The Confounding Role of Graft-Versus-Host Disease in Animal Models of Cancer Immunotherapy: A Systematic Review.

BACKGROUND: Cancer immunotherapy has emerged as a transformative approach for treating various malignancies, including melanoma, lung cancer, breast cancer, and leukemia. Animal models have been instrumental in elucidating the mechanisms and potential of these therapies. However, graft-versus-host disease (GVHD) is an inherent challenge in these studies, primarily because the introduction of foreign immune cells or tissues often triggers immune responses. METHODS: A detailed systematic search was conducted across various scientific databases, including PubMed, Scopus, Embase, and Web of Science. The search aimed to identify peer-reviewed articles published in English from January 2000 to September 2023. Keywords and phrases used in the search included "Graft-versus-Host Disease", "GVHD", "animal models", "cancer immunotherapy", and combinations thereof. Boolean operators (AND/OR) were employed to refine the search. Finally, 6 articles were included in this systematic review, which is registered on PROSPERO (ID number CRD42024488544). RESULTS: Our systematic review identified several mechanisms employed in animal studies to mitigate the confounding effects of GVHD. These included genetically modified mouse models, immunosuppressive drugs, and humanized mice. Furthermore, the review highlights innovative approaches such as selective T-cell depletion and the use of specific cytokine inhibitors. CONCLUSION: By systematically identifying and mitigating the confounding effects of GVHD, we can significantly improve the predictive validity of preclinical trials, obtain broadly applicable findings, improve the efficiency of drugs, enhance safety profiling, and develop better therapeutic strategies. This approach is crucial in ensuring that the immunotherapeutic strategies developed in the laboratory are reflective of the human physiological response, thereby bridging a critical translational gap in oncological research.

Exploring the main effects of phoenix dactylifera on destructive changes caused by cyclophosphamide in male reproductive system in mice.

Cyclophosphamide leaves an undesirable effect on testes. This study was conducted to explore the effects of the Phoenix dactylifera (DP) on testes following the cyclophosphamide treatment. Thirty-six male mice were divided into six groups, one control, one cyclophosphamide, two groups of cyclophosphamide with a dose of 200 mg kg-1 and a dose of 400 mg kg-1 DP, and two of only high and low doses of DP. All groups were gavaged daily for 28 days. The animals were euthanized 24 hr after implementing the last treatment. Then, the testes and epididymis samples were removed and weighed. The main sperm characteristics such as the number of sperm and sperm viability, the morphometric changes, biochemical analysis of testes and enzyme activity were investigated. With the cyclophosphamide group, only body weight, testes weight, epididymis weight, sperm viability and the fertilization percentage were decreased significantly compared to the control group. Moreover, the spermatogenesis indices and morphometric parameters in this group indicated a significant decrease. Furthermore, the morphological changes were observed in the testicular tissue, including seminiferous tubule atrophy, vacuolation, hyperemia of blood vessels and increased space in the interstitial tissue. In the biochemical study of cyclophosphamide group, the amount of glutathione peroxidase in serum was decreased, whereas, the amount of malondialdehyde in testicular tissue showed a significant increase. The DP group included the antioxidant and anti-apoptotic properties. It seemed that the compounds in the DP would lead to the inhibition of the production of active metabolites released from the cyclophosphamide.

Daily rhythms of locomotor and demand-feeding activities in Schizothorax pelzami (Kessler, 1870).

A study was carried out to investigate the daily rhythms of locomotor and feeding activity of Khajoo, Schizothorax pelzami, a candidate species for freshwater aquaculture. Using self-feeder juvenile Khajoo were exposed to a 12/12 LD cycle to determine the rhythms of locomotor and feeding activity. The effects of feeding on locomotor and feeding activity of fish were also examined. Finally, the endogenous rhythmicity under different lighting condition tested. Fish displayed a strictly diurnal feeding and locomotor activities with 98% and 84% of the total activity occurred in the photophase, respectively. In scheduled feeding, both the L-group (fed in light) and the D-group (fed in the dark) showed a diurnal locomotor activity pattern. However, the L-group had a peak of locomotor activity near the feeding time, but the D-group had a scarce locomotor activity in the scatophase with no significant change at the mealtime. Most of the individuals display free-running rhythms when exposed to different lighting condition including, constant darkness, ultradian 45:45 min LD cycle and reversed DL photo cycle. Taken together the results of this study showed that both locomotor and feeding activity have diurnal rhythms in Khajoo S. pelzami, even fish feeding had taken place at night. Additionally, the free-running locomotor activity of the fish in the absence of external light stimuli, suggests the existence of an endogenous timing mechanism in this fish species.

[Mechanism of the dysfunction of the bull spermatozoa treated with cadmium].

OBJECTIVE: Heavy metals such as cadmium (Cd) are widely distributed in the environment as industrial pollutants and characterized by their ability to affect the male reproductive system. The objective of the present study was to test the effect of Cd in the concentration range from 10 to 1000 micromol/L, in vitro, on the membrane and DNA integrity, motility, and ability of sperm to undergo acrosomal exocytosis in Holstein bull spermatozoa. METHODS: Bull semen samples were processed for sperm analyses using semen-diluting fluid, PBS. Membrane integrity of the processed bull sperm was evaluated by lipoperoxidation (LPO) test. Gelatin digestion test was performed to determine the ability of bull spermatozoa to undergo acrosomal exocytosis. Single cell gel electrophoresis (SCGE) assay was performed to detect the DNA strand breaks and alkali labile damages in the individual cell. RESULTS: We found a significant increase in the lipoperoxidation (LPO) indicating the deleterious effect of Cd on the sperm membrane integrity. This effect was prominent at the concentration of 1000 micromol/L Cd. There was a negative correlation between LPO rate and the percentage of motile spermatozoa (r = -0.94, P < 0.001). The gelatin digestion test indicated that Cd caused a decline in the percentage of acrosomal exocytosis of bull spermatozoa. A reverse correlation was also found between LPO rate and the percentage of halos (r = -0.97, P < 0.001). Data obtained from the comet assay revealed that Cd was capable of inducing DNA breaks in the sperm nuclei. Almost 93% of DNA damages were double-stranded breaks. The correlation between LPO rate and the percentage of DNA breaks was found to be 0.95 (P < 0.001). CONCLUSION: Collectively, Cd induced membrane impairments, lowered motility, DNA breaks and a decreased rate in the acrosome reaction of bull spermatozoa, leading to sperm dysfunction. Entering Cd in the male gonads and seminal plasma may exert deleterious effects on the animal sperm cells.