testis were higher in LD (1.23 ± 0.2 millions) than in controls (0.65 ± 0.1 millions, p < .05). Spermatogenic efficiency (DSP/g) was higher in LD (5.4 ± 0.4 million) than in controls (3.2 ± 0.2 million, p < .01). In conclusion, r-met-hu-G-CSF raises spermatogenic efficiency in prepubertal Brahman bulls.

Dystocia and cesarean section in a free-ranging ocelot (Leopardus pardalis) after traumatic spinal cord injury resulting from dog (Canis familiaris) attack.

Background: Ex situ breeding programs are essential to establish genetic resource banks and produce offspring to strengthen the in situ conservation of endangered species. However, many programs fail to maintain viable ex situ populations due to reproductive problems, including dystocia in pregnant females. Dystocia encompasses different emergency obstetric situations for the lives of dams and fetuses that require urgent intervention. This condition has been studied in domesticated species but published records in wildlife, specifically in felines species, are scarce. Case Description: An adult female ocelot (Leopardus pardalis) was referred to the wildlife hospital of the Universidad San Francisco de Quito after being attacked by dogs (Canis familiaris). Neurological tests revealed traumatic spinal cord injury at a thoracolumbar level. Complementary tests (laboratory exams, radiographs, and ultrasound) revealed a full-term pregnancy, failure in the labor progress, and critical fetal stress. A cesarean section was performed, and the newborns received resuscitation care after assessing their viability using the Apgar score system. The neonate with the lowest Apgar score died within the first hour after birth, while the second one showed an increase in Apgar score after resuscitation care and survived the procedure. Conclusion: We provide new obstetric data that could be relevant to save the lives of dams and newborns in related cases for ocelots and other species of wild felids. Furthermore, this study confirms the adverse effects that domestic dogs have on wildlife species.

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T).

The perception of mitochondria as only the powerhouse of the cell has dramatically changed in the last decade. It is now accepted that in addition to being essential intracellularly, mitochondria can promote cellular repair when transferred from healthy to damaged cells. The artificial mitochondria transfer/transplant (AMT/T) group of techniques emulate this naturally occurring process and have been used to develop therapies to treat a range of diseases including cardiac and neurodegenerative. Mitochondria accumulate damage with time, resulting in cellular senescence. Skin cells and its mitochondria are profoundly affected by ultraviolet radiation and other factors that induce premature and accelerated aging. In this article, we propose the basis to use AMT/T to treat skin aging by transferring healthy mitochondria to senescent cells, possibly revitalizing them. We provide insightful information about how skin structure, components, and cells could age rapidly depending on the amount of damage received. Arguments are shown in favor of the use of AMT/T to treat aging skin and its cells, among them the possibility to stop free radical production, add new genetic material, and provide an energetic boost to help cells prolong their viability over time. This article intends to present one of the many aspects in which mitochondria could be used as a universal treatment for cell and tissue damage and aging.

Variations in the Temperature-Humidity Index and Dorsal Fat Thickness during the Last Trimester of Gestation and Early Postpartum Period Affect Fertility of Bos indicus Cows in the Tropics.

In order to measure the influence of the temperature-humidity index (THI) and the variation of fat thickness on reproductive performance, ninety-two Bos indicus cows kept under grazing conditions were used in two farms in Veracruz (Mexico) and Puntarenas (Costa Rica). THI was calculated with the average environmental temperature and relative humidity. Measurements of fat thickness (FAT) were taken two weeks apart from the last trimester of gestation to approximately 80 days postpartum (dpp). Natural breeding was used in both farms. Time to conception was calculated based on the interval from days at risk to conception (DRC), which had to be at least 28 dpp. THI was between 65.4 ± 2.9 and 73.2 ± 1.5 in Veracruz and 75.4 ± 0.26 and 76.5 ± 0.55 in Puntarenas. Variations in THI were observed in Puntarenas whereas in Veracruz THI variations were more prominent. In Veracruz, loss of fat during the last trimester of gestation was on average 8.5%, whereas in the postpartum period it was 18.4% (P = 0.042). In Puntarenas, the variation in the last trimester of gestation was on average 18.7% and in the postpartum period was 10.5% (P = 0.012). The relative change in FAT in Veracruz was 36.7%, and in Puntarenas it was 29.3%. Overall, 60% of the cows became pregnant. FAT decreased the interval of DRC (R2=0.06; P=0.033) with a high relationship (R2=0.76; P< 0.0001) between THI and time to conception, in both farms. In conclusion, THI levels influence the reproductive performance in early postpartum period affecting DRC.